Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a ‘genome-wide association study (GWAS) by subtraction,’ subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal ‘cognitive’ and ‘non-cognitive’ factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear.

Using data from up to 5517 youth (ages 9–11) of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and cognition, risk tolerance, decision-making & personality, substance initiation, psychopathology, and brain structure (e.g. volume, fractional anisotropy [FA]). Within-sibling analyses estimated whether observed genetic associations may be consistent with direct genetic effects.

Both PGSs were associated with greater cognition and lower impulsivity, drive, and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk tolerance, increased odds of choosing delayed reward, and decreased likelihood of ADHD and bipolar disorder; the non-cognitive PGS was associated with lack of perseverance and reward responsiveness. Cognitive PGS were more strongly associated with larger regional cortical volumes; non-cognitive PGS were more strongly associated with higher FA. All associations were characterized by small effects.

While the small sizes of these associations suggest that they are not effective for prediction within individuals, cognitive and non-cognitive PGS show unique associations with phenotypes in childhood at the population level.

Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.

Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange.

The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39).

Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed.

ClinicalTrials.gov Identifier: NCT02458690

INDUCT (Interdisciplinary Network for Dementia Using Current Technology), and DISTINCT (Dementia Inter-sectorial strategy for training and innovation network for current technology) are two Marie Sklodowska-Curie funded International Training Networks that aimed to develop a multi-disciplinary, inter-sectorial educational research framework for Europe to improve technology and care for people with dementia, and to provide the evidence to show how technology can improve the lives of people with dementia.

In INDUCT (2016-2020) 15 Early Stage Researchers worked on projects in the areas of Technology to support everyday life; technology to promote meaningful activities; and healthcare technology. In DISTINCT (2019-2023) 15 Early Stage Researchers worked on technology to promote Social health in three domains: fulfilling ones potential and obligations in society, managing one’s own life, and participation in social and other meaningful activities.

Both networks adopted three transversal objectives: 1) To determine practical, cognitive and social factors needed to make technology more useable for people with dementia; 2) To evaluate the effectiveness of specific contemporary technology; 3) To trace facilitators and barriers for implementation of technology in dementia care.

The main recommendations resulting from all research projects are integrated in a web-based digital Best Practice Guidance on Human Interaction with Technology in Dementia which was recently updated (Dec 2022 and June 2023) and will be presented at the congress. The recommendations are meant for different target groups, i.e. people in different stages of dementia, their (in)formal carers, policy makers, designers and researchers, who can easily find the recommendations relevant to them in the Best Practice Guidance by means of a digital selection tool.

The INDUCT/DISTINCT Best Practice Guidance informs on how to improve the development, usage, impact and implementation of technology for people with dementia in various technology areas. This Best Practice Guidance is the result of intensive collaborative partnership of INDUCT and DISTINCT with academic and non-academic partners as well as the involvement of representatives of the different target groups throughout the projects.

Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.

This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.

The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).

Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.

In recent years, rates of alcohol consumption and alcohol use disorder have steadily increased among adults age 60 and older. Large studies have demonstrated that moderate-to-heavy alcohol consumption (>7 drinks per week) is a risk factor for developing various types of dementias. The effects of alcohol-related problems on cognition are less clear, and are particularly understudied in older adults. Similarly, while there is an established link between worse cognition and financial exploitation vulnerability in older adults, no studies have examined relationships between alcohol-related problems and financial exploitation in this population. The current study therefore explores whether alcohol-related problems are associated with neuropsychological performance and financial exploitation vulnerability in a sample of older adults.

Participants were a community sample of cognitively unimpaired adults over the age of 50 (N = 55, Age M(SD) = 69.1(6.2), 74.5% female, Years of education M(SD) = 16.8(2.3)). Interested individuals were excluded if they reported current or past substance use disorders. Participants completed a laboratory visit that included a neuropsychological assessment. Measures included the NIH Cognition toolbox, CVLT-II, Digit Span, Trails A/B, Benson Complex Figure Recall, and Verbal Fluency: Phonemic and Semantic, from the Alzheimer’s Disease Centers’ Uniform Data Set (UDS) version 3. Participants completed the CAGE Alcohol Abuse Screening Tool and the Short Michigan Alcohol Screener Test - Geriatric Version (SMAST) to assess alcohol-related problems. Both measures are used as clinical screening tools to measure likelihood of a substance use disorder and produce a summary score (0-4 for CAGE, 010 for SMAST) tabulating symptoms of alcohol-related problems. Participants also completed the Perceived Financial Vulnerability Scale (PFVS) to assess financial exploitation vulnerability. As a significant number of participants reported no drinking and therefore no alcohol-related problems, negative binomial regressions were used to test associations between neuropsychological measures, financial exploitation vulnerability, and alcohol-related problems.

After covarying for age and sex, SMAST was negatively associated with NIH toolbox total cognition (B(SE) = -.14(.07), p<.05) and marginally negatively associated with fluid cognition (B(SE) = -.07(.04), p=.06). Neither SMAST nor CAGE scores were significantly associated with performance on any other neuropsychological test (ps = .13-.99). SMAST was positively associated with financial exploitation vulnerability (B(SE) = .31(.16), p = .05); this effect remained significant after covarying for NIH total composite score in a secondary analysis.

In a community sample of cognitively unimpaired, low-drinking adults over the age of 50, more alcohol-related problems were associated with worse NIH toolbox cognition scores. Similarly, more alcohol-related problems were associated with greater financial exploitation vulnerability, and this relationship was not driven by worse cognition. These results suggest that even low amounts of drinking and alcohol-related problems may be associated with cognition and financial exploitation vulnerability in cognitively unimpaired older adults. This study also corroborates the use of the SMAST over the CAGE in older adult populations that may be more sensitive to cognitive changes.

Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).

This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.

Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.

The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.

Convergent evidence has suggested atypical relationships between brain structure and function in major psychiatric disorders, yet how the abnormal patterns coincide and/or differ across different disorders remains largely unknown. Here, we aim to investigate the common and/or unique dynamic structure–function coupling patterns across major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ).

We quantified the dynamic structure–function coupling in 452 patients with psychiatric disorders (MDD/BD/SZ = 166/168/118) and 205 unaffected controls at three distinct brain network levels, such as global, meso-, and local levels. We also correlated dynamic structure–function coupling with the topological features of functional networks to examine how the structure–function relationship facilitates brain information communication over time.

The dynamic structure–function coupling is preserved for the three disorders at the global network level. Similar abnormalities in the rich-club organization are found in two distinct functional configuration states at the meso-level and are associated with the disease severity of MDD, BD, and SZ. At the local level, shared and unique alterations are observed in the brain regions involving the visual, cognitive control, and default mode networks. In addition, the relationships between structure–function coupling and the topological features of functional networks are altered in a manner indicative of state specificity.

These findings suggest both transdiagnostic and illness-specific alterations in the dynamic structure–function relationship of large-scale brain networks across MDD, BD, and SZ, providing new insights and potential biomarkers into the neurodevelopmental basis underlying the behavioral and cognitive deficits observed in these disorders.

Emotional functioning is linked to HIV-associated neurocognitive impairment, yet research on this association among diverse people with HIV (PWH) is scant. We examined emotional health and its association with neurocognition in Hispanic and White PWH.

Participants included 107 Hispanic (41% primarily Spanish-speakers; 80% Mexican heritage/origin) and 216 White PWH (Overall age: M = 53.62, SD = 12.19; 86% male; 63% AIDS; 92% on antiretroviral therapy). Emotional health was assessed via the National Institute of Health Toolbox (NIHTB)-Emotion Battery, which yields T-scores for three factor-based summary scores (negative affect, social satisfaction, and psychological well-being) and 13 individual component scales. Neurocognition was measured via demographically adjusted fluid cognition T-scores from the NIHTB-cognition battery.

27%–39% of the sample had problematic socioemotional summary scores. Hispanic PWH showed less loneliness, better social satisfaction, higher meaning and purpose, and better psychological well-being than Whites (ps <.05). Within Hispanics, Spanish-speakers showed better meaning and purpose, higher psychological well-being summary score, less anger hostility, but greater fear affect than English speakers. Only in Whites, worse negative affect (fear affect, perceived stress, and sadness) was associated with worse neurocognition (p <.05); and in both groups, worse social satisfaction (emotional support, friendship, and perceived rejection) was linked with worse neurocognition (p <.05).

Adverse emotional health is common among PWH, with subgroups of Hispanics showing relative strengths in some domains. Aspects of emotional health differentially relate to neurocogntition among PWH and cross-culturally. Understanding these varying associations is an important step towards the development of culturally relevant interventions that promote neurocognitive health among Hispanic PWH.