Study Title:

Mild Cognitive Decline Reflects Early Alzheimer Changes

Study Abstract

Objective: To test the hypothesis that frequent cognitive activity predicts slower cognitive decline before dementia onset in Alzheimer disease (AD) and faster decline thereafter.

Methods: As part of a longitudinal cohort study, older residents of a geographically defined population were assessed at 3-year intervals with brief cognitive performance tests from which a composite measure of global cognition was derived. After each wave of testing, a subset was sampled for clinical evaluation. The present analyses are based on 1,157 participants. They were free of dementia at study enrollment at which time they rated frequency of participation in common cognitively stimulating activities from which a previously validated summary measure was derived. They were sampled for clinical evaluation a mean of 5.6 years after enrollment and subsequently followed a mean of 5.7 years with brief cognitive performance testing at 3-year intervals.

Results: On clinical evaluation, 614 people had no cognitive impairment, 395 had mild cognitive impairment, and 148 had AD. During follow-up, the annual rate of global cognitive decline in persons without cognitive impairment was reduced by 52% (estimate = 0.029, SE = 0.010, p = 0.003) for each additional point on the cognitive activity scale. In the mild cognitive impairment group, cognitive decline rate was unrelated to cognitive activity (estimate = –0.019, SE = 0.018, p = 0.300). In AD, the mean rate of decline per year increased by 42% (estimate = 0.075, SE = 0.021, p < 0.001) for each point on the cognitive activity scale.

Conclusion: Mentally stimulating activity in old age appears to compress the cognitive morbidity associated with AD by slowing cognitive decline before dementia onset and hastening it thereafter.

From press release:

Simply getting older is not the cause of mild memory lapses often called senior moments, according to a new study by researchers at the Rush Alzheimer's Disease Center. The study, published in the September 15, 2010, online issue of Neurology, the medical journal of the American Academy of Neurology, found that even the very early mild changes in memory that are much more common in old age than dementia are caused by the same brain lesions associated with Alzheimer's disease and other dementias.

"The very early mild cognitive changes once thought to be normal aging are really the first signs of progressive dementia, in particular Alzheimer's disease." said Robert S.Wilson, PhD, neuropsychologist at Rush University Medical Center. "The pathology in the brain related to Alzheimer's and other dementias has a much greater impact on memory function in old age than we previously recognized."

The study involved over 350 nuns, priests and brothers who participated in Rush's Religious Orders Study and completed up to 13 years of annual cognitive testing. After death, the brains were examined for the lesions associated with dementia: neurofibrillary tangles, cerebral infarction (stroke), and Lewy bodies.

Researchers looked at the rate of change in cognitive function over time. The last four to five years of life showed a very rapid decline. The preceding years showed a much more gradual decline that would be described as normal aging.

As expected, pathologic lesions were related to the rapid decline, but researchers were somewhat surprised to find the pathology was very strongly predictive of the mild changes in cognitive function.

Higher tangle density adversely affected all forms of cognition at all trajectory points. Both Lewy bodies and stroke approximately doubled the rate of gradual memory decline, and almost no gradual decline was seen in the absence of lesions.

"Our study finds that Alzheimer's disease and related dementias are the root cause of virtually all loss of cognition and memory in old age. They aren't the only contributing factors; other factors affect how vulnerable we are to the pathology and to its effects. But the pathology does appear to be the main force that is driving cognitive decline in old age," said Wilson.

According to Wilson, recognizing that the earliest changes in memory are related to Alzheimer's pathology can lead to early diagnosis and will be critical information if a treatment is developed that can alter the pathologic course of the disease.

Study Information

R.S. Wilson, PhD, L.L. Barnes, PhD, N.T. Aggarwal, MD, P.A. Boyle, PhD, L.E. Hebert, ScD, C.F. Mendes de Leon, PhD and D.A. Evans, MD.
Cognitive activity and the cognitive morbidity of Alzheimer disease
2010 September
Rush Alzheimer's Disease Center, Rush University Medical Center.

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