I, like many of my patients, have elderly parents. Years ago, my mother started having balance problems and over time developed short term memory loss. Both symptoms are now severe. My father has been her caretaker but as he turned 90 developed multiple medical problems. Even though he is a theoretical physicist and writes and publishes articles in prestigious journals (in which the only words I truly understand are “the” and “or”), he too has what I call “cognitive slow down”. So when I came across an article about early Alzheimer’s disease in the clinical practice section of The New England Journal of Medicine I paid special attention. The author described a 72 year-old business man who was seen by a physician at the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University. This individual had occasional lapses of memory and his wife was concerned that this indicated early Alzheimer’s disease.
We all have memory lapses, so how do we or our family know when to seek help? How is a definitive diagnosis made?
First, let me list some of the statistics that were reviewed in the article…”Alzheimer’s is the most frequent cause of dementia in Western countries affecting an estimated 5 million people in the US and 17 million worldwide.” It affects about 1% of the population between the ages of 60 and 70, this increases to 6 to 7% at the age of 85 and in countries were survival to the age of 80 is not uncommon it is present in up to 30% of these older individuals!
When pathologists look at the brain of patients who had Alzheimer’s disease, they find plaques of a specific protein (beta-amyloid) and deposits of tau protein that cause tangles at the ends of neurons. These plaques and deposits then disconnect and destroy the brain cells. A family history seems to be one of the most important risk factors for Alzheimer’s disease. First degree relatives of those who had late-onset disease have twice the usual lifetime risk of developing Alzheimer’s disease. A single mutation can sometimes be found in rare families with early–onset Alzheimer’s. More frequently there is a genetic change or variant that codes for a protein called APOE e4 which is associated with late onset Alzheimer’s. If a person inherits one allele (i.e. this variant is on one of 2 chromosomes they get from their parents) they have a double to triple risk of lifetime disease. If they have inherited 2 of these alleles (one from each parent), the risk increases by a factor of 5! (Note a test for this allele can be done but many individuals who are positive don’t develop the disease hence it’s not a part of general screening tests…no I haven’t done it on myself.)
So how do clinicians make a diagnosis of Alzheimer’s disease? We all start complaining about trouble recalling names (as in “who was the actor in that movie about, you know?” …or “I know I met that person at what’s her names event”… or recent events; “Did I have chicken or fish for dinner yesterday? Or more commonly; “Where did I put my reading glasses?” In the early stages of Alzheimer’s, there is an increasing inability to retain recently acquired information whereas memory of remote events is usually spared until the disease has progressed. There may be a decline in verbal memory and the ability to perform sequential tasks. (The more medical term is “executive function”…with no specificity for MBA’s). As the disease progresses, this is followed by a reduced independence in daily activities.
Clinicians can administer a test that measures functional cognitive status; it’s called the Clinical Dementia Rating scale; the higher the score the greater the severity of impairment. (Note the test takes 30 to 45 minutes and often will require a special referral). And as memory declines, patients may have changes in mood, suffer delusions or can exhibit psychotic behavior. The latter can make dealing with Alzheimer’s patients difficult. (I know this from very upsetting personal circumstances and have to tell myself that I can’t argue this behavior away) Brain imaging has come a long way in helping identify early Alzheimer’s. Radiologists can detect areas of atrophy (inactive and “shrunken”) with MRI that occur in certain areas of the brain in patients who are likely to go from mild cognitive impairment to full blown Alzheimer’s. But there is no standard technique for doing this and these scans are too expensive to become the routine for diagnosis. Pet scans that look at metabolism, blood flow as well as ameloid binding of specific injected substances in certain areas of the brain, have also been used to predict progression of the disease but this too is costly and not widely available. There are also tests that measure levels of specific plaque associated proteins in the fluid that surrounds the spine and the brain, but this requires a lumbar puncture (“spinal tap”) and obviously is not done as a first line diagnostic test. Often the diagnosis is made by exclusion of other causes of dementia.
So what treatments are available? We have all seen the ads about medications that will help our loved ones keep their memory for longer and retain function (usually around the beach or on vacation). The author of the NEJM article lists 4 medications that are FDA approved for drug therapy for Alzheimer’s. They are Aricept, Exelon. Razadyne and Namenda. He states that “randomized , placebo-controlled clinical trials of cholinesterase inhibitors (I won’t go into that phrase but it includes the first three drugs) for mild-to-moderate Alzheimer’s have shown significant but clinically marginal benefits with respect to cognition, daily function and behavior. The rate of decline of patients on these meds was slower than untreated patients. He then went on to state that 27 studies showed no clinical difference on cognitive performance between the drugs but on the basis of 14 studies that measured daily function, Aricept was modestly more effective than Exelon. (Note they all have side effects so one may cause less for a particular patient than another.) Nemanda was also found to have marginal benefit for 6 months and has been used in patients with severe disease in combination with Aricept.
Since none of these therapies seem to “cure” Alzheimer’s and at best can stall progression for an all too short a time. What about alternative therapies…vitamins, statins hormones or anti-inflammatory drugs? Unfortunately, randomized trials have not shown any consistent benefit. And ginko biloba, carnitine, lecithin, curcumin, periwinkle and phosphtidylserine (that are touted by the salespeople in the health food sites and stores) have likewise not been shown to help in randomized trials.
So what can be done for that 72-year-old patient (and our relatives)? The diagnosis may be difficult, and the clinician has to try to establish that there are no mini strokes, no vitamin B12 deficiency, central nervous infection, substance abuse, medication reactions, HIV infection or cancer (with brain metastases). Mental exams should be done and, if necessary, a brain MRI. One of the above mentioned medications might help….but ultimately it is the caregiver who with patience and understanding will have to ensure that the patient is kept safe and loved for as long as possible. The author (and I) can’t offer much more advice. I wish I could end this article on a more positive note…I am currently trying to get my parents to agree to have a full time caretaker live with them. So far they refuse.