Activity Tied to Cognition, Despite Brain Pathologies

Higher levels of physical activity and motor abilities were independently associated with better cognition in older adults, even when brain lesions or biomarkers linked to dementia were present, a post-mortem study showed.

The study also showed no evidence that a more active lifestyle or better motor abilities modified associations between dementia pathologies and cognitive function, suggesting the cognitive reserve associated with activity may be unrelated to them, Aron Buchman, MD, of the Rush University Medical Center in Chicago, and colleagues wrote in Neurology.

“Physical activity may provide cognitive reserve to maintain function independent of accumulating brain pathologies,” Buchman told MedPage Today.

“Similar findings have been reported for late-life cognitive activities,” he added. “Together, these suggest that even in the absence of treatment for Alzheimer’s disease and related disorders, a more active lifestyle including physical and cognitive activities may help maintain cognition in older adults.”

Numerous observational studies have supported an association between physical exercise and reduced cognitive decline, but the mechanisms remain unknown, noted James Mortimer, PhD, of the University of South Florida in Tampa, and Yaakov Stern, PhD, of Columbia University in New York, in an accompanying editorial.

“The results of randomized trials of physical exercise suggest that exercise leads to increases in brain tissue, including in the hippocampus, where atrophy is an early and important finding in Alzheimer’s disease,” they wrote. One trial showed aerobic exercise led to increased levels of brain-derived neurotrophic factor (BDNF) and increased hippocampal volume; other studies suggested higher BDNF gene expression may help slow cognitive decline. “Alternatively, physical exercise itself might reduce brain pathology,” Mortimer and Stern added: mouse models have shown that higher physical activity levels reduce Alzheimer’s pathology accumulation.

The study drew on data from the Rush Memory and Aging Project, a community-based cohort of older adults who agreed to annual detailed clinical examination and brain donation at the time of death. The analysis included 454 participants with an average age at death of 91; 73% were female. A total of 191 participants had been diagnosed with dementia and 263 with no dementia.

The researchers incorporated 10 supervised motor performance tests to determine a global motor ability score and relied on continuous multi-day accelerometer recordings to monitor physical activity. Activity results were collected about 2 years before death and were measured in counts/day. The overall average was 156,000 counts/day, with participants without dementia averaging 180,000 counts/day, and people with dementia averaging 130,000 counts/day.

At autopsy, the researchers assessed brain tissue for:

• Alzheimer’s disease pathology (neuritic plaques, diffuse plaques, and neurofibrillary tangles)
• Nigral neuronal loss
• Lewy body disease pathology
• TAR DNA-binding protein 43
• Hippocampal sclerosis
• Macroscopic cerebral infarcts
• Cerebral atherosclerosis
• Microscopic cerebral infarcts
• Cerebral arteriolosclerosis
• Cerebral amyloid angiopathy

On average, participants had three different brain pathologies, with one or more pathologies observed in nearly all cases.

Buchman and colleagues performed regression analyses to “examine whether motor abilities or the quantity of daily physical activity attenuates the association of indices of AD pathology with the level of cognitive function proximate to death,” they wrote. Higher levels of total daily activity (estimate 0.148 ± 0.049, 95% CI 0.053–0.0.244, P=0.003) and better motor abilities (estimate 0.283 ± 0.055, 95% CI 0.175–0.390, P<0.001) both were independently associated with better global cognition proximate to death. These independent associations remained significant when interaction terms for Alzheimer's disease and other pathologies were added.

Each standard deviation increase of total daily activity or motor capacity was associated with a reduction of dementia risk (total daily activity 31%; motor abilities 55%). These associations were additive, as the association of total daily physical activity with cognition did not vary with motor abilities.

“These data provide support for the idea that strategies or behaviors that lead to a more active lifestyle and better motor abilities may provide cognitive reserve, which may maintain cognitive function in older adults despite the accumulation of Alzheimer’s disease and other common brain pathologies,” the researchers wrote. “Further work is needed to clarify to what extent the risk factors and the types and duration of interventions to increase total daily physical activity and motor abilities are distinct and can be disentangled.”

The authors noted several limitations to their research: the data were cross-sectional and causal inferences cannot be drawn. It’s possible some of the association resulted from reverse causality (that lower cognitive function led to less activity). Accelerometers used in the study did not differentiate between various physical activities (such as steps vs arm movements) And the researchers assessed activity only at one point later in life; whether physical activity in early life may have played a role is unknown.