Effects of Physical Exercise on Alzheimer’s Disease Biomarkers: A Systematic Review of Intervention Studies

Abstract

Physical exercise may be an important adjunct to pharmacological treatment of Alzheimer's disease (AD). Animal studies indicate that exercise may be disease modifying through several mechanisms including reduction of AD pathology. We carried out a systematic review of intervention studies of physical exercise with hippocampal volume (on MRI), amyloid-β, total tau, phosphorylated tau in cerebrospinal fluid (CSF), 18F-FDG-PET or amyloid PET as outcome measures in healthy subjects, patients with subjective memory complaints, mild cognitive impairment, or AD. We identified a total of 8 studies of which 6 investigated the effects of exercise on hippocampal volume in healthy subjects and 1 on CSF biomarkers and 1 on hippocampal volume in AD, and none investigating the remaining outcome measures or patient groups. Methodological quality of identified studies was generally low. One study found a detrimental effect on hippocampal volume and one found a positive effect, whereas the remaining studies did not find an effect of exercise on outcome measures. The present systematic study identified a relatively small number of studies, which did not support an effect of exercise on hippocampal volume. Methodological issues such small to moderate sample sizes and inadequate ramdomization procedures further limits conclusions. Our findings highlight the difficulties in conducting high quality studies of exercise and further studies are needed before definite conclusions may be reached.

Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer’s disease mice

“…Currently, there are no disease-modifying drugs available for Alzheimer's disease and available pharmacological and supportive therapy are aimed at slowing disease progression. Clinical studies suggest physical exercise improves cognitive function and reduces the risk of developing AD [20]. The majority of the relevant studies are focused on the benefits of aerobic exercise, with only relatively few studies addressing whether resistance exercise, especially on a short-term basis, can improve learning and memory.…”

Accelerated loss of hypoxia response in zebrafish with familial Alzheimer’s disease-like mutation of Presenilin 1

“…Delaying the onset of this failure might delay the onset of Alzheimer's disease. At present, physical exercise that maintains vascular health is one of the few potential protective treatments available for LOAD [55][56][57][58]. Indeed, a recent systematic review has revealed for the first time an association between physical exercise and better cognitive outcomes at expected symptom onset in individuals with fAD [59].…”

Moderate‐ to high‐intensity exercise does not modify cortical β‐amyloid in Alzheimer's disease

“…Specifically, exercise seems to reduce pathological changes, such as Ab deposition [10,11,13,14], tau pathology [15], and hippocampal atrophy [11,16] in animal models of AD. In humans, most of the studies have focused on exercise and hippocampal volume [17]. Results have been divergent, although most studies have shown a lack of association in both intervention [18][19][20][21][22] and observational studies [23][24][25][26][27][28].…”