Prodromal Alzheimer’s phase ‘may span decades’

By Eleanor McDermid, Senior medwireNews Reporter

Marked reductions in cognitive performance are present up to 18 years before people develop Alzheimer’s disease (AD) dementia, research shows.

“If, as widely hypothesized, evidence of AD dementia pathophysiology precedes cognitive impairment in preclinical AD dementia, these results imply a very long duration for the prodromal phase of clinical manifestation of AD dementia, one that may span decades”, write the researchers in Neurology.

The cognitive differences between study participants who did and did not develop AD dementia were largest in the years immediately before diagnosis, but were statistically significant throughout the 18-year follow-up.

In total, 442 of the 2125 older adults participating in the population-based Chicago Health and Aging Project developed AD during the course of the study.

Between 0.1 and 0.9 years before diagnosis, participants who developed AD had an average composite cognitive test score of –0.645, compared with 0.301 among those who remained free of the condition. Between 1.0 and 3.9 years before diagnosis the corresponding scores were –0.138 and 0.524.

The differences between the two groups were smaller earlier in the study, but still significant, with the scores in the AD group being 0.258 between 13.0 and 17.9 years before diagnosis, compared with 0.579 in the non-AD group at the same time point.

At this point, each standard deviation decrease in the composite cognitive test score was associated with a significant 3.39-fold increased risk of later AD dementia, after accounting for age, gender, race and education. The risk increase was larger among European Americans than African Americans, even after accounting for age, gender and education.

The composite cognitive test score was based on the average across the Mini-Mental State Examination, the Symbol Digits Modalities Test and the Immediate and Delayed Recall of the East Boston Story.

Participants who did and did not develop AD also showed significant differences in performance on the individual tests, but at the earliest time point (13.0–17.9 years) the differences appeared statistically stronger for general cognition and executive function than for memory “perhaps suggesting that loss in executive function might precede loss in episodic memory.”

Kumar Rajan (Rush University Medical Center, Chicago, Illinois, USA) and study co-authors note that the pathophysiological changes of AD are thought to accumulate for some time before cognitive impairment becomes evident.

If this is true, “then the processes that constitute preclinical AD dementia may span a very long duration”, they conclude.

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