CME Author: Vicki Brower
Study Authors: Aron S. Buchman, Lei Yu, et al.; James A. Mortimer, Yaakov Stern
Target Audience and Goal Statement:
Neurologists, neuropsychologists, neuropsychiatrists, psychiatrists, gerontologists, primary care physicians, family medicine specialists, and internists
The goal was to study the associations of physical activity, Alzheimer’s disease (AD) and other brain pathologies, and cognition in older adults living in the community.
- What is the relationship, if any, between physical activity, motor abilities, and common brain pathologies in community-dwelling older adults?
- What are possible explanations for the association, found in this study and elsewhere, between physical activity and cognitive function in this group of elderly individuals?
Study Synopsis and Perspective:
In an ongoing longitudinal cohort study of 450 older adults, average age of 91 at death, researchers found that higher levels of physical activity and better motor ability were independently associated with better cognition, even in the presence of brain lesions or dementia-linked biomarkers.
Aron S. Buchman, MD, of Rush University Medical Center in Chicago, and colleagues monitored individuals’ daily activity, tested motor performance, and conducted postmortem brain autopsies to detect 10 brain pathologies, based on data from the Rush Memory and Aging Project. The project is a community-based cohort of older adults who agreed to annual detailed clinical examinations, and brain donation at the time of death.
The analysis included 454 participants, 73% of whom were women. A total of 191 participants had been diagnosed with dementia, and 263 with no dementia.
As described in the study online in Neurology, the team conducted 10 supervised motor performance tests to determine global motor ability scores and used continuous multi-day accelerometer recordings to monitor physical activity.
Activity results were collected about 2 years before death, and 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.
Buchman and co-authors tested study participants for five cognitive abilities: semantic memory, episodic memory, working memory, perceptual speed, and visuospatial abilities.
At autopsy, the researchers assessed brain tissue for the following:
- 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
A total of 85% of study participants had two or more different brain pathologies.
The team performed regression analyses to examine whether motor abilities or the amount of daily physical activity attenuated the association of indices of AD pathology with the level of cognitive function proximate to death.
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) were both independently associated with better global cognition proximate to death. These independent associations remained significant when interaction terms for AD and other pathologies were added, the researchers reported.
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%). Moreover, these associations were additive, as the association of total daily physical activity with cognition did not vary with motor abilities.
“Physical activity may provide cognitive reserve to maintain function independent of accumulating brain pathologies,” Buchman told MedPage Today. Still, the investigators said, it is possible that “the association between total daily activity and cognition may have been observed because higher total daily activity may lead to better cognition or because poorer cognition, ie., dementia, might lead to reduced daily activity.”
In their analysis, the researchers concluded that motor abilities remained independently associated with better cognition and that poorer cognition did not account for the association of total daily activity and motor abilities with cognition proximate to death.
“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.”
Source References: Neurology, online Jan. 16, 2019; DOI: 10.1212/WNL.0000000000006954f
Editorial: Neurology, online Jan. 16, 2019; DOI: 10.1212/WNL.0000000000006935
Study Highlights: Explanation of Findings
Buchman and co-researchers found that in this group of elderly adults, “a more active lifestyle and better motor abilities proximate to death were independently associated with better cognitive function and reduced odds of dementia with controlling for AD and nine other common age-related brain pathologies.” The associations between both physical activity and motor abilities with better cognition and lower risk of dementia are “independent and additive,” the team noted.
“Moreover, there was also no evidence that a more active lifestyle or better motor abilities modified the associations of these brain pathologies with cognitive function proximate to death,” the researchers wrote, concluding that “together, these data suggest that the cognitive reserve associated with physical activities and motor abilities is unrelated to the presence of common brain pathologies and that the molecular mechanisms that underlie this reserve remain to be identified.”
The researchers explained that previous studies, including one from the same patient cohort, have suggested that higher levels of physical activity may slow the rate of cognitive decline and reduce the risk of AD dementia, but the mechanisms whereby this may occur remain unclear. Studies in animals indicate that more physical activity may prevent the accumulation and progression of AD pathology, and brain imaging research in older adults suggests that higher levels of physical activity are associated with lower levels of infarcts and better white matter brain integrity.
In addition, studies with PET imaging show that higher levels of β-amyloid deposits are associated with poorer motor function. But Buchman et al. noted that in the few studies that have focused on physical activity, there has not been a consistent relationship with physical activity level and brain imaging levels of β-amyloid or cerebral spinal fluid (CSF) markers of AD.
The lack of human data “makes it difficult to explicate the pathologic mechanisms” that underlie the association of a more active lifestyle with better cognition in older adults, the researchers wrote.
In an accompanying editorial, James Mortimer, PhD, of the University of South Florida in Tampa, and Yaakov Stern, PhD, of Columbia University in New York City, echoed Buchman and co-authors, noting that numerous observational studies have supported an association between physical exercise and reduced cognitive decline.
“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,” the editorialists wrote. For example, one trial showed that aerobic exercise led to increased levels of brain-derived neurotrophic factor (BDNF) and increased hippocampal volume; other studies suggested that higher BDNF gene expression may help slow cognitive decline. “Alternatively, physical exercise itself might reduce brain pathology,” and mouse models have shown that higher physical activity levels reduce the accumulation of AD pathology, Mortimer and Stern added.
Buchman and co-authors noted that while their cross-sectional results should be interpreted with caution, the findings do provide support for the idea that even in the absence of treatment for AD and related disorders, a more active lifestyle, including physical and cognitive activities, may help maintain cognition in older adults.
Study limitations, the team said, include that because the data were cross-sectional, causal inferences cannot be drawn. It is also possible that some of the association resulted from reverse causality (i.e., that lower cognitive function led to less activity).
In addition, the accelerometers used in the study did not differentiate between various physical activities (such as steps vs arm movements), and activity was assessed only at one point later in life, so it remains unknown whether physical activity in early life may have played a role.
Mortimer and Stern also stated that in order to prove causation, longitudinal studies of physical activity and cognition with brain imaging would be needed to document the influence of pathology on the demonstrated association.