Longitudinal Maintenance of Cognitive Health in Centenarians in the 100-plus Study

Abstract

Importance: Some individuals who reach ages beyond 100 years in good cognitive health may be resilient against risk factors associated with cognitive decline. Exploring the processes underlying resilience may contribute to the development of therapeutic strategies that help to maintain cognitive health while aging.

Objective: To identify individuals who escape cognitive decline until extreme ages and to investigate the prevalence of associated risk factors.

Design, setting, and participants: The 100-plus Study is a prospective observational cohort study of community-based Dutch centenarians enrolled between 2013 and 2019 who were visited annually until death or until participation was no longer possible. The centenarians self-reported their cognitive health, as confirmed by a proxy. Of the 1023 centenarians approached for study inclusion, 340 fulfilled the study criteria and were included in analyses. Data analysis was performed from April 2019 to December 2019.

Main outcomes and measures: Cognition was assessed using the Mini-Mental State Examination (MMSE). To identify centenarians who escape cognitive decline, this study investigated the association of baseline cognition with survivorship and cognitive trajectories for at least 2 years of follow-up using linear mixed models, adjusted for sex, age, and education. This study investigated the prevalence of apolipoprotein E (APOE) genotypes and cardiovascular disease as risk factors associated with cognitive decline.

Results: At baseline, the median age of 340 centenarians was 100.5 years (range, 100.0-108.2 years); 245 participants (72.1%) were female. The maximum survival estimate plateaued at 82% per year (95% CI, 77% to 87%) across centenarians who scored 26 to 30 points on the baseline MMSE (hazard ratio, 0.56; 95% CI, 0.42 to 0.75; P < .001), suggesting that an MMSE score of 26 or higher is representative of both cognitive and physical health. Among the 79 centenarians who were followed up for 2 years or longer, those with baseline MMSE score less than 26 experienced a decline in MMSE score of 1.68 points per year (95% CI, -2.45 to -0.92 points per year; P = .02), whereas centenarians with MMSE scores of 26 or higher at baseline experienced a decline of 0.71 point per year (95% CI, -1.08 to -0.35 points per year). For 73% of the centenarians with baseline MMSE scores of 26 or higher, no cognitive changes were observed, which often extended to ensuing years or until death. It is estimated that this group is representative of less than 10% of Dutch centenarians. In this group, 18.6% carried at least 1 APOE-ε4 allele, compared with 5.6% of the centenarians with lower and/or declining cognitive performance.

Conclusions and relevance: Most centenarians who scored 26 or higher on the MMSE at baseline maintained high levels of cognitive performance for at least 2 years, in some cases despite the presence of risk factors associated with cognitive decline. Investigation of this group might reveal the processes underlying resilience against risk factors associated with cognitive decline.

Figure 1.. Flowchart of the Sample and Different Subgroups and Percentage of Subgroups of Centenarians Within Longitudinal Analysis

MMSE indicates Mini-Mental State Examination. ^aOne centenarian scored less than 26 on the MMSE at baseline, but had a score greater than or equal to 26 after 2 years of follow-up.

Figure 2.. Association of Mini-Mental State Examination (MMSE) Scores With Survival

A, Graph shows yearly survival estimates for the 100-plus Study cohort. Dashed orange line shows the survival fraction of the individuals aged 100 years within the Dutch general population, which was derived from the Netherlands Central Bureau of Statistics. Dotted lines show mean survival percentage of centenarians with baseline MMSE score less than 24 (bottom) and mean survival percentage of centenarians with baseline MMSE score less than 26 (top). Solid line and shaded area show mean (95% CI) survival for participants in the 100-plus Study cohort. The MMSE scores were associated with survival using sliding windows with a size of 3 MMSE points. B, Graph shows Kaplan-Meier survival curves of centenarians with high (≥26 [gray]) and low (<26 [orange]) MMSE scores at baseline.

Figure 3.. Trajectories of Mini-Mental State Examination (MMSE) and Barthel Index Scores

Linear mixed-models fixed effects of MMSE score (range, 0-30) and Barthel Index scores (range, 0-20) over 2 years stratified for subgroups are shown according to baseline MMSE (≥26 vs <26) and whether the centenarian’s scores declined or remained stable. A, MMSE trajectories of centenarians with baseline MMSE scores 26 or higher and less than 26. B, Barthel Index trajectories of centenarians with baseline MMSE scores 26 or higher and less than 26. (Note that the upper limit of the 95% CI is clipped at the maximum score of 20.) C, MMSE trajectories of centenarians with baseline MMSE scores 26 or higher and less than 26 at baseline and who declined or were stable on the MMSE after 2 years. D, Barthel Index trajectories of centenarians with baseline MMSE scores 26 or higher and less than 26 at baseline and who declined or were stable on the MMSE after 2 years. (Note that the upper limit of the 95% CI is clipped at the maximum score of 20.) ^aCentenarians who scored less than 26 on the MMSE at baseline. Because of the high level of frailty and mortality in this group, many of them could not be followed up for 2 years. Hence, the decline in MMSE and Barthel Index observed in the models for this specific subgroup possibly represents an underestimation of the cognitive and physical decline.