Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Department of Clinical Psychology, Neuropsychology, and Developmental Psychology, Faculty of Behavioural and Movement Sciences, Vrije Universiteit, Amsterdam, the Netherlands.
JAMA Netw Open. 2020 Feb 5;3(2):e200094. doi: 10.1001/jamanetworkopen.2020.0094.
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.
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.
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.
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.
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.
一些在认知健康方面能达到 100 岁以上的个体可能对与认知能力下降相关的风险因素具有弹性。探索潜在的弹性机制可能有助于开发治疗策略，帮助人们在衰老过程中保持认知健康。
确定能够避免认知能力下降至极高年龄的个体，并调查相关风险因素的患病率。
设计、地点和参与者：100 岁以上研究是一项针对荷兰社区百岁老人的前瞻性观察队列研究，研究对象为 2013 年至 2019 年间招募的年龄在 100 岁以上且每年接受一次随访的参与者，直至死亡或参与者不再参与研究。百岁老人通过自我报告其认知健康状况，由代理人进行确认。在被邀请参加研究的 1023 名百岁老人中，有 340 名符合研究标准并纳入分析。数据分析于 2019 年 4 月至 2019 年 12 月进行。
使用简易精神状态检查（MMSE）评估认知能力。为了确定避免认知能力下降的百岁老人，本研究使用线性混合模型，对基线认知与生存和至少 2 年随访的认知轨迹进行了关联分析，调整了性别、年龄和教育因素。本研究还调查了载脂蛋白 E（APOE）基因型和心血管疾病等与认知能力下降相关的风险因素的患病率。
在基线时，340 名百岁老人的中位年龄为 100.5 岁（范围，100.0-108.2 岁）；245 名参与者（72.1%）为女性。最大生存估计在基线 MMSE 评分为 26 至 30 分的百岁老人中达到 82%/年（95%CI，77%-87%）（风险比，0.56；95%CI，0.42 至 0.75；P<0.001），这表明 MMSE 评分为 26 或更高表明认知和身体健康都较好。在 79 名随访时间达到 2 年或以上的百岁老人中，基线 MMSE 评分低于 26 分的老人每年 MMSE 评分下降 1.68 分（95%CI，-2.45 至-0.92 分/年；P=0.02），而基线 MMSE 评分在 26 分或更高的老人每年 MMSE 评分下降 0.71 分（95%CI，-1.08 至-0.35 分/年）。在基线 MMSE 评分为 26 分或更高的 73%的百岁老人中，没有观察到认知变化，这种情况通常会持续到随后的几年或直至死亡。据估计，这一组代表了不到 10%的荷兰百岁老人。在这一组中，18.6%的人携带至少 1 个 APOE-ε4 等位基因，而认知表现较低和/或下降的百岁老人中，这一比例为 5.6%。
大多数在基线 MMSE 评分为 26 或更高的百岁老人在至少 2 年内保持了较高的认知水平，在某些情况下，即使存在与认知能力下降相关的风险因素也是如此。对这一群体的研究可能会揭示与认知能力下降相关的风险因素的潜在弹性机制。
