Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
J Alzheimers Dis. 2023;95(2):615-624. doi: 10.3233/JAD-230466.
The association between obesity and Alzheimer's disease (AD) is complex. Recent studies indicated the relationships between obesity and AD may differ by sex, and women may benefit from being overweight in terms of AD risk.
We investigated whether sex modifies the associations of obesity with tau positron emission tomography (PET), amyloid PET, and cognition in preclinical AD.
We included 387 cognitively-unimpaired amyloid-positive participants (221 women, 166 men, 87.6% non-Hispanic White) with available 18F-flortaucipir PET, 18F-florbetapir PET, and completed the Preclinical Alzheimer Cognitive Composite (PACC) tests from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study. Participants were categorized based on body mass index (BMI: kg/m2): normal-weight (BMI: 18.5-25), overweight (BMI: 25-30), and obese (BMI≥30).
Significant sex by BMI category interactions on PACC and its components: Mini-Mental State Examination (MMSE) and Reminding Test-Free+Total Recall (FCSRT96) revealed that overweight and obese women outperformed normal-weight women on FCSRT96, while obese men showed poorer MMSE performance than normal-weight men. These interactions were independent of APOE4. There were no significant interactions of sex by BMI category on tau and amyloid PET. However, sex-stratified analyses observed obesity was associated with less regional tau and mean cortical amyloid in women, not in men.
This study found that in preclinical AD, overweight and obesity were associated with better verbal memory in women, whereas obesity was associated with worse global cognition among men. Future studies focusing on the mechanism for this relationship may inform sex-specific interventions for AD prevention.
肥胖与阿尔茨海默病（AD）之间的关系很复杂。最近的研究表明，肥胖与 AD 之间的关系可能因性别而异，女性超重可能会降低 AD 风险。
我们研究了性别是否会改变肥胖与tau 正电子发射断层扫描（PET）、淀粉样 PET 以及 AD 前认知之间的关系。
我们纳入了 387 名认知正常的淀粉样阳性参与者（221 名女性，166 名男性，87.6%为非西班牙裔白人），这些参与者有可用的 18F-flortaucipir PET、18F-florbetapir PET，并完成了 A4 研究中的预临床阿尔茨海默认知综合评分（PACC）测试。参与者根据体重指数（BMI：kg/m2）分类：正常体重（BMI：18.5-25）、超重（BMI：25-30）和肥胖（BMI≥30）。
PACC 及其组成部分（简易精神状态检查（MMSE）和再认测试-自由回忆+总回忆（FCSRT96））的 BMI 类别与性别之间存在显著的交互作用，表明超重和肥胖女性在 FCSRT96 上的表现优于正常体重女性，而肥胖男性的 MMSE 表现差于正常体重男性。这些相互作用与 APOE4 无关。性别与 BMI 类别之间没有显著的交互作用，与 tau 和淀粉样 PET。然而，性别分层分析观察到肥胖与女性的区域性 tau 和皮质平均淀粉样减少相关，而与男性无关。
本研究发现，在 AD 前阶段，超重和肥胖与女性的语言记忆能力提高有关，而肥胖与男性的整体认知能力下降有关。未来关注这种关系机制的研究可能会为 AD 预防的性别特异性干预提供信息。
