Higher levels of purpose in life reduce the deleterious effects of Alzheimer’s disease (AD) pathologic changes on cognition in advanced age, according to a longitudinal, epidemiologic and clinicopathologic study in the May issue of the Archives of General Psychiatry.

“Given the lack of effective therapies, the identification of factors that promote cognitive health in elderly persons is urgently needed to decrease the burden of AD,” wrote the study authors. “Although relatively few such factors have been identified, compelling evidence indicates that positive psychological and experiential factors are associated with maintenance of cognitive function. Furthermore, novel neuroimaging and clinicopathologic findings have shown that some of these factors confer protective benefit (i.e., provide neural reserve) by reducing the deleterious effects of AD pathologic changes on cognition."

In this study, Patricia A. Boyle, PhD, from the Rush Alzheimer’s Disease Center and the department of behavioral sciences at Rush University Medical Center in Chicago, and colleagues included 246 community-based elderly persons to test the hypothesis that purpose in life reduces the deleterious effects of AD pathologic changes on cognition in advanced age.

The researchers assessed purpose in life via structured interview, and evaluated cognitive function annually and proximate to death. On post-mortem exam, they quantified three indexes of AD pathologic features: global AD pathologic changes, amyloid and tangles. The associations of disease pathologic changes and purpose in life with cognition were examined using linear regression and mixed models.

For quantification of molecularly specific measures of amyloid and tau tangles, multiple tissue blocks from the entorhinal cortex proper, hippocampus (CA1/subiculum), superior frontal cortex, dorsolateral prefrontal cortex, inferior temporal cortex, angular gyrus cortex, anterior cingulate cortex and calcarine cortex were embedded in paraffin and cut into 20-um slices. They labeled amyloid-B with an N-terminus-directed monoclonal antibody (10D5, 1:1000; provided by Elan Pharmaceuticals), and performed immunohistochemical analysis.

Purpose in life modified the association between the global measure of AD pathologic changes and cognition (mean parameter estimate, 0.532), such that participants who reported higher levels of purpose in life exhibited better cognitive function despite the burden of the disease, according to the study authors.

Boyle and colleagues reported that the purpose in life also reduced the association of tangles with cognition (parameter estimate, 0.042) and the protective effect of purpose in life persisted even after controlling for several potentially confounding variables. Furthermore, in analyses examining whether purpose in life modified the association between AD pathologic effects and the rate of cognitive decline, they found that higher levels of purpose in life reduced the effect of AD pathologic changes on cognitive decline (parameter estimate, 0.085).

“Our study showed that people who reported greater purpose in life exhibited better cognition than those with less purpose in life even as plaques and tangles accumulated in their brains,” said Boyle in a statement. “These findings suggest that purpose in life protects against the harmful effects of plaques and tangles on memory and other thinking abilities. This is encouraging and suggests that engaging in meaningful and purposeful activities promotes cognitive health in old age.”

Boyle and colleagues noted that much of the Alzheimer's research that is ongoing seeks to identify ways to prevent or limit the accumulation of plaques and tangles in the brain, which has proven quite difficult. Studies such as the current one are needed because, until effective preventive therapies are discovered, strategies that minimize the impact of plaques and tangles on cognition are urgently needed.

“These studies are challenging because many factors influence cognition and research studies often lack the brain specimen data needed to quantify Alzheimer's changes in the brain,” Boyle said. “Identifying factors that promote cognitive health even as plaques and tangles accumulate will help combat the already large and rapidly increasing public health challenge posed by AD.”

This study was funded by the National Institutes on Aging.