High-Intensity Physical Activity Modulates Diet Effects on Cerebrospinal Amyloid-β Levels in Normal Aging and Mild Cognitive Impairment

Abstract

We previously showed that amyloid-β 1-42 (Aβ₄₂) levels in cerebrospinal fluid (CSF) were markedly altered in response to a 4-week dietary intervention in normal aging and mild cognitive impairment (MCI). Here, we re-examined the data to assess whether diet-induced effects on CSF Aβ₄₂ were modulated by high intensity physical activity (hi–PA). Normal older adults (n = 18, mean age = 68.6 ± 7.4 y) and adults with amnestic MCI (n = 23, mean age = 68.0 ± 6.5 y) received a low saturated fat/low glycemic index (LOW) diet or a high saturated fat/high glycemic index (HIGH) diet, and CSF levels of Aβ₄₂, tau, and IL-8 were measured at baseline and week 4. Pre-study activity levels were assessed using a 7-d questionnaire, and weekly duration of hi–PA was quantified. At baseline, increased hi–PA in normals predicted lower CSF levels of tau (r = −0.54, p = 0.020) and IL-8 (r = −0.70, p = 0.025). Diet-induced effects on CSF Aβ₄₂ during the intervention study were modulated by hi–PA, and the nature of this effect differed for normals and MCI (ANOVA, p = 0.039). That is, for normal adults, increased hi–PA attenuated the effects of the HIGH diet on CSF Aβ₄₂ whereas in MCI, increased hi–PA potentiated the effects of the LOW diet. Our results suggest that normal adults who engage in hi–PA are less vulnerable to the pathological effects of an unhealthy diet, while in MCI, the benefit of a healthy diet on Aβ modulation is greatest when paired with hi–PA. Exercise may thus interact with diet to alter pathological processes that ultimately modify risk of Alzheimer's disease.