Cognitive Deficits Present Years Before Alzheimer's Develops

July 07, 2015

Deficits in cognitive function can be present up to 18 years before the development of clinically evident Alzheimer's disease (AD), a new study shows.

Led by Kumar B. Rajan, PhD, investigators at Rush University in Chicago, Illinois, found that overall performance on tests of cognitive function differed substantially between individuals who subsequently developed Alzheimer's and those who remained free of the disease up to 18 years before diagnosis.

Strong associations with executive function and global cognition were observed at the farthest time from diagnosis that appeared stronger than episodic memory, perhaps suggesting that loss in executive function might precede loss in episodic memory, the authors note.

The study was published online June 24 in Neurology.

Future Risk

Noting that pathophysiologic changes are generally thought to precede the emergence of cognitive impairment in AD, the researchers suggest that the processes that constitute preclinical AD may therefore span a very long duration of several decades. Studies aimed at improving clinical understanding of the earliest manifestations of the disease process with a view to prevention may need to start during midlife.

For the current study, 2125 individuals aged 65 years and older at baseline from 4 Chicago neighborhoods underwent a battery of cognitive tests that were repeated every 3 years. During the 18-year follow-up period, 21% of the sample developed clinical AD.

Results showed that participants who scored lower overall on the cognitive tests had an increased risk of developing the disease. During the first year of the study, people with lower test scores were about 10 times more likely to be diagnosed with AD than their counterparts with higher scores, with the odds increasing by 10 for every standard deviation (SD) that the score was lower than the average.

On the basis of tests completed 13 to 18 years before the final assessments took place, 1 unit lower in performance of the standardized cognitive test score was associated with an 85% greater risk for future dementia.

"This indicates how subtle declines in cognitive function affect future risk," said Dr Rajan.

The magnitude of association between composite cognitive test score and development of AD increased from an odds ratio of 3.39 at 13.0 to 18 years before to 9.84 the year before per SD increment. These associations were consistently larger among European Americans than among African Americans.

The study was supported by the National Institute on Aging and the International Alzheimer's Association.

Neurology. Published online June 24, 2015. Abstract

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