Science and Research Questions

It would suggest that you talk with your mom’s doctor about perphenazine. This is an antipsychotic medication that was probably started to reduce agitation or psychosis, or to relieve anxiety or insomnia. Perphenazine, initially sold under the brand name Trilafon, may have been a reasonable choice at one time; unfortunately, the medication may have outlived its value and may now be contributing to your mother’s discomfort. Older adults who take these antipsychotic medications are especially prone to develop uncomfortable restlessness (what clinicians call “akathisia”) or even a persistent disturbance of movements called “tardive dyskinesia” after long-term use. Please consult a neurologist, who may wish to find a replacement for the perphenazine and also consider some other possible explanations for her excessive activity.

Without knowing much more detail, the most important advice I can give you is to follow up with your neurologist and ask what role the chemotherapy may have played in your symptoms. You are not alone in experiencing memory and sensory problems that may be linked to the use of cancer chemotherapy medications, and your neurologist will consider the “bigger picture” that includes your age, past medical history, current medications (and whether you are still getting taking anti-cancer medications), alcohol use, overall symptom picture, family history, and results from blood tests and neuroimaging. Based on those additional pieces of information, your doctor(s) will assess the most important causes of your symptoms and which, if any, of the available treatments might be most valuable.

There is no credible evidence that cholesterol medications cause Alzheimer’s disease, though patients and some researchers are in agreement that the cholesterol-lowering statins such as atorvastatin make some people feel slowed down or less sharp. On the other hand, there is considerable evidence that untreated hypercholesterolemia during middle age increases the risk for dementia in later years.

As research data about Alzheimer’s disease have accumulated, our understanding of the underlying genetics has deepened. The current view is that many genes may be involved in the risk for Alzheimer’s disease, and the early-onset cases known as FAD (Familial Alzheimer’s Disease) account for only about 1 in 20, or 5%, of all cases. FAD does can indeed become symptomatic earlier than other cases of Alzheimer’s disease, occurring even in the 30s and 40s, but the majority of those affected show their first symptoms in their 50s or early 60s, an age range that still includes your mother. You may wish to consult a geneticist for family counseling and more detailed advice, and you are likely to find the following book of interest: Decoding Darkness: The Search for the Genetics Causes of Alzheimer's Disease by Rudolph Tanzi and Ann Parson, Perseus Press.

Although it’s not typical for serious symptoms in Alzheimer’s disease to reverse for long, it’s not unusual to see some waxing and waning of severity from day to day. The patient who recently seemed to say her final words may surprise everyone by speaking again; the patient who stopped eating independently may temporarily regain that skill; and the patient who seems to have stopped walking may take further steps. This could just be waxing and waning of Alzheimer’s symptoms, but there is also the possibility that this patient had a temporary illness such as a flu or minor painful injury that’s now better, or that the dementia is actually a case of Lewy body disease, which is more typically a condition that waxes and wanes and includes falls. When an improvement such as this occurs, it’s a challenge for caregivers to enjoy the change but not be too painfully disappointed if it fails to persist.

Seeking an explanation of these distressing feelings for 25 years must have been an extremely frustrating experience. I don’t think I can provide the definitive answer you’ve been looking for, but I can suggest a course of action. There are many things that can contribute to the symptoms that you have been experiencing; however, they appear to be consistent with an anxiety condition. Over the years, I’m sure you have noticed various things that make it better or worse, such as sleep, caffeine, exercise or stress, and if you haven’t already done this you might make a careful list of the factors that affect your symptoms. Then, find a doctor who has expertise in treating anxiety disorders. The assessment of your symptoms will include consideration of atypical headaches, focal seizures, nutritional deficiencies, toxicities, and sleep disorders among other problems. If, after a thorough evaluation, it seems that anxiety is the most probable explanation, you may be given medication and encouragement to participate in cognitive/behavioral psychotherapy. Don’t give up—there is probably a clinician who can help you feel better!

I always like to emphasize that aggression and agitation are complicated symptoms, not diseases in themselves, and they can be caused by so many different things that no treatment fits every patient.

The first steps should involve a thorough assessment of the conditions under which agitation or aggression occurs, the responses these behaviors elicit, and your husband’s reaction to the staff’s responses. This “behavioral analysis” might identify one or more important causes of his disruptive behavior and it may be something as simple and obvious as painfully tight shoes, constipation, more serious medical conditions, upsetting interactions with specific residents or staff, sensory problems such as difficulty hearing what people are saying, or the frustration of being asked to do things that are too challenging for him.

There are so many possible causes that an individualized assessment is needed, it is recommend that you find a clinician who has this particular skill. Once that assessment and a medical examination are completed, it is important not to move too quickly to prescribing medications. They are definitely not the only solution, and in many cases they’re not even the most effective or safest solution. Behavioral interventions, such as having a quiet and less stimulating place to go to, listening to his favorite music, looking at photos that evoke happy memories, or smelling pleasant aromatherapy while having a hand massage might be adequate to reduce the agitation.

If medications are used, many clinicians like to start with the SSRI antidepressants, such as citalopram (though there is a new cardiac risk warning for high doses that must be taken into consideration), before moving on to stronger agents. In most cases, agitation can be successfully managed and it’s very possible that the riskier medications can be avoided.

Acetylcholine, an important brain chemical (neurotransmitter), plays a key role in the process of remembering. The cholinesterase inhibitors like donepezil, widely used in treating Alzheimer’s disease, increase brain availability of acetylcholine and are believed to be effective on that basis because an abnormal decline in acetylcholinergic  (for simplicity, also called cholinergic) function is associated with Alzheimer’s disease. Anticholinergic effects (blocking the effect of acetylcholine) are characteristic of many medications, and anticholinergic medications have indeed been shown to interfere with cognitive functioning.

On the other hand, Dr. Boudreau and colleagues, authors of the study you found, found no evidence to suggest that patients on concurrent cholinergic and anticholinergic drugs were more likely to die or move into a nursing home, outcomes that might reflect severe adverse effects on cognition. It seems possible that some anticholinergic medications (maybe those that have less of their effect on the brain and more on the part of the body outside of the central nervous system) create less of an obstacle to the benefits of the cholinesterase inhibitors (which have their therapeutic effects on the brain), but reasonable treatment considerations might include these suggestions:

• Clinicians caring for an older adult should periodically review ALL their medications to make sure that a complete list is available and to look for potential interactions, especially when there are multiple prescribers;
• When possible, avoid mixing anticholinergic medications with cholinergic enhancers;
• When mixing is necessary, favor the anticholinergic medications with less central nervous system penetration;
• In general, minimize the dose of an anticholinergic medication in an older patient to minimize adverse effects.