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INTRODUCTION: Loneliness has a rising public health impact, but research involving neuropathology and representative cohorts has been limited. METHODS: Inverse odds of selection weights were generalized from the autopsy sample of Rush Alzheimer's Disease Center cohorts (N = 680; 89 ± 9 years old; 25% dementia) to the US-representative Health and Retirement Study (N = 8469; 76 ± 7 years old; 5% dementia) to extend external validity. Regressions tested cross-sectional associations between loneliness and (1) Alzheimer's disease (AD) and cerebrovascular pathology; (2) five cognitive domains; and (3) relationships between pathology and cognition, adjusting for depression. RESULTS: In weighted models, greater loneliness was associated with microinfarcts, lower episodic and working memory in the absence of AD pathology, lower working memory in the absence of infarcts, a stronger association of infarcts with lower episodic memory, and a stronger association of microinfarcts with lower working and semantic memory. DISCUSSION: Loneliness may relate to AD through multiple pathways involving cerebrovascular pathology and cognitive reserve. HIGHLIGHTS: Loneliness was associated with worse cognition in five domains. Loneliness was associated with the presence of microinfarcts. Loneliness moderated cognition-neuropathology associations. Transportability methods can provide insight into selection bias.
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OBJECTIVE: To examine the relation of menstrual cyclicity abnormalities to hyperandrogenism (HA) and dynamic state insulin resistance (IR) in oligo-ovulatory women with polycystic ovary syndrome (PCOS). DESIGN: Prospective cross-sectional study. SETTING: Tertiary-care academic center. PATIENT(S): Fifty-seven women with PCOS (1990 National Institutes of Health criteria) and 57 healthy control women matched by body mass index (BMI). INTERVENTION(S): Short insulin tolerance test (ITT). MAIN OUTCOME MEASURE(S): Menstrual cyclicity, sex hormone-binding globulin (SHBG), measures of HA (i.e., modified Ferriman-Gallwey score, total and free testosterone, dehydroepiandrosterone sulfate), and the rate constant for plasma glucose disappearance (kITT) derived from the short ITT. RESULT(S): Adjusting for age, BMI, and ethnicity, the mean androgen measures were higher and SHBG trended lower, kITT was lower, and the prevalence of IR was higher in PCOS than in controls, independent of menstrual cyclicity. The optimal cutoff point for IR was set at kITT value of 3.57%/minute or lower. Overall, 79% of the women with PCOS had IR. To control further for the effect of ethnicity, a subgroup of 46 non-Hispanic white PCOS participants were studied; those who exhibited amenorrhea (n = 15) or oligomenorrhea (n = 19) had or tended toward having a lower kITT and a higher prevalence of IR than the women with PCOS and oligo-ovulatory eumenorrhea (n = 12). The kITT trended lower and the prevalence of IR trended higher in women with PCOS and amenorrhea than those with oligomenorrhea. The measures of SHBG and HA were similar across the three menstrual groups. CONCLUSION(S): Oligo-ovulatory women with PCOS and overt oligo/amenorrhea have greater degrees of IR but not HA when compared with oligo-ovulatory eumenorrheic women with PCOS, suggesting that IR and hyperinsulinemia but not HA play a role in determining the degree of menstrual dysfunction, which can be used as a clinical marker for the degree of IR in oligo-ovulatory PCOS.