Science and Research Questions

In families afflicted by the heritable form of Alzheimer's disease (familial Alzheimer's disease (FAD), also known as early-onset AD) it is certainly possible to have half or more of the children affected by Alzheimer's disease if one of the parents carries an associated disease mutation. It is possible that in your great-grandmother (or your great-grandfather) passed an FAD-associated mutant gene on to their children. It is also possible that because all the siblings presumably grew up under the same environmental conditions, an environmental influence (such as exposure to toxins or other external factors) may have contributed to the high incidence of AD in this family. Except in cases of FAD, it is generally unusual to have more than half of the siblings in a family afflicted by Alzheimer's disease

For Alzheimer's disease research, there are numerous organizations and research groups that would graciously accept donation of a brain or brain tissue. A list of some of these groups is noted below. In addition, you can try contacting the neurology or neuroscience departments of research institutions or medical universities near you to see if they have any such programs in place. Please note that many of these institutions require that the donated brain be from a patient already enrolled in one of their research studies. Depending on your location in relation to the institution, it may be possible to participate in the research programs. You will have to contact them directly to find out additional details. Some programs accepting brain donations include:

• Baylor College of Medicine Brain Donation Autopsy Program
• Boston University Alzheimer's Disease Center
• Northwestern University Brain Endowment program
• University of Pennsylvania Center for Neurodegenerative Disease Research

Additionally, a list of brain banks in several states that can perform postmortem diagnosis of Alzheimer's disease and may accept brain tissue for donation has been compiled by the Alzheimer Research Forum.

Two studies published earlier this year in the journal of Neurology as part of the Women’s Health Initiative (WHI) report that women taking hormone replacement therapy (HRT), such as for treatment of menopausal symptoms, had slightly reduced brain volumes in areas of the brain associated with thinking and memory, the frontal cortex and the hippocampus. Previous studies had indicated that HRT carried a higher risk for women to have issues with cognition and memory later in life, which had been thought to be due to an increased incidence of mini-strokes leading to brain lesions. These new studies, however, found not lesions in the brains of women taking HRT, but smaller brain volumes. Brain shrinkage due to HRT therefore may put these women at an increased risk to develop dementia or Alzheimer's disease.

Although there have not been many formal studies examining the effects of HRT in Alzheimer's disease (AD) patients, based upon these newer findings it would appear that HRT could potentially hasten disease progression by further shrinking the brain areas known to be affected by AD—the frontal cortex and the hippocampus. In fact, a recently published review of the clinical databases found that overall, estrogen replacement therapy (ERT) or hormone replacement therapy (which includes estrogens combined with progestagen) in women with dementia was associated with worse performance on memory, skill and cognitive tasks. Further studies clearly need to be conducted in dementia patients to confirm or refute these findings.

The APOE4 (apolipoprotein-E4) and TOMM40 (translocase of outer mitochondrial membrane 40) genes have both been linked to Alzheimer’s disease through genetic studies. In particular, researches have found that specific rare mutations (called single nucleotide polymorphisms (SNPs)) in the TOMM40 gene, which is located close to and is “linked” to the APOE4 gene, can influence the level of ApoE protein that is found in the cerebrospinal fluid. The genetic studies indicate that TOMM40 (along with the two other closely linked genes, PVRL2 and APOC1) may be associated with a predisposition to developing late-onset Alzheimer’s disease.

While it is possible to be genetically tested to determine which version of the APOE gene you carry (e.g., ApoE2, ApoE3, or ApoE4), at the moment testing for TOMM40 is only performed for research purposes. If you want to be tested to see if you carry the APOE4 gene, you should contact your primary care physician about the possibility of genetic testing. Your doctor can refer you to a genetic counselor, who can take a family history and decide on the best course of action. The tests can be expensive and may not be covered by your health insurance plan.

Just remember that even if you are found to have the ApoE4 gene, it only means that you have a slightly higher risk of developing Alzheimer’s disease than the general population; it does not mean that you will definitely get Alzheimer’s disease.

Psychosis, paranoia and memory loss can occur in both schizophrenia and dementia, particularly as a patient ages and the associated risk of developing dementia increases. As you mentioned, there is a definite higher risk for schizophrenic patients to develop dementia later in life. Several studies have indicated, for example, that when schizophrenia develops late in life (>60 years), there is a higher likelihood that dementia will also be diagnosed.

Because of the overlapping nature of the diseases, research has focused on whether or not there are underlying causes in common, such as genetic or early environmental influences on the development of the brain. Scientists are also trying to determine if the same or similar genes are involved in psychiatric and neurological disorders, and also whether or not these genetic targets could be used either to develop new therapies or to provide better diagnostic techniques. Once researchers can determine the shared pathways that many of these neuropsychological diseases affect, it will only be a matter of time before new and better treatments are found.

The gene called Apolipoprotein E (ApoE) appears to be a risk factor for the late-onset form of Alzheimer's disease. There are three forms of this gene: ApoE2, ApoE3 and ApoE4. Roughly one in four Americans has the ApoE4 gene and one in twenty has ApoE2. While inheritance of ApoE4 increases the risk of developing the late-onset form of Alzheimer's disease, inheritance of ApoE2 substantially protects against the disease. Therefore, even though you have the ApoE4 gene, it only means that you have a slightly higher risk of developing Alzheimer’s disease than the general population. There is no need to be retested because the results would be the same. Having the ApoE4 gene does not mean that you will definitely get Alzheimer’s disease. Remember that about a quarter of the population have the ApoE4 gene—the majority of these people never go on to develop Alzheimer’s disease.

Although there is no sure-fire way to completely prevent Alzheimer’s disease, research findings generally suggest that the best approach to reducing your risk of developing Alzheimer's involves a combination of measures normally thought of as good for maintaining a healthy heart, such as eating a healthy diet that is low in saturated and trans fats, exercising regularly and reducing stress. Foods that are rich in antioxidants have also been reported (though not proven) to help reduce the risk of developing Alzheimer's disease. Foods considered antioxidant-rich include blackberries, blueberries, spinach, strawberries, red bell peppers, walnuts, artichoke hearts and tomatoes, among many others. Green tea, dark chocolate and red wine all contain antioxidants too.

Exercise, both physical and mental, has emerged as a possible preventative measure against developing Alzheimer's, as has reducing stress. Maintaining a relaxed attitude can help to lower stress levels, and lowering stress is beneficial overall for your body and mind. A calm, non-stressed person will typically have lower stress hormone levels and lower blood pressure, which is good for your heart, your immune system, and your brain among other things. For example, lower blood pressure can reduce your risk of heart disease and stroke, both of which have been implicated as potential contributing factors for the development of dementia. And having a relaxed attitude is good for your memory as well. Studies have indicated that reducing stress not only acts to aid short-term memory, but can also improve a person’s general emotional well-being, which is good for long-term cognitive health.

So eating a healthy diet rich in antioxidants and low in saturated and trans fats, exercising both body and mind, and reducing overall stress all may contribute to lowering a person's risk of developing Alzheimer's disease.

Just remember that with Alzheimer's disease, most patients will have "good" days and "bad" days. Unfortunately, the good days tend to become less common as the disease progresses. Sometimes caregivers will notice that their loved one's condition suddenly worsens and will mistakenly attribute the symptoms to a new medication (or an existing medication's new dose). Donepezil is generally well-tolerated with an overall low incidence rate of adverse effects. Sometimes also there is a period of adjustment when taking a new medication which requires monitoring by a doctor in order to achieve an optimal dosage.

Therefore, it could be pure chance that her recent confusion has coincided with the newly prescribed drug. However, to be on the safe side, it cannot hurt to contact her primary care physician and let him or her know about this new behavior. The doctor may want to reevaluate the prescribed dose, or perhaps even try a different medication altogether.

I am very sorry for your loss! The way to identify Alzheimer's disease (AD) until this day is postmortem examination of the brain. I don't think Aricept or Namenda will cause Alzheimer's disease in normal individuals. AD is a very complex disease and researchers are working on different projects worldwide in order to understand the causes and pathology of AD. Hopefully, we will have more accurate diagnosis method and efficient treatments of AD in near future.