Science and Research Questions

This apparently straightforward question turns out to be an area of real uncertainty and even controversy. Among studies that try to find a connection between dietary folate and cognitive decline, some (but not all) find that low self-reported dietary folate or low measured plasma folate levels are linked with greater cognitive decline. Similarly, low folate serum levels have been linked specifically with an increased risk of Alzheimer's disease in more than one (but not in every) observational study. Whether this means that taking folic acid is a good idea is less clear, because studies in which folic acid was given to people with Alzheimer's disease as a way of trying to improve cognitive functioning have not shown impressive or consistent results.

For people with low dietary folic acid, the supplementation might be more clearly beneficial. One study done in the Netherlands (where food is not supplemented with folate as it is in the United States) found that older adults without dementia benefited in global cognitive function and memory when they received supplemental folate. Scientists reviewing this study point out that the high baseline homocysteine levels in these subjects suggest that many were folate deficient to start.

An authoritative systematic review of this question (Cochrane Database Syst Rev. 2008 Oct 8;(4):CD004514) reported that no consistent benefit of folate has been found in cognitively impaired older adults but that one pilot study of people with Alzheimer's disease found that the addition of folic acid (1 milligram per day) seemed to improve the response to cholinesterase inhibitors.

The bottom line, in my opinion, is that a diet naturally high in folate would be advisable, and that folate supplementation might help cognitively if your fasting homocysteine level is elevated or if you are taking a cholinesterase inhibitor. It is always prudent to review any supplementation with your personal physician, who is aware of your medical conditions and medication regimen. Further research will provide a more definitive answer to your question.

Alzheimer's disease can sometimes cause patients to repeat certain behaviors, such as asking a question, pacing back and forth, opening and closing drawers, etc. Therefore, your wife may be scratching herself more out of “habit” then because she actual feels itchy. If this is the case, no amount of ointments or anti-itch medications may help, as you have probably now learned.

You can try making your wife wear thick gloves so that she cannot scratch herself, assuming she will keep them on. If this does not work, you can try a more drastic measure to discourage this behavior: special clothing designed for Alzheimer's patients that prevent them from removing their clothes (and thus getting access to their skin.) These anti-strip jumpsuits and pajamas have back zipper closures, and therefore the clothes cannot be removed by the wearer. If the patient cannot remove her clothes, then she may not be able to scratch at her skin either. Some websites that carry this type of clothing include: Silvert's, Adaptive Clothing, and Nurnia. Or just search for “Alzheimer anti-strip suit” in your web browser to find other sites and/or related products.

A study performed in 2003 found that, in women, the longer the period of time that a person went untreated for depression, the greater the observed shrinkage of brain areas involved in memory (such as the hippocampus). Because these women then had smaller “reserves” of neurons in areas of the brain that are commonly affected by AD, they are believed to be at a higher risk for later developing dementia.

More recent studies in both men and women have suggested that depression may be a risk factor for cognitive decline in elderly patients, and this cognitive decline is associated with a higher likelihood of developing dementia. For example, several studies have indicated a correlation between depression and Alzheimer's disease, wherein a history of depression (particularly in patients under the age of 60) is associated with a greater risk of developing Alzheimer's disease. Researchers believe that depression—particularly long-term untreated depression—may change the brain’s overall chemistry, making it more vulnerable to insults and neurodegeneration. Further research is clearly needed to confirm these conclusions.

Alzheimer's disease typically does not cause gastrointestinal problems by itself. However, some of the more commonly reported side effects of the cholinesterase inhibitor drugs (such as donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne), or tacrine (Cognex)) prescribed to Alzheimer's disease patients include nausea and vomiting. If your wife is currently taking a cholinesterase inhibitor, please check with your wife’s prescribing physician to see if her medications can be adjusted. Even if your wife is not taking one of these medications, you should consider consulting her doctor to rule out other medical issues that may be causing her symptoms.

There are numerous studies indicating that anosmia, or the loss of the sense of smell, is associated with dementia and neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson’s disease (PD), and Lewy body disease (LBD). Even though the scientific community seems to be in agreement that there is a relationship between olfactory impairments and neurodegenerative diseases, the nature of this relationship has not been fully established. For example, some research indicates that the loss of smell can be a predictive factor for developing AD, PD, or LBD, but other studies report that this symptom is not pronounced enough to be of diagnostic value. Additionally, it does not appear that an impaired sense of smell can be used in the absence of other symptoms or diagnostic tests to differentiate between the different neurodegenerative conditions.

Serious Alzheimer’s disease research is being conducted worldwide, and in the United States all clinical trials must be registered with the government. You can search the 797 Alzheimer’s disease trials currently listed in order to look at specific treatments that are being tested. Many of these clinical trials are being carried out at government funded research programs called Alzheimer’s Disease Research Centers (ADCs). Please also visit the research grants section of our website. Alzheimer's Disease Research (ADR) has awarded more than $71 million to support promising Alzheimer's disease research in fields ranging from molecular biology to epidemiology. ADR is currently supporting 62 outstanding biomedical researchers.

The term “epidemic” is derived from Greek roots “epi” (“above”) and “demic” (“pertaining to “people”) and is used to describe the occurrence of a disease beyond what would be expected based on prior experience in a given population. In the past, infectious diseases were typically described in this way, but Alzheimer’s disease and other noninfectious diseases are also described as epidemics when the number of people affected becomes so large as to raise concern about the effect on our entire population. Such concern is certainly warranted for Alzheimer’s disease, which currently affects an estimated 5.3 million individuals in the United States alone, and by 2050, the number could increase to 15 million.

Apolipoprotein E or ApoE genotype is a genetic factor that has been shown to affect risk for development of cognitive decline and Alzheimer’s disease. Each of us inherits two versions (alleles) of the gene for ApoE, one from father and one from mother, and there are 3 main types of this gene (E2 E3, and E4). We can inherit two E4 alleles, two E3 alleles, two E2 alleles, or any combination of 2 types. The ApoE3 genotype is considered neutral so far as this risk is concerned, while ApoE2 appears protective and ApoE4 increases the risk for developing cognitive decline and Alzheimer’s disease. It’s important to emphasize that not everyone with Alzheimer’s disease has an ApoE4 allele and not everyone with an ApoE4 allele develops Alzheimer’s disease.

As you mention, your research has turned up the important influence that ApoE genotype has on the effects of other risk factors for Alzheimer’s disease and even perhaps on the effects of treatments, though much remains to be learned about these topics. One possible explanation for ApoE genotype influence is that the brains of people with the higher-risk ApoE genotypes (one or two of the ApoE4 alleles) may have less capacity to repair wear and tear on the brain associated with the other risk factors. For example, it appears that possession of an ApoE4 genotype reduces the benefits otherwise associated with light to moderate alcohol consumption.

NSAIDS (non-steroidal anti-inflammatory drugs), believed on the basis of epidemiologic studies to reduce the risk for Alzheimer’s disease, have not consistently been shown to do so in treatment trials (and there is even evidence of increased risk associated with these medications in some trials). In one observational study that reported a decreased Alzheimer’s disease risk with midlife use of NSAIDs (Hayden et al. Neurology 2007;69:275-82), the protective effect of NSAIDs was actually greater in those with one or more ApoE4 alleles.

Oxidative stress is suspected to be one contributor to the pathologic brain changes associated with Alzheimer’s disease, and ApoE4 genotype is associated with reduced capacity to repair oxidative damage. This would suggest that antioxidants might be more rather than less beneficial in people with the ApoE4 genotype, yet overall the findings regarding high levels of antioxidant intake have not provided a consistent basis for recommendations, according to the very comprehensive evidence review recently published by the NIH.

Exercise has convincingly been shown in both observational studies and treatment trials to benefit the brain (as well as other parts of the body). Nichol and colleagues (Alzheimers Dement 2009;5:287-94) reported that the effect of “wheel-running” on ApoE4 mice was even greater than on mice without that genotype in improving cognition and hippocampal plasticity. In humans, too, aerobic exercise may be even more important when ApoE4 alleles are present, as concluded by Etnier and colleagues (Med Sci Sports Exerc 2007;39:199-207). They reported an association between aerobic fitness and cognitive performance that was larger when E4 alleles were present.

Regarding hormone replacement therapy (HRT), this remains a confusing area with some conflicting pieces of data. Estrogen use alone has not consistently been related to Alzheimer’s disease risk, though the Women’s Health Initiative Study reported an increased risk for Alzheimer’s disease in women treated with the combination of estrogen and progesterone. ApoE genotype does seem to interact with the effects of HRT, and one observational study (Burkhardt et al. J Alzheimers Dis 2004;6:221-8) reported an association of HRT with better cognitive performance in women without the ApoE4 genotype.

Clearly, more needs to be learned about the interaction between the ApoE genotype and other Alzheimer’s disease risk factors, but as you can see the relationship is not the same for all the factors.

Immobility and muscle rigidity are occasionally seen in advanced Alzheimer’s disease, but there are also many other potential causes of these symptoms. If your husband’s diagnosis is Dementia with Lewy Bodies (DLB) or one of the other dementias with Parkinsonian features, for example, periods of muscle rigidity (called catatonia) can be part of the basic disease itself. For some patients, medications result in unwanted muscle rigidity. Certain types of strokes can produce catatonia as well, and Alzheimer’s disease in some cases is complicated by the addition of strokes. Also, medications induce changes in muscle tone, and the antipsychotic medications, in particular, can produce this problem. The combination of antipsychotic medications with DLB is especially prone to inducing muscle rigidity. A review of your husband’s diagnosis and medications may suggest a way to reduce or alleviate these episodes, so I suggest that you work with your husband’s clinicians to and discuss the options.