AD Symptoms May Appear Early

The signs and symptoms of Alzheimer disease (AD) may appear well before the clinical diagnosis of the disease, according to new research out of Rush University in Chicago.

AD is currently treated with medications that block acetylcholinesterase and the breakdown of the neurotransmitter acetylcholine, or with a glutamate antagonist, and sometimes with combinations of these approaches. Current treatments serve to delay the progression of AD, but do not halt neurodegeneration, cell loss, memory loss, and other associated symptoms. AD has no cure. New treatments that prevent AD progression are greatly needed. Earlier detection of AD will be most effective for the prevention of brain cell loss in the limbic and cortical regions that are affected by AD.

Led by Kumar Rajan, an associate professor of internal medicine at Rush University Medical Center, the current study utilized four brief cognitive tests and followed subjects up to clinical diagnosis of AD dementia, over a period of 18 years. Tests included measurements of episodic memory, executive function, and overall cognition.

A total of 2,125 African Americans and European Americans who initially had no clinical dementia participated in the study. Of these, 442 (21%) developed AD and dementia. Lower cognitive test scores 18 years prior to the follow-up period predicted the development of AD dementia. In fact, the risk of AD dementia increased correspondingly with lower scores achieved 18 years prior. The researchers found that associations between the tests and eventual AD were stronger for European Americans than for African Americans.

In their report, the investigators concluded that “Our findings indicate that overall performance on a brief cognitive test battery and on tests measuring specific cognitive functions differ substantially on average between those who subsequently develop clinically evident AD dementia and those who remain free of AD dementia up to 18 years before diagnosis in a biracial population sample.”

The researchers noted in their report that the study has strengths, as well as weaknesses. Strengths, according to the authors, included “that it was of large size, conducted in a clearly defined, well-characterized sample of the general population, included adequate numbers of both African Americans and European Americans for meaningful analysis, and had a lengthy follow-up observation.” Many studies focus on European Americans exclusively.

As a weakness, they noted that more extensive cognitive tests, rather than the brief ones used, could be more sensitive to predicting future AD and dementia. They noted that even earlier prediction of AD might be achieved with the use of extensive tests.

Overall, however, the results have promising implications for the possible earlier prediction of AD. According to the study authors, “these results imply a very long duration for the prodromal phase of clinical manifestation of AD dementia, one that may span decades.”

With the development of strategies that prevent cell loss, such as neuroprotective medicines, or even specific lifestyle changes, this research suggests the possibility that AD may ultimately be delayed or even prevented in people who are at risk for the disease.

Key Points

• The signs of AD may appear well before the clinical diagnosis of the disease.

• A study conducted in African Americans and European Americans found that cognitive test scores predict AD dementia 18 years prior to the clinical diagnosis.

• AD may be predicted earlier than previously believed and ultimately this may aid in AD prevention.