Memory Composite Scores Research Articles

Personalised estimation of exposure to ambient air pollution and application in a longitudinal cohort analysis of cognitive function in London-dwelling older adults.

Accurate estimates of personal exposure to ambient air pollution are difficult to obtain and epidemiological studies generally rely on residence-based estimates, averaged spatially and temporally, derived from monitoring networks or models. Few epidemiological studies have compared the associated health effects of personal exposure and residence-based estimates. To evaluate the association between exposure to air pollution and cognitive function using exposure estimates taking mobility and location into account. Residence-based dispersion model estimates of ambient NO2, PM10 and PM2.5 were assigned to 768 London-dwelling participants of the English Longitudinal Study of Ageing. The London Hybrid Exposure Model was implemented to adjust estimates per pollutant to reflect the estimated time-activity patterns of each participant based on age and residential location. Single pollutant linear mixed-effects models were fit for both exposure assessment methods to investigate the associations between assigned pollutant concentrations and cognitive function over a follow-up period of up to 15 years. Increased long-term exposures to residence-based ambient NO2 (IQR: 11.10 µg/m3), PM10 (2.35 µg/m3), and PM2.5 (2.50 µg/m3) were associated with decreases of -0.10 [95% CI: -0.20, 0.00], -0.07 [-0.11, -0.02] and -0.14 [-0.21, -0.06], respectively, in composite memory score. Similar decreases were observed for executive function scores (-0.38 [-0.58, -0.18], -0.11 [-0.20, -0.02] and -0.14 [-0.29, 0.01], respectively). When applying personalised exposure estimates, which were substantially lower, similar decreases were observed for composite memory score per IQR, but a consistent pattern of slightly more adverse effects with executive function score was evident. The present study constructed a framework through which time-activity information derived from a representative sample could be applied to estimates of ambient air pollution concentrations assigned to individuals in epidemiological cohort studies, with the intention of adjusting commonly used residence-based estimates to reflect population mobility and time spent in various microenvironments. Estimates of exposure were markedly lower when incorporating time-activity, likely because people in European populations spend a large proportion of their time indoors, where their exposure to ambient air pollution may be reduced through infiltration, which is not taken into account in residence-based ambient estimates. Further work into such methods could provide insights into the efficacy of personalising exposure estimates.

The Influence of Race on Time to Symptom Resolution Following Sport Concussion in Collegiate Athletes.

Race has been shown to influence computerized neurocognitive test scores, motor function test scores, and reported symptomology following sport-related concussion (SRC). However, the effect race may have on recovery time following SRC remains unknown. The objective of this study was to determine the influence of race on days until symptom free from SRC in NCAA Division 1 collegiate athletes. Prospective cohort study. Participants were Black (n = 53 [28% female]) and White (n = 150 [43.3% female]) who were on average 19.0 (1.21) and 20.2 (1.3)years of age, respectively. Data were collected from the 2015-2016 to 2020-2021 collegiate sport seasons. Participants were evaluated before and after an SRC at empirically derived time points. The primary outcome measure was time until symptom free (days). Additional outcomes included baseline and postinjury Immediate Postconcussion Assessment and Cognitive Test and Sensory Organization Test (SOT) scores. A Mann-Whitney U test compared days to symptom free between groups. Immediate Postconcussion Assessment and Cognitive Test and SOT outcome scores were analyzed using a 2 (group) × 2 (time) analysis of variance. White participants had a longer median recovery time (9d) to symptom free compared with Black participants (6d [P = .04]). Statistically significant differences were observed between Black 87.3 (9.84) and White 90.4 (8.30) groups for Immediate Postconcussion Assessment and Cognitive Test's verbal memory composite score (P = .03). Postinjury, White participants scored significantly higher 44.5 (5.63) on visual motor speed compared with Black participants (42.4 (5.90) [P = .02]). Within-group SOT differences between baseline and postinjury testing were observed in both groups (all P < .001). Black collegiate athletes achieved symptom resolution sooner than White athletes. We did not explore underlying sociocultural factors such as socioeconomic status or previous concussion education, which may have influenced our results. Future studies should explore factors that may contextualize these findings.

A - 70 Contextualizing Racial/Ethnic Differences in Baseline Assessment among Collegiate Athletes

Abstract Objective Compared to other factors that influence neuropsychological test performance, few studies have examined the relationship between racial/ethnic identity and baseline assessment performance in collegiate athletes, and even fewer have contextualized results using structural factors linked to test performance (e.g., premorbid cognitive ability). This study examined racial/ethnic differences in baseline assessment performance before and after controlling for premorbid functioning. We hypothesized that there would be racial/ethnic differences in performance but that controlling for premorbid functioning would reduce these differences. Method Participants included 875 collegiate athletes who were grouped based on racial/ethnic identity (White = 661, Black = 165, Another Race = 49) and underwent a comprehensive neuropsychological battery. Cognitive composite scores and intraindividual variability (IIV) were calculated for two neurocognitive domains: attention/processing speed and memory. Premorbid functioning was assessed with the Wechsler Test of Adult Reading (WTAR). ANCOVAs were used to examine racial/ethnic differences in these four cognitive domains before and after controlling for WTAR scores. Results Before controlling for WTAR scores, there were significant racial/ethnic differences in the attention/processing speed and memory composite scores and in attention/processing speed IIV, p’s &amp;lt; 0.001, ηp2 = 0.02–0.03. However, there were no significant racial/ethnic differences in memory IIV, p = 0.97. After controlling for WTAR scores, there were no significant racial/ethnic differences in the attention/processing (p = 0.530, ηp2 = 0.001) or memory (p = 0.183, ηp2 = 0.004) composite scores, and the relationship between racial/ethnic identity and attention/processing speed IIV became less significant (p = 0.014, ηp2 = 0.01). Conclusions Results suggest that racial/ethnic differences at baseline assessment can be largely accounted for by premorbid functioning, which underscores the importance of considering sociocultural context when assessing racially/ethnically diverse athletes.

A - 3 The Relationship between Memory and Depression In an Elderly Chinese Cohort: a Baseline Analysis

Abstract Objective Explore the relationship between depression and memory aged 60 years and older while controlling for age, gender, and education. Method This study utilized data from the Characterization of Dementia in Asian-Pacific Islanders study by Bruce Miller, M.D., and Howie Rosen, M.D., at the Memory and Aging Center at UCSF. Inclusion criteria included participants age 60+ who completed the Benson Figure Test, GDS-30, and the Chinese Version Verbal Learning Test (CVVLT) in English, Cantonese, or Mandarin. Exclusion criteria included participants under age 60 and or experience history of neurological strokes or injuries, and disabilities related to memory. The final sample yielded 136 participants, including 41 (30.1%) males, 95 (69.9%) females, 120 (88.2%) right-handed, 3 (2.2%) left-handed, and 7 (5.1%) ambidextrous. Average age of participants was 71.46 (SD = 7.26). A memory composite score was computed based on average of performances on the Benson Figure Task delay and the CVVLT 10-minute delay. Raw GDS-30 scores represented depression. Results There was a weak positive correlation between memory composite scores, gender, and education, and a weak negative correlation between memory composite scores, age, and GDS-30 scores. Conclusions Findings indicate some evidence for a relationship between depression and memory in elderly Chinese populations. However, the sample was skewed, and consisted of less depressed and higher memory functioning participants. Despite these limitations, it is pertinent to explore how healthcare providers may outreach to this population to monitor risk factors, improve timeliness of dementia diagnosis, and maximize treatment of reversible causes, adherence to treatment plans, and help families care plan.

Beat-to-beat blood pressure variability, hippocampal atrophy, and memory impairment in older adults.

Visit-to-visit blood pressure variability (BPV) predicts age-related hippocampal atrophy, neurodegeneration, and memory decline in older adults. Beat-to-beat BPV may represent a more reliable and efficient tool for prospective risk assessment, but it is unknown whether beat-to-beat BPV is similarly associated with hippocampal neurodegeneration, or with plasma markers of neuroaxonal/neuroglial injury. Independently living older adults without a history of dementia, stroke, or other major neurological disorders were recruited from the community (N = 104; age = 69.5 ± 6.7 (range 55-89); 63% female). Participants underwent continuous blood pressure monitoring, brain MRI, venipuncture, and cognitive testing over two visits. Hippocampal volumes, plasma neurofilament light, and glial fibrillary acidic protein levels were assessed. Beat-to-beat BPV was quantified as systolic blood pressure average real variability during 7-min of supine continuous blood pressure monitoring. The cross-sectional relationship between beat-to-beat BPV and hippocampal volumes, cognitive domain measures, and plasma biomarkers was assessed using multiple linear regression with adjustment for demographic covariates, vascular risk factors, and average systolic blood pressure. Elevated beat-to-beat BPV was associated with decreased left hippocampal volume (P = .008), increased plasma concentration of glial fibrillary acidic protein (P = .006), and decreased memory composite score (P = .02), independent of age, sex, average systolic blood pressure, total intracranial volume, and vascular risk factor burden. In summary,beat-to-beat BPV is independently associated with decreased left hippocampal volume, increased neuroglial injury, and worse memory ability. Findings are consistent with prior studies examining visit-to-visit BPV and suggest beat-to-beat BPV may be a useful marker of hemodynamic brain injury in older adults.

Association of Basal Forebrain Atrophy With Cognitive Decline in Early Alzheimer Disease.

In early Alzheimer disease (AD), β-amyloid (Aβ) deposition is associated with volume loss in the basal forebrain (BF) and cognitive decline. However, the extent to which Aβ-related BF atrophy manifests as cognitive decline is not understood. This study sought to characterize the relationship between BF atrophy and the decline in memory and attention in patients with early AD. Participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who completed Aβ-PET imaging and repeated MRI and cognitive assessments were included. At baseline, participants were classified based on their clinical dementia stage and Aβ status, yielding groups that were cognitively unimpaired (CU) Aβ-, CU Aβ+, and mild cognitive impairment (MCI) Aβ+. Linear mixed-effects models were used to assess changes in volumetric measures of BF subregions and the hippocampus and changes in AIBL memory and attention composite scores for each group compared with CU Aβ- participants. Associations between Aβ burden, brain atrophy, and cognitive decline were evaluated and explored further using mediation analyses. The cohort included 476 participants (72.6 ± 5.9 years, 55.0% female) with longitudinal data from a median follow-up period of 6.1 years. Compared with the CU Aβ- group (n = 308), both CU Aβ+ (n = 107) and MCI Aβ+ (n = 61) adults showed faster decline in BF and hippocampal volumes and in memory and attention (Cohen d = 0.73-1.74). Rates of atrophy in BF subregions and the hippocampus correlated with cognitive decline, and each individually mediated the impact of Aβ burden on memory and attention decline. When all mediators were considered simultaneously, hippocampal atrophy primarily influenced the effect of Aβ burden on memory decline (β [SE] = -0.139 [0.032], proportion mediated [PM] = 28.0%) while the atrophy of the posterior nucleus basalis of Meynert in the BF (β [SE] = -0.068 [0.029], PM = 13.1%) and hippocampus (β [SE] = -0.121 [0.033], PM = 23.4%) distinctively influenced Aβ-related attention decline. These findings highlight the significant role of BF atrophy in the complex pathway linking Aβ to cognitive impairment in early stages of AD. Volumetric assessment of BF subregions could be essential in elucidating the relationships between the brain structure and behavior in AD.

18F-Flortaucipir (AV1451) imaging identifies grey matter atrophy in retired athletes

BackgroundThe long-term consequences of concussions may include pathological neurodegeneration as seen in Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). Tau-PET showed promise as a method to detect tau pathology of CTE, but more studies are neededObjectiveThis study aimed (1) to assess the association of imaging evidence of tau pathology with brain volumes in retired athletes and (2) to examine the relationship between tau-PET and neuropsychological functioning.MethodsFormer contact sport athletes were recruited through the Canadian Football League Alumni Association or the Canadian Concussion Centre clinic. Athletes completed MRI, [18F]flortaucipir tau-PET, and a neuropsychological battery. Memory composite was created by averaging the Rey Auditory Verbal Learning Test and Rey Visual Design Learning Test z-scores. Grey matter (GM) volumes were age/intracranial volume corrected using normal control MRIs. Tau-PET % positivity in GM was calculated as the number of positive voxels (≥ 1.3 standardized uptake value ratio (SUVR)/total voxels).Results47 retired contact sport athletes negative for AD (age:51 ± 14; concussions/athlete:15 ± 2) and 54 normal controls (age:50 ± 13) were included. Tau-PET positive voxels had significantly lower GM volumes, compared to tau-PET negative voxels (− 0.37 ± 0.41 vs. − 0.31 ± 0.37, paired p = .006). There was a significant relationship between GM tau-PET % positivity and memory composite score (r = − .366, p = .02), controlled for age, PET scanner, and PET scan duration. There was no relationship between tau-PET measures and concussion number, or years of sport played.ConclusionA higher tau-PET signal was associated with reduced GM volumes and lower memory scores. Tau-PET may be useful for identifying those at risk for neurodegeneration.

Association of modified dementia risk score with cerebrospinal fluid biomarkers and cognition in adults without dementia.

This study aimed to investigate the cognitive profile and prospective cognitive changes in non-demented adults with elevated Modified Dementia Risk Scores (MDRS), while also exploring the potential relationship between these associations and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology and neuroinflammation. Within the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database, 994 participants without dementia were assessed on MDRS, CSF biomarkers and cognition. We examined the associations of the MDRS with CSF biomarkers and cognitive scores using linear regressions. Causal mediation analyses were conducted to analyze the associations among MDRS, brain pathologies, and cognition. The Alzheimer's Disease Neuroimaging Initiative (ADNI) study was used to validate the mediation effects and to investigate the longitudinal association between MDRS and cognitive decline. The results revealed that higher MDRS were linked to poorer cognitive performance (Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) and increases in CSF levels of phosphorylated tau (P-tau, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001), total tau (T-tau, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001), P-tau/Aβ42 ratio (Model 1: PFDR = 0.023; Model 2: PFDR = 0.028), T-tau/Aβ42 ratio (Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) and soluble triggering receptor expressed on myeloid cells 2 (sTrem2, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) in the CABLE study. The impact of MDRS on cognition was partially mediated by neuroinflammation and tau pathology. These mediation effects were replicated in the ADNI study. Baseline MDRS were significantly associated with future cognitive decline, as indicated by lower scores on the Mini-Mental State Examination (MMSE, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001), ADNI composite memory score (ADNI-MEM, Model 1: PFDR = 0.005; Model 2: PFDR < 0.001), ADNI composite executive function score (ADNI-EF, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001), and higher score on the Alzheimer's Disease Assessment Scale (ADAS13, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001). The findings of this study revealed significant associations between MDRS and cognitive decline, suggesting a potential role of tau pathology and neuroinflammation in the link between MDRS and poorer cognitive performance in individuals without dementia. Consequently, the MDRS holds promise as a tool for targeted preventive interventions in individuals at high risk of cognitive impairment.

Relationship of cognitive measures to mRNA levels in lymphocytes from patients with schizophrenia and controls

Patients with schizophrenia show substantial cognitive deficits and abnormalities in neurotransmitter-related levels of mRNA in brain or peripheral blood lymphocytes. However, the relationship of cognitive deficits as measured by the MATRICS battery and mRNA levels in brain or lymphocytes has not been sufficiently explored. We measured levels of methylation or neurotransmitter-related mRNAs in lymphocytes of 38 patients with chronic schizophrenia (CSZ) and 33 non-psychotic controls (controls) by qPCR using TaqMan probes. We assessed cognitive function in these patients and controls with the MATRICS battery. We used correlation analysis and scatter plots to assess the relationship of lymphocyte mRNA levels to MATRICS domain and composite scores. CSZ subjects had a consistently negative correlation between mRNA levels in lymphocytes and MATRICS cognitive variables of speed of processing, attention-vigilance, working memory, visual learning, and overall composite score. It is uncertain whether these negative correlations represent a causative relation between specific mRNA levels and cognitive deficits. Controls had either positive correlations or non-significant correlations between mRNA and most of the MATRICS variables. There were statistically significant differences in the correlations between mRNA and MATRICS variables between CSZ vs controls for several mRNAs (DNMT1, DNMT3A, BDNF, NR3C1, FPRF3, CNTNAP2). Our data show a different relationship between mRNA levels in peripheral blood lymphocytes and MATRICS cognitive variables in CSZ vs controls. The substantive significance of these differences needs further investigation.

Associations of cerebrovascular disease and Alzheimer’s disease pathology with cognitive decline: Analysis of the National Alzheimer’s Coordinating Center Uniform Data Set

Cerebrovascular disease (CVD) and Alzheimer’s disease (AD) often co-occur and may impact specific cognitive domains. This study’s goal was to determine effects of CVD and AD burden on cross-sectional and longitudinal executive function (EF) and memory in older adults.Longitudinally followed participants from the National Alzheimer Coordinating Center database (n = 3342) were included. Cognitive outcomes were EF and memory composite scores. Baseline CVD presence was defined by moderate-to-severe white matter hyperintensities or lacunar infarct on MRI. Baseline AD pathology was defined by amyloid positivity via PET or CSF. Linear mixed models examined effects of CVD, AD, and time on cognitive outcomes, controlling for sex, education, baseline age, MoCA score, and total number of study visits.At baseline, CVD associated with lower EF (p < 0.001), while AD associated with lower EF and memory (ps < 0.001). Longitudinally only AD associated with faster declines in memory and EF (ps < 0.001).These results extend our understanding of CVD and AD pathology, highlighting that CVD does not necessarily indicate accelerated decline.

Serum albumin and white matter hyperintensities

People living with HIV and those diagnosed with alcohol use disorders (AUD) relative to healthy individuals commonly have low levels of serum albumin, substantiated as an independent predictor of cardiovascular events. White matter hyperintensities (WMH)—a neuroimaging feature of cerebral small vessel disease—are also related to cardiovascular disease. Despite consensus regarding associations between high levels of urine albumin and WMH prevalence, and low serum albumin levels and impaired cognitive functioning, relations between serum albumin and WMH burdens have rarely been evaluated. Here, a sample including 160 individuals with AUD, 142 living with HIV, and 102 healthy controls was used to test the hypothesis that serum albumin would be inversely related to WMH volumes and directly related to cognitive performance in the two diagnostic groups. Although serum albumin and periventricular WMH volumes showed an inverse relationship in both AUD and HIV groups, this relationship persisted only in the HIV group after consideration of traditional cardiovascular (i.e., age, sex, body mass index (BMI), nicotine use, hypertension, diabetes), study-relevant (i.e., race, socioeconomic status, hepatitis C virus status), and disease-specific (i.e., CD4 nadir, HIV viral load, HIV duration) factors. Further, serum albumin contributed more significantly than periventricular WMH volume to variance in performance on a verbal learning and memory composite score in the HIV group only. Relations in both HIV and AUD groups between albumin and hematological red blood cell markers (e.g., hemoglobin, hematocrit) suggest that in this sample, serum albumin reflects hematological abnormalities. Albumin, a simple serum biomarker available in most clinical settings, may therefore help identify periventricular WMH burden and performance levels in specific cognitive domains in people living with HIV. Whether serum albumin contributes mechanistically to periventricular WMH in HIV will require additional investigation.

Examining the role of depression on the relationship between performance-based and self-reported cognitive functioning after sport-related concussion.

Little is known about the relationship between neuropsychological test performance, cognitive symptom reporting, and depressive symptoms after sport-related concussion. Accordingly, this cross-sectional study examined these relationships in collegiate athletes. It was hypothesized that depressive symptoms would moderate and mediate the relationship between performance-based and self-reported cognitive functioning after concussion. After sustaining a sport-related concussion, 110 collegiate athletes completed a neuropsychological battery, the Post-Concussion Symptoms Scale, and the Beck Depression Inventory-Fast Screen. Neuropsychological test performance, depressive symptoms, and their interactions were entered into distinct hierarchical linear regression analyses with self-reported cognition as the dependent variable to assess moderation. Mediation was analyzed using the PROCESS macro with 5000 bootstrap samples and a 95% confidence interval. There was a significant interaction between the mean memory composite and depressive symptoms when predicting cognitive symptom reporting, p = 0.047. Simple effects tests revealed that for athletes who had a lower memory composite score, an increase in depressive symptoms led to an increase in self-reported cognitive dysfunction, p < 0.001, ηp2 = 0.11. Depressive symptoms partially mediated the relationship between the memory composite and cognitive symptom reporting, indirect effect = -0.26, 95%CI[-0.58,0.001], but this relationship was not found for any other neurocognitive domain. For tests of memory, depressive symptoms moderated and partially mediated the relationship between performance-based and self-reported cognitive functioning after sport-related concussion. Athletes reporting high depressive symptoms and cognitive dysfunction may need more comprehensive evaluations to inform return-to-play decisions, and depression could be a treatment target for athletes who report high levels of cognitive dysfunction after concussion.

Temporal tau asymmetry spectrum influences divergent behavior and language patterns in Alzheimer‘s disease

Understanding the psychiatric symptoms of Alzheimer s disease (AD) is crucial for advancing precision medicine and therapeutic strategies. The relationship between AD behavioral symptoms and asymmetry in spatial tau PET patterns is not well-known. Braak tau progression implicates the temporal lobes early. However, the clinical and pathological implications of temporal tau laterality remain unexplored.This cross-sectional study investigated the correlation between temporal tau PET asymmetry and behavior assessed using the neuropsychiatric inventory and composite scores for memory, executive function, and language, using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. In the entire cohort, continuous right and left temporal tau contributions to behavior and cognition were evaluated, controlling for age, sex, education, and tau burden on the contralateral side. Additionally, a temporal tau laterality index was calculated to define “asymmetry-extreme” groups (individuals with laterality indices greater than two standard deviations from the mean).695 individuals (age = 73.9 ± 7.6 years, 372 (53.5 %) females) were included, comprising 281 (40%) cognitively unimpaired (CU) amyloid negative, 185 (27%) CU amyloid positive, and 229 (33%) impaired (CI) amyloid positive participants. In the full cohort analysis, right temporal tau was associated with worse behavior (B = 8.14, p-value = 0.007), and left temporal tau was associated with worse language (B = 1.4, p-value < 0.001). Categorization into asymmetry-extreme groups revealed 20 right- and 27 left-asymmetric participants. Within these extreme groups, there was additional heterogeneity along the anterior-posterior dimension.Asymmetrical tau burden is associated with distinct behavioral and cognitive profiles. Wide multi-cultural implementation of social cognition measures is needed to understand right-sided asymmetry in AD.

Impact of APOE-ε alleles on brain structure and cognitive function in healthy older adults: A VBM and DTI replication study.

The Apolipoprotein E (APOE) gene has been established in the Alzheimer's disease (AD) literature to impact brain structure and function and may also show congruent effects in healthy older adults, although findings in this population are much less consistent. The current study aimed to replicate and expand the multimodal approach employed by Honea et al. Structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and neuropsychological measures were used to investigate the impact of APOE-ε status on grey matter structure, white matter integrity, and cognitive functioning. Data were obtained from the Alzheimer's Disease Initiative Phase 3 (ADNI3) database. Baseline MRI, DTI and cognitive composite scores for memory (ADNI-Mem) and executive function (ADNI-EF) were acquired from 116 healthy controls. Participants were grouped according to APOE allele presence (APOE-ε2+ N = 17, APOE-ε3ε3 N = 64, APOE-ε4+ N = 35). Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to compare grey matter volume (GMV) and white matter integrity, respectively, between APOE-ε2+ and APOE-ε3ε3 controls, and again between APOE-ε4+ and APOE-ε3ε3 controls. Multivariate analysis of covariance (MANCOVA) was used to examine the effects of APOE polymorphism on memory and EF across all APOE groups with age, sex and education as regressors of no interest. Cognitive scores were correlated (Pearson r) with imaging metrics within groups. No significant differences were seen across groups, within groups in MRI metrics, or cognitive performance (p>0.05, corrected for multiple comparisons). The current study partially replicated and extended previous findings from an earlier multimodal study (Honea 2009). Future studies should clarify APOE mechanisms in healthy ageing by adding other imaging, cognitive, and lifestyle metrics and longitudinal design in larger sample sizes.

Large Neutral Amino Acids Moderate the Effects of Metabolic Syndrome on Cognitive Performance in Middle-Aged Adults

Introduction: Two large neutral amino acids (LNAA), tryptophan and tyrosine, are precursors to cerebral neurotransmitters and are involved in cognitive function. Higher levels of LNAA in young adults are associated with improved cognition, although these associations appear to reverse over time. Given that exposure to metabolic syndrome (MetS) may induce premature cognitive aging, the current project aims to fill the gap in the literature by examining the effect of LNAA on cognitive performance in midlife adults with metabolic risks. Methods: Eighty-eight adults, ages 40–61 years, participated in this cross-sectional study. LNAA metabolites were quantified, MetS components were measured using high-performance liquid chromatography, and MetS components were assessed in the laboratory. Composite verbal memory and executive functioning scores were computed using principal component analysis. We used linear regression models to test the interaction between LNAA and MetS while covarying for sex, age, and education. Results: The kynurenine/tryptophan ratio moderated the relation between MetS and verbal memory, even after adjusting for relevant covariates. Tyrosine metabolites were not significant moderators of the association between MetS and executive functioning. Conclusion: Our findings suggest that the detected weaker memory performance in adults with a high number of MetS components may be related to relative tryptophan depletion and possible decreases in serotonin production. Further investigation is warranted to examine the potential role of LNAA in associations between cognitive performance and metabolic risks over time.

A remote digital memory composite to detect cognitive impairment in memory clinic samples in unsupervised settings using mobile devices

Remote monitoring of cognition holds the promise to facilitate case-finding in clinical care and the individual detection of cognitive impairment in clinical and research settings. In the context of Alzheimer’s disease, this is particularly relevant for patients who seek medical advice due to memory problems. Here, we develop a remote digital memory composite (RDMC) score from an unsupervised remote cognitive assessment battery focused on episodic memory and long-term recall and assess its construct validity, retest reliability, and diagnostic accuracy when predicting MCI-grade impairment in a memory clinic sample and healthy controls. A total of 199 participants were recruited from three cohorts and included as healthy controls (n = 97), individuals with subjective cognitive decline (n = 59), or patients with mild cognitive impairment (n = 43). Participants performed cognitive assessments in a fully remote and unsupervised setting via a smartphone app. The derived RDMC score is significantly correlated with the PACC5 score across participants and demonstrates good retest reliability. Diagnostic accuracy for discriminating memory impairment from no impairment is high (cross-validated AUC = 0.83, 95% CI [0.66, 0.99]) with a sensitivity of 0.82 and a specificity of 0.72. Thus, unsupervised remote cognitive assessments implemented in the neotiv digital platform show good discrimination between cognitively impaired and unimpaired individuals, further demonstrating that it is feasible to complement the neuropsychological assessment of episodic memory with unsupervised and remote assessments on mobile devices. This contributes to recent efforts to implement remote assessment of episodic memory for case-finding and monitoring in large research studies and clinical care.

Abstract P250: Vascular Contributions to Alzheimer's Disease

Introduction: Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder that affects over 50 million people worldwide. The role of vascular risk factors have been described as a contributor to and a major comorbidity of AD pathogenesis; yet there is discordant evidence of this complex relationship between cardiovascular diseases (CVD) and its risk factors (like hypertension, hyperlipidemia, obesity, etc.) with AD pathophysiology and cognitive decline. AD associated Genome-wide association studies (GWAS) and derived polygenic risk scores (AD PRS) have uncovered some significant common genetic variants relating to CVD risk factors; however, we are still yet to unravel the comprehensive impact of these vascular genetic contributions to AD pathogenesis and cognitive decline. Method: In this study, we used 1800 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort spanning the full spectrum of clinical and pathological diagnoses of the AD spectrum, as our target dataset used for polygenic risk score calculation. Thereafter, we obtained GWAS summary statistics for cumulative cardiovascular risk by searching the Polygenic Score (PGS) GWAS Catalog using CVD as the ‘mapped trait” and then calculated cardiovascular-based PRS using HRS-based imputed GWAS data of the ADNI cohort. We conducted association analysis using a multivariate linear regression model with appropriate covariates (age, sex, APOE, education, etc.) between CVD-related polygenic risk score (CVD-PRS) with the different clinical AD diagnoses groups (Cognitively Normal/CN, Significant Memory Concerns/SMC, Mild Cognitive Impairment/MCI, Alzheimer's Disease/AD). We also performed association analysis of this CVD-PRS with white matter hyperintensity (WMHI) values, a vascular biomarker, at baseline using a linear regression model. Furthermore, we extended our analyses of CVD-related PRS with cognitive performance at baseline using composite scores for memory (MEM) and executive functioning (EF). Results and Conclusion: We found significantly strong correlation of CVD-related PRS with only certain AD Diagnoses groups (Significant Memory Concerns: SMC and Alzheimer's: AD) in the AD continuum. Additionally, we found strong associations (p &lt; 0.05) of this cardiovascular based- polygenic risk score with baseline memory as well as White Matter Hyperintensity (WMH) in our sample, specifically the group with a clinical diagnosis of AD. Furthermore, we are performing longitudinal association analysis of CVD-related PRS with longitudinal cognitive decline using a linear mixed effects model. Our findings will help us understand 1) how a cumulative CVD-related PRS associates with different AD diagnoses subgroups as well as vascular biomarkers for AD and 2) how CVD-related PRS associates with cognitive performance and longitudinal cognitive decline.

Cross-sectional associations between neighborhood characteristics, cognition and dementia risk factor burden in middle-aged and older Australians

Dementia disproportionately affects individuals from disadvantaged backgrounds, including those living in areas of lower neighborhood-level socioeconomic status. It is important to understand whether there are specific neighborhood characteristics associated with dementia risk factors and cognition which may inform dementia risk reduction interventions. We sought to examine whether greenspace, walkability, and crime associated with the cumulative burden of modifiable dementia risk factors and cognition. This was a cross-sectional analysis of 2016–2020 data from the Healthy Brain Project, a population-based cohort of community-dwelling individuals across Australia. Participants were aged 40–70 and free of dementia. Measures included greenspace (greenspace % in the local area, and distance to greenspace, n = 2,181); and intersection density (n = 1,159), and crime (rate of recorded offences; n = 1,159). Outcomes included a modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score to index the burden of modifiable vascular dementia risk factors; and composite scores of both memory and attention, derived from the Cogstate Brief Battery. Linear regressions adjusted for age, sex, education, and personal socio-economic status, demonstrated distance to greenspace (b ± SE per 2-fold increase = 0.09 ± 0.03, p =.005) and crime rate (b ± SE per 2-fold increase = 0.07 ± 0.03, p =.018) were associated with higher modified CAIDE. Higher crime was associated with lower memory performance (b ± SE = -0.03 ± 0.01, p =.018). The association between distance to greenspace and modified CAIDE was only present in low-moderate socioeconomic status neighborhoods (p interaction = 0.004). Dementia prevention programs that address modifiable risk factors in midlife should consider the possible role of neighborhood characteristics.

A randomized feasibility trial of the modified Atkins diet in older adults with mild cognitive impairment due to Alzheimer's disease.

Alzheimer's disease (AD) is increasing in prevalence, but effective treatments for its cognitive impairment remain severely limited. This study investigates the impact of ketone body production through dietary manipulation on memory in persons with mild cognitive impairment due to early AD and explores potential mechanisms of action. We conducted a 12-week, parallel-group, controlled feasibility trial of a ketogenic diet, the modified Atkins diet (MAD), compared to a control diet in patients with cognitive impairments attributed to AD. We administered neuropsychological assessments, including memory tests, and collected blood samples at baseline and after 12 weeks of intervention. We performed untargeted lipidomic and targeted metabolomic analyses on plasma samples to detect changes over time. A total of 839 individuals were screened to yield 38 randomized participants, with 20 assigned to receive MAD and 18 assigned to receive a control diet. Due to attrition, only 13 in the MAD arm and nine in the control arm were assessed for the primary endpoint, with two participants meeting ketosis levels used to define MAD adherence criteria. The average change from baseline in the Memory Composite Score was 1.37 (95% CI: -0.87, 4.90) points higher in the MAD group compared to the control group. The effect size of the intervention on baseline MAD change was moderate (Cohen's D = 0.57, 95% CI: -0.67, 1.33). In the 15 participants (nine MAD, six control) assessed for lipidomic and metabolomic-lipidomics and metabolomics, 13 metabolites and 10 lipids showed significant changes from baseline to 12 weeks, including triacylglycerols (TAGs, 50:5, 52:5, and 52:6), sphingomyelins (SM, 44:3, 46:0, 46:3, and 48:1), acetoacetate, fatty acylcarnitines, glycerol-3-phosphate, and hydroxy fatty acids. Attrition was greatest between baseline and week 6. All participants retained at week 6 completed the study. Despite low rates of adherence by criteria defined a priori, lipidomic and metabolomic analyses indicate significant changes from baseline in circulating lipids and metabolites between MAD and control participants at 12-week postrandomization, and MAD participants showed greater, albeit nonsignificant, improvement in memory.

The Association of Body Mass Index with Cognition and Alzheimer's Disease Biomarkers in the Elderly with Different Cognitive Status: A Study from the Alzheimer's Disease Neuroimaging Initiative Database.

The association of body mass index (BMI) with cognition and Alzheimer's disease (AD) biomarkers of the elderly remains inconclusive. To investigate the relationship between BMI and cognition as well as AD biomarkers in the elderly with different cognitive status. Participants with cognitively normal (CN) were included as the CN group. Participants with mild cognitive impairment and mild dementia were included as the cognitive impairment (CI) group. The relationship between BMI and AD biomarkers (cerebrospinal fluid Aβ42 and p-tau181, hippocampal volume [HV]), global cognition (Mini-Mental State Examination [MMSE]), memory, and executive function were explored. In the CI group, BMI was associated with MMSE (β= 0.03, p = 0.009), Aβ42 (β= 0.006, p = 0.029), p-tau181/Aβ42 ratio (β= -0.001, p = 0.011), and HV (β= 0.05, p < 0.001). However in the CN group, BMI exhibited associations with p-tau181 (β= 0.012, p = 0.014) and memory composite score (β= -0.04, p = 0.038), but not with p-tau181/Aβ42 ratio and HV. Moreover, mediation analysis showed that in the CI group, the positive effect of BMI on HV and MMSE score was partially mediated by diastolic blood pressure. The association of BMI with cognition and AD biomarkers varies across different cognitive status. In particular, a lower BMI was associated with worse cognition, higher Aβ burden, and lower HV in individuals with CI. Clinical practice should strengthen the monitoring and management of BMI in patients with AD.