Menopause mind meets menopause moment

I gave my package addressed to Philadelphia, PA to the middle-aged clerk to weigh. She looked at the destination and smiled.

"I've been there," she said. "Alcatraz was fascinating."

That stopped me cold. Information went to central processing and did not compute. What was wrong with that statement?

"I loved the Golden Gate Bridge," she added.

Contact! Now in touch with destination neurons.

"Oh, I think you mean San Francisco," I finally countered. She nodded in agreement and gestured to the package.

"I've been there too! Next I'd like to go to Niagara Falls."

That's in Florida, right?
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Want to know why you get menopause moments, or how to tell a menopause moment from the beginning of a real dementia deal, check out Menopause Moments. Please feel free to leave a moment of your own for others to share.

"My toe hurts!"

One of the many best things about being a doctor is that I can be first responder to medical complaints and questions from friends and family. I don't know what your average adult daughter of an elderly parent would do if Mom or Dad complained of a sore toe, but I sat her right down and pulled off her shoe and sock. Here's what I found:

All the toes on the foot, especially the big one, were a dusky red. As I raised her foot for a closer inspection, the color changed to a waxy white. Oh-oh, dependent rubor! That's medical shorthand for the color change that occurs in limbs with arterial insufficiency. When they're hanging down or dependent, gravity pulls red, oxygenated blood into the capillaries. When they're hoisted up, the capillaries empty out, and the foot pales.

Next step, I compared sore foot with other. Both feet were swollen, and have been for several weeks. That's a different story for a different post (venous insufficiency). But painful right foot was cool and shiny, relatively normal left foot was pink and warm, and the skin had a normal texture. Normal feet have two palpable pulses where arterial pulsation can be felt. I checked her dorsalis pedis pulse (top of the foot) and posterior tibial pulse (just behind the ankle bone on the big toe side) and found no pulses at all.

I then pulled out my reading glasses for a closer inspection. No ulcerations on any of the toes, but the tip of the big toe was especially tender to touch. The nails were thick and deformed, another sign of not enough blood flow.

So why did Mom complain of big toe pain while walking? The muscular activity in her leg called for more blood flow, and her aging arteries just couldn't deliver blood all the way to the tip of the toe. As soon as she sat down, she had enough blood to toe to relieve the pain.

So all the wiser for my exam, but what to do? I called the nurse and showed her what was going on. I asked her to leave my Mom in slippers through the day to reduce pressure and trauma to her foot. She hardly walks at all, so hopefully her sore toe, which is only sore on walking, will not be a bother to her. She's not a candidate for revascularization or bypassing narrowed arteries in her leg (a big deal operation with big deal complications for little old people), so it's just another step in the downward road.

Dinnertime chat

My Mom looked around the dining room thoughtfully as she chewed her sandwich.

"Did all these women commit some kind of crime?"

She was relieved to discover that she was not, after all, in a women's correctional facility. "I wondered what I'd done to be here."

After finishing another bit of sandwich, she asked, "Then where am I?"

Slow-Eater-Tiny Bite-Taker

I used to take Aunt Lottie out to eat. We'd go to McDonald's, and she'd order a regular hamburger (39 cents in those days!). To my everlasting amazement, it would take her at least a half hour to finish the sandwich.

Last night, I sat with Mom through her dinner. About 1/3 of the way through her scoop of chocolate ice cream--and some 20 minutes into it--she declared "I just don't have patience for eating anymore. We laughed as I told her she'd become Aunt Lottie, and then I remembered the Mrs. Piggle Wiggle story about the Slow-Eater-Tiny Bite-Taker.

If you never read a Mrs. Piggle Wiggle book, then hurry out and get one from the library. This delightful lady was the savior of many a difficult child, returning domestic peace to their families by curing their bad habits. The Slow-Eater-Tiny Bite-Taker was driving his parents crazy as he minced his way particle by particle through his meals. Mrs. Piggle Wiggle eased him into normal eating habits through the use of successively smaller dishes and teenier portions until the young fellow was weak and famished, ready to devour a regular meal at a regular pace.

Mom enjoyed hearing about Mrs. PW's solution, so I brought the book in today to share with her. She was having a bad brain day, somewhat dazed and sleepy. I settled her into bed for a nap and read her the first chapter of the book, including the description of Mrs. PW's upside down house with a chandelier that sprouted out of the floor.

Mom had her eyes closed and a smile on her face the entire time I read. I finished the chapter unsure whether or not she was asleep, but pleased to see that the smile remained.

Location, location, location

People watching at the ballet last night. Women wearing dresses the likes of which I will never wear again. Actually, the likes of which I've never owned in my life. The successful wearing of which depends entirely on the positioning of breasts on chest, and age plus a couple of kids puts mine south of success.

Avast the Avandia

I give up, no more Avandia. The future is not rosy for rosiglitazone. This diabetic medication has been under fire for some time now as studies link it to increased risk of heart attack, congestive heart failure, and death.

The latest damning evidence comes from a study just published in the Journal of the American Medical Association. Previous negative statistics came from clinical trials, looking at studies studying the efficacy of this drug in controlling diabetes. On average, such research on diabetic drugs is conducted on patients younger than 65. This latest research looked at a 'real-world population,' the over-65 set that has the highest prevalence of diabetes of any age group.

Nearly 160,000 such oldsters were followed for nearly 4 years. As expected in this kind of group, a fair number--around 8%--were hospitalized for congestive heart failure (CHF), and a similar number experienced heart attacks (MI). 19% pitched over dead. Matching the unfortunates on Avandia compared with those on other classes of diabetic drugs, the Avandiful were at 1.6 times greater risk for CHF, 1.4 times higher for MI, and 1.29 times moreso for death.

Given that diabetics, particularly older diabetics, are a high risk group for heart-related troubles, these numbers are strong arguments against the use of Avandia. GlaxoSmithKline, the maker of Avandia, had this to say:

These conclusions are inconsistent with a more robust body of evidence from large, long-term, prospective, well-designed clinical studies, including A Diabetes Outcome Progression Trial (ADOPT) and the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD). These long-term trials in diabetic patients comparing rosiglitazone with other oral antidiabetic medicines show no increased risk for cardiovascular events compared with other commonly used medications, other than the well-known risk of congestive heart failure with thiazolidinediones.

Dr. Steve Nissen of the Cleveland Clinic, a long-time critic of Avandia, countered that it is: impossible to ignore the evidence of increased risk of MI with rosiglitazone, which has been shown in four meta-analyses and now in this independent observational study. The conclusion that rosiglitazone increases the risk of MI is simply inescapable. The contrary 'evidence' cited by GlaxoSmithKline is not credible.

I'm going with Steve on this one. We have good alternatives for diabetic treatment.

Parkinson's disease

I'm often found hanging around a nursing home lately, and my observations confirm that women live longer than men, AND women live more years with disability than men. My casual diagnoses in the dining room based on who can independently and successfully get food to mouth also support the gender statistics on Parkinson's Disease--I'd guess 2 out of 3 old gents at the men's table struggle with it compared with 3 in 20 of the women.

Parkinson's Disease takes out the dopamine-producing motor neurons in the brain in charge of ease and fluidity of movement. Ms. B at my mother's table demonstrates all 4 of the most common symptoms: tremor, slowness of movement, stiffness, and postural instability. As she sits near motionless, slumped sideways in her wheelchair, she also speaks in a whisper-soft voice, another characteristic of Parkinson's. By leaning in close this evening, my ear near her mouth, I could barely make out her German-accented recitation of the recipe for walnut torte.* Unfortunately for Ms. B, the rest of her tablemates are hard of hearing, so I bellowed her words to them...and the rest of the room.

Good heavens, how to save the dopaminergic neurons of my substantia nigra? Be female (check), keep up the estrogen (check), avoid pesticides (hmm?), drink coffee (oh yeah), smoke cigarettes (well, I'll pass on that), and maybe take neuroprotective supplements (melatonin? Prevagen?).
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*Walnut torte, per Ms. B, is heavy on butter, nuts, and whipped cream. This is my kind of dessert. We were all eating institutional orange sherbet at the time.

New Age Old Ladies

I had my favorite female bank president in yesterday for her annual exam. She in clunky black Merrill clogs, me in clunky black suede Clark's. Welcome to senescent high fashion.

A mother's work...

is never done. My patient M is 89. She lives in her own home, cooking for her grandson who lives with her, and for her son who lives next door. Bent over with lumbar stenosis,* she had to give up ironing several years ago due to pain.

But she wasn't in today about herself. She'd driven her seventy-something son over to the office because she was worried sick about his depression and overuse of pain medication. He suffers from esophageal dysplasia (abnormal cells in the esophagus with a high risk of progression to cancer), undiagnosed abdominal pain, anxiety, and depression. When I asked him why he had discontinued his antidepressant one month ago, first he said he was worried it would interact with his other medications, then he allowed as how he couldn't afford it. Out of the corner of my eye I could see M in the other consultation chair shaking her head. The monthly copay for a generic antidepressant was apparently not the problem. Occasionally she'd clear her throat to speak, but when she finally did, her son exploded in exasperation.

Good heavens, thought I as I moderated this geriatric family counseling session, is it possible that thirty-some years hence I'll be driving my son to the doctor's office?
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*A condition where arthritis plus bulging discs in the lumbar spine narrow the space available for the spinal cord to pass through. As a result, nerve impingement causes pain, especially in the upright position. Bending forward from the waist relieves the pain...slightly.

When you just can't keep a promise...

I hadn't seen my eighty-something year old patient in months. She'd been going downhill with dementia and Parkinson's disease. When she came in last week, the immobility of the two diseases working together had made her so stiff she couldn't even get out of her wheelchair alone nor support her own weight once upright. She also was clearly suffering from that failure to thrive thing that turns the frail elderly into shrunken shadows of their former selves.

Her conversation rambled from completely coherent to totally out to lunch. When her caretaker eased her out of her chair, her backside had several 'hot spots,' red and tender areas where the skin was breaking down under pressure on its way to open bedsores. Her husband, who hovered anxiously by her side, also walked with a Parkinsonian shuffle and was in pain from degenerative disc disease and a torn rotator cuff.

"I promised her," he declared as we held a brief conversation out in the hall, "that I would never ever put her in a nursing home." I could've cried...well actually I did. I had made that promise to my Mom, and I couldn't keep it. How many make that pledge only to find out that even tiny little ladies are near impossible to move from bed to commode when they can no longer move themselves?

This is the conversation I wish I'd had with my Mom, and that I've already had with my daughter. Home is always preferable, but there are circumstances where it's just not feasible. When and if that happens, tell your loved ones now while you've got your wits intact that they have your permission to move you to a skilled care facility.

An arterial spin on blood flow to brain

A new technique called arterial spin MRI somehow labels red cells in a way that allows researchers to track the rate of blood flow to various regions of the brain. As a result, they've discovered that persons with Alzheimer's Disease (AD) aren't sending normal amounts of oxygenated blood to areas in charge of memory function. And hypertension plus AD reduces blood flow even more to the parts of the brain where memories are formed and stored.

Previous studies have indicated that controlling blood pressure, particularly with a class of drugs such as Norvasc that dilate blood vessels, decreased risk of developing AD later in life. Dr. Cyrus Raji of the University of Pittsburgh noted: "We cannot say that hypertension triggers Alzheimer's disease, but there does appear to be a relationship to Alzheimer's disease pathology."

Hypertension is already linked to another kind of dementia that results from multiple strokes. Controlling blood pressure clearly is good for the brain.

No free rides

And antidepressants are no exception. The class of antidepressants known as SSRIs-- Prozac, Zoloft, Paxil, and others--have absolutely revolutionized the treatment of depression and anxiety in the last 20 years. Research published this year in the Archives of Internal Medicine, however, suggests that which is good for the brain is bad to the bone.

Canadian researchers studied a group of 5,000 some adults over 50, following their health outcomes over 5 years for incidence of falls and fractures. In particular, they were checking for 'fragility fractures' or those broken bones resulting from minimal trauma such as falling out of bed.

Those subjects who were under treatment with SSRIs were 1.5 times more likely to pitch over in a fall and 2 times more likely to break a bone--not necessarily related to those increased falls--than their colleagues who were toughing out the modern world without the support of medications.

This adds another tough decision in our 'better living through chemistry' kind of lives. SSRIs can literally be life-saving, and their benefits most definitely enhance life's journey for many. As the authors note: "These risks must be balanced against the benefits gained by the treatment of depression with SSRIs."

Transient Global Amnesia (TGA)

For the third time since spring, my Mom experienced TGA. She was sleeping deeply when I arrived at the nursing home; attempts to rouse her for lunch were unsuccessful. I sat reading by her bedside until she started to stir. As she came to, I chatted with her idly about the events of my day. She looked at me with no particular alarm or recognition; her first words several minutes later were "Who are you?".

As the hospice social worker put him, I am 'letting go of letting go,' so I've long ceased concluding rapidly that 'this is it,' call the family, she's on her way out. Instead, I chatted on, casually reorienting her, none of which stuck.

So which parts of her brain were out of blood? Studies using fMRI and PET scanning, both of which are functional scans which indicate what part of the brain is actively metabolizing sugar and receiving blood flow, indicate that brain areas involved in memory function are short on blood during TGA. Specifically, the thalamus, amygdala, and hippocampus are affected. The amygdala is also involved in emotional arousal, and its hypoxic state may have explained why she did not demonstrate the sort of alarm that you'd think someone would feel about coming to in a world that made no sense.

The Electrical Basis of Consciousness

The posterior parietal cortex (PPC) is connected to the medial temporal lobe (MTL) is connected to the prefrontal cortex (PFC) all of which is goosed from below by the ascending reticular activating system (ARAS) rising up out of the brainstem. This crosstalking network keeps us alert and oriented. Per neuroscientists in Georgia and Tennessee, disruption of these circuits can take out IQ points in old folks and the seriously ill. Furthermore, if you happen to be both old and critically ill as in eligible for the ICU, the disruption of these connections takes delirium (temporarily out-to-lunch) and turns it into dementia (permanently out-to-lunch).

The matter with old gray matter is that it starts to dry up. The PPC, MTL, and the PFC all atrophy with age, leaving the ARAS in charge of activating increasingly balky connections. Pain medication, sedatives, and overwhelming systemic illness, however, cause the ARAS to falter. Once the critical threshold of normal functioning is passed, the very sick and the very old lose their tenuous hold on reality. Dr. Max Gunther and his colleagues theorize that this may be why delirium is common in the ICU.*

And I always thought it was the perpetual fluorescent lights, equipment alarms, and overhead pages that put patients over the ICU edge.
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*Gunther, ML et al. Medical Hypotheses Volume 69, Issue 6, 2007, Pages 1179-1182

Spice curries favor with aging brains

My turmeric has arrived. No ethnic cooking with these 300 capsules of East Indian spice, however, because they're brain food for me. Every so often I come across research so compelling that I shut down the word processor and search the web for the best price on a priceless new product. And 150 days worth of turmeric for $9.00 at www.puritan.com seems like a bargain. Here's why.

Alzheimer's disease causes the accumulation of an abnormal protein called beta amyloid (Abeta) in the brain. Great glumps of Abeta destroy brain cells, perhaps by setting off an inflammatory process in much the same way that cholesterol deposits lead to the destruction of blood vessel walls. Anti-amyloid agents theoretically could prevent this degenerative process.

Enter curcumin or turmeric, the yellow curry pigment which is already known to possess antioxidant and anti-inflammatory properties. Scientists working on mouse brains (both inside and outside the mouse) found that curcumin was a potent inhibitor of Abeta aggregation. In other words, a dash of spice on a mucked-up mouse brain prevented little Abeta clumps from growing into big nasty plaques. Furthermore, Tg2576 mice--bred to be particularly susceptible to senility--with advanced amyloid guck in their brains actually reversed their Abeta plaques when Indian curry replaced their standard American chow.

The authors of this UCLA study published a few months ago in the Journal of Biological Chemistry concluded: "These data suggest that low dose curcumin effectively disaggregates Abeta... supporting the rationale for curcumin use in clinical trials preventing or treating AD." They are currently undertaking just that to see if curcumin can improve mental status in patients already affected by Alzheimer's disease.

Topical pain relief for arthritis

This is a topical topic indeed for an aging population trying to stay active yet leery of the side effects of pain-relieving drugs. As you are well aware, non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin are a mixed blessing of benefits and detriments. While relieving the pain of inflamed joints, these drugs also interfere with the lining of the entire GI tract raising risk of gastritis, ulcers, diarrhea, and colitis. In addition, NSAIDs can restrict blood flow to the kidneys and cause loss of kidney function, and acetaminophen (aka Tylenol) is also known to be toxic to the liver.

I have any number of patients who are unable to take NSAIDs for the above reasons. One middle-aged teacher with severe osteoarthritis had a stomach hemorrhage from aspirin taken for her chronic headaches. We keep seeking alternative relief for her--unfortunately, the latest attempt at using Cymbalta (an antidepressant AND a chronic pain reliever) to control her pain caused her blood pressure to soar. Another teacher/patient developed Stage I renal insufficiency from ibuprofen. We have developed a more or less satisfactory pain program for her with low dose, long-acting narcotics.

So the recent FDA approval of Novartis's Voltaren Gel may be the very thing for joints on fire. The topical application of this longtime NSAID produced significant relief for hand and knee pain in clinical trials. Because it is absorbed and works locally, there may be less potential for the kind of systemic side effects noted above. Per rheumatologist Raymond Flores, MD: "The advantage to this preparation [compared with oral painkillers] is that it seems like it's providing comparable relief but with little systemic absorption."

Blood Pressure Shot?

This is something entirely new and different under investigation. The problem with blood pressure medication is that it must be taken daily and forever. Daily and forever is rough, and people are reluctant to comply with this D&F business. And even if you do take those BP pills each morning, they are often long gone by the early a.m. hours of the following day when blood pressure rises in readiness for upgetting. As a result, early a.m. hours are the most common time for strokes and heart attacks, especially early Monday a.m.'s.

A Swiss company that apparently specializes in searching for vaccines for all that ails you (nicotine addiction, obesity, Alzheimer's, melanoma, etc) has developed a vaccine against angiotensin II, that pesky little molecule that constricts your blood vessels and causes a rise in blood pressure. Now if you happen to be dehydrated or hemorrhaging or slogging through the mall the day after Thanksgiving looking for Christmas gifts, a little angiotensin boost to the blood pressure assures that you will stay alive long enough to get water, blood, or a seat at Cinnabons. But if your kidneys are a little misguided and working overtime in the mistaken impression that your blood pressure is low, poof! angiotensin II is not a good thing.

Enter CYT006-AngQb (well they're going to have to come up with a new name, aren't they, if this shot ever has a shot at market popularity). This is a "viruslike particle-based conjugate vaccine that targets angiotensin II" meaning that it presents an angiotensin-ish sort of look-alike molecule to your immune system that then learns to personally dispose of too much of this bad boy.

In phase II trials, CYT006-AngQb was safe, well-tolerated, AND effective. Blood pressure fell a modest 5.6/2.8 points by day in the vaccinated group compared to those who got a painful placebo shot. That means those with elevated blood pressures of say 140/90 fell to about 134/87, a drop that would produce significantly less risk of heart attack and stroke over time. Better yet, the ones who got a real shot at the real shot experienced a wee hours BP drop of 25/13 so that those same hypertensives who registered BPs of 140/90 at study's start were mellowed down to 115/77 in the early a.m. 14 weeks later.

Ideal blood pressure is 115/75. Cardiovascular risk starts to rise with anything more than that. In case you were still laboring under the impression that 120/80 is okay, sorry, they've changed the rules on you! But soon, perhaps, you will have a shot at normal blood pressure, and you'll perhaps only need a booster every 4 months or so.

End stage renal disease and EGFR

Well who really gives their kidneys a thought? Patients all worry about cancer, and rightly so, and everyone is finally heeding the call to worry about their hearts. But headline news at medpagetoday.com alerts us that baby boomers are entering the age of end-stage kidney disease.

This coincident with the addition of a new lab value on routine lab printouts--EGFR. This stands for estimated glomerular filtration rate which is a fairly accurate estimate of the efficiency of kidney function. The National Kidney Foundation encourages that all persons "know their GFR number," so now we've got another number to add to our blood pressure, blood sugar, and serum cholesterol statistics. If you know your creatinine (a measure of waste in the blood included on most standard lab panels), you can know your GFR with this handy tool: EGFR calculator.

My discussions with patients about their routine lab work has, therefore, acquired a new level of complexity. The lowered thresholds for fasting blood sugar and optimal cholesterol already require extra time to interpret, but no way to explain EGFR and its implications in a sentence or two.

Results of this screening test are divided into normal (>60), and low. The things that make GFR drop are prevalent in an aging American population, and include hypertension, obesity, diabetes or even prediabetes, and the overuse of analgesics such as Tylenol and Advil. Regular use of diuretics can also contribute to diminished kidney function.

There is information that routinely passes right over the heads of most of my patients (extra weight is bad for you) and some results that finally cause them to sit up and take notice (you have diabetes). Unfortunately, 'you ought to lose weight,' when ignored for years, result in 'you have diabetes.' 'Your kidney function is low' is turning out to be an eye-opening phrase and is one best heeded while lifestyle changes can turn the trend around.

Nutmeg

I never think about nutmeg except briefly at Thanksgiving to once again note that I have none on my shelf when it's time to make pumpkin pie. Thanks to Dr. Jacob Schor, however, I must reconsider my nutmegless status in the interest of keeping my marbles intact.

This Denver naturopath is a wealth of knowledge about natural remedies of the herbal variety and their value in keeping body and mind intact. He muses over nutmeg whilst grinding same for his holiday recipes, and he includes both recipes and scientific abstracts in his current newsletter.

Of particular interest to me in my never-ending quest for brain protective strategies is news from India about the acetylcholinesterase inhibiting qualities of this spice. Acetylcholine is a neurotransmitter which allows neurons in charge of memory functions to communicate with one another in order to both make 'em and keep 'em (memories that is).* Acetylcholinesterase is the enzyme that breaks down acetylcholine, and the inhibitor of same allows acetylcholine to work longer in the gap between memory-preserving neurons.

That is how current medications for Alzheimer's disease, including Aricept and Exelon, work. London pharmacologists screened a number of Indian herbs for this activity and found that even weensy bits of nutmeg extract diminished the activity of acetylcholinesterase inhibitor by 50%.

I don't even know if I really like nutmeg between never having it in the cupboard and not having a very discerning palate. I think I could learn to like it, however, if it supports my aging brain!
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*This is why anticholinergic medications like benadryl and other antihistamines (used for allergies and sleep), oxybutynin (used for bladder control), and amitryptilline (used for sleep and chronic pain control) can befuddle susceptible older persons and should not be used.

Leftover life to stow

Residual stuff. Another one of the problems with dying is a lifetime of memories in the form of treasured stuff, and what to do with it all. Hire someone, one friend told me, "I know a great gal who will pack up all her clothes and belongings for $35/hr." Oh my, that just doesn't feel right to me, so I'm going the PYOS route.

The low point? Advertising furniture on Craigslist.com and having a rocket scientist and his MD wife show up and dicker with me over the price of two lovely chairs from her living room. The high points? Three sets of warm and wonderful people coming by to take her plants...for free. One young lady smiled at the grouping of pots around her at the elevator and chirped "Hi guys." She then sent me an e-mail a week later to tell me how much she was enjoying "the pleasure of their company."

Another fellow showed up after work on a brisk and blustery late afternoon. He struggled to get the really big plants out the door with nary a leaf lost, then fretted over whether or not the shock of the cold air would harm then. He too sent a note of thanks with assurances that all plants survived the drive to their new home.

This weekend, my mom's caretaker from heaven (who allowed me to keep her home weeks past when it was really feasible) came and picked up the beds and loads of linen. That which she can't use is destined for family in El Salvador.

My lesson? I would much rather send all these things complete with attached memories out the door with people who appreciate them, and free works for me. That strategy makes for bright moments in a difficult undertaking.

Tea Drinking May Help Preserve Hip Structure in Elderly Women

Better hip structure, well who doesn't need that? The news, however, on an in-depth read is all about bone density and not about shapely. Oh well, this is good news nevertheless.

Australian researchers checked out aging Aussie hips in tea drinkers compared with their tealess peers. Over 4 years of analysis, those who took tea topped the teatotalers with respect to bone mineralization, losing a mere 1.6% of their hip density compared to 4.0% lost by the non-tea group.

I just bought a box of green tea powder from some hyped up tea-selling teenager at Park Meadows Mall. It's sort of disgusting, but if it helps me hang onto my hips, I'll choke it down.

The trouble with dying

Well, I suppose there's lots of troubles with dying. But the one that strikes me most through the years, and now most immediately as my mom winds down, is how difficult the process is, far more so than the actual final event.

Unless one dies suddenly and unexpectedly, one never goes from lively to dead in a quick and easy process. I spent the summer waiting for my mom to have the big one, a quick and catastrophic stroke. Instead, she has had a series of tiny strokes that gradually have cut her easy mobility down to a standstill. First we battled bedsores from the lack of movement, now it's the lungs.

No movement means no deep breathing and no clearing of secretions. Her oxygen levels are now dropping, and it's taking more and more supplemental O2 to get them back up to near normal. I suspect she's throwing tiny clots from her barely moving legs and pelvis into her lungs, and these pulmonary emboli are blocking off the interface between air and blood that's critical to oxygen uptake into the bloodstream.

What a sad and slow downward slope this continues to be.

ACE inhibitors back in mobility news

I just read an interesting item about ACE inhibitors, a class of drugs used to treat hypertension, heart failure, and also known to help prevent kidney disease in diabetics.

Previous research suggested that ACEIs (such as lisinopril, enalopril, Altace, etc.) may provide a boost to aging muscles as well as to the heart. Over 600 women participating in the Women's Health and Aging Study were sorted into groups based on the type of blood pressure medication they were on. Over the three years of the study, those subjects on ACE inhibitors had significantly less loss of quadriceps muscle strength and far less decline in walking speed.*

The latest study was conducted by Deepa Sumukadas, M.D., of the University of Dundee, and colleagues (1). The researchers randomized 130 oldsters--all of whom had mobility problems--to receive an ACEI called perindopril or placebo over the course of 5 months. Those in the real deal group displayed improvement equivalent to six months of exercise training, motoring 31.4 meters further in six minutes than the control group. Perhaps creeping is more the operative word here than motoring, but those extra meters crept represented significantly more mobility.

Ann Cranney, M.D., of the Ottawa Health Research Institute had this to say, "Their results are promising and lend support to the hypothesis that ACE inhibition has a positive effect on physical function, possibly through effects on skeletal muscle."

Well why not, I'll see if a course of ACEIs brings back the fidgets to my immobile old mom.
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*Diminished walking speed and muscle strength have been shown to predict the onset of disability, and worse--nursing home admissions and death--in older adults.

(1) Sumukadas D et al. "Effect of perindopril on physical function in elderly people with functional impairment: a randomized controlled trial." CMAJ 2007;177(8):867-74.

Dying of Immobility

This past summer, I assumed my mom would die of a massive stroke. Clearly, however, her blood-to-brain troubles are of the small vessel variety, and no one directly dies of from the death of a few neurons here and a few neurons there.

Her demise, it seems, will be the consequence of her increasing inability to move. Our bodies were built for movement, and the little fidgets, the yawns, the coughs, the throat clearings, the up from the chair and down again even if only to get the last piece of cake from the kitchen are necessary to the healthy functioning of our body. Okay, maybe not the cake, but certainly the effort spent to get it.

I'm not sure what took out those little adjustments in my mom's daily life--weakness, pain, the little strokes--but she doesn't even shift her weight in her chair anymore. As a result, she's got several 'hot spots' where the skin is red and inflamed, ready to break down into bedsores and chairsores. She increasingly chokes a little on her food, and her cough is weak and ineffective. She is now susceptible to pneumonia, a UTI, skin infections, and blood clots.

This is the way the world ends
This is the way the world ends
This is the way the world ends
Not with a bang but a whimper.
T.S. Eliot

Vertical ridges in nails

Ridgy and brittle, that's nails after menopause. While these vertical ridges may be a 'normal' part of aging, either the ridgy nature of the nail or the underlying cause of the ridges makes for nails that break under ordinary circumstances such as brushing your fingertips on the wall as you switch on a light.

After noting how my aging not-so-goldilocks responded to local progesterone cream, I decided to try the same on my not-so-goodlooking nails. Now, 18 months into the experiment, only two of my nails remain beridged and bedraggled. All the other groovy spots have grown out, leaving the attractive oval nails of old that I had when I was young.

I used over-the-counter progesterone cream (Puritan is a good place to buy) for the nail purpose. I wonder if I might've seen quicker results with the prescription strength cream I use on my scalp.

Dementia Dialing

I commented to a friend recently on my mother's habit of pulling out her personal phone book on good days and dialing friends and family. She informs us, then, of her latest whereabouts on an art museum tour, in a motel, or in a research facility, and then chats of the ordinary as if nothing about the call is extraordinary.

My friend noted that this reminded her of her mother's 'drunk dialing,' and others have also remarked on the similarities with phone tears they've been on when inebriated. I wonder what short circuits underlie this habit, and whether or not the two conditions--dementia and drunkeness--are at all alike in a brain sort of sense. Maybe the common denominator is simply a lack of impulse control.

Brainstorms: The aftermath

Mom's latest stroke event on Sunday left her immobile and speechless that day. As always, and to my ongoing amazement, she recovered her speech and movement by the next day, although each function was just a bit more impaired. But this time, she returned profoundly depressed.

After sitting around with her for an hour, quietly inspecting the scene out the window (no point in talking--all conversational gambits met with 'I don't care'), I cornered her doctor in the hallway to come discuss med adjustments.

He entered the room with nary a greeting nor a glance in her direction, talking all the while to me about the difficulty of treating post-stroke depression. Even when I specifically asked him to include her in the discussion, he never once spoke or looked at her. I seriously considered the possibility that he himself was neurologically impaired so bizarre his behavior.

As he examined mom, remarking about her lack of breath sounds (had the man not read her chart nor examined her before?!?), my mom and I started making faces at one another. At least his visit lightened the day, along with the chocolate cake on the dinner tray and a couple of Advil for the stiff joints from sitting all day.

On searching Medline tonight, I find that post-stroke depression can be treated, and not just with cake and Advil. I don't know how anyone survives medical care without an advocate on their case.

The dangers of low HDL

High density lipoprotein (HDL) is a carrier protein that takes cholesterol out of tissues such as your blood vessel walls (where you do NOT want it) and carts it back to the liver for elimination. Low density lipoprotein, on the other hand, carries cholesterol from the liver where it has been manufactured or the gut where it has been absorbed from dietary sources and moves it out to the cells. Some cholesterol is essential to life (we make cellular membranes and hormones out of it for example), but too much in the wrong place can lead to an unwanted build-up of fatty schmutz in the arteries.

The 'my oh my will you look at that low LDL' attitude that caused us doctors to beam at you patients is starting to change. A study out of the Palo Alto VA medical Center* emphasizes the importance of HDL levels to cardiovascular health.

Researchers there retrospectively studied the old vets (average age 65) to correlate HDL levels with the incidence of hospitalization for ischemic heart disease including heart attack. All of the 6,357 subjects had an enviable LDL level below 60 mg/dl.

Those patients in the lowest HDL quartile with HDL levels of 28 or below had a 1-year incidence of ischemic heart related troubles of 8.5% compared with those in the top HDL quartile whose HDL levels were 64 or above.

Too bad its currently very difficult to boost HDL levels. Clinical trials of Pfizer's HDL-raising torcetrapib were abruptly halted at the end of last year due to a pesky 60% increased risk of death in the groups receiving the drug plus Lipitor compared to those on Lipitor alone. Meanwhile, weight loss, exercise, and a whiff of alcohol as part of a healthy lifestyle are helpful in nudging HDL levels upward.
_____
deGoma, EM. Presentation at the annual session of the American Heart Association

Shining light on prostate cancer risk...

UV light that is. I've mentioned previously that vitamin D is a chemopreventive agent against several types of cancers. North Carolina investigators wondered if exposure to sunlight early in life has a more potent protective effect against prostate cancer than fun in the sun later in life.

They examined data from the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study*. Using solar radiation in the state of birth as a measure of sun exposure in early life, the researchers looked for correlation between childhood sun exposure and subsequent development of prostate cancer in adulthood.

Men born in regions with high solar radiation had half the prostate cancer risk compared with men born in cloudier regions. Those who moved away from overcast skies to sunnier climes as adults halved their risk of fatal prostate cancer although their overall prostate cancer risk remained the same as peers who stayed with the gray.
_____

*Cancer Epidemiology Biomarkers & Prevention 16, 1283-1286, June 1, 2007.

Got Cake?

Mauigirl commented on a previous post about weight loss in dementia about the possible correlation between lost pounds and diminished taste perception. Here's an item of interest:

Turkish researchers have discovered the reason why aging women might cut themselves a big piece for breakfast. Their study, published several years ago in the British Dental Journal, found that postmenopausal women had a significantly diminished ability to sense sweets rolling over their palates.

While the women demonstrated no altered sensitivity to salt, sour, or bitter tastes compared to an age-matched group of old guys, they were not near so moved by a gob of Turkish taffy crammed in their mouths as the gents were. Nearly half the female test subjects noted that they had changed their eating habits in favor of sweeter food.

If you are enjoying your a.m. pastry and coffee with nary a care for the consequences, the researchers warn, "The crucial issue to be aware of is that the possible changes due to menopause can lead to more serious health problems, although these changes may not be uncomfortable to the patient."

Flax Facts

Apparently giving us fifty-something ladies with hot flashes our daily crushed flax seed may decrease the heat by half.

Investigators took a group of our colleagues* with at least 14 flashes per week and fed them crushed flax seed. The phytoestrogenic facets of flax--i.e. its ability to occupy cellular estrogen receptors and tweak them in an estrogenic sort of way--made this strategy an appealing one for temperature control. Indeed, those ladies who did not find themselves distended and gassy from the addition of flax were pleased to find an improvement in their symptoms.

One observation about hot flashes from years of personal and professional experience: When I ask women if they are flashing, and they hedge and say well perhaps maybe occasionally they might feel something like that, they are NOT having hot flashes. If it's a hot flash, you KNOW it.
_____
*Pruthi S, et al "Pilot Evaluation of Flaxseed for the Management of Hot Flashes" J Soc for Integrative Oncology 2007; 5: doi 10.2310/7200.2007.007.

Weight loss and dementia

Women who develop dementia are much more likely than men to be involved in making meals, and, therefore, it is likely a loss of interest in food preparation and eating during the prodromal phase of the disease has an impact on their weight.
---David Knopman, MD Mayo Clinic

Calorie deprivation prolongs life. Skinny yeast cells, fruit flies, threadworms, monkeys, and women are more likely to become skinny old yeast cells, fruit flies, etc. The problem, however, with skinny old ladies is that they are more likely to be demented when old than their fleshier colleagues.

Mayo Clinic investigators reported in Neurology* that women who lost cognitive functioning lost significantly more weight in the decade prior to the dementia diagnosis than a control group of aging women who maintained brain function through the years. Interestingly, there was no such correlation for old guys getting goofy, suggesting that the problem was not so much eating well when presented with food as buying and preparing the food period.

Dr. Knopman notes that this obseravation is not useful for diagnosis as "the weight loss was so subtle and so small and nonspecific." So skinniness does not beget dementia, but rather the first glimmering of dementia (a loss of interest in usual activities such as food preparation) leads to weight loss.

Shoot, I lost interest in food preparation after number one child left home. I am completely enthusiastic, however, about food prepared by others.
______
Knopman, D et al. Neurology. 2007;69:739-746.

Estrogen for neuroprotection

My Dad died with Alzheimer's some years back, and now my Mom is checking out with multi-stroke dementia. As a result, my interest in neuroprotection--i.e. strategies to bring all neurons to the finish line along with the rest of me--is stronger than ever. A new study from the Mayo Clinic confirms my belief that estrogen is an important part of my save-the-brain program.

After the Women's Health Initiative rocked the menopausal set with the news that hormone therapy may increase risk of dementia, neurobiologists were disturbed that these results did not fit with hundreds of studies on cells, lab animals, and humans that suggested otherwise. They conjectured that estrogen has a different effect on healthy brain cells compared to its effects on brains already gummed up with the effects of Alzheimer's or compromised blood supply.

Dr. Walter Rocca and his Minnesota colleagues identified a group of women who had their ovaries removed before age 50 twenty or more years earlier. The incidence of dementia in those women who did not receive estrogen post-oopherectomy was 10% compared with a 6.6% rate in the sub-group who did take estrogen after surgery. The researchers concluded that estrogen replacement therapy is beneficial to brains in this younger population.

Per Dr. Rocca: Where and when estrogen switches from being protective to harmful is the next big question. One of my patients would say most definitely that the benefits extend to the after-50 newly menopausal set. She is a media spokeswoman for a large organization. Prior to starting estrogen, we began to work her up for early dementia as she lost the ability to find the right word at the right time during press releases. We called off the work-up, however, after she began estrogen therapy and regained her ease at interviews. And that's just one of many stories I have to support the estrogen-brain connection.

Postural hypotension

Assuming the upright position is a recurrent battle against gravity. Our cardiovascular needs to adjust in order to assure an uninterrupted supply of oxygenated blood to the brain. Old people lose some of that vascular tone that allows for seamless postural transitions.

I've mentioned before that my Mom is having postural TIAs. Within 10-15 minutes of getting out of bed, parts of her brain start to shut down due to lack of blood flow. She abruptly loses the ability to find the right word, a condition known as expressive aphasia. A brief but deep sleep often restores her language function.

Susan Moon's mother blacks out from postural hypotension. Here's an excerpt from her poem in the latest issue of JAMA:

Before my mother folds inward from her knees,
I fight gravity's tug by pushing her forward--
just a few more steps to the chair--
but she is already leaving me,
hip and knee closing like books
all the way to the floor.
A few heartbeats later
she opens her eyes, gazes around as if
she's never seen this world before.

Ectopic calcifications

Right mineral (calcium), wrong spot (skin, muscles, tendons, etc.). KGMom commented on a possible connection between the class of drugs called bisphosphonates (Fosamax, Actonel, Boniva, Reclast) and calcifications in the body.

I'd not read of such a connection, so I looked it up on PubMed. No articles reported a connection between the drug and ectopic calcifications. In fact, check this out:

Bisphosphonates are an old class of compounds. They were used in the 1930s as antiscaling and anticorrosion agents in washing powders and water to prevent the deposition of calcium crystals. Those basic functions were later utilized in an attempt to prevent ectopic calcifications in humans. The early studies demonstrated that bisphosphonates had a strong affinity for bone. That property was first exploited when the compounds were used for "bone scans." Currently, the drugs are used for treatment of hypercalcemic conditions, abnormal bone remodeling, Paget disease, malignancy, and osteoporosis.
--Rodd, C. Peritoneal Dialysis Int. 2001;21 Suppl 3:S256-60.

Now how do you feel about a year-long injection of an antiscaling agent? Amazing where these drugs come from.

The Perfect Storm of...

midlife crises begins. Son to college today. Nest empties. Husband retires and vacates office Saturday. Nest fills. Mom to nursing home Monday. Heart breaks.

Reclast

Will Sally Fields jump ship from Boniva to Reclast? Maybe Meryl Streep or Susan Sarandon will be signed on instead.

The FDA just approved this once-a-year treatment for osteoporosis. One fifteen minute IV infusion, and your bones are set against untimely fractures for 12 months. A trial on more than 7,700 women of age found that Reclast decreased vertebral fracture risk by 70%.

What creeps me out, however, is the possibility that this drug, like it's chemical cousin Zolmeta which is also delivered by IV infusion, will increase risk of osteonecrosis of the jaw. This condition occurs rarely in patients who have received bisphosphonates, particularly by IV, and then undergo dental procedures. It causes dead bone in the mouth, resulting in the horrific sort of scenario that both fascinated and repelled those of us who flipped through medical textbooks when young. Also the sort of scenario that attracts personal injury lawyers.

I have no idea whatsoever if this drug is associated with ONJ. I am reluctant, however, to recommend IV drugs for osteoporosis prevention or treatment for this reason.

Menopausal women are having less sex and it's impacting our relationships. I have heard that a lot of women would rather go shoe shopping than have sex, and that concerns me.
---Karen Giblin, Founder of the Red Hot Mamas organization

Makes me nod my head and laugh.

At home 'til the cows came home

I give. I just can't do this home care thing anymore. Two episodes that helped me realize it was time to move Mom to a nursing home:

1) She had a TIA that took out her ability to stand and walk.

2) Those darling cows above--Elsie the Cow and Ferdinand the Bull--took up residence in the corner of her bathroom.

Hallucinations and too weak to walk is too much for me.

Blood pressure meds and the oldest of old

[This study] is fascinating and hopefully will convert the very last knuckleheads who still argue that blood-pressure elevation in the elderly is a compensatory phenomenon serving to force blood through sclerotic arteries to the target organ.
---Franz Messerli MD, Columbia University

Dr. Messerli is referring to the HYVET, aka Hypertension in the Very Elderly Trial which studied the use of blood pressure medication in 80+ year olds with respect to decreasing the risk of stroke and dying. Preliminary results were so significantly favorable that the trial was halted, and those oldsters in the control group will now be offered the real deal meds.

Through the years, controversy has surrounded the issue of whether or not to treat hypertension in this population. Those who say nay argue that blood pressure elevations in this group are largely a result of their stiff old arteries. Furthermore, they note, lowering blood pressure diverts blood from those vessels most blocked by cholesterol schmutz.

So back off nay-saying knuckleheads and treat granny's elevated pressure with meds.

Polypharmacy, polydocs

One of my favorite eighty-somethings came in today to talk about simplification of her medical care. She was on six drugs, five supplements, and visited at least nine doctors including me.


The drugs were gold--two for hypertension, one for cholesterol, one to duck a second stroke, one for depression, and one for osteoporosis. She also took vitamins E and C. As I've mentioned before, the evidence in favor of these antioxidants is weak; in fact they may decrease the efficacy of the lovastatin she takes to lower cholesterol(1) and E may increase her risk of congestive heart failure(2).


The docs? A veritable medical village to support this senior! She had four(!) orthopedic specialists to hold up her skeleton alone--a podiatrist for the feet, a hand specialist for her trigger finger, a back-up man to prop up her spine, and slightly more general type orthopedist who graciously agreed to care for her knees as well as her hips.


No way to to pare this roster down to a pair o' docs. Now how ironic was this--after her visit to simplify her care, she hit her leg on her car door as she left and tore a huge flap of skin up off her leg. I would've sent her to a surgeon, but skin that fragile can't be sutured. We steri-stripped her leg and sent her home.
_____

1. Cheung, MC et al. Arterioscler Thromb Vasc Biol. 2001 Aug;21(8):1320-6.
2. Marchioli, R et al. J Cardiovasc Med (Hagerstown). 2006 May;7(5):347-50.

Not bad for a short person

I recently went out to the waiting room to retrieve my first patient of the day. "Whoa Judy," she hooted from her seat, "Have you gotten shorter?"

Argh, do not tell a middle-aged woman she's getting shorter. My face must've fallen because she quickly backtracked: "It's just that you look so tiny." As if that improved the situation--she may as well have remarked 'But you don't sweat much for a small woman.'

The entire incident made me feel a little short with her.

I give up...

two blogs are too many for this busy midlife. While I will occasionally park a thought here in the future, please visit Denver Doc Online for up-to-date health news for the young and aged alike.

Your momma is so tired...

she couldn't even climb up the Iowa Fatigue Scale. Actually, my momma is so tired she can't even turn on the computer.

If you are dragging your sorry back end through this summer and wondering if it's more than just the heat, check out The Iowa Fatigue Scale and see if you pass or fail. Life's too short to be so tired.

Too many toes sign...

Get a buddy to stand behind you and look at your feet. A positive 'too many toes sign' is present if more than the pinky toe can be viewed from the back. This toeful look is created by the outward splay of a foot caving inward due to a fallen arch.

Who knew? I knew my arches went to ground years ago following months of burning pain. Today I found out that my acquired flatfeet, right worse than left, are taking my knees on an inward collapsing course which is painfully grinding away the outside compartment of the joint.

The good news is that getting my arches off the ground and my ankles back in alignment may save my knees from degenerative destruction.

Don't give up on the calcium and D!

A number of my patients quit taking calcium and D in 2006 after getting the wrong impression from news reports out of the WHI that these supplements did not help preserve bone density.

As an editorial(1) accompanying the article points out, calcium and D are necessary to prevent bone loss, but not necessarily sufficient to do the job alone in women at risk for osteoporosis. As Dr. Joel Finkelstein points out:

Calcium with vitamin D supplementation is akin to the ante for a poker game: it is where everyone starts. If the clinical data suggest that the risk of fracture is significant, however, a woman probably needs something more.

Furthermore, Dr. Finkelstein and others have noted that the vitamin D dose used in this sub-study of the WHI was only 400 units, and other studies have suggested that doses of 700 units or more are needed to positively affect bones.

Here's the other part of the report that never made it into the popular media. Only 59% of study subjects actually stuck with the program and took the calcium and D as directed. If the data was analyzed for hip fracture protection in the compliant group alone, there was a 29% risk reduction.(2)
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1. NEJMVolume 354:750-752 February 16, 2006 Number 7
2, NEJMVolume 354:669-683 February 16, 2006 Number 7

Perturbation-based Balance Training

Here's a chance to push around an old person and get away with it.

Now it's not entirely clear how these Toronto doctors perturbed their elderly subjects, but Dr. Brian Maki and associates did make it clear that their subjects wore safety harnesses. They were suspended from the ceiling perhaps? The test group was then pushed and pulled about in a challenging and unpredictable manner during a training program. At the end of the study, the tottery oldsters had greatly improved their balance-recovery reactions.

Improved balance control decreases the risk of falling and improves the physical confidence of older individuals. Falls resulting in grave physical injuries such as a fractured hip and pelvis often initiate a downward and ultimately terminal chain of events in the elderly.

Sunday morning's splitting headache of a mini-stroke dealt the final blow to my mom's ability to form new memories. Dying, from what I've seen, is not so hard, but the road there is a helluva journey. I wish us all someone near and dear to go the distance with us on that final trip.

Ritalin miracles

Coincidental or cause and effect? Yesterday I started my elderly mom on Ritalin, just a teensy dose, to see if its neurostimulating effects might put her aging brain cells back in touch with one another.

The phone rang early this a.m. Ordinarily, early a.m. phone calls are either disasters or my friend J calling because some new symptom makes her think she has cancer. Neither disaster nor phobias this a.m...the caller was my mother full of enthusiasm and tales of a night of interesting dreams. Her usual state of mind at 7 a.m. is befuddled if she's even awake at all. This caller, however, was my previous mom working with parts of her brain's frontal lobe that haven't fired in weeks.

Jacking up granny

My mother is increasingly dispirited and contentless as the result of numerous 'mini-strokes.' Doubtless over the last 5 years, and certainly in the last few months, she has lost small glumps of neurons to these little vascular blows, no one of which notable in its effects, but collectively devastating. As a result, certain critical connections have been lost, and now they've become numerous enough to leave her more than a bit unstuck in time and space.

As I sat and talked with her today--or rather she sat and I talked--I wondered if a little nudge to the noggin might not improve her situation. Ritalin certainly restores content to the distracted teenaged brain--so why not to the ischemic elderly one?

I used my handy daughter-as-doctor option to implement the plan on the spot. 5 mg. of Ritalin and one hour later, the change was astounding. She began adding her own observations to my conversational gambits, putting together concepts, pulling up related memories, and, best of all, when her sister called to chat, began laughing with pleasure over a story my aunt shared.

Her blood pressure rose from 80/60 (barely enough to pump blood up north to the head) to 134/80. While an increase in blood pressure and heart rate might not necessarily be the best long-term option for old hearts, the pleasure of laughter is worth it for us.

In praise of chiropractors

What does the aging parent of a soon-to-be college student do after a day at freshman orientation?

Speed down I-25 from Greeley to Denver, scarcely able to flex my right knee to hold the accelerator steady at 80 MPH. What was the big hurry? Had to get that aching knee and its cracked lateral meniscus to the local chiropractor before his office shut down for the day. And I made that university to office drive in one hour and 10 minutes door to door.

Now Dr. Visentin, the capable if somewhat unusual chiropractor who practices next door to The Mozart Lounge whose patrons smoke out front on the sidewalk for want of an outdoor patio, is not going to fix my aging meniscus. There's no give-backs on damaged cartilage. He can and did, however, line up my knee as best it could be lined after I stumbled and jerked it into misalignment this a.m. as I rushed to get the incipient student out of his bed.

If it takes a village to keep a half-century-plus doctor on her toes, count Dr. V in my census.

Stay cool AND dry

Here's a news flash for hot, older women. Ditropan, tried and true for the agony of the overactive bladder, has a favorable effect on diminishing the agony of the menopausal hot flash.

Denver Hospice

Wednesday was Bridge Day for my mom. Two weeks ago, however, her bridge group found her doubled over in pain and unable to express what was wrong. They called me at work, and as I sped to her house down I-25, I pondered what I would find and what I would do.

My mother's express wish for some time now has been to pass up 911 and ERs and any sort of diagnostic tests. Yet if she was in pain, if she was having a stroke, how could I just keep her at home and keep her comfortable?

Fortunately, the episode that day was not the big one, just one in a series of more or less transient little ones. She recovered her speech, and lord only knows what the abdominal pain was about. The entire episode, however, was a wake-up call as in wake-up and get a plan. This downward decline is a stepwise path to the end of the line, and we need help.

I called Denver Hospice at 1 p.m., and at 4 p.m. sharp their admissions nurse (a large and gentle man who looked like an ex-college linebacker) was at the door. Within an hour, we had a team in place--nurse, CNA, social worker, and chaplain.

Now I've got a replacement number to 911; I can call 303-321-2828 with our emergencies, we don't have to go this route alone.

Bad Brain Day

Or more correctly, bad brain daze. Now that my mother is firmly entrenched in this piecemeal loss of brain tissue, neuron by neuron, day by day, the events of the last several years make more sense.

Dr. Sherwin Nuland, author of How We Die, describes the cumulative effects of multiple tiny strokes:

Many strokes are so small that there are few or no immediate significant symptoms to indicate what has taken place. But with time, such little strokes accumulate, and the evidence of gradual deterioration becomes evident to even the most casual observer..The subtle process of infarcting brain may go on and on, accumulating irregular stepwise degenerations in cerebral function for as long as a decade or more...

He goes on to note that those elderly persons so affected are 'betrayed by their cerebral circulation.'

Dr. Nuland and pathologist Dr. Walker Smith reviewed autopsy results on 23 old ladies and men with an average age of 88 at death. While 7 of the subjects officially had heart attacks as their final exit line and only 4 had strokes listed on their death certificates, 'Every one of these twenty-three people had advanced atheromatous in the vessels of the heart or the brain, and almost all had it in both.'

In retrospect, on a host of days in the past few years when my mom's been dizzy or tired, she was having a 'bad brain day,' sending a few more neurons into oblivion.

Postural confusion

Turns out that an old heart has trouble perfusing an old brain through upstream corroded blood vessels when the old owner gets out of bed. I just figured out that why my mom has transient ischemic attacks or TIAs every mid-morning. At that point of the day, she's been up in a chair for an hour or so, and those narrowed cerebral blood vessels just shut down as her blood pressure falls.

Great. By then, she's too confused and weak to remember to lie down.

Imploding into eternity

...we die of old age because we've been worn and torn and programmed to cave in. The very old do not succumb to disease--they implode their way into eternity.
Sherwin Nuland, MD, "How We Die"

As my 87 year old mother implodes her way piecemeal towards the end, one neuron at a time, I was most comforted by Dr. Nuland's book, particularly the chapter "Doors to Death of the Aged." The inevitability of death for the aged supports our decision to mark this passage for Mom in her home with no ERs, no 911, no tests, no hospitalizations.

Nevertheless, it's rough.

We've come a long way...

Here's a backpacking metaphor for the Boomer's aging transition.

Our generation was the first to strap on baby, throwing Junior into a Snugli and heading out wherever we needed to go. Junior, fortunately and at last, is out the door and on his own (well perhaps not financially, but at least no longer on site). Now the makers of Snuglis bring us AirLift so we can strap on our oxygen tanks and step out, somewhat more slowly, wherever we care to step.

Pristiq: Non-hormonal rx for hot flashes

Wyeth is working hard to bring new products into the menopausal market after losing their leading edge when Premarin got such bad press out of the Women's Health Initiative.

Investigators recently reported that desvenlafaxine, a metabolite of Effexor that will be dubbed Pristiq had a significant effect on hot flashes and sleep disturbances associated with dwindling estrogen levels during the transition into menopause. Dr. Margery Gass called it "a major breakthrough for women: the first nonhormonal therapy for menopausal symptoms."

The results of these studies presumably will soon be presented to the FDA as Wyeth seeks approval to bring Pristiq to pharmacy shelves.

Coffee a lifesaver?

Well sure, coffee in the a.m. is a bit of a lifesaver. But in elderly persons with normal blood pressure, research suggests that it may be the real deal.

Researchers worked over the data from the National Health and Nutrition Examination Study (NHANESI), checking out who checked out with cardiovascular disease as correlated with their coffee-drinking habits. Those persons 65 and over without severe hypertension who knocked back 4 or more cups of coffee each day were nearly 50% less likely to end up dead from heart disease compared with the decaff gaffers.

So what's the explanation? Investigators aren't sure but speculate that coffee's pressor effect (i.e. its ability to raise blood pressure) may protect old quaffers from the harmful hypotensive effects of eating. This drop in blood pressure after a big meal has been linked to heart attacks and death.

So drink up, and brew a cup after dinner for your old mum as well. That caffeine buzz may keep your tickers ticking.

If Barbara Hillary...

can make it to the North Pole on skis...at age 75...after winning a battle with lung cancer at 67...you can make it to the gym today!

Beans, beans, good for your heart...

I suppose we could live without part 2 of that childhood ditty, but just know that line 1 is scientifically proven.

Epidemiologists sorted through the health and dietary records of nearly 10,000 participants in the First National Health and Nutrition Examination Survey (NHANES I), correlating the incidence of heart disease over 19 years of follow-up with the intake of beans.

Their conclusion?

Legume consumption was significantly and inversely associated with risk of coronary heart disease after adjustment for established cardiovascular risk factors.

You eat beans four or more times per week and you fall out with heart disease 22% less often than the underbeaned.

For those of you who have bean there but don't particularly like to go there often, here's a recipe for a bean smoothie that's mighty good. Actually, it's more a bean soup, but still provides that easy intake of nutrients without all that tedious chewing. This recipe is a done deal in 5 minutes, and heated up in another 5, but careful, the ingredients fill a standard-sized blender to about 1/18 of an inch from the top:

Chickpea Soup with Garam Masala and Cilantro*

2 16-ounce cans chickpeas, drained
1 14-ounce can light coconut milk
1 cup low-sodium chicken broth
1/2 cup prepared salsa
1 1/2 tsps. garam masala (blend of Indian spices, McCormick brand or other)
1 tsp. ginger
2 Tbs. frozen apple juice concentrate
1/4 cup packed cilantrol leaves
Garnish with plain yogurt and/or thinly sliced green onions
Blend it all but garnishes, heat up in large saucepan, simmer 4-5 minutes, drink to your heart's content.

*Recipe from Parade Magazine

Aspirin or not?

I take one before bed every night. It takes away my little aches and itches that get in the way of becoming one with the bed. And the long-term use of aspirin may (or may not depending on what you read) be associated with a decreased risk of cancer.

How much and how often you pop the pain reliever seems to be an important issue as to whether or not aspirin use will relieve your cancer risk as well as your pain. Itty bitty heart-disease preventing doses do not seem to help per the women of Iowa. The nurses of the Nurses Health Study, however, proved that if a little won't help, a bit more may do.

Over twenty years of follow-up, the dedicated health professional subjects of the NHS faithfully reported their aspirin use to investigators every 2 years. Those who took two or more regular strength (325 mg) aspirins per week for at least 10 years enjoyed a 33% reduced risk of colon cancer. Just last month, nearly 150,000 participants in the Cancer Prevention Study II Nutrition Cohort (dubbed a "relatively elderly population") confirmed that same 1/3 risk reduction for colon cancer with the regular use of aspirin.

So why wouldn't we all just do it, just down a daily Bayer? Consider a couple of stories from my practice before you conclude that aspirin does not cause stomach problems. Remember that each of these patients had no history of gastric distress.

Years ago, a thirty-something patient of mine called me in the middle of the night vomiting blood. She took aspirin on a regular basis for neck pain. Call an ambulance, head for the ER! Can't, said she, nothing to do with her young son, no one to care for him. The obvious solution? She got in a cab, dropped young son off at my house to spend the night until his dad could come get him, then she proceeded to the hospital where she was treated for bleeding from an aspirin-induced stomach ulcer.

Patient number 2 walked unsteadily into my office more recently, white as a sheet and dizzy after days of passing black stools (digested blood from the upper intestine emerges black out the back end). His problem? Blood loss from a gastric ulcer caused by daily use of low-dose aspirin for prevention of heart attack. No warning, no pain, just loss of half his blood volume down the toilet.

So aspirin or no? Like all the things we do for health, this one's a weighted decision.

D problem with aging brains

Higher intakes of calcium and vitamin D have been promoted in recent years as a way to prevent bone loss with aging. We are concerned that some of this extra calcium may end up in the blood vessel walls rather than the bone.
--Dr. Martha Payne, Duke University

Dang, if it's not one thing, it's another. Just the other day, as I explained that calcifications seen on CT scans of coronary arteries were markers for significant coronary disease, a patient asked me if it was a problem then to take extra calcium. Oh no, I assured her, the calcifications were an injury response, not a result of dietary intake.

So now Dr. Payne and colleagues have studied the correlation between intake of calcium and vitamin D in a group of elderly subjects with the appearance of brain lesions on MRI scans. These lesions are believed to represent areas of atherosclerosis in small blood vessels causing an interruption of blood flow to the white matter in the brain.

Not only did they find a significant relationship between the intake of these two bone supportive nutrients, but the relationship remained when they statistically controlled for the effects of age, hypertension, diabetes, and heart disease. Further analysis suggested that the total volume of screwed-up brain areas was significantly associated only with D intake.

Too much of a good thing, perhaps.

A nice-blended scotch of a pill?*

At least that is the market strategy of Wyeth Pharmaceuticals who will release Aprela within the next two years. This two-fer pill is Premarin wrapped up with Wyeth's new selective estrogen receptor modulator (SERM) drug called bazedoxifene or more lyrically by its brand name Viviant.

SERMs are molecules that are sort of estrogen-shaped and act more or less like estrogen at cellular receptors, turning their estrogen-based actions on or off. Currently available SERMs all have their good and their not-so-good qualities: Clomiphene hyperstimulates the ovaries to produce eggs for the infertile who take them. Tamoxifen blocks estrogen at the breast to prevent breast cancer recurrence but acts like estrogen on the uterus and can be associated with the development of endometrial cancer. Evista acts like estrogen on bone receptors thus slowing postmenopausal bone loss, blocks estrogen at the breast like tamoxifen, but screws around with brain estrogen receptors and can make hot flashes worse.

So the race is on to build a better SERM, and Wyeth is winning to be #2 on the market with Viviant having just been issued an 'approvable' letter from the FDA. So no big deal yet, just another SERM against osteoporosis competing with Evista. So here's Wyeth's ace-in-the-hole: one acronym...TSEC.

Tissue selective estrogen complex or the TSEC class of compounds was developed to offer a new menopausal treatent option "that, for the first time, partners a selective estrogen receptor modulator (SERM) with estrogens." The SERM protects the bones and uterus, the estrogen quiets the fire of the flashes. No information is available as to how the breasts fare in this mad dash for the estrogen receptors.
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*See April 28th post

There's going to be a day before each of us die, and you have to think about how you want that day filled.
---Elizabeth Edwards

Scot-free menopausal treatment?

We're not going to find a 'single-molecule' solution, so we're going to blend them — like a nice blended Scotch. You put it together, and you get something that, on the whole, will be better.
--David Barad, MD, director of assisted reproductive technology at the Center for Human Reproduction in New York City

Bring it on! I'm ready to settle into these golden years with a nice blended Scotch of a therapy. Check in later for a look at that which Dr. Barad rhapsodizes on.

"Time is Brain"

The American Heart Association's Stroke Council certainly knows how to turn a phrase. The Council notes that only 1/3 of actue stroke victims call for emergency medical services to transport them quickly for prompt care which can reverse the blockage to brain blood flow. As a result, they urge:

As emergency medical services offers the most prompt care, all patients with the acute onset of stroke symptoms should use services such as telephoning 911.

Shrinking BRAINS at risk!

Biologically Resilient Adults in Neurologic Studies (BRAINS, of course) is a 65+ year-old group of "highly educated and motivated subjects who represent the healthy extreme on the normal aging spectrum." This philanthropic group has not only agreed to undergo regular testing of cognitive and physical functioning but also will hand over their brains at death for further analysis.

All 136 of them underwent baseline MRI scans of their brains in 1999. After 5 years, 23 had developed mild cognitive impairment (MCI), demonstrating loss of some memory and cognitive functioning. Individuals with MCI are known to progress to Alzheimer's disease at an increased rate compared to those without impairment. Nine BRAINS subjects developed Alzheimer's disease in this same time frame.

When the investigators compared MRI morphometry--brain size measurements obtained from the original scans--those subjects who developed MCI or AD had measurable and significant volume loss in their temporal lobes and the left anglular gyrus. This shrinkage was visible years before any demonstrated loss of brain function.

Damage to the left angular gyrus (which sits above and behind your ear) causes a condition called anomia or severe word-finding difficulty. (Oh dear, that sounds familiar). Stimulation of the angular gyrus can cause out-of-body experiences; one subject described the feeling of being on the ceiling.

While I have wished, at times, to be on the ceiling, I am more likely to struggle with a sluggish gyrus and grope for words than I am to travel upwards due to its overstimulation.

Kinetin may slow skin aging

Rough, wrinkled, and brown. It's not the worst thing that can happen whilst aging, but not particularly what you want for your cheeks, your neck, or the backs of your hands. N6-furfuryladenine, aka kinetin, promotes cell growth in plants and perhaps in your skin.

Here's one enthusiastic endorsement for kinetin kream from drugstore.com:

I absolutely love this product! As a woman of 50, I've found that Kinerase has given my skin a clarification or glow that I have not seen in years. I use it twice daily with my other moisturizer. When one of my friends asked me if I had some type of treatment (i.e. Botox), I knew this was the right product. Results do take time.

Dr. Suresh I. S. Rattan, PhD, DSc, Associate Professor of Biogerontology at the University of Aarhus, Denmark, who happens to be the patent holder for N6-furfuryladenine for use on aging skin says:

...when you grow normal cells in the lab they have a limited number of times they multiply and divide—termed a cell's replicative life span. But when I added N6-furfuryladenine to these cultures the cells did not age as fast, the process slowed down dramatically.

In a year-long study of 96 subjects with sun-damaged old skin, the majority of the studied leathernecks noted a decrease in fine wrinkles and roughness. A lucky third of them noticed less 'mottled hyperpigmentation.'

A final note of caution from Dr. Rattan, who basically warns that if a little is good, a lot is not better:

In cell cultures when a concentration of say 250 micromolars of N6-furfuryladenine was used, we got good results, but when we used 500 micromolars of N6-furfuryladenine the cells started dying.

Am I going to buy this stuff? I think not; a one month supply costs $65!

...A young cell is plump, round, smooth. As the cells age, they become irregular, flattened, and large, full of debris
--Dr. Suresh I. S. Rattan, PhD, DSc

Yuck, who wants that? How does Doc Rattan suggest we avoid the cellular debris in our aging skin? Stay tuned.

HairMax LaserComb

Aim this low-level cold-beam laser at your scalp if you're seeing too much of it through your thinning mane. Now FDA-approved, this gadget proved successful in 93% of the balding participants enrolled in the clinical trial.

How much new hair do you get for your $545? Here's the summary:

The study concluded that 93% of the participants (ages 30-60) using the HairMax LaserComb had an increase in the number of terminal (thick) hairs. The average number of terminal hairs per square centimeter increased by 19 hairs/cm2 over a six-month period.

Your average scalp has 250 hairs per square centimeter. People shelling out big bucks for this LaserComb are obviously not your average-scalped sort of customers. If the average skull has 600 cm2 of scalp, this device could add 11,400 hairs to their heads.

Worth it? Hard to say, but here's what one medical commentator had to say:

The LaserComb makers have failed to advertise that their product can double as a handy pointer during CME [continuing medical education] presentations...Even though the FDA has concluded the device is safe, what if one sustains retinal damage from using it incorrectly? Sure, I've been literally blinded by my own vanity, in both eyes--but my hair is positively lustrous.

Sleep apnea: A visual primer

These pictures demonstrate why susceptible persons, particularly those with short, thick necks or small jaws, tend to stop breathing when they sleep on their backs.

Supplements and statins

I ask a lot of people about their use of vitamins. There's hardly a soul, it seems, who doesn't take a little bit of something or other from the vitamin section in search of better health.

Vitamins E and C continue as favorites despite evidence of possible harm from E and a lackluster track record for supplemental C. In fact, one study published in 2001 in the New England Journal of Medicine showed that the use of C and E along with Zocor and niacin for elevated cholesterol canceled out some of the benefits of the prescription meds.

18,000 JELIS Japanese (as in participants with the Japan EPA Lipid Intervention Study) proved, however, that fish oil is a worthy partner with medications such as Zocor (now sold generically as simvastatin) and Lipitor. When eicosapentaenoic acid (EPA) was added to statin therapy over the course of 5 years, investigators found a significant drop in the incidence of bad heart outcomes.

The other major component of fish oil--DHA-- is known to decrease the incidence of Alzheimer's disease. My fish oil capsules are moving to the front of the vitamin shelf. They were briefly shelved when a particularly fishy batch made me gag just opening the bottle.

Reduce the reductase...

and save your hair. If you're wondering just what is sending your former glorious locks into the bathroom drain, it's 5-alpha reductase. This enzyme turns testosterone into the more potent dihydrotestosterone form in your hair follicles, causing them to jump off your scalp and onto the floor.

Progesterone is an excellent inhibitor of this enzyme which is why prescription strength progesterone cream to scalp can save the mane.

Grewsome news

Not often that one gets to gain height as an adult instead of weight. But since I started neuro-kinetics therapy--a one-of-a-kind program here in Denver--to unravel the degenerative scoliosis that plagues my lower back, that's one of my goals.

Therapist Bob Gaas claims that these aging curves are more about muscle spasm and scarring then about permanent spinal changes. He hopes this program will not only free me from stiff-woman syndrome--so tightly wound was I that I could scarcely step into my jeans in the a.m.--but also it will give me back a significant portion of the 1&1/2 inches of height I've lost through the years.

Indeed, I grew some after just the first visit. Better yet, early morning jean-stepping is not a problem. And best of all, I'm no longer the only lady in the Jazzercise class who can't shake her hips!

The D-lemma

If you've been reading my newsletters, you know that I have picked up D passion. This vitamin's star is rising not only with respect to its importance to bone density but also its anti-cancer properties. Worries about D toxicity are dropping off; many experts recommend as much as 4,000 units per day during winter months in northern climes. Some UK health experts also recommend a new public health policy of daily sunscreenless interludes outside when there's sun to be had.*

Here in sunny Denver, some of my pasty white patients haven't heard the news. In the last week alone, I checked D levels on two middle-aged ladies in search of bone strength. Their levels were virtually non-existent!

Are you a visual learner? Check out the cancer incidence maps at
Sunlight, Nutrition, and Health Resource Center.

Got sunshine? Got D? Then you got cancer protection.
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*Sunlightrobbery

The Pain Matrix

I find that a challenging yoga class brings a little thrill of fear to me which is not necessarily a pleasant sensation. A new study utilizing fancy brain-imaging techniques may explain the connection.

Researchers at the University of Manchester used PET scan imaging to see what parts of the brain lit up when people ached in their arthritic old knees. This technique involves injecting a person with a tagged sugar molecule called F-fluorodeoxyglucose or FDG. FDG is concentrated in neurons as they suck up sugar while at work reacting to the task at hand.

Neurobiologists already know which brain pathways activate when volunteers are pinched or kicked or however it is that researchers induce experimental pain. This same 'pain matrix' is also activated by arthritic pain. These UK scientists were surprised, however, to find that pain from degenerative joints "was associated with increased activity in the cingulate cortex, the thalamus, and the amygdala. These areas are involved in the processing of fear, emotions, and in aversive conditioning."

So if yoga induces pain in degenerating knee joints--and despite all that soothing patter from the instructor, I find it often does--aging yoginis might feel fear.

Silent brain infarctions

Clinically identified stroke represents the tip of the iceberg in terms of cerebral vascular disease by at least an order of magnitude...It is hard to believe, however, that loss of brain tissue should go without consequences. The brain may reorganize functional networks to adapt to lesions and recover function. But with each subsequent stroke, the capacity to do so is diminished.
--Brian J. Murray, MD

Scary new news on SBIs--one-fourth of persons with obstructive sleep apnea (the bedmate who keeps you awake as you wait for him to take his next breath) were found in a Japanese study to have evidence of extensive silent strokes on MRI imaging.

For more information on diagnosing tiny strokes and their devastating consequences, see
The white matter matter.

Relative to those who drink virtually no caffeine per day, old people who toss back more than four cups daily have about half the risk of pitching over dead from cardiovascular disease. This per current year issue of the American Journal of Clinical Nutrition.

(Soy) Nuts to you!

Too bad soy nuts are so disgusting. Previous research shows they squelch the heat and support the bones. A new study suggests that women on the road to diabetes improve their disordered metabolism by substituting soy nuts for meat protein.

Soy nut meals decreased insulin resistance and fasting blood sugar. Probably all the chewing involved in getting through the meal without choking.

HRT: NAMS is singing a new tune

In this day and age, the life span of any position statement is a maximum of 2 or 3 years. In the face of so much new information, we felt an update was due.
--Dr. Wolf Utian, Executive director of the North American Menopause Society

And their new position is that the benefits of hormone therapy outweigh its risks in healthy perimenopausal and early postmenopausal women with menopause-related symptoms and a low baseline risk of stroke.

"Oldest old support ratio"

It may take a village to raise a child, but don't forget that part of the village needed to care for the frail elderly.

Swiss investigators, noting that resources to care for the oldest old are increasingly scarce, set out to quantify the problem. They developed a parameter called the oldest old support ratio, defined as the ratio of people aged 50-75 to those aged 85 years and older. This number not only reflects the demographic shift of populations to the older range, but also--as I can personally attest to--the number of aging children in charge of their frail parents.

So what's the scoop on the oldest old support ration in Switzerland? While it stood at 139.7 in 1890 (scads of middle-aged helpers to a smattering of little old people), it had fallen to 13.4 by 2003. Dr. Francis Herrmann and company predict that this ration will fall to around 4 in both Switzerland and the US by 2050.

By my calculations, that won't be near enough helpers and resources to care for 99 year old me.

An Aged Athlete

From a simpler time, when old was old, and physically fit was not (old that is):

An old-time champion pedestrian, whose record 30 or 40 years ago aroused the country, has recently at the age of nearly 70 performed the feat of walking from Philadelphia to New York, a distance of 96 miles, in a little over 23 hours and finished the task in excellent physical condition. This is a good example of the fact that the physical organization of man need not necessarily go to pieces before the allotted three score and ten, when, according to some, the system is worn out and useless. Of course, this man is an exceoptional case, but he shows what the possibilities are, and probably a great man other individuals of as great age could do likewise.

----JAMA, June 23, 1906

Like fertilizer on a sparse lawn...

...a chemical enticement encourages the skin to fill in hair-growing structures.*

---RJ Davenport

Dr. Davenport goes on to explain why hair gets increasingly pathetic with age. People are born with all the hair follicles they'll ever have. Over time, hair follicle performance 'falters,' and these hair-replenishing structures spend more time resting than growing. Follicles, along with every thing else that's fresh and young in humans, shrink with age.

Is there good news? A molecule called beta-catenin can induce new hair follicles, at least in mice. Dr. Davenport feels that this research may hold hope that hair can be saved as we age.
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*R. J. Davenport, Hair Trigger. Sci. Aging Knowl. Environ. 2005 (27), nf54 (2005)

Measuring up on the SSWO score

Fraility in the elderly is all about loss--stamina, weight, muscle mass, energy--all of it yesterday's news as vibrant 70-somethings shrivel into tiny 80-somethings. Dutch researchers examined whether 17 weeks of exercise and micronutrient supplementation could up the SSWO (scale of subjective well-being for older persons) scores for scores of frail, old Dutchmen and women.

Their conclusion? No, it's not enough, or perhaps too little too late. They did find, however, a strong correlation between deficiencies in vitamins B6, D, and folate and crazy low SSWO scores.

In addition, they theorized that the lack of improvement in SSWO scores might reflect that subjective assessments of well-being are stable and relatively insensitive to actual changes in health status. In other words, even though the interventions may have changed the participants health for the better, these little, old people had a fixed notion of how they felt at this stage of the game, and self-appraisals are more about attitude than fitness and nutritional status.

D upright vitamin for the old folks

I'm not sure when my mom last got out in the sun. She, like other housebound seniors, is at high risk for D vitamin deficiency. A Harvard study recently published in the Journal of the American Geriatric Society confirms that extra D--800 or more units/day--can significantly prevent the elderly from going to ground.
.
The investigators randomized a group of old old folks (average age 89) to various levels of D supplementation. Defining a fall as "a sudden, unintentional change in position causing a resident to fall to the ground," they checked out which doddery test subject experienced such sudden changes as a function of their D intake.

While daily D doses of 400 units or less didn't make a bit of D-ference with respect to unintentional position changes, those residents assigned to the 800 unit group were 72% less likely to end up on the ground over 5 months compared to their colleagues.

While D alone will not necessarily keep the old perpendicular to the floor, the vitamin does promote muscle strength as well as bone strength and should be considered an important nutrtional supplement for the elderly.