Results of the 'Harvard Aging Brain Study' suggest that higher physical activity has a protective effect against β amyloid-associated cognitive decline and neurodegeneration.
The pathophysiological processes in Alzheimer's disease begin decades before clinical symptoms occur and are characterized by an early accumulation of β amyloid (Aβ).1 This preclinical stage provides the opportunity to intervene before a substantial neuronal loss and clinical limitations occur. Various studies that attempted to make Aβ a target during the symptomatic phase produced disappointing results. In the absence of disease-modifying drugs for Alzheimer's disease, the identification of modifiable risk factors that can delay disease progression is of utmost importance.
Greater physical activity significantly reduced Aβ-associated cognitive decline and loss of gray matter in 182 clinically normal older adults (with a median of 73 years), as reported in a longitudinal study published in July 2019 in the Journal of the American Medical Association (JAMA) by the Harvard Medical School, Boston, USA.2
Physical activity was determined at baseline by a pedometer over one week and the Aβ load through positron emission tomography (PET). Over a follow-up period of 6 years, cognitive performance was assessed using annual Preclinical Alzheimer's Cognitive Composite (PACC) tests and MRI neurodegeneration checks that focused on total gray matter volume and regional cortex thickness.
Physical activity also remained significant under correction for vascular risk factors, age, gender, education, ApoE (apolipoprotein E) ε4 status and intracranial volume. Vascular risk was independently associated with slower Aβ-related cognitive decline and volume loss of gray matter.
The results support interventions targeting both physical activity and management of vascular risk factors to halt cognitive decline and neurodegeneration in preclinical Alzheimer's dementia. These lifestyle interventions could be combined with anti-Aβ or anti-tau therapies if they become available.
References:
1. Jack, C. R. et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement 14, 535-562 (2018).
2. Rabin, J. S. et al. Associations of Physical Activity and β-Amyloid With Longitudinal Cognition and Neurodegeneration in Clinically Normal Older Adults. JAMA Neurol (2019). doi:10.1001/jamaneurol.2019.1879