Active lifestyle may delay Alzheimer’s disease progression
An active lifestyle, regardless of vascular risk, may delay the progression of Alzheimer’s disease (AD) by slowing down cognitive decline and neurodegeneration, according to a study presented at the Alzheimer’s Association International Conference (AAIC 2019).
“One of the most striking findings from our study was that greater physical activity not only appeared to have positive effects on slowing cognitive decline, but also on slowing the rate of brain tissue loss over time in normal people who had high levels of amyloid plaque in the brain,” said study author Assistant Professor Jasmeer Chhatwal from the Massachusetts General Hospital (MGH), Charlestown, Massachusetts, US.
Participants in this longitudinal, observational study were 182 older adults (mean age 73.4 years, 56.6 percent female) enrolled in the Harvard Aging Brain Study. The participants were clinically normal at baseline (Clinical Dementia Rating score of 0, Geriatric Depression Scale score of <11, and Mini-Mental State Examination [MMSE] score ≥27), though the population included individuals with elevated β-amyloid levels who were at high risk for cognitive decline.
Mean steps/day was representative of daily physical activity at baseline and was measured with a pedometer over 7 consecutive days. Vascular risk was determined using the Framingham Heart Study cardiovascular disease risk score, cognitive decline using the Preclinical Alzheimer Cognitive Composite (PACC), and neurodegeneration by changes in total grey matter volume. Participants had also undergone β-amyloid positron emission tomography (PET) imaging and magnetic resonance imaging (MRI).
Higher levels of physical activity were tied to a slower progression in β-amyloid-related cognitive decline (β, 0.03, 95 percent confidence interval [CI], 0.02–0.05; p<0.001) and total grey matter volume loss (β, 482.07, 95 percent CI, 189.40–774.74; p=0.002), with the findings remaining significant after adjusting for vascular risk. [JAMA Neurol 2019;doi:10.1001/jamaneurol.2019.1879]
“Beneficial effects were seen at even modest levels of physical activity, but were most prominent at around 8,900 steps,” said study co-author Professor Reisa Sperling, also from MGH.
Individuals with fewer vascular risk factors also experienced slower β-amyloid-related decline (β, -0.04, 95 percent CI, -0.06 to -0.02; p<0.001) and total grey matter volume loss (β, -483.41, 95 percent CI, -855.63 to -111.20; p=0.01).
“These findings suggest that physical activity and vascular risk have independent and additive effects on β-amyloid-related cognitive decline and neurodegeneration [in asymptomatic older adults],” said Chhatwal and co-authors.
β-amyloid begins to accumulate decades before symptoms of AD appear, and this early accumulation is a prime point to introduce interventions that may delay AD progression, they said.
“Because there are currently no disease-modifying therapies for AD, there is a critical need to identify potential risk-altering factors that might delay progression of the disease,” added Chhatwal. “[I]nterventional approaches that target both physical activity and management of vascular risk factors may have additive beneficial effects on delaying the progression of AD in asymptomatic individuals,” the authors noted.
Exploratory analysis showed that the slower progression in in β-amyloid-related cortical thinning associated with physical activity occurred in the medial temporal, lateral temporal, insula, and medial parietal regions. Post hoc analyses showed that a higher level of physical activity was associated with slower β-amyloid-related decline in measures of memory ie, the Free and Cued Selective Reminding Test, Wechsler Memory Scale–Revised Logical Memory delayed recall, and MMSE, but not in processing speed, ie, the Wechsler Adult Intelligence Scale–Revised Digit Symbol Coding Test.
Proposed mechanisms behind the effect of physical activity on cortical thinning and cognition include, among others, decreased inflammation and increased cerebral blood flow. Future research should investigate the mechanisms behind the specific associations, suggested the authors. They also acknowledged limitations of this study, such as the exclusion of patients with cerebrovascular disease (eg, stroke, cortical infarcts) and the short duration and lack of information on type and intensity of physical activity assessed, which need to be addressed in future research.