Summary: For people who carry a genetic mutation that causes early-onset Alzheimer’s disease, engaging in at least 150 minutes (2.5 hours) of physical activity per week may help delay cognitive decline and reduce Alzheimer’s-related brain changes, including tau accumulation. Researchers suggest these findings could have implications for more common forms of Alzheimer’s disease as well.
Source: Alzheimer’s Association.
Exercise, Genetics, and Alzheimer’s: Key Finding
A new study published as a corrected proof in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association reports that individuals with autosomal dominant Alzheimer’s disease (ADAD)—a rare, genetically driven form of Alzheimer’s—who met current physical activity recommendations experienced better cognitive performance and showed fewer Alzheimer’s-related biomarkers in cerebrospinal fluid. Specifically, taking part in at least 150 minutes of weekly physical activity (walking, running, swimming, aerobics, etc.) was associated with improved cognition and lower levels of tau, a protein linked to neurodegeneration in Alzheimer’s disease.
Study Design and Participants
The research team, led by Christoph Laske, M.D., at the University Hospital of Tübingen, Germany, analyzed data from participants in the Dominantly Inherited Alzheimer’s Network (DIAN), an international observational study focused on families affected by ADAD. The analysis included 275 mutation carriers with an average age of 38.4 years. Participants were classified into two groups based on their reported weekly physical activity: high activity (>150 minutes per week) and low activity (<150 minutes per week). The frequency and type of exercise were corroborated by a third party, such as a family member or friend, although exercise intensity was not specifically measured. This cross-sectional analysis evaluated relationships among physical activity, cognitive performance, functional status, and cerebrospinal fluid biomarkers of Alzheimer’s pathology.
Measured Outcomes
Researchers used established clinical and cognitive measures to evaluate outcomes. Cognitive and functional performance were assessed with the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Sum of Boxes (CDR-SOB). Cerebrospinal fluid analysis measured AD-related biomarkers, including tau proteins. Comparisons between higher-activity and lower-activity mutation carriers examined whether meeting the recommended 150 minutes per week threshold corresponded with measurable differences in cognition and biomarkers.
Main Results
The study found that mutation carriers who engaged in at least 150 minutes of physical activity per week scored significantly better on the MMSE and had lower CDR-SOB scores, indicating better cognitive and functional status. These higher-activity individuals also showed lower levels of Alzheimer’s-related biomarkers in cerebrospinal fluid, including reduced tau. Based on cross-sectional modeling, high-activity mutation carriers scored approximately 3.4 points higher on the MMSE at the expected age of symptom onset and were diagnosed with very mild dementia roughly 15.1 years later than low-activity counterparts. The authors note this study did not assess individual cognitive trajectories over time, since it is cross-sectional rather than longitudinal.
Interpretation and Public Health Relevance
The investigators conclude that a physically active lifestyle may be achievable for people with genetic risk for Alzheimer’s and could play a meaningful role in delaying the clinical onset and progression of ADAD. In this study, about 70% of mutation carriers participating in DIAN reported meeting the 150-minute weekly activity level, indicating that the recommended goal is realistic for many individuals. While the findings come from a rare, genetically determined form of Alzheimer’s, the Alzheimer’s Association and the study authors emphasize the potential broader significance: if physical activity delays symptom onset in ADAD, similar effects might be observed in late-onset Alzheimer’s disease, which affects millions worldwide.
Maria C. Carrillo, Ph.D., Chief Science Officer of the Alzheimer’s Association, and other leaders point to growing evidence that lifestyle factors—including physical activity and vascular risk factor control—can reduce the risk of cognitive decline. They highlight the importance of large clinical trials and public health efforts to evaluate whether lifestyle interventions can protect brain health in at-risk older adults.
Ongoing and Related Research
To build more definitive evidence about lifestyle impacts on brain health, the Alzheimer’s Association is sponsoring large trials that test multi-domain lifestyle interventions. One such effort is a multi-year study designed to evaluate whether interventions that target multiple risk factors can protect cognitive function in older adults at increased risk for decline. Combining lifestyle strategies with medical therapies may represent a promising model for future Alzheimer’s prevention and treatment, analogous to combined approaches used in cardiovascular disease.
This study, titled “Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer’s disease,” was conducted by Stephan Müller and colleagues and supported by the Dominantly Inherited Alzheimer’s Network (DIAN), the U.S. National Institute on Aging, the German Center for Neurodegenerative Diseases (DZNE), and other international funding agencies. The analysis and results were published in Alzheimer’s & Dementia and released as a corrected proof in September 2018. Original research authors include investigators from multiple institutions collaborating within the DIAN framework. doi: 10.1016/j.jalz.2018.06.3059
Abstract (Condensed)
Introduction: The effects of physical activity in genetically driven, early-onset autosomal dominant Alzheimer’s disease are not well understood.
Methods: The Dominantly Inherited Alzheimer Network examined the cross-sectional relationship between physical activity and measures of cognition, daily functioning, and cerebrospinal fluid Alzheimer’s biomarkers. Mutation carriers were grouped according to whether they met the World Health Organization recommendation of at least 150 minutes of activity per week.
Results: Mutation carriers with higher physical activity demonstrated significantly better cognitive and functional performance and showed less Alzheimer’s-type pathology in cerebrospinal fluid than those with lower activity. Higher-activity carriers scored better on cognitive testing at expected symptom onset and had a substantially later estimated onset of very mild dementia compared with low-activity carriers.
Discussion: These findings support a beneficial association between physical activity, cognition, and Alzheimer’s pathology even in individuals with genetically driven autosomal dominant Alzheimer’s disease.