Mental Activity Best Hope Against Late Cognitive Decline

Pauline Anderson

April 04, 2012

April 4, 2012 — The rate of cognitive decline appears to sharply increase, and the differences between cognitive abilities tend to disappear in the 2 to 3 years before death, a new study shows.

Robert S. Wilson, PhD

"The results suggest that new factors must be coming into play to cause such a precipitous loss in cognitive function as well as to sort of erase the distinctions between different cognitive abilities," lead author, Robert S. Wilson, PhD, Rush University Medical Center, Chicago told Medscape Medical News. "So whatever is biologically driving this seems to be affecting the brain as a whole, affecting it rather severely."

The study provides substantial evidence in support of the hypothesis that cognitive abilities become increasingly correlated, or "de-differentiated," in later life, he added.

A second study by Dr. Wilson and colleagues, published in the same issue of Neurology, shows that participation in cognitively stimulating activities, such as reading and playing chess, has a positive influence on subsequent cognitive health.

The study appears to be the first to rule out reverse causation: that previous cognitive decline explains lower participation in cognitively stimulating activities.

The reports are published online April 4 in Neurology.

Gradual Decline

In the first paper, the researchers analyzed data on 174 older but nondemented Catholic nuns, priests, and monks who participated in the Religious Orders Study. The participants had annual cognitive testing for the 6 to 15 years before they died, after which a brain autopsy was performed. From this, investigators derived a composite measure of plaques and tangles.

The study found that decline in each cognitive domain began relatively gradually and that the rates of change in different cognitive domains were moderately correlated, ranging from 0.25 (episodic memory–working memory) to 0.46 (episodic memory–semantic memory).

But then, decline accelerated rapidly some 2 to 3 years before death (the terminal period). The rate of decline in episodic memory, for example, increased 15-fold between the preterminal and terminal phases.

The study also found that changes in cognitive abilities became increasingly inter-related just before death. Intercorrelations in this phase ranged from 0.83 to 0.89.

"What's important here is that cognitive decline in old age appears to go through different phases where it's as though different pathological processes come into play," said Dr. Wilson.

Alzheimer's disease (AD) pathology was not associated with rates of terminal decline in the different cognitive domains. "This suggests that the precipitous decline that occurs right before death doesn't seem to be terribly well explained by AD pathology," said Dr. Wilson. "We found that the AD pathway was predictive of when this period would begin, but it didn't really predict how fast you would decline during it."

In an accompanying editorial, Hitoko H. Dodge, PhD, from Oregon Health and Science University, Portland, and a member of the American Academy of Neurology, and Daniel C. Marson, PhD, Department of Neurology, University of Alabama, Birmingham, called the study design "innovative and elegant'.

The study deepens understanding of terminal cognitive decline, they write. "The findings suggest that the changes in mental abilities during the 2 to 3 years before death are not driven directly by processes related to Alzheimer's disease, but instead that the memory and other cognitive decline may involve some biological changes in the brain specific to the end of life."

Among the clinical implications of the study is that treatments that target the AD pathologic process should focus on earlier rather than later cognitive changes, they said.

Cognitively Stimulating Activities

In the second study, the analysis included data on 1076 participants without dementia from the Rush Memory and Aging Project, an ongoing longitudinal clinical-pathologic cohort study of common chronic conditions of older age. The participants had a mean baseline age of 80.4 years; 74.2% were women and 89.5% were non-Hispanic white. They were followed annually for a mean of 4.9 years.

At each annual evaluation, participants were asked to rate the frequency of participating in 7 cognitively stimulating activities, including reading the newspaper, writing letters, and playing games such as chess and checkers, over the previous year.

Also at each evaluation, researchers assessed cognitive function. Using a battery of tests, they measured episodic memory, semantic memory, working memory, and perceptual speed.. From these tests, researchers developed a composite measure of global function.

Researchers found mean annual decreases of 0.077 unit in the global cognitive measure and 0.066 unit in the cognitive activity measure. The analysis indicated an association between cognitive activity in a given year and global cognitive function in the following year. However, the level of global cognitive function at a particular time was not related to the level of cognitive activity in the subsequent year.

After exclusion of the 29.7% of the sample who met the criteria for mild cognitive impairment at baseline, the results were essentially the same. And after the analysis was repeated for specific cognitive functions, cognitive activity predicted the subsequent level of function in all 4 cognitive domains.

Other studies have looked at the relationship between cognitive function and participation in cognitively stimulating activities but were smaller and included fewer cognitive assessments, said Dr. Wilson.

"To our knowledge, this is the first study to investigate this very question of the direction of the association with enough data to actually answer it."

Association Direction

Asked to comment, Daniel C. Potts, MD, from Alabama Neurology and Sleep Medicine and associate clinical professor, College of Community Health Sciences, the University of Alabama School of Medicine, Tuscaloosa, and member of the American Academy of Neurology, praised the study.

"The rigor of follow-up assessment, the large sample size, the exclusion of demented individuals and the minimization of participant dropout make the study more valid than some," he told Medscape Medical News.

The study's "sound methodology" also helps solve the "chicken-egg" question of whether individuals with cognitive decline participate in fewer cognitively enhancing activities because they're in cognitive decline, or whether the degree of participation somehow predetermines cognitive decline, said Dr. Potts. "It seems the latter may be true."

He noted that the benefits of cognitive stimulation don't seem to be specific to any particular activity. "We tend to look for gimmicks, but the truth of the matter is that no one activity has a corner on the dementia prevention market."

The studies were funded by the National Institute on Aging and the Illinois Department of Health. Dr. Wilson serves as a Consulting Editor for Aging, Neuropsychology and Cognition and Psychology and Aging, has served as a consultant for Pain Therapeutics Inc, and receives research support from the National Institutes of Health/National Institute on Aging. For conflict of interest information on other authors, see original paper. Dr. Potts has disclosed no relevant financial relationships.

Neurology. 2012;78:1116-1122, 1123-1129, 1110-1111. Abstract, Abstract, Editorial extract

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