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BackgroundEpidemiological research on dementia is hampered by differences across studies in how dementia is classified, especially where clinical diagnoses of dementia may not be available.ObjectiveWe apply structural equation modeling to estimate dementia likelihood across heterogeneous samples within a multi-study consortium and use the twin design of the sample to validate the results.MethodsUsing 10 twin studies, we implement a latent variable approach that aligns different tests available in each study to assess cognitive, memory, and functional ability. The model separates general cognitive ability from components indicative of dementia. We examine the validity of this continuous latent dementia index (LDI). We then identify cut-off points along the LDI distributions in each study and align them across studies to distinguish individuals with and without probable dementia. Finally, we validate the LDI by determining its heritability and estimating genetic and environmental correlations between the LDI and clinically diagnosed dementia where available.ResultsResults indicate that coordinated estimation of LDI across 10 studies has validity against clinically diagnosed dementia. The LDI can be fit to heterogeneous sets of memory, other cognitive, and functional ability variables to extract a score reflective of likelihood of dementia that can be interpreted similarly across studies despite diverse study designs and sampling characteristics. Finally, the same genetic sources of variance strongly contribute to both the LDI and clinical diagnosis.ConclusionThis latent dementia indicator approach may serve as a model for other research consortia confronted with similar data integration challenges.

INTRODUCTION: Dementia predicts increased mortality. We used case‐control and co‐twin control models to investigate genetic and shared environmental influences on this association. METHODS: Case‐control design, including 987 twins with dementia and 2938 age‐ and sex‐matched controls in the Swedish Twin Registry. Co‐twin control design, including 90 monozygotic (MZ) and 288 dizygotic (DZ) twin pairs discordant for dementia. To test for genetic and environmental confounding, differences were examined in mortality risk between twins with dementia and their matched or co‐twin controls. RESULTS: Twins with dementia showed greater mortality risk than age‐ and sex‐matched controls (HR = 2.02 [1.86, 2.18]). Mortality risk is significantly elevated but attenuated substantially in discordant twin pairs, for example, comparing MZ twins with dementia to their co‐twin controls (HR = 1.48 [1.08, 2.04]). DISCUSSION: Findings suggest that genetic factors partially confound the association between dementia and mortality and provide an alternative hypothesis to increased mortality due to dementia itself. Highlights: We studied dementia and mortality in twin pairs discordant for dementia.People without dementia outlived people with dementia.Identical twins with dementia and their co‐twin controls had similar survival time.Findings suggest genotype may explain the link between dementia and mortality. [ABSTRACT FROM AUTHOR]

Introduction: Dementia predicts increased mortality. We used case-control and co-twin control models to investigate genetic and shared environmental influences on this association., Methods: Case-control design, including 987 twins with dementia and 2938 age- and sex-matched controls in the Swedish Twin Registry. Co-twin control design, including 90 monozygotic (MZ) and 288 dizygotic (DZ) twin pairs discordant for dementia. To test for genetic and environmental confounding, differences were examined in mortality risk between twins with dementia and their matched or co-twin controls., Results: Twins with dementia showed greater mortality risk than age- and sex-matched controls (HR = 2.02 [1.86, 2.18]). Mortality risk is significantly elevated but attenuated substantially in discordant twin pairs, for example, comparing MZ twins with dementia to their co-twin controls (HR = 1.48 [1.08, 2.04])., Discussion: Findings suggest that genetic factors partially confound the association between dementia and mortality and provide an alternative hypothesis to increased mortality due to dementia itself. Highlights We studied dementia and mortality in twin pairs discordant for dementia. People without dementia outlived people with dementia. Identical twins with dementia and their co-twin controls had similar survival time. Findings suggest genotype may explain the link between dementia and mortality., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Latent variable models can create a latent dementia index (LDI) using cognitive and functional ability to approximate dementia likelihood. The LDI approach has been applied across diverse cohorts. It is unclear whether sex affects its measurement properties. We use Wave A (2001-2003) of the Aging, Demographics, and Memory Study ( n  = 856). Multiple group confirmatory factor analysis (CFA) was used to test measurement invariance (MI) using informant-reported functional ability and cognitive performance tasks, which we group into verbal, nonverbal, and memory. Partial scalar invariance was found, allowing for testing sex differences in LDI means ( M Diff  = 0.38). The LDI correlated with consensus panel dementia diagnosis, Mini-Mental State Examination (MMSE), and dementia risk factors (low education, advanced age, and apolipoprotein ε4 [APOE-ε4] status) for men and women. The LDI validly captures dementia likelihood to permit estimation of sex differences. LDI sex differences indicate higher dementia likelihood in women, potentially due to social, environmental, and biological factors., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Introduction: Hormones may be one possible mechanism underlying sex differences in dementia incidence. We examined whether presumed differential prenatal hormone milieu is related to dementia risk by comparing dementia rates in same- and opposite-sex dizygotic twin pairs in male and female twins., Methods: The sample comprised 43,254 individuals from dizygotic twin pairs aged 60 and older from the Swedish Twin Registry. Survival analyses were conducted separately for females and males., Results: Female twins from opposite-sex pairs had significantly lower dementia risk than female twins from same-sex pairs, but the differences emerged only after age 70 (hazard ratio = 0.64, P = 0.004). Results were not explained by postnatal risk factors for dementia, and no interaction between twin type and apolipoprotein E ( APOE ) ε4 was found. Male twins from same-sex versus opposite-sex pairs did not differ significantly., Discussion: The results suggest that relatively masculine prenatal hormone milieus correlate with lower dementia risk in females., Competing Interests: The authors have no conflicts of interest., (© 2020 the Alzheimer's Association.)