Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 17165, Stockholm, Sweden.
School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, Yokosuka, Japan.
BMC Med. 2021 Oct 18;19(1):248. doi: 10.1186/s12916-021-02104-3.
Frailty has been identified as a risk factor for cognitive impairment and dementia. However, it is not known whether familial factors, such as genetics and shared environmental factors, underlie this association. We analyzed the association between frailty and the risk of dementia in a large twin cohort and examined the role of familial factors in the association.
The Rockwood frailty index (FI) based on 44 health deficits was used to assess frailty. The population-level association between FI and the risk of all-cause dementia was analyzed in 41,550 participants of the Screening Across the Lifespan Twin (SALT) study (full sample, aged 41-97 years at baseline), using Cox and competing risk models. A subsample of 10,487 SALT participants aged 65 and older who received a cognitive assessment (cognitive sample) was used in a sensitivity analysis to assess the effect of baseline cognitive level on the FI-dementia association. To analyze the influence of familial effects on the FI-dementia association, a within-pair analysis was performed. The within-pair model was also used to assess whether the risk conferred by frailty varies by age at FI assessment.
A total of 3183 individuals were diagnosed with dementia during the 19-year follow-up. A 10% increase in FI was associated with an increased risk of dementia (hazard ratio [HR] 1.17 (95% confidence interval [CI] 1.07, 1.18)) in the full sample adjusted for age, sex, education, and tobacco use. A significant association was likewise found in the cognitive sample, with an HR of 1.13 (95% CI 1.09, 1.20), adjusted for age, sex, and cognitive level at baseline. The associations were not attenuated when adjusted for APOE ɛ4 carrier status or considering the competing risk of death. After adjusting for familial effects, we found no evidence for statistically significant attenuation of the effect. The risk conferred by higher FI on dementia was constant after age 50 until very old age.
A higher level of frailty predicts the risk of dementia and the association appears independent of familial factors. Targeting frailty might thus contribute to preventing or delaying dementia.
虚弱已被确定为认知障碍和痴呆的危险因素。然而，家族因素（如遗传和共享环境因素）是否是这种关联的基础尚不清楚。我们在一个大型双胞胎队列中分析了虚弱与痴呆风险之间的关系，并研究了家族因素在这种关联中的作用。
使用基于 44 种健康缺陷的 Rockwood 虚弱指数（FI）来评估虚弱。使用 Cox 和竞争风险模型，在 Screening Across the Lifespan Twin（SALT）研究的 41550 名参与者（全样本，基线时年龄为 41-97 岁）中，分析 FI 与全因痴呆风险之间的人群相关性。使用 SALT 研究中 10487 名年龄在 65 岁及以上接受认知评估的参与者（认知样本）进行敏感性分析，以评估基线认知水平对 FI-痴呆关联的影响。为了分析家族效应对 FI-痴呆关联的影响，进行了个体内分析。还使用个体内模型来评估 FI 评估时的年龄对虚弱相关风险的影响。
在 19 年的随访期间，共有 3183 人被诊断为痴呆。在全样本中，FI 增加 10%与痴呆风险增加相关（调整年龄、性别、教育程度和吸烟状况后的危险比[HR]为 1.17（95%置信区间[CI] 1.07，1.18））。在调整了年龄、性别和基线认知水平后，在认知样本中也发现了显著的相关性，HR 为 1.13（95% CI 1.09，1.20）。当调整 APOE ɛ4 携带者状态或考虑死亡的竞争风险时，相关性并未减弱。在调整家族效应后，我们没有发现统计学上显著减弱效应的证据。FI 较高对痴呆的风险在 50 岁以后一直到非常高龄时保持不变。
较高的虚弱水平预示着痴呆的风险，这种关联似乎独立于家族因素。因此，针对虚弱可能有助于预防或延迟痴呆。
