Cognitive Activity and Onset Age of Incident Alzheimer Disease Dementia
Abstract
Objective
To test the hypothesis that higher level of cognitive activity predicts older age at dementia onset in Alzheimer disease (AD) dementia.
Methods
As part of a longitudinal cohort study, 1,903 older persons without dementia at enrollment reported their frequency of participation in cognitively stimulating activities. They had annual clinical evaluations to diagnose dementia and AD, and the deceased underwent neuropathologic examination. In analyses, we assessed the relation of baseline cognitive activity to age at diagnosis of incident AD dementia and to postmortem markers of AD and other dementias.
Results
During a mean of 6.8 years of follow-up, 457 individuals were diagnosed with incident AD at a mean age of 88.6 (SD 6.4, range 64.1–106.5) years. In an extended accelerated failure time model, higher level of baseline cognitive activity (mean 3.2, SD 0.7) was associated with older age at AD dementia onset (estimate 0.026; 95% confidence interval 0.013–0.039). Low cognitive activity (score 2.1, 10th percentile) was associated with a mean onset age of 88.6 years compared to a mean onset age of 93.6 years associated with high cognitive activity (score 4.0, 90th percentile). Results were comparable in subsequent analyses that adjusted for potentially confounding factors. In 695 participants who died and underwent a neuropathologic examination, cognitive activity was unrelated to postmortem markers of AD and other dementias.
Conclusion
A cognitively active lifestyle in old age may delay the onset of dementia in AD by as much as 5 years.
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© 2021 American Academy of Neurology.
Publication History
Received: January 28, 2021
Accepted: May 27, 2021
Published online: July 14, 2021
Published in issue: August 31, 2021
Disclosure
Robert S. Wilson, Tianhao Wang, Lei Yu, Fran Grodstein, David A. Bennett, and Patricia A. Boyle have no disclosures to report. Go to Neurology.org/N for full disclosures.
Study Funding
This study was supported by NIA grants R01AG17917 and R01AG34374.
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As medical students, we were eager to provide some comments on this neurologic study.1 The authors discuss the appearance of dementia in Alzheimer's disease and cognitive activity in old age. This topic is of special interest to us.
A recent article by Garcia-Gorro et. al. mentions that a cognitively active lifestyle confers physical and intellectual benefits in multiple neurodegenerative diseases.2 It is proposed that Huntington's disease can provide a model to study the effects and neural mechanisms of cognitive engagement in neurodegeneration. The authors suggest that it may promote brain maintenance by modulating the executive control resting-state network and conferring protection against neurodegeneration, which results in a delayed onset of symptoms and improved performance in executive functions.
The study by Hartman and colleagues examines physical activity, sedentary behavior, and characteristics of ambulatory and community-dwelling in patients with dementia.3 Patients were compared to cognitively healthy age-, sex-, and weight-matched controls. The study concludes that dementia patients have elevated sedentary behavior and perform less physical activity than cognitively healthy controls.
To conclude, there is an evident relationship between these concepts. Furthermore, the inclusion of cognitive activity as therapy and its impact on cognitive degeneration are promising factors to be studied.
Disclosure
The authors report no relevant disclosures. Contact [email protected] for full disclosures.
References
We appreciate the interest in our research.1 In the cohort study of older persons who developed incident Alzheimer's disease (AD), we found that a lower level of cognitive activity was associated with earlier age of dementia onset.1 According to the reverse-causality hypothesis, a low level of cognitive activity is not a risk factor for AD but an early sign of the disease. As a test of this hypothesis, we computed the correlations of cognitive activity with markers of AD at the time of study enrollment, as well as related dementias during a postmortem neuropathological examination. These correlations were not significant, which we concluded provided no support for the reverse-causality hypothesis.
Dr. Krauss notes in their comment that the study fails to fully disprove the reverse causality hypothesis, due to possible changes in brain structure or function that are not captured on postmortem evaluation. We agree that our study does not disprove the reverse-causality hypothesis. However, observations in this research and previous studies that measurements of cognitive activity are related to risk of dementia but not to the neuropathologies thought to underlie dementia is certainly inconsistent with the reverse-causality hypothesis.2,3 Further, one may question the scientific value of a hypothesis if it depends on disease markers that cannot be specified and are apparently unrelated to neuropathologic markers traditionally associated with AD and related dementias.
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The author reports no relevant disclosures. Contact [email protected] for full disclosures.
References
The authors of this study note that postmortem markers of Alzheimer Disease (AD) and other dementias may be distinct from the self-report measure of cognitive activity, which they state provides no support for the reverse causality hypothesis.1 The authors suggest that cognitive activities may lead to changes in brain structure and function that could enhance cognitive reserve. Isn't it just as likely that there are features of brain structure or function that have not been discerned in postmortem evaluation, thus failing to fully disprove the reverse causality hypothesis?
Disclosure
The author reports no relevant disclosures. Contact [email protected] for full disclosures.
References