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INTRODUCTION: Social connectedness is associated with slower cognitive decline among older adults. Recent research suggests that distinct aspects of social networks may have differential effects on cognitive resilience, but few studies analyze brain structure. METHODS: This study includes 117 cognitively impaired and 59 unimpaired older adults. The effects of social network characteristics (bridging/bonding) on brain regions of interests were analyzed using linear regressions and voxel‐wise multiple linear regressions of gray matter density. RESULTS: Increased social bridging was associated with greater bilateral amygdala volume and insular thickness, and left frontal lobe thickness, putamen, and thalamic volumes. Increased social bonding was associated with greater bilateral medial orbitofrontal and caudal anterior cingulate thickness, as well as right frontal lobe thickness, putamen, and amygdala volumes. DISCUSSION: The associations between social connectedness and brain structure vary depending on the types of social enrichment accessible through social networks, suggesting that psychosocial interventions could mitigate neurodegeneration. Highlights: Distinct forms of social capital are uniquely linked to gray matter density (GMD).Bridging is associated with preserved GMD in limbic system structures.Bonding is associated with preserved GMD in frontal lobe regions.Bridging is associated with increased brain reserve in sensory processing regions.Bonding is associated with increased brain reserve in regions of stress modulation. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early‐onset Alzheimer's disease (EOAD). METHODS: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non‐Alzheimer's disease (EOnonAD) participants from the Longitudinal Early‐Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification. Voxel‐wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden. RESULTS: EOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE ε4 non‐carriers had greater amyloid PET burdens and greater gray matter atrophy than female ε4 carriers. EOnonAD female ε4 non‐carriers also had greater gray matter atrophy than female ε4 carriers. DISCUSSION: The effects of sex and APOE ε4 must be considered when studying these populations. HIGHLIGHTS: Novel analysis examining the effects of biological sex and apolipoprotein E ε4 (APOE ε4) carrier status on neuroimaging biomarkers among early‐onset Alzheimer's disease (EOAD), early‐onset non‐AD (EOnonAD), and cognitively normal (CN) participants.Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex.The effect of APOE ε4 carrier status on pathology burden was the most impactful in females across all cohorts. [ABSTRACT FROM AUTHOR]

Background: We studied the effect of apolipoprotein E (APOE) ε4 status and sex on rates of cognitive decline in early‐ (EO) and late‐ (LO) onset Alzheimer's disease (AD). Method: We ran mixed‐effects models with longitudinal cognitive measures as dependent variables, and sex, APOE ε4 carrier status, and interaction terms as predictor variables in 998 EOAD and 2562 LOAD participants from the National Alzheimer's Coordinating Center. Results: APOE ε4 carriers showed accelerated cognitive decline relative to non‐carriers in both EOAD and LOAD, although the patterns of specific cognitive domains that were affected differed. Female participants showed accelerated cognitive decline relative to male participants in EOAD only. The effect of APOE ε4 was greater in EOAD for executive functioning (p < 0.0001) and greater in LOAD for language (p < 0.0001). Conclusion: We found APOE ε4 effects on cognitive decline in both EOAD and LOAD and female sex in EOAD only. The specific patterns and magnitude of decline are distinct between the two disease variants. Highlights: Apolipoprotein E (APOE) ε4 carrier status and sex differentiate rates of cognitive decline in early‐onset (EO) and late‐onset (LO) Alzheimer's disease (AD).APOE ε4 in EOAD accelerated decline in memory, executive, and processing speed domains.Female sex in EOAD accelerated decline in language, memory, and global cognition.The effect of APOE ε4 was stronger for language in LOAD and for executive function in EOAD.Sex effects on language and executive function decline differed between EOAD and LOAD. [ABSTRACT FROM AUTHOR]

Background: Apolipoprotein‐ε4 (APOE‐ε4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). APOE‐ε4 has been associated with younger onset of AD symptoms in multiple studies. Some have hypothesized that APOE‐ε4 effect shows a peak between ages 65‐75 years [1, 2] suggesting that in the early‐onset AD variant (EOAD), APOE‐ε4 might be counterintuitively associated with later disease onset. Here we explored the association of APOE‐ε4 genotype with age of symptom onset in a large sample of late‐onset AD (LOAD) and EOAD subjects from the National Alzheimer's Coordinating Center's (NACC) database. Method: We analyzed the data of 988 EOAD and 2503 LOAD NACC participants (age at symptom onset < or ≥ 65). T‐tests and Fisher's exact tests were used to compare the age of onset in APOE‐ε4 carrier and non‐carrier in the EOAD and LOAD subjects separately. Result: Diagnosis of AD was established by clinical consensus at all NACC participating sites. EOAD and LOAD were defined by age at symptom onset < or ≥ 65 years, respectively. Table shows the demographic characteristics of the EOAD and LOAD groups. In LOAD mean symptom onset was 73.0 (+/‐5.4) vs. 76.2 years (+/‐6.1) APOE‐ε4 carriers vs. noncarriers, respectively (p‐value<0.0001). In EOAD mean symptom onset was 57.9 (+/‐5.0) vs. 56.7 years (+/‐5.3) for APOE‐ε4 carriers vs. noncarriers, respectively (p‐value=0.0006). The age at symptom onset distributions can be seen in Figure. The top portion of the figure shows APOE‐ε4 carriers and noncarriers by disease subtype and the bottom potion shows the overlay within disease subtypes. Conclusion: Despite the fact that the dataset used for our analyses is primarily focused on LOAD and thus recruitment of EOAD participants might have been limited, we found that in EOAD APOE‐ε4 is associated with later disease onset as hypothesized. Prospective multi‐site studies such as the Longitudinal Early‐Onset AD study (LEADS) focused exclusively on EOAD will further characterize the genetic influences of APOE‐ε4 and other genetic risk factors on disease onset and progression in this disease variant. [ABSTRACT FROM AUTHOR]

Introduction: Social connectedness is associated with slower cognitive decline among older adults. Recent research suggests that distinct aspects of social networks may have differential effects on cognitive resilience, but few studies analyze brain structure., Methods: This study includes 117 cognitively impaired and 59 unimpaired older adults. The effects of social network characteristics (bridging/bonding) on brain regions of interests were analyzed using linear regressions and voxel-wise multiple linear regressions of gray matter density., Results: Increased social bridging was associated with greater bilateral amygdala volume and insular thickness, and left frontal lobe thickness, putamen, and thalamic volumes. Increased social bonding was associated with greater bilateral medial orbitofrontal and caudal anterior cingulate thickness, as well as right frontal lobe thickness, putamen, and amygdala volumes., Discussion: The associations between social connectedness and brain structure vary depending on the types of social enrichment accessible through social networks, suggesting that psychosocial interventions could mitigate neurodegeneration., Highlights: Distinct forms of social capital are uniquely linked to gray matter density (GMD). Bridging is associated with preserved GMD in limbic system structures. Bonding is associated with preserved GMD in frontal lobe regions. Bridging is associated with increased brain reserve in sensory processing regions. Bonding is associated with increased brain reserve in regions of stress modulation., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD)., Methods: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification. Voxel-wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden., Results: EOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE ε4 non-carriers had greater amyloid PET burdens and greater gray matter atrophy than female ε4 carriers. EOnonAD female ε4 non-carriers also had greater gray matter atrophy than female ε4 carriers., Discussion: The effects of sex and APOE ε4 must be considered when studying these populations., Highlights: Novel analysis examining the effects of biological sex and apolipoprotein E ε4 (APOE ε4) carrier status on neuroimaging biomarkers among early-onset Alzheimer's disease (EOAD), early-onset non-AD (EOnonAD), and cognitively normal (CN) participants. Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex. The effect of APOE ε4 carrier status on pathology burden was the most impactful in females across all cohorts., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: We studied the effect of apolipoprotein E (APOE) ε4 status and sex on rates of cognitive decline in early- (EO) and late- (LO) onset Alzheimer's disease (AD)., Method: We ran mixed-effects models with longitudinal cognitive measures as dependent variables, and sex, APOE ε4 carrier status, and interaction terms as predictor variables in 998 EOAD and 2562 LOAD participants from the National Alzheimer's Coordinating Center., Results: APOE ε4 carriers showed accelerated cognitive decline relative to non-carriers in both EOAD and LOAD, although the patterns of specific cognitive domains that were affected differed. Female participants showed accelerated cognitive decline relative to male participants in EOAD only. The effect of APOE ε4 was greater in EOAD for executive functioning (p < 0.0001) and greater in LOAD for language (p < 0.0001)., Conclusion: We found APOE ε4 effects on cognitive decline in both EOAD and LOAD and female sex in EOAD only. The specific patterns and magnitude of decline are distinct between the two disease variants., Highlights: Apolipoprotein E (APOE) ε4 carrier status and sex differentiate rates of cognitive decline in early-onset (EO) and late-onset (LO) Alzheimer's disease (AD). APOE ε4 in EOAD accelerated decline in memory, executive, and processing speed domains. Female sex in EOAD accelerated decline in language, memory, and global cognition. The effect of APOE ε4 was stronger for language in LOAD and for executive function in EOAD. Sex effects on language and executive function decline differed between EOAD and LOAD., (© 2022 the Alzheimer's Association.)