BackgroundSystemic inflammation is implicated in cognitive aging, yet whether interleukin-6 (IL-6) represents a shared versus group-specific marker of cognitive impairment across racially and ethnically diverse older adults remains unclear. This study examined associations among depressive symptoms, plasma IL-6, and cognitive impairment while testing mediation and ethnoracial moderation.MethodsParticipants were drawn from the Health and Aging Brain Study–Health Disparities (HABS-HD). In the full multi-ethnic complete-case sample (N = 2,187; 963 non-Hispanic White, 277 Black, and 947 Hispanic participants), logistic regression models tested the association of log₁₀-transformed plasma IL-6 with binary cognitive impairment (mild cognitive impairment or dementia versus cognitively unimpaired status), adjusting for age, education, sex, Geriatric Depression Scale (GDS) total score, ethnoracial group, and APOE ε4 carrier status. Parallel models examined GDS–cognitive impairment associations. Mediation models tested whether IL-6 statistically mediated the association between GDS scores and cognitive impairment. Moderation analyses tested IL-6 × ethnoracial group interactions. Sensitivity analyses repeated the main-effect, interaction, and mediation models in 1:1 matched Black/White (N = 554) and Hispanic/White (N = 794) subsamples that were matched exactly on sex and cognitive status and balanced on age and education.ResultsHigher plasma IL-6 was associated with greater odds of cognitive impairment in the full sample (OR = 1.87, 95% CI [1.31, 2.68], p < 0.001), and this association did not significantly differ by ethnoracial group (χ2 = 3.52, df = 2, p = 0.172). Higher GDS scores were also independently associated with cognitive impairment (OR = 1.06 per point, 95% CI [1.04, 1.08], p < 0.001). IL-6 statistically mediated a small proportion of the GDS–cognitive impairment association (indirect effect = 0.0025, Sobel p = 0.014). The IL-6 association remained significant in the Black/White (OR = 2.62, 95% CI [1.27, 5.46], p = 0.009) and Hispanic/White (OR = 2.24, 95% CI [1.27, 3.97], p = 0.005) matched samples, with no significant matched-sample IL-6 × ethnoracial group interactions.ConclusionPlasma IL-6 emerged as a consistent inflammatory correlate of cognitive impairment across Black, Hispanic, and non-Hispanic White older adults. The findings support IL-6 as a potentially generalizable biomarker while highlighting the need for longitudinal studies to clarify its role in depression-related cognitive decline in diverse populations.
IntroductionProtein proteoforms generated by post-translational modification are increasingly recognized as important regulators of neuronal function and neurodegenerative disease. However, methods for acutely interrogating specific intracellular proteoforms in living neuronal populations remain limited. We evaluated cationic liposomal delivery (CLD) as a strategy for introducing full-length functional antibodies into living neurons and used this approach to investigate the role of a phosphorylated tau proteoform recognized by the monoclonal antibody PHF-1.MethodsCationic liposomes composed of DOPC+ were complexed with antibodies or molecular probes and applied to cultured neuronal cell lines and primary mouse cortical neurons. Intracellular delivery, cellular localization, viability, and biological activity were assessed using fluorescence microscopy and live-cell imaging.ResultsCLD efficiently delivered full-length antibodies and molecular probes into living neuronal cells and primary neurons without detectable toxicity. Internalized antibodies retained target specificity, producing intracellular staining patterns consistent with the known localization of tau, vinculin, paxillin, and Fyn. Delivery was observed across essentially all cells in treated cultures and remained effective under standard culture conditions. Intracellular delivery of PHF-1 produced a rapid and striking morphological response characterized by neurite retraction and cell-body rounding within hours of treatment. These effects were not observed with heat-inactivated PHF-1, vehicle controls, or other intracellular antibodies, supporting a specific effect of intracellular engagement of PHF-1-reactive tau species.DiscussionThese findings establish CLD as a practical platform for the intracellular delivery of functional full-length antibodies into living neuronal populations. Beyond validating a delivery technology, the study demonstrates that acute intracellular engagement of PHF-1-reactive phosphorylated tau rapidly alters neuronal morphology, suggesting that this tau proteoform contributes to the maintenance of neurite integrity. CLD provides a versatile approach for probing the function of intracellular proteoforms that are difficult to study using conventional genetic or biochemical methods.
Dementia prevention requires policies that address upstream, modifiable risk factors—particularly loneliness, depressed mood, and low social participation—which disproportionately affect linguistically diverse and historically marginalized communities. This Perspective argues that linguistic inclusion, cultural responsiveness, and trust-building practices should be treated as core quality domains in dementia prevention policy and delivery. We describe the Multimodal Intergenerational Social Contact Intervention (MISCI), a community-embedded program designed to reduce loneliness and depressed mood—established risk factors for dementia—through culturally meaningful intergenerational engagement. While MISCI outcomes are limited to feasibility, acceptability, and descriptive trends, we integrate these findings with existing literature to derive policy and systems recommendations. These include reimbursement pathways for social connection interventions, strengthened language access standards, equity-stratified reporting, and cross-sector partnerships. Aligning policy mechanisms with community-embedded programs may support scalable, culturally responsive approaches to reducing dementia risk while advancing health equity.
IntroductionThis study examined family caregivers’ experiences of dementia village care and explored their associations with caregiver reactions and residents’ thriving.MethodsThe study utilized an explanatory sequential mixed-methods design. Thirty family caregivers completed questionnaires assessing caregiver reactions, health-related quality of life, and resident thriving. Subsequently, 16 of these caregivers participated in semi-structured interviews. Quantitative data were analysed using descriptive statistics and correlation analyses, while qualitative data were analysed using thematic analysis.ResultsFamily caregivers reported high levels of caregiver esteem and low levels of burden, and residents were perceived as thriving, particularly through positive relationships with staff and high-quality care. Although admission was emotionally challenging, caregivers experienced relief, reassurance, and increased trust. Resident wellbeing was linked to meaningful activities, social engagement, supportive staff, and outdoor access. However, caregivers also reported challenges regarding communication, involvement in care decisions, and balancing resident autonomy with safety. Overall, caregiver experiences reflected an adaptive process marked by both trust and uncertainty.DiscussionThe findings indicate that dementia villages promote resident thriving through supportive environments, social relationships, and meaningful engagement. Family caregivers viewed the model positively and maintained active involvement post-admission, suggesting that dementia villages foster more sustainable care by bridging professional support with ongoing family partnership.
