The 1-HMR metabolomics-based MetaboHealth score, comprised of 14 serum metabolic markers, associates with disease-specific mortality, but it is unclear whether the score also reflects cognitive changes and functional impairment. We aimed to assess the associations between the MetaboHealth score with cognitive function and functional decline in older adults at increased cardiovascular risk. A total of 5292 older adults free of dementia at baseline with mean age 75.3 years (SD = 3.4) from the Prospective Study of Pravastatin in the Elderly (PROSPER). MetaboHealth score were measured at baseline, and cognitive function and functional independence were measured at baseline and every 3 months during up to 2.5 years follow-up. Cognitive function was assessed using the Stroop test (selective attention), the Letter Digit Coding test (LDCT) (processing speed), and the two versions of the Picture Learning test (delayed and immediate; memory). Two tests of functional independence were used: Barthel Index (BI) and instrumental activities at daily living (IADL). A higher MetaboHealth score was associated with worse cognitive function (in all domains) and with worse functional independence. For example, after full adjustments, a 1-SD higher MetaboHealth score was associated with 9.02 s (95%CI 7.29, 10.75) slower performance on the Stroop test and 2.79 (2.21, 3.26) less digits coded on the LDCT. During follow-up, 1-SD higher MetaboHealth score was associated with an additional decline of 0.53 s (0.23, 0.83) on the Stroop test and − 0.08 (− 0.11, − 0.06) points on the IADL. Metabolic disturbance, as reflected by an increased metabolomics-based health score, may mark future cognitive and functional decline.

基于 1-HMR 代谢组学的 MetaboHealth 评分由 14 个血清代谢标志物组成，与疾病特异性死亡率相关，但尚不清楚该评分是否也反映了认知变化和功能障碍。我们旨在评估 MetaboHealth 评分与心血管风险增加的老年人认知功能和功能下降之间的关联。共有 5292 名基线时没有痴呆的老年人，平均年龄 75.3 岁 （SD = 3.4），来自老年人普伐他汀前瞻性研究 （PROSPER）。在基线时测量 MetaboHealth 评分，在基线时测量认知功能和功能独立性，在长达 2.5 年的随访中每 3 个月测量一次。使用 Stroop 测试 （选择性注意）、字母数字编码测试 （LDCT） （处理速度） 和两个版本的 Picture Learning 测试 （延迟和立即;记忆） 评估认知功能。使用了两项功能独立性测试： Barthel 指数 （BI） 和日常生活中的工具活动 （IADL）。较高的 MetaboHealth 评分与较差的认知功能 （在所有领域） 和功能独立性较差相关。例如，完全调整后，MetaboHealth 评分高 1-SD 与 Stroop 测试性能降低 9.02 秒 （95%CI 7.29， 10.75） 和 LDCT 编码数字减少 2.79 （2.21， 3.26） 相关。在随访期间，MetaboHealth 评分高出 1-SD 与 Stroop 测试额外下降 0.53 秒 （0.23， 0.83） 和 IADL -0.08 （- 0.11， - 0.06） 分相关。代谢紊乱，如基于代谢组学的健康评分增加所反映的那样，可能标志着未来的认知和功能下降。