Dang Christa, Harrington Karra D, Lim Yen Ying, Ames David, Hassenstab Jason, Laws Simon M, Yassi Nawaf, Hickey Martha, Rainey-Smith Stephanie R, Robertson Joanne, Rowe Christopher C, Sohrabi Hamid R, Salvado Olivier, Weinborn Michael, Villemagne Victor L, Masters Colin L, Maruff Paul
Department of Obstetrics and Gynaecology, Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia.
The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia.
Arch Clin Neuropsychol. 2019 Jul 26;34(5):585-598. doi: 10.1093/arclin/acy078.
To prospectively examine 8-year risk of clinical disease progression to mild cognitive impairment (MCI)/dementia in older adults ≥60 with superior episodic memory (SuperAgers) compared to those cognitively normal for their age (CNFA). Additionally, to determine the extent to which SuperAgers were resilient to the negative effects of elevated amyloid-beta (Aβ+) on cognition.
Participants were classified as SuperAgers based on episodic memory performance consistent with younger adults aged 30-44 and no impairment on non-memory tests (n = 179), and were matched with CNFA on age, sex, education, and follow-up time (n = 179). Subdistribution hazard models examined risk of clinical progression to MCI/dementia. Linear mixed models assessed the effect of Aβ on cognition over time.
Prevalence of Aβ+ and APOE ε4 was equivalent between SuperAgers and CNFA. SuperAgers had 69%-73% reduced risk of clinical progression to MCI/dementia compared to CNFA (HR: 0.27-0.31, 95% CI: 0.11-0.73, p < .001). Aβ+ was associated with cognitive decline in verbal memory and executive function, regardless of SuperAger/CNFA classification. In the absence of Aβ+, equivalent age-related changes in cognition were observed between SuperAgers and CNFA.
SuperAgers displayed resilience against clinical progression to MCI/dementia compared to CNFA despite equivalent risk for Alzheimer's disease (AD); however, SuperAgers had no greater protection from Aβ+ than CNFA. The deleterious effects of Aβ on cognition persist regardless of baseline cognitive ability. Thus, superior cognitive performance does not reflect resistance against the neuropathological processes associated with AD, and the observed resilience for SuperAgers may instead reflect neuropsychological criteria for cognitive impairment.
前瞻性研究60岁及以上具有卓越情景记忆能力的老年人（“超级老人”）相较于认知水平与其年龄相符的正常人群（CNFA），临床疾病进展为轻度认知障碍（MCI）/痴呆症的8年风险。此外，确定“超级老人”对淀粉样蛋白β升高（Aβ+）对认知的负面影响的耐受程度。
根据情景记忆表现与30-44岁年轻人一致且非记忆测试无损伤，将参与者分类为“超级老人”（n = 179），并在年龄、性别、教育程度和随访时间上与CNFA进行匹配（n = 179）。亚分布风险模型检查临床进展为MCI/痴呆症的风险。线性混合模型评估Aβ随时间对认知的影响。
“超级老人”和CNFA之间Aβ+和APOE ε4的患病率相当。与CNFA相比，“超级老人”临床进展为MCI/痴呆症的风险降低了69%-73%（风险比：0.27-0.31，95%置信区间：0.11-0.73，p <.001）。无论“超级老人”/CNFA分类如何，Aβ+与言语记忆和执行功能的认知衰退相关。在没有Aβ+的情况下，“超级老人”和CNFA之间观察到同等程度的与年龄相关的认知变化。
尽管患阿尔茨海默病（AD）的风险相当，但与CNFA相比，“超级老人”在临床进展为MCI/痴呆症方面表现出耐受性；然而，“超级老人”对Aβ+的防护并不比CNFA更强。无论基线认知能力如何，Aβ对认知的有害影响持续存在。因此，卓越的认知表现并不反映对与AD相关的神经病理过程的抵抗力，而观察到的“超级老人”的耐受性可能反而反映了认知障碍的神经心理学标准。
