Cognitively defined Alzheimer's dementia subgroups have distinct atrophy patterns.

INTRODUCTION: We sought to determine structural magnetic resonance imaging (MRI) characteristics across subgroups defined based on relative cognitive domain impairments using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to compare cognitively defined to imaging-defined subgroups. METHODS: We used data from 584 people with Alzheimer's disease (AD) (461 amyloid positive, 123 unknown amyloid status) and 118 amyloid-negative controls. We used voxel-based morphometry to compare gray matter volume (GMV) for each group compared to controls and to AD-Memory. RESULTS: There was pronounced bilateral lower medial temporal lobe atrophy with relative cortical sparing for AD-Memory, lower left hemisphere GMV for AD-Language, anterior lower GMV for AD-Executive, and posterior lower GMV for AD-Visuospatial. Formal asymmetry comparisons showed substantially more asymmetry in the AD-Language group than any other group (p = 1.15 × 10-10 ). For overlap between imaging-defined and cognitively defined subgroups, AD-Memory matched up with an imaging-defined limbic predominant group. DISCUSSION: MRI findings differ across cognitively defined AD subgroups.

Investigation of the association of military employment and Parkinson's disease with a validated Parkinson's disease case-finding strategy.

INTRODUCTION: Persons with military involvement may be more likely to have Parkinson's disease (PD) risk factors. As PD is rare, case finding remains a challenge, contributing to our limited understanding of PD risk factors. Here, we explore the validity of case-finding strategies and whether military employment is associated with PD. MATERIALS AND METHODS: We identified Adult Changes in Thought (ACT) study participants reporting military employment as their longest or second longest occupation. We used self-report and prescription fills to identify PD cases and validated this case-finding approach against medical record review. RESULTS: At enrollment, 6% of 5,125 eligible participants had military employment and 1.8% had prevalent PD; an additional 3.5% developed PD over follow-up (mean: 8.3 years). Sensitivity of our case-finding approach was higher for incident (80%) than prevalent cases (54%). Specificity was high (>97%) for both. Military employment was not associated with prevalent PD. Among nonsmokers, point estimates suggested an increased risk of incident PD with military employment, but the result was non-significant and based on a small number of cases. CONCLUSIONS: Self-report and prescription medications can accurately identify incident PD cases relative to the reference method of medical record review. We found no association between military employment and PD.

Correction: Genetic data and cognitively defined late-onset Alzheimer's disease subgroups.

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Genetic data and cognitively defined late-onset Alzheimer's disease subgroups.

Categorizing people with late-onset Alzheimer's disease into biologically coherent subgroups is important for personalized medicine. We evaluated data from five studies (total n = 4050, of whom 2431 had genome-wide single-nucleotide polymorphism (SNP) data). We assigned people to cognitively defined subgroups on the basis of relative performance in memory, executive functioning, visuospatial functioning, and language at the time of Alzheimer's disease diagnosis. We compared genotype frequencies for each subgroup to those from cognitively normal elderly controls. We focused on APOE and on SNPs with p < 10-5 and odds ratios more extreme than those previously reported for Alzheimer's disease (<0.77 or >1.30). There was substantial variation across studies in the proportions of people in each subgroup. In each study, higher proportions of people with isolated substantial relative memory impairment had ≥1 APOE ε4 allele than any other subgroup (overall p = 1.5 × 10-27). Across subgroups, there were 33 novel suggestive loci across the genome with p < 10-5 and an extreme OR compared to controls, of which none had statistical evidence of heterogeneity and 30 had ORs in the same direction across all datasets. These data support the biological coherence of cognitively defined subgroups and nominate novel genetic loci.

Association of Lifetime TBI and Military Employment with Late Life ADL Functioning: A Population-Based Prospective Cohort Study.

OBJECTIVE: To determine associations of traumatic brain injury (TBI) and military employment with activities of daily living (ADL) in late life. DESIGN: Population-based prospective cohort study with biennial follow-up and censoring at the time of dementia diagnosis. SETTING: Community-based integrated health care delivery system. PARTICIPANTS: Participants (N=4953) were men (n=2066) and women (n=2887) aged ≥65 years who were dementia free. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: ADL difficulties at baseline and accumulation during follow-up. RESULTS: TBI with loss of consciousness (LOC) before the age of 40 years was associated with slightly higher ADL difficulty at baseline for women (rate ratio [RR], 1.44; 95% confidence interval [CI], 1.08-1.93; P=.01). For men, TBI with LOC at any age was associated with greater ADL difficulty at baseline (age <40y: RR, 1.58; 95% CI, 1.20-2.08; P=.001; age ≥40y: RR, 2.14; 95% CI, 1.24-3.68; P=.006). TBI with LOC was not associated with the rate of accumulation of ADL difficulties over time in men or women. There was no evidence of an association between military employment and either outcome, nor of an interaction between military employment and TBI with LOC. Findings were consistent across a variety of sensitivity analyses. CONCLUSIONS: Further investigation into factors underlying greater late life functional impairment among survivors of TBI is warranted.

How Do Treatment Priorities Differ Between Patients in HIV Care and Their Providers? A Mixed-Methods Study.

Evidence suggests priorities differ between patients in HIV care and their providers regarding topics most important to address in care. At five U.S. sites, we asked patients and providers to prioritize 25 potential topic areas to address during routine visits, and invited patients to discuss selection rationale. Patients (n = 206) and providers (n = 17) showed high discordance in rank order priorities (X2 (24, 223) = 71.12; p < 0.0001). Patients ranked social domains such as HIV stigma highly; a higher proportion of providers prioritized substance use domains. HIV stigma was a higher priority for patients in care fewer than 6 years (Fisher's exact p = 0.0062), nonwhite patients (Fisher's exact p = 0.0114), and younger patients (Fisher's exact p = 0.0281). Patients' priorities differed between men and women (X2 (24, 188) = 52.89; p < 0.0001), white race vs. other races (X2 (24, 206) = 48.32; p = 0.0023), and Latinos vs. non-Latinos (X2 (24, 206) = 48.65; p = 0.0021). Interviews (n = 79) revealed perceived impact of social context on health and health behaviors.

Development and content validation of the Multifactoral assessment of perceived social support (MAPSS), a brief, patient-reported measure of social support for use in HIV care.

Low perceived social support (SS) negatively impacts health outcomes. We developed a measure of perceived SS for use in HIV care. We sought and categorized legacy items, selecting strongest items within categories. We elicited SS concepts from patients in English/Spanish, coded transcripts to match item pool content, and developed new items for salient unrepresented content. In focus groups, patients prioritized highly-matched items. We conducted cognitive interviews on high-priority items, and validity testing on final items against two legacy measures. From interviews (n = 32), we matched the following concepts: sense of belonging/inclusion; communication; emotional support; feeling accepted by others as a person; companionship; and practical support. We identified a new concept: support from friends/family in remaining healthy. Focus groups (n = 23) prioritized emotional support, communication, and support to remain healthy. Cognitive interviews (n = 30) found items were well-understood. The final 8-item measure performed well with patients (n = 708), with good construct validity. We used an Item Response Theory program to create a 3-item Short Form version of the measure, which captures 96% of patients indicating low social support. We developed the Multifactoral Assessment of Perceived Social Support (MAPSS) and Short Form (MAPSS-SF); brief, clinically relevant, sufficiently unidimensional measures of SS for use in HIV care.

Health literacy, sociodemographic factors, and cognitive training in the active study of older adults.

OBJECTIVE: Health literacy is critical for understanding information from health-care providers and correct use of medications and includes the capacity to filter other information in navigating health care systems. Older adults with low health literacy exhibit more chronic health conditions, worse physical functioning, and poorer mental health. This study examined the relationship between sociodemographic variables and health literacy, and the impact of cognitive training on change in health literacy over 10 years in older adults. METHODS: Participants (N = 2,802) aged 65 years and older completed assessments, including reading and numeracy health literacy items, as part of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study. We evaluated baseline sociodemographic variables and change in health literacy over a 10-year period in individuals exposed to cognitive training in reasoning, processing speed, memory, or a no-contact control condition. RESULTS: Age, sex, race, education level, and general cognitive functioning at baseline were all associated with baseline health literacy in older adults. Predictors of change in health literacy over the 10-year follow-up were age, race, education level, general cognitive functioning, and neighborhood income; disparities in health literacy because of race attenuated over time, while the effect of age increased over time. Health literacy was generally stable across the ACTIVE intervention groups over 10 years. CONCLUSIONS: The present study showed important disparities in health literacy level and change over 10 years. Cognitive training did not significantly impact health literacy, suggesting that alternative approaches are needed to reduce the disparities.

Associations between recent and established ophthalmic conditions and risk of Alzheimer's disease.

INTRODUCTION: Identifying ophthalmic diseases associated with increased risk of Alzheimer's disease (AD) may enable better screening and understanding of those at risk of AD. METHODS: Diagnoses of glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR) were based on International Classification of Diseases, 9th revision, codes for 3877 participants from the Adult Changes in Thought study. The adjusted hazard ratio for developing probable or possible AD for recent (within 5 years) and established (>5 years) diagnoses were assessed. RESULTS: Over 31,142 person-years of follow-up, 792 AD cases occurred. The recent and established hazard ratio were 1.46 (P = .01) and 0.87 (P = .19) for glaucoma, 1.20 (P = .12) and 1.50 (P < .001) for AMD, and 1.50 (P = .045) and 1.50 (P = .03) for DR. DISCUSSION: Increased AD risk was found for recent glaucoma diagnoses, established AMD diagnoses, and both recent and established DR. People with certain ophthalmic conditions may have increased AD risk.

Development and Content Validation of a Patient-Reported Sexual Risk Measure for Use in Primary Care.

BACKGROUND: Patient-provider sexual risk behavior discussions occur infrequently but may be facilitated by high-quality sexual risk screening tools. OBJECTIVE: To develop the Sexual Risk Behavior Inventory (SRBI), a brief computer-administered patient-reported measure. DESIGN: Qualitative item development/quantitative instrument validation. PARTICIPANTS: We developed SRBI items based on patient interviews (n = 128) at four geographically diverse US primary care clinics. Patients were diverse in gender identity, sex, sexual orientation, age, race/ethnicity, and HIV status. We compared sexual risk behavior identified by the SRBI and the Risk Assessment Battery (RAB) among patients (n = 422). APPROACH: We constructed an item pool based on validated measures of sexual risk, developed an in-depth interview guide based on pool content, and used interviews to elicit new sexual risk concepts. We coded concepts, matched them to item pool content, and developed new content where needed. A provider team evaluated item clinical relevance. We conducted cognitive interviews to assess item comprehensibility. We administered the SRBI and the RAB to patients. KEY RESULTS: Common, clinically relevant concepts in the SRBI included number of sex partners; partner HIV status; partner use of antiretroviral medication (ART)/pre-exposure prophylaxis (PrEP); and recent sex without barrier protection, direction of anal sex, and concern regarding HIV/STI exposure. While 90% reported inconsistent condom use on the RAB, same-day SRBI administration revealed that for over one third, all their partners were on ART/PrEP. CONCLUSION: The SRBI is a brief, skip-patterned, clinically relevant measure that ascertains sexual risk behavior across sex, sexual orientation, gender identity, partner HIV serostatus, and partner treatment status, furnishing providers with context to determine gradations of risk for HIV/STI.

Comparing Variability, Severity, and Persistence of Depressive Symptoms as Predictors of Future Stroke Risk.

OBJECTIVE: Numerous studies show that depressive symptoms measured at a single assessment predict greater future stroke risk. Longer-term symptom patterns, such as variability across repeated measures or worst symptom level, might better reflect adverse aspects of depression than a single measurement. This prospective study compared five approaches to operationalizing depressive symptoms at annual assessments as predictors of stroke incidence. DESIGN: Cohort followed for incident stroke over an average of 6.4 years. SETTING: The Adult Changes in Thought cohort follows initially cognitively intact, community- dwelling older adults from a population base defined by membership in Group Health, a Seattle-based nonprofit healthcare organization. PARTICIPANTS: 3,524 individuals aged 65 years and older. MEASUREMENTS: We identified 665 incident strokes using ICD codes. We considered both baseline Center for Epidemiologic Studies-Depression scale (CES-D) score and, using a moving window of three most recent annual CES-D measurements, we compared most recent, maximum, average, and intra-individual variability of CES-D scores as predictors of subsequent stroke using Cox proportional hazards models. RESULTS: Greater maximum (hazard ratio [HR]: 1.18; 95% CI: 1.07-1.30), average (HR: 1.20; 95% CI: 1.05-1.36) and intra-individual variability (HR: 1.15; 95% CI: 1.06-1.24) in CES-D were each associated with elevated stroke risk, independent of sociodemographics, cardiovascular risks, cognition, and daily functioning. Neither baseline nor most recent CES-D was associated with stroke. In a combined model, intra-individual variability in CES-D predicted stroke, but average CES-D did not. CONCLUSIONS: Capturing the dynamic nature of depression is relevant in assessing stroke risk. Fluctuating depressive symptoms may reflect a prodrome of reduced cerebrovascular integrity.

Impact of home visit capacity on genetic association studies of late-onset Alzheimer's disease.

INTRODUCTION: Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits. METHODS: We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators. RESULTS: LOAD associations nominally differed for 4 of 21 variants; CR1 and APOE variants were significant after Bonferroni correction. DISCUSSION: Estimates of genetic associations may differ for studies limited to clinic-only designs. Home visit capacity should be explored as a possible source of heterogeneity and potential bias in genetic studies.

Incidence of cognitively defined late-onset Alzheimer's dementia subgroups from a prospective cohort study.

INTRODUCTION: There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia. METHODS: We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments. RESULTS: During 32,286 person-years of follow-up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), language (71, 9%), and executive functioning (66, 8%). The group with isolated relative memory impairments had higher proportions with ≥ APOE ε4 allele, more extensive Alzheimer's-related neuropathology, and higher proportions with other Alzheimer's dementia genetic risk variants. DISCUSSION: A cognitive subgrouping strategy may identify biologically distinct subsets of people with Alzheimer's dementia.

Importance of home study visit capacity in dementia studies.

INTRODUCTION: The importance of home research study visit capacity in Alzheimer's disease (AD) studies is unknown. METHODS: All evaluations are from the prospective Adult Changes in Thought study. Based on analyses of factors associated with volunteering for a new in-clinic initiative, we analyzed AD risk factors and the relevance of neuropathologic findings for dementia comparing all data including home visits, and in-clinic data only. We performed bootstrapping to determine whether differences were greater than expected by chance. RESULTS: Of the 1781 people enrolled during 1994-1996 with ≥1 follow-up, 1369 (77%) had in-clinic data, covering 61% of follow-up time. In-clinic data resulted in excluding 76% of incident dementia and AD cases. AD risk factors and the relevance of neuropathologic findings for dementia were both different with in-clinic data. DISCUSSION: Limiting data collection in AD studies to research clinics alone likely reduces power and also can lead to erroneous inferences.

Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

BACKGROUND: Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR). METHODS AND FINDINGS: We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49), fasting glucose (NSNPs = 36), insulin resistance (NSNPs = 10), body mass index (BMI, NSNPs = 32), total cholesterol (NSNPs = 73), HDL-cholesterol (NSNPs = 71), LDL-cholesterol (NSNPs = 57), triglycerides (NSNPs = 39), systolic blood pressure (SBP, NSNPs = 24), smoking initiation (NSNPs = 1), smoking quantity (NSNPs = 3), university completion (NSNPs = 2), and years of education (NSNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3)). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8)). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3)), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this study include the small proportion of intermediate trait variance explained by genetic variants and other implicit limitations of MR analyses. CONCLUSIONS: Inherited lifetime exposure to higher SBP is associated with lower AD risk. These findings suggest that higher blood pressure--or some environmental exposure associated with higher blood pressure, such as use of antihypertensive medications--may reduce AD risk.

Patient and provider priorities for self-reported domains of HIV clinical care.

We sought to understand how HIV-infected patients, their providers, and HIV care researchers prioritize self-reported domains of clinical care. Participants rank-ordered two lists of domains. A modified Delphi process was used for providers and researchers. Approximately 25% of patients were interviewed to discuss rationale for rank order choices. List 1 included anger, anxiety, depression, fatigue, physical function, pain, and sleep disturbance. List 2 included alcohol abuse, cognitive function, HIV stigma, HIV and treatment symptoms, medication adherence, positive affect, sexual risk behavior, sexual function, social roles, spirituality/meaning of life, and substance abuse. Seventy-four providers, 80 HIV care researchers, and 66 patients participated. Patients ranked context-based domains, such as HIV stigma, more highly than providers, while health behaviors, such as drug or alcohol use, ranked lower. Patients described a need to address wider-context challenges such as HIV stigma in order to positively impact health behaviors. Divergent patient and provider priorities highlight the importance of incorporating views from all stakeholders and suggests the need for a care approach that more effectively addresses contextual barriers to adverse health behaviors.

Differential item functioning due to cognitive status does not impact depressive symptom measures in four heterogeneous samples of older adults.

OBJECTIVE: The objective of this study is to determine whether differential item functioning (DIF) due to cognitive status impacted three depressive symptoms measures commonly used with older adults. METHODS: Differential item functioning in depressive symptoms was assessed among participants (N = 3558) taking part in four longitudinal studies of cognitive aging, using the Geriatric Depression Scale, the Montgomery-Åsberg Depression Rating Scale, and the Center for Epidemiologic Studies Depression Scale. Participants were grouped by cognitive status using a general cognitive performance score derived from each study's neuropsychological battery and linked to a national average using a population-based survey representative of the US population. The Clinical Dementia Rating score was used as an alternate grouping variable in three of the studies. RESULTS: Although statistically significant DIF based on cognitive status was found for some depressive symptom items (e.g., items related to memory complaints, appetite loss, lack of energy, and mood), the effect of item bias on the total score for each scale was negligible. CONCLUSIONS: The depressive symptoms scales in these four studies measured depression in the same way, regardless of cognitive status. This may reduce concerns about using these depression measures in cognitive aging research, as relationships between depression and cognitive decline are unlikely to have been due to item bias, at least in the ways that were measured in the datasets we considered.

Demographic characteristics do not decrease the utility of depressive symptoms assessments: examining the practical impact of item bias in four heterogeneous samples of older adults.

OBJECTIVE: Previous studies have identified differential item function (DIF) in depressive symptoms measures, but the impact of DIF has been rarely reported. Given the critical importance of depressive symptoms assessment among older adults, we examined whether DIF due to demographic characteristics resulted in salient score changes in commonly used measures. METHODS: Four longitudinal studies of cognitive aging provided a sample size of 3754 older adults and included individuals both with and without a clinical diagnosis of major depression. Each study administered at least one of the following measures: the Center for Epidemiologic Studies Depression scale (20-item ordinal response or 10-item dichotomous response versions), the Geriatric Depression Scale, and the Montgomery-Åsberg Depression Rating Scale. Hybrid logistic regression-item response theory methods were used to examine the presence and impact of DIF due to age, sex, race/ethnicity, and years of education on the depressive symptoms items. RESULTS: Although statistically significant DIF due to demographic factors was present on several items, its cumulative impact on depressive symptoms scores was practically negligible. CONCLUSIONS: The findings support substantive meaningfulness of previously reported demographic differences in depressive symptoms among older adults, showing that these individual differences were unlikely to have resulted from item bias attributable to demographic characteristics we examined.

Efficacy of a Telephone-Delivered Self-Management Intervention for Persons With Multiple Sclerosis: A Randomized Controlled Trial With a One-Year Follow-Up.

OBJECTIVE: To evaluate the efficacy of a telephone-delivered self-management intervention for fatigue, pain, and depression in adults with multiple sclerosis (MS). DESIGN: Single-center, randomized (1:1), single-blind (outcome assessors), parallel-group trial with a primary endpoint of posttreatment (9-11 wk postrandomization) and long-term follow-up at 6 and 12 months. SETTING: Telephone-delivered across the United States. PARTICIPANTS: Adults with MS (N=163) with fatigue, chronic pain, and/or moderate depressive symptoms (age range, 25-76 y). INTERVENTIONS: Eight-week individual telephone-delivered self-management intervention (T-SM) (n=75) versus an 8-week individual telephone-delivered MS education intervention (T-ED) (n=88). MAIN OUTCOME MEASURES: The primary outcome was the proportion who achieved a ≥50% decrease in 1 or more symptoms-fatigue impact, pain interference, and/or depression severity. Secondary outcomes included continuous measures of pain, fatigue impact, depression, self-efficacy, activation, health-related quality of life, resilience, and affect. RESULTS: For our primary outcome, 58% of those in the T-SM group and 46% of those in the T-ED group had a ≥50% reduction in 1 or more symptoms; this difference was not statistically significant (odds ratio, 1.50; 95% confidence interval, .77-2.93; P=.238). Participants in both groups significantly improved from baseline to posttreatment in primary and secondary outcome measures (P<.05). T-SM participants reported significantly higher treatment satisfaction and therapeutic alliance and greater improvements in activation, positive affect, and social roles. Improvements were generally maintained at 6 and 12 months. CONCLUSIONS: Both interventions resulted in short- and long-term, clinically meaningful benefits. The study demonstrated that the telephone is an effective method for engaging participants in care and extending the reach of rehabilitation for individuals with MS.

Eye Adult Changes in Thought (Eye ACT) Study: Design and Report on the Inaugural Cohort.

Background: Conflicting research on retinal biomarkers of Alzheimer's disease and related dementias (AD/ADRD) is likely related to limited sample sizes, study design, and protocol differences. Objective: The prospective Eye Adult Changes in Thought (Eye ACT) seeks to address these gaps. Methods: Eye ACT participants are recruited from ACT, an ongoing cohort of dementia-free, older adults followed biennially until AD/ADRD, and undergo visual function and retinal imaging assessment either in clinic or at home. Results: 330 participants were recruited as of 03/2023. Compared to ACT participants not in Eye ACT (N = 1868), Eye ACT participants (N = 330) are younger (mean age: 70.3 versus 71.2, p = 0.014), newer to ACT (median ACT visits since baseline: 3 versus 4, p < 0.001), have more years of education (17.7 versus 16.2, p < 0.001) and had lower rates of visual impairment (12% versus 22%, p < 0.001). Compared to those seen in clinic (N = 300), Eye ACT participants seen at home (N = 30) are older (77.2 versus 74.9, p = 0.015), more frequently female (60% versus 49%, p = 0.026), and have significantly worse visual acuity (71.1 versus 78.9 Early Treatment Diabetic Retinopathy Study letters, p < 0.001) and contrast sensitivity (-1.9 versus -2.1 mean log units at 3 cycles per degree, p = 0.002). Cognitive scores and retinal imaging measurements are similar between the two groups. Conclusions: Participants assessed at home had significantly worse visual function than those seen in clinic. By including these participants, Eye ACT provides a unique longitudinal cohort for evaluating potential retinal biomarkers of dementia.