Wagenknecht, Lynne

Abstract Background The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) randomized trial ( n = 977;ClinicalTrials.gov:NCT03243422) demonstrated that hearing intervention slowed 3‐year cognitive decline by 48% among a subgroup of participants. To further investigate differences by treatment with respect to cognitive benefit, we tested the hypothesis that hearing intervention is associated with improved neurodegeneration blood biomarkers 3‐years post‐randomization and assessed whether combining biomarkers and cognitive results improved power in the trial design. Method The ACHIEVE study is a multicenter, parallel‐arm, randomized trial (hearing intervention vs health education control) on 3‐year cognitive decline among adults 70–84years with untreated hearing loss and without substantial cognitive impairment. Participants were recruited from two populations: (1) a long‐standing cardiovascular health observational study (Atherosclerosis Risk in Communities [ARIC]), and (2) de novo community volunteers. Plasma was collected in year 3 in a subsample ( n = 540) while ARIC participants ( n = 164) also had baseline plasma. Glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) neurodegenerative biomarkers were derived using the Alamar CNS protein panel. Regression models estimated the association of treatment with 3‐year biomarkers and global cognitive differences in the combined sample and by recruitment source and annualized change from baseline in the ARIC sample. We included a simple composite score of the standardized outcomes (Table 2). Result Among the subsample, baseline characteristics were balanced by treatment. There were no significant differences on 3‐year neurodegeneration biomarker levels by treatment in the combined (Table 1) or de novo groups (Table 2). Among ARIC participants, intervention resulted in lower 3‐year GFAP (mean:‐0.415;95%CI:‐0.712,‐0.118) and NfL (mean:‐0.349;95%CI:‐0.652,‐0.046) (Table 2). Annualized change from baseline analyses among ARIC participants (Table 3) revealed intervention was associated with a slower rate of cognitive decline (difference‐in‐means:0.059;95%CI:0.018,0.100) and a slower rate of increase in GFAP (difference‐in‐means: ‐0.060;95%CI:‐0.112,‐0.009). Differences in estimates suggest combined score, relative to cognition alone, may increase power in clinical trials that show a positive effect (ARIC subgroup: p = 0.02vs. 0.08[Table 2] and p = 0.0009vs.0.048[Table 3]). Conclusion Hearing intervention was associated with positive 3‐year effects on neurodegeneration blood biomarkers in ARIC participants which parallels cognitive decline results. Results provides objective evidence of brain changes following hearing intervention and potential signal of a more powerful combined outcome approach for future brain health clinical trials.

Abstract The Atherosclerosis Risk in Communities (ARIC) study started in 1987‐1989 (visit 1), when participants from four U.S. communities were 45‐64yo. Participants have been seen at up to 10 additional in‐person visits with annual/semi‐annual telephone calls to ascertain clinical events, hospitalizations, and other health outcomes. In 2011‐2013, at ARIC visit 5, the ARIC Neurocognitive Study (ARIC‐NCS) was initiated for surviving participants, incorporating neuropsychological assessments at multiple in‐person visits and informant interviews to support cognitive adjudication. A subset of participants have undergone brain MRI with measurement of brain volumes, cortical thickness, arterial disease and vascular lesions, with a smaller subset having brain florbetapir PET. Blood‐based Alzheimer's disease (AD) biomarkers are available at multiple visits along with extensive measurement of vascular risk factors, vascular markers, and ‐omic (e.g.genomic and proteomic) data. This presentation will focus on the available data in ARIC, the methods underlying its collection and subsequent analysis, and some of the primary contributions of this study to the field. With 37 years of follow‐up, a great strength of ARIC is the ability to evaluate risk factors in midlife; ARIC studies have supported an association of midlife hypertension, diabetes, physical inactivity, and other vascular risk factors with reduced dementia risk, even among those with increased genetic risk for dementia. ARIC studies have demonstrated associations between stroke and dementia, and have linked vascular risk factors with blood‐based and imaging biomarkers of AD‐related dementias. ARIC has demonstrated the importance of hearing loss in dementia risk, and a subset of ARIC participants were recruited into (and were those who most benefited from the intervention of) the ACHIEVE study of hearing aid use for reduction of dementia. Proteomic studies have identified markers of dementia risk when evaluated in midlife. Recently, ARIC data informed updated estimates on lifetime risk of dementia, where it was estimated that among individuals surviving beyond age 55, 42% would develop dementia over their lifetime through age 95. ARIC studies continue to focus on risk factors for dementia, particularly now in the oldest old, and on contributors to cognitive reserve and resilience. ARIC follows a model of data sharing and broad collaboration.