Alzheimer Disease (AD) is the most common cause of dementia in America. The accumulation of amyloid plaque and neurofibrillary tangles, initially described by Alois Alzheimer in a 51-year-old woman, is characteristic of the disease. Progressive memory decline is a hallmark characteristic of the disease. Approximately 80% of patients with known AD are over the age of 75, and the incidence accelerates with age. Survival after diagnosis varies between 4 to 8 years, depending on symptoms, but can last a decade or more. Nearly two-thirds of the patients are women.
Recent studies show, however, that 30% of people clinically diagnosed with AD do not have amyloid plaque accumulation! So what do they have?!! See other posts on this site for Alzheimer Mimics.
Various risk factors have been identified for AD, including vascular risk factors, sleep disorders, and traumatic brain injury. On the other hand, increased education, exercise, and continued social engagement seem to decrease the risk of AD.
Genetic risk factors also exist. A family history and the presence of two APOE4 alleles increase the risk, because of amyloid transport, tau phosphorylation and precipitation, reduced metabolism, and other factors. The immune and inflammatory pathways play a role as well, and next-generation sequencing (Whole Exome Sequencing, or WES, and Whole Genome Sequencing, or WGS) may shed further light on the genetic links to AD.
Despite these risk factors, other causes of memory decline need to be ruled out. Laboratory blood tests, as well as appropriate brain scanning with CT, MRI, and/or PET scanning if necessary, should be carried out. Structural changes in the hippocampus (the brain structure critical for memory) are usually present in such imaging, and a relatively specific pattern of abnormality on amyloid and FDG PET scanning is present. Tau PET is available only for research, and we at the RNI are carrying out a study of this. EEG is frequently helpful to rule out silent seizure activity, which can disturb memory for weeks. In the US, Medicare pays for FDG PET, to differentiate between AD and frontotemporal dementia (FTD).
When acquired cognitive impairment is present, but it does not interfere with daily function, then the clinical state is referred to as MCI, or mild cognitive impairment. This diagnosis is really a statistical differentiation without a difference, and frequently represents the first stages of AD or another dementia. However, and this cannot be emphasized strongly enough, other causes for cognitive decline need to be ruled out.
As we learn more about AD, and other causes of dementia, we have begun to realize that the brain pathologic changes present in AD, amyloid and tau accumulation, are frequently associated with pathology found in other disorders, such as vascular brain injury, Lewy body dementia, TDP-43 inclusions (FTD), and hippocampal sclerosis.
So we have a lot to learn about AD. Despite billions of dollars of research, we don’t know the cause, and we don’t have a cure. But we do know some medications to avoid if possible, like anti-psychotics, and we know some medications that can help the cholinergic and glutamate transmitters in the brain. And we know difficult behaviors should be managed without medications if possible.
We need more research, so that someday perhaps our children, and our children’s children, will not have to put up with this devastating disease.
