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Original Investigation |

Association of Lifetime Intellectual Enrichment With Cognitive Decline in the Older Population ONLINE FIRST

Prashanthi Vemuri, PhD1; Timothy G. Lesnick, MS2; Scott A. Przybelski, BS2; Mary Machulda, PhD, LP3; David S. Knopman, MD4; Michelle M. Mielke, PhD2; Rosebud O. Roberts, MB, ChB2,4; Yonas E. Geda, MD3,5,6; Walter A. Rocca, MD, MPH2,4; Ronald C. Petersen, PhD, MD4; Clifford R. Jack Jr, MD1
[+] Author Affiliations
1Department of Radiology, Mayo Clinic, Rochester, Minnesota
2Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
3Department of Psychology, Mayo Clinic, Rochester, Minnesota
4Department of Neurology, Mayo Clinic, Rochester, Minnesota
5Department of Psychiatry, Mayo Clinic, Scottsdale, Arizona
6Department of Neurology, Mayo Clinic, Scottsdale, Arizona
JAMA Neurol. Published online June 23, 2014. doi:10.1001/jamaneurol.2014.963
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Importance  Intellectual lifestyle enrichment throughout life is increasingly viewed as a protective strategy against commonly observed cognitive decline in the older population.

Objectives  To investigate the association of lifetime intellectual enrichment with baseline cognitive performance and rate of cognitive decline in an older population without dementia and to estimate the years of protection provided against cognitive impairment by these factors.

Design, Setting, and Participants  Prospective analysis of individuals enrolled from October 1, 2004, and in 2008 and 2009 in the Mayo Clinic Study of Aging, a longitudinal, population-based study of cognitive aging in Olmsted County, Minnesota. We studied 1995 individuals without dementia (1718 cognitively normal individuals and 277 individuals with mild cognitive impairment) who completed intellectual lifestyle enrichment measures at baseline and underwent at least 1 follow-up visit.

Main Outcomes and Measures  We studied the effect of lifetime intellectual enrichment by separating the variables into 2 nonoverlapping principal components: education/occupation score and mid/late-life cognitive activity based on self-report questionnaires. A global cognitive z score served as the summary cognition measure. Linear mixed-effects models were used to investigate the associations of demographic and intellectual enrichment measures with global cognitive z score trajectories.

Results  Baseline cognitive performance was lower in older individuals; individuals with lower education/occupation score, lower mid/late-life cognitive activity, and APOE genotype; and men (P < .001). The interaction between the 2 intellectual enrichment measures was significant (P < .03) such that the beneficial effect of mid/late-life cognitive activity on baseline cognitive performance was reduced with increasing education/occupation score. Only baseline age, mid/late-life cognitive activity, and APOE4 genotype were significantly associated with longitudinal change in cognitive performance from baseline (P < .05). For APOE4 carriers with high lifetime intellectual enrichment (75th percentile of education/occupation score and midlife to late-life cognitive activity), the onset of cognitive impairment was approximately 8.7 years later compared with low lifetime intellectual enrichment (25th percentile of education/occupation score and mid/late-life cognitive activity).

Conclusions and Relevance  Higher education/occupation scores were associated with higher levels of cognition. Higher levels of mid/late-life cognitive activity were also associated with higher levels of cognition, but the slope of this association slightly increased over time. Lifetime intellectual enrichment might delay the onset of cognitive impairment and be used as a successful preventive intervention to reduce the impending dementia epidemic.

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Figure 1.
Predicted Cognitive Global z Scores as a Function of Time From Baseline for Different Levels of Intellectual Enrichment Measures

The graphs illustrate the interaction between education/occupation score and mid/late-life cognitive activity. Low and high intellectual enrichment were defined by 25th and 75th percentiles.

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Figure 2.
Differences in the Predicted Times to Reach a Cognitive Threshold Associated With Subtle Cognitive Impairment

Figure depicts the results for an 80-year-old APOE4 carrier who never underwent the neuropsychological battery of tests before baseline. Low and high intellectual enrichment were defined by 25th and 75th percentiles. H indicates high mid-late cognitive; L, low mid-late cognitive.

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Figure 3.
Predicted Cognitive Global z-Score Trajectories for Different Baseline Ages Separated by APOE Carrier Status and Sex

The mean trajectories are shown for participants 75, 85, and 95 years old.

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