Science and Research Questions

Increasing evidence supports the idea that factors such as head injury, activity, social engagement, and diet may influence the development of Alzheimer’s disease. Data regarding the significance of toxic environmental exposures paints a murkier picture. A recent NIH conference addressed the state of current knowledge regarding environmental agents that might cause Alzheimer’s disease, and concluded that too little is known about this topic to provide more than a tentative answer. Limited data are available regarding long-term effects of exposure to solvents, pesticides, lead, aluminum, and electromagnetic fields, each of which has been suspected of increasing the risk for Alzheimer’s. The most convincing association was found for chronic exposure to organophosphate pesticides. If the tenants diagnosed with Alzheimer’s disease shared a pesticide exposure, it’s possible that the exposure was a factor in the development of their diseases. Otherwise, it may be that they shared the most significant risk factor for Alzheimer’s disease, which is advanced age.

The relationship between general anesthesia and Alzheimer’s has been attracting attention for a number of years, given cell culture and animal experiments that suggest several mechanisms by which some anesthetics (particularly the inhaled anesthetic isoflurane) might exacerbate cellular changes associated with Alzheimer’s. Supporters of the connection between isoflurane use and Alzheimer’s point out demonstrated effects on amyloid processing, tau hyperphosphorylation, and apoptosis (cell death). On the other side, some studies have failed to demonstrate a relationship between general anesthesia and a subsequently increased risk for dementia or cognitive decline.

In the case of your father, of course, an effect of anesthesia would be difficult to separate from other risk factors. For example:

1. Progression of the vascular dementia
2. Age
3. Other factors during the operation that might have harmed him independently of anesthesia.

Vascular dementia can be progressive and the vascular risk factors that presumably preceded his dementia may require further attention. Cerebrovascular disease, too, is a risk factor for Alzheimer’s disease and people who have both these conditions are not rare. Age is considered the largest overall risk factor for development of Alzheimer’s disease. Finally, there can be other factors that can occur during an operation (such as temporary hypoxia*) that result in later cognitive symptoms.

* hypoxia occurs when the body or a particular tissue in the body is deprived of adequate oxygen supply.

When Alois Alzheimer observed the brain of a patient affected by the disease that later was named after him, he sketched two characteristic microscopic abnormalities that continue to be the focus of modern research. Within many brain cells (neurons), he saw tangles of the internal neurofibrils (microtubules) that represent a disruption of the normal intracellular transport system. These tangles result when chemical changes (hyperphosphorylation) are made to a protein (tau protein) that otherwise serves to stabilize the microtubules. When tau protein is altered, as in Alzheimer’s disease, the microtubules collapse into a tangled clump that no longer properly transports nutrients within the cell. Other diseases in which disordered tau protein is important (the “tauopathies”) include Pick’s disease, corticobasal degeneration, and progressive supranuclear palsy. Several new therapies under investigation aim to treat Alzheimer’s disease by stabilizing tau proteins.

Dr. Alzheimer also noted intracellular clumps of material that he called “military foci.” Later investigations have shown these “plaques” to consist of aggregated “beta-amyloid” and inflammatory reactive changes. Beta-amyloid is the name given to a family of polypeptides (chains of amino acids, which are the building blocks of proteins) that result from the enzymatic snipping of protein fragments off of a larger protein (Amyloid Precursor Protein) embedded in the membranes of neurons. These fragments, called oligomers, vary in length from 39 to 43 amino acids and the fragment that is 42 amino acids long (Aβ42) is particularly damaging to brain cells. Both in the blood-borne oligomer form and in intercellular plaques in the brain, Aβ42 is believed to cause much of the damage associated with Alzheimer’s disease. Many Alzheimer’s disease medications in current development, therefore, aim to decrease the presence of Aβ42 in the bloodstream and/or brain. Amyloid is considered important not only in Alzheimer’s disease but also in Lewy body dementia, inclusion body myositis (a muscle disease), and cerebral amyloid angiopathy (a disease of the blood vessels in the brain).

Modern neuroimaging techniques have demonstrated great promise in making possible the earlier diagnosis of Alzheimer’s disease. Early signs of beta-amyloid accumulation in the brain, for example, can be identified through the use of Positron EmissionTomography (PET) scans along with a technique that uses radioactively labeled tracer molecules to find where amyloid concentrations are elevated in the brain.

There are some very good reasons to strive for an early diagnosis of Alzheimer’s. Early diagnosis may help a person and his or her support system understand confusing changes in function and behavior, and research has shown that education of families increases the success of treatment and home residence. Furthermore, early identification of Alzheimer’s disease allows a person and support system to plan ahead regarding such potential concerns as medication adherence, safety (for example with driving, stove use, or wandering), advance planning for a time when the person may no longer be competent to make prudent decisions (testament, power of attorney, advance directives), and whether or not to volunteer for studies investigating potential new treatments (many of which are tested in the early phases of disease process). In time, it is hoped that treatments will be available that will be particularly beneficial in the disease’s early stages.

An important caveat with early diagnosis, however, is that it must be very accurate and reliable! The potential consequences of assigning an incorrect Alzheimer’s disease diagnosis could be devastating.

Epilepsy is a disease characterized by recurrent disordered electrical signals in the brain, resulting in seizures. Seizures are typically brief episodes of disordered brain functioning that may appear as changes in consciousness, muscle activity, or autonomic functioning. Some cases of epilepsy have no clearly identifiable cause, but many seizures are attributable to a specific factor, such as withdrawal from alcohol. Seizures are seen in up to one fifth of Alzheimer’s disease patients, and typically these seizures occur in patients with early-onset disease and/or in the later stage of the disease. Often these seizures are described as “seizures secondary to Alzheimer’s disease” rather than as epilepsy, though they could be considered a “secondary epilepsy” (an epilepsy attributable to a specific cause). When seizures occur in an Alzheimer’s disease patient, it can be valuable to examine further with neurological assessment, an imaging study such as an MRI, and an electroencephalogram (EEG) in order to see whether there is a stroke or other non-Alzheimer’s contributing factor. If an anti-seizure medication is used, it’s important to recognize that these medications sometimes affect cognition.

While it remains unclear whether depression actually causes Alzheimer’s disease, the occurrence of depression and depressive symptoms is noticeably quite frequent among people with dementia. Several recent studies have suggested that depression may be a predictor or even a risk factor for the onset of Alzheimer’s disease. For example, 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 this neurological disorder. 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.

You can read more about the association between depression and Alzheimer’s disease in the following articles:

Apathy and Depression Predict Progression From MCI to Dementia

Depression May Nearly Double Risk of Dementia

Because of the progressive degenerative nature of Alzheimer’s disease, most all areas of the brain are eventually affected by the disease. Typically, the brain areas concerned with memory, cognition and perception are affected first, followed by brain regions involved in speech, movement and bodily functions. Of course, this progression is different for each person, and that is why no two people experience the same exact symptoms at the same time. In your wife’s case, the disease has advanced to the point where it is now clearly affecting her ability to walk, eat and speak. Based upon your description, therefore, it would seem that your dear wife is in late-stage Alzheimer’s disease (stage 3 according to our scale, and stage 7 according to other clinical scales). This stage typically may last for 1 to 3 years.

Depressive symptoms and depression are common among people with dementia, and some studies have suggested that depression is a predictor or even risk factor for the onset of Alzheimer’s disease. Several studies, though not all, support the value of using antidepressants in individuals who suffer simultaneously from both Alzheimer’s disease and depression. Also, many clinicians have wondered whether addressing depressive symptoms might also aid cognitive functioning in individuals who already impaired. No consistent evidence, however, supports the intriguing suggestion that antidepressant treatment will forestall Alzheimer’s disease in previously depressed people. Among the several observational studies that have looked into this possibility, findings have differed and at present the value of using an antidepressant for this purpose remains speculative.