Physical Activity During Midlife Influences Late Life Verbal Memory Performance

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Modifiable risk factors (eg, smoking, hypertension, sedentary behavior, overweight/obesity, and social engagement) contribute to nearly half of documented dementia cases.
Modifiable risk factors (eg, smoking, hypertension, sedentary behavior, overweight/obesity, and social engagement) contribute to nearly half of documented dementia cases.

Alzheimer disease (AD) is the most common form of dementia that affects approximately 40 million people over the age of 60 worldwide.1 Projected estimates indicate that the prevalence of AD will quadruple by the year 2050.2 It has been documented, however, that the prevalence of this aging-related dementing disorder could be reduced by up to 50% by delaying its onset by 5 years.2

Available evidence indicates that modifiable risk factors such as smoking, hypertension, sedentary behavior, overweight/obesity, insufficient social engagement, and mood alterations may contribute to nearly half of dementia cases. However, insufficient characterization of the underlying pathophysiological mechanisms and substrates responsible for illness onset and progression has significantly limited the development of effective treatments and prevention strategies.2,3

Provided the foregoing limitation, researchers studying AD have largely focused on individuals over the age of 60 or 70 years of age – often after cognitive decline has already commenced – to identify methods of halting disease progression. Data indicate that focusing on modifiable risk factors may significantly decrease the prevalence of dementing disorders, but there is a paucity of studies that primarily aim to identify potential risk factors during midlife that contribute to late life cognitive decline. These data could then be used to develop potential preventative strategies.2,4

In a recent study, Szoeke et al. (2016) examined longitudinal data from the population-based Women's Healthy Ageing Project with the overarching aim of identifying key risk factors during midlife (ie, 45-55 years of age) that affect cognitive decline later in life. Delayed recall from a 10-item supraspan word list score from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-DR), a measure of verbal episodic memory, a domain known to be sensitive to early AD changes, was the primary outcome measure.

Results indicate that modifiable risk factors including physical activity and vascular risk factors (eg, hypertension and lipid profiles) significantly influence the magnitude of cognitive decline above and beyond the expected effects of senescence with age. Notably, self-reported physical activity levels and optimal high density lipoprotein levels were identified as the most significant predictors of cognitive performance with physical activity exhibiting the most statistically significant effect on cognition among all candidate covariates. Conversely, both high systolic and diastolic blood pressure were reported to negatively impact verbal memory performance on the CERAD-DR over time.4

Taken together, the authors suggest that mitigating the hazards posed by various modifiable risks factors for developing AD is an important preventative measure that warrants further investigation parallel to efforts toward the slowing/halting of neurodegeneration and disease progression in the absence of more specific pathologic characterization of this dementing disorder.2, 3


1. Scheltens P, Blennow K, Breteler MM et al. Alzheimer's disease. Lancet 2016.

2. Reitz C. Toward precision medicine in Alzheimer's disease. Ann Transl Med 2016;4(6):107.

3. Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol 2011;10(9):819-828.

4. Cassandra Szoeke PLVWHLDPDSC. Predictive Factors for Verbal Memory Performance Over Decades of Ageing: Data From the Women's Healthy Ageing Project. The American Journal of Geriatric Psychiatry 2016.

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