Biomarker profiling to determine clinical impact of microRNAs in cognitive disorders.

Alzheimer's disease (AD) and post-stroke cognitive impairment (PSCI) are the leading causes of progressive dementia related to neurodegenerative and cerebrovascular injuries in elderly populations. Despite decades of research, patients with these conditions still lack minimally invasive, low-cost, and effective diagnostic and treatment methods. MicroRNAs (miRNAs) play a vital role in AD and PSCI pathology. As they are easily obtained from patients, miRNAs are promising candidates for the diagnosis and treatment of these two disorders. In this study, we performed complete sequencing analysis of miRNAs from 24 participants, split evenly into the PSCI, post-stroke non-cognitive impairment (PSNCI), AD, and normal control (NC) groups. To screen for differentially expressed miRNAs (DE-miRNAs) in patients, we predicted their target genes using bioinformatics analysis. Our analyses identified miRNAs that can distinguish between the investigated disorders; several of them were novel and never previously reported. Their target genes play key roles in multiple signaling pathways that have potential to be modified as a clinical treatment. In conclusion, our study demonstrates the potential of miRNAs and their key target genes in disease management. Further in-depth investigations with larger sample sizes will contribute to the development of precise treatments for AD and PSCI.

Comparison of cognitive performance measures in individuals with systemic lupus erythematosus.

OBJECTIVE: Cognitive impairment is a common complaint in SLE, but approaches to measuring cognitive performance objectively vary. Leveraging data collected in a population-based cohort of individuals with validated SLE, we compared performance and potential impairment across multiple measures of cognition. METHODS: During a single study visit (October 2019-May 2022), times to complete the Trail Making Test B (TMTB; N=423) were recorded; potential impairment was defined as an age-corrected and education-corrected T-score <35 (>1.5 SD longer than the normative time). A clock drawing assessment (CLOX; N=435) with two parts (free clock draw (CLOX1) and copy (CLOX2)) was also performed (score range: 0-15; higher scores=better performance); potential impairment was defined as CLOX1 <10 or CLOX2 <12. Fluid cognition (N=199; in-person visits only) was measured via the National Institutes of Health (NIH) Toolbox Fluid Cognition Battery and expressed as age-corrected standard scores; potential impairment was defined by a score <77.5 (>1.5 SD lower the normative score). RESULTS: Participants (mean age 46 years; 92% female; 82% black) had a median (IQR) TMTB time of 96 (76-130) s; median (IQR) CLOX1 and CLOX2 scores of 12 (10-13) and 14 (13-15); and a mean (SD) fluid cognition standard score of 87.2 (15.6). TMTB time and fluid cognition score (ρ=-0.53, p<0.001) were the most highly intercorrelated measures. Overall, 65%, 55% and 28% were potentially impaired by the TMTB test, CLOX task and NIH Toolbox Fluid Cognition Battery, respectively. While there was overlap in potential impairment between TMTB and CLOX, more than half (58%) had impairment by only one of these assessments. Few (2%) had impairment in fluid cognition only. CONCLUSION: The TMTB, CLOX and NIH Fluid Cognition Battery each provided unique and potentially important information about cognitive performance in our SLE cohort. Future studies are needed to validate these measures in SLE and explore interventions that maintain or improve cognitive performance in this population.

Cognitive Impairment following Mild Traumatic Brain Injury (mTBI): A Review.

Background: Mild Traumatic Brain Injury (mTBI) has been increasingly recognized as a public health concern due to its prevalence and potential to induce long-term cognitive impairment. We aimed to consolidate this observation by focusing on findings of neuropsychological assessments, neuroimaging, risk factors, and potential strategies for intervention to prevent and treat mTBI-associated cognitive impairments. Methods: A thorough search of PubMed, PsycINFO, and Embase databases was performed for studies published until 2024. Studies focusing on cognitive impairment after mTBI, with neurocognitive assessment as a primary outcome, were included. Results: We found consistent evidence of cognitive deficits, such as memory and attention impairments, and affected executive functions following mTBI. Neuroimaging studies corroborate these findings, highlighting structural and functional changes in the brain. Several risk factors for developing cognitive impairment post-mTBI were identified, including age, gender, genetics, and pre-existing mental health conditions. The efficacy of interventions, including cognitive rehabilitation and pharmaceutical treatment, varied across studies. Conclusions: Mild TBI can lead to significant long-term cognitive impairments, impacting an individual's quality of life. Further research is necessary to validate and standardize cognitive assessment tools post-mTBI, to elucidate the underlying neural mechanisms, and to optimize therapeutic interventions.

[Associations between components of metabolic syndrome and cognitive impairment in patients with schizophrenia]. / Svyazi mezhdu komponentami metabolicheskogo sindroma i kognitivnymi narusheniyami u bol'nykh shizofreniei.

OBJECTIVE: To study the relationship between the individual components of the metabolic syndrome and cognitive dysfunction in patients with schizophrenia. MATERIAL AND METHODS: A total of 133 patients with schizophrenia were examined. To assess cognitive functioning, the Brief Assessment of Cognition in Schizophrenia (BACS) was used. The components of the metabolic syndrome were determined in accordance with the criteria of the International Diabetes Federation. RESULTS: Hyperglycemia in patients with schizophrenia led to a decrease in cognitive functioning in two domains: verbal fluency (ß=-10.67; p=0.019) and attention stability (ß=-9.519; p=0.043). Abdominal obesity was associated with lower indicators of executive functions (ß=-8.856; p=0.026). CONCLUSION: It is assumed that drug treatment of some components of the metabolic syndrome may affect cognitive functions in patients with schizophrenia.

Structural brain networks correlating with poststroke cognition.

Cognitive deficits are a common and debilitating consequence of stroke, yet our understanding of the structural neurobiological biomarkers predicting recovery of cognition after stroke remains limited. In this longitudinal observational study, we set out to investigate the effect of both focal lesions and structural connectivity on poststroke cognition. Sixty-two patients with stroke underwent advanced brain imaging and cognitive assessment, utilizing the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE), at 3-month and 12-month poststroke. We first evaluated the relationship between lesions and cognition at 3 months using voxel-based lesion-symptom mapping. Next, a novel correlational tractography approach, using multi-shell diffusion-weighted magnetic resonance imaging (MRI) data collected at both time points, was used to evaluate the relationship between the white matter connectome and cognition cross-sectionally at 3 months, and longitudinally (12 minus 3 months). Lesion-symptom mapping did not yield significant findings. In turn, correlational tractography analyses revealed positive associations between both MoCA and MMSE scores and bilateral cingulum and the corpus callosum, both cross-sectionally at the 3-month stage, and longitudinally. These results demonstrate that rather than focal neural structures, a consistent structural connectome underpins the performance of two frequently used cognitive screening tools, the MoCA and the MMSE, in people after stroke. This finding should encourage clinicians and researchers to not only suspect cognitive decline when lesions affect these tracts, but also to refine their investigation of novel approaches to differentially diagnosing pathology associated with cognitive decline, regardless of the aetiology.

Lower glomerular filtration rate after mild stroke induces cognitive impairment by causing endothelial dysfunction.

The incidence of post stroke cognitive impairment (PSCI) is high in patients with mild stroke (MIS), and the risk factors and mechanism are uncertain. Increased cystatin C (CysC) levels after stroke may reflect lower glomerular filtration rate (GFR) and renal impairment. Previous studies have suggested endothelial dysfunction (ED) is closely related to renal impairment and cognitive impairment, respectively. We aimed to observe whether lower GFR estimated by CysC after MIS leaded to a high incidence of PSCI, and the role of ED in this process. 256 patients were enrolled in this prospective observational study. Renal function was assessed using GFR estimated by serum CysC. Endothelial function was evaluated by reactive hyperemia index (RHI) which calculated automatically by peripheral arterial tonometry (PAT). The cognitive function at baseline and 3 months was evaluated by MoCA score, and MoCA score ≤ 26 indicates the presence of PSCI. Spearman correlation analysis and linear regression were conducted to explore the factors affecting ED. Univariate and multivariate analysis was used to identify the independent risk factors of PSCI. The receiver operating characteristic (ROC) curve was applied to explore the optimal cutoff value of the independent risk factors levels for predicting PSCI. A total of 141 patients (55.1%) suffered from ED. Multiple linear regression analysis showed that there was a strong linear correlation between eGFRcys and RHI (p < 0.001). At the three-month follow-up, a total of 150 (58.6%) patients had been diagnosed with PSCI. Multivariate logistic regression analysis showed that RHI was an independent factor affecting the occurrence of PSCI (p < 0.05). ROC curve showed that the area under the curve was 0.724, and the optimal cut-off value of RHI was 1.655, with the sensitivity and specificity for PSCI were 72.7% and 73.6%, respectively. The lower eGFRcys level after MIS was significantly associated with ED, and ED may mediate the higher incidence of PSCI at 3 months after MIS.

Relationship of Perivascular Space Markers With Incident Dementia in Cerebral Small Vessel Disease.

BACKGROUND: Recent studies, using diffusion tensor image analysis along the perivascular space (DTI-ALPS), suggest impaired perivascular space (PVS) function in cerebral small vessel disease, but they were cross-sectional, making inferences on causality difficult. We determined associations between impaired PVS, measured using DTI-ALPS and PVS volume, and cognition and incident dementia. METHODS: In patients with lacunar stroke and confluent white matter hyperintensities, without dementia at baseline, recruited prospectively in a single center, magnetic resonance imaging was performed annually for 3 years, and cognitive assessments, including global, memory, executive function, and processing speed, were performed annually for 5 years. We determined associations between DTI-ALPS and PVS volume with cerebral small vessel disease imaging markers (white matter hyperintensity volume, lacunes, and microbleeds) at baseline and with changes in imaging markers. We determined whether DTI-ALPS and PVS volume at baseline and change over 3 years predicted incident dementia. Analyses were controlled for conventional diffusion tensor image metrics using 2 markers (median mean diffusivity [MD] and peak width of skeletonized MD) and adjusted for age, sex, and vascular risk factors. RESULTS: A total of 120 patients, mean age 70.0 years and 65.0% male, were included. DTI-ALPS declined over 3 years, while no change in PVS volume was found. Neither DTI-ALPS nor PVS volume was associated with cerebral small vessel disease imaging marker progression. Baseline DTI-ALPS was associated with changes in global cognition (ß=0.142, P=0.032), executive function (ß=0.287, P=0.027), and long-term memory (ß=0.228, P=0.027). Higher DTI-ALPS at baseline predicted a lower risk of dementia (hazard ratio, 0.328 [0.183-0.588]; P<0.001), and this remained significant after including median MD as a covariate (hazard ratio, 0.290 [0.139-0.602]; P<0.001). Change in DTI-ALPS predicted dementia conversion (hazard ratio, 0.630 [0.428-0.964]; P=0.048), but when peak width of skeletonized MD and median MD were entered as covariates, the association was not significant. There was no association between baseline PVS volume, or PVS change over 3 years, and conversion to dementia. CONCLUSIONS: DTI-ALPS predicts future dementia risk in patients with lacunar strokes and confluent white matter hyperintensities. However, the weakening of the association between change in DTI-ALPS and incident dementia after controlling for peak width of skeletonized MD and median MD suggests part of the signal may represent conventional diffusion tensor image metrics. PVS volume is not a predictor of future dementia risk.

Subjective Cognitive Complaints in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Subjective cognitive complaints (SCCs) in Parkinson's disease (PD) are reported frequently, but their prevalence and association with changes on objective testing are not fully known. OBJECTIVE: We aimed to determine the prevalence, clinical correlates, and predictive value of SCCs in PD. METHODS: We conducted a systematic review and meta-analysis. From 204 abstracts, we selected 31 studies (n = 3441 patients), and from these, identified the prevalence, clinical features, associations with neuropsychiatric symptoms, and predictive values of SCCs in PD. RESULTS: The meta-analysis showed an SCC prevalence of 36%. This prevalence, however, was significantly moderated by study heterogeneity regarding female sex, disease severity, levodopa equivalent daily dosage, exclusion from the overall sample of patients with objective cognitive impairment, and measurement instrument. SCC prevalence did not differ between de novo and treated PD patients. SCCs were weakly and negligibly associated with cognitive changes on objective testing in cross-sectional studies. However, in cognitively healthy patients, SCCs had a risk ratio of 2.71 for later cognitive decline over a mean follow-up of 3.16 years. Moreover, SCCs were moderately related to co-occurring symptoms of depression, anxiety, or apathy and were more strongly related to these neuropsychiatric symptoms than objective cognitive functioning. CONCLUSION: Our analyses suggest that SCCs in patients with and without objective cognitive impairment are frequent, occurring in more than one third of PD patients. Establishing uniform measurement instruments for identifying PD-related SCCs is critical to understand their implications. Even in cases lacking evidence of objective cognitive impairment and where SCCs might reflect underlying neuropsychiatric symptoms, the possibility of later cognitive deterioration should not be excluded. Therefore, SCCs in PD patients warrant close monitoring for opportunities for targeted and effective interventions. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Association between serum insulin-like growth factor 1 levels and the improvements of cognitive impairments in a subgroup of schizophrenia: Preliminary findings.

BACKGROUND: Numerous studies have implicated abnormal insulin-like growth factor 1 (IGF-1) in the pathophysiology of schizophrenia, but findings have been inconsistent. METHODS: We conducted a meta-analysis to compare IGF-1 levels in schizophrenia patients with healthy controls and explored factors contributing to variability between estimates. In an independent sample (58 chronic schizophrenia patients and 30 healthy controls), we investigated differences in IGF-1 levels among schizophrenia subgroups with distinct cognitive profiles, identified using k-means clustering based on five cognitive domains from The Repeatable Battery for the Assessment of Neuropsychological Status. Associations between serum IGF-1 levels and clinical and neurocognitive improvements were also examined. RESULTS: The meta-analysis revealed significantly lower serum IGF-1 levels in schizophrenia patients compared to healthy controls, albeit with high heterogeneity. Medication status, BMI, and severity of negative symptoms were identified as potential contributors to this heterogeneity. In our independent study, antipsychotic treatment led to a significant increase in IGF-1 levels, and lower pre-treatment serum IGF-1 levels correlated with greater improvement in cognitive deficits, particularly in a subgroup with more severe cognitive symptoms. CONCLUSIONS: Our findings support the "IGF-1 deficiency hypothesis" in the pathogenesis of schizophrenia. Further research is crucial to elucidate the role of IGF-1 in the cognitive impairments associated with schizophrenia.

Cognitive dysfunction in de novo Parkinson disease: Remitting vs. progressive cognitive impairment.

INTRODUCTION: Parkinson's disease (PD) exhibits divergent cognitive trajectories; however, the factors contributing to these variations remain elusive. This study aimed to examine the clinical features of patients with different long-term cognitive trajectories in de novo PD over a five-year follow-up. METHODS: We analyzed 258 patients who completed every annual evaluation for five years. According to the Montreal Cognitive Assessment (MoCA) scores, we classified patients into three groups: cognitively normal (n = 118, CN), remitting MoCA decline (n = 74, RMD), and progressive MoCA decline (n = 66, PMD). RESULTS: The RMD group was associated with lower olfactory scores (Odds Ratio (OR) = 0.958, p = 0.040), whereas PMD was associated with higher depression scores (OR = 1.158, p = 0.045), probable RBD (OR = 3.169, p = 0.002), older age (OR = 1.132, p < 0.001) and lower educational attainment (OR = 0.828, p = 0.004). PMD had higher neurofilament light chain protein values than CN and RMD (p = 0.006, 0.015, respectively). Longitudinally, PMD showed a greater decline in all cognitive scores and hippocampus volumes (p = 0.004). Meanwhile, RMD exhibited intermediate cognitive and volumetric trajectories between CN and PMD and displayed worse score changes in memory tasks than CN. CONCLUSIONS: While PMD exhibited known risk factors for cognitive impairment, along with worse cognitive performance and hippocampal volume decline, RMD displayed baseline lower olfactory scores and intermediate cognitive and hippocampal volume decline between the two groups. These findings suggest individuals in RMD may still be at risk for cognitive deficits. However, further long-term follow-up data are needed to unravel the determinants and dynamics of cognitive functions.

Functional network disorganization and cognitive decline following fractionated whole-brain radiation in mice.

Cognitive dysfunction following radiotherapy (RT) is one of the most common complications associated with RT delivered to the brain, but the precise mechanisms behind this dysfunction are not well understood, and to date, there are no preventative measures or effective treatments. To improve patient outcomes, a better understanding of the effects of radiation on the brain's functional systems is required. Functional magnetic resonance imaging (fMRI) has shown promise in this regard, however, compared to neural activity, hemodynamic measures of brain function are slow and indirect. Understanding how RT acutely and chronically affects functional brain organization requires more direct examination of temporally evolving neural dynamics as they relate to cerebral hemodynamics for bridging with human studies. In order to adequately study the underlying mechanisms of RT-induced cognitive dysfunction, the development of clinically mimetic RT protocols in animal models is needed. To address these challenges, we developed a fractionated whole-brain RT protocol (3Gy/day for 10 days) and applied longitudinal wide field optical imaging (WFOI) of neural and hemodynamic brain activity at 1, 2, and 3 months post RT. At each time point, mice were subject to repeated behavioral testing across a variety of sensorimotor and cognitive domains. Disruptions in cortical neuronal and hemodynamic activity observed 1 month post RT were significantly worsened by 3 months. While broad changes were observed in functional brain organization post RT, brain regions most impacted by RT occurred within those overlapping with the mouse default mode network and other association areas similar to prior reports in human subjects. Further, significant cognitive deficits were observed following tests of novel object investigation and responses to auditory and contextual cues after fear conditioning. Our results fill a much-needed gap in understanding the effects of whole-brain RT on systems level brain organization and how RT affects neuronal versus hemodynamic signaling in the cortex. Having established a clinically-relevant injury model, future studies can examine therapeutic interventions designed to reduce neuroinflammation-based injury following RT. Given the overlap of sequelae that occur following RT with and without chemotherapy, these tools can also be easily incorporated to examine chemotherapy-related cognitive impairment.

Identifying and distinguishing cognitive profiles among virally suppressed people with HIV.

OBJECTIVE: Cognitive deficits are common among people with HIV (PWH), even when virally suppressed. We identified cognitive profiles among virally suppressed PWH and determined how sociodemographic, clinical/behavioral, and HIV disease characteristics distinguish profile membership. METHOD: Participants included 704 virally suppressed PWH (Mage = 43.9 [SD = 10.2], 88% male, 58.9% non-Hispanic White) from the HIV Neurobehavioral Research Program. Demographically adjusted T scores were derived from a neuropsychological evaluation comprised of 13 tests. We implemented a pipeline involving dimension reduction and clustering to identify profiles of cognitive performance. Random forest models on a 70/30 training/testing set with internal cross-validation were used to identify sociodemographic, clinical/behavioral, and HIV disease correlates of profile membership. RESULTS: Six cognitive profiles were identified: (a) "unimpaired" (19.9%); (b) weakness in verbal learning and memory (15.5%); (c) weakness in executive function and learning (25.8%); (d) weakness in motor, processing speed, and executive function (8.1%); (e) impaired learning and recall with weak-to-impaired motor, processing speed, and executive function (13.1%); (f) global deficits (17.6%). The most discriminative sociodemographic, clinical/behavioral, and HIV disease characteristics varied by profile with self-reported mood symptoms and cognitive/functional difficulties (e.g., language/communication, memory, and overall everyday function complaints) most consistently associated with profile membership. CONCLUSIONS: Cognitive profiles and their associated factors among PWH are heterogeneous, but learning/memory deficits were most common and self-reported mood, and cognitive/functional difficulties were most consistently related to profile membership. This heterogeneity in cognitive profiles and their correlates in PWH suggests that differing mechanisms contribute to cognitive deficits and, thus, underscores the need for personalized risk reduction and therapeutic strategies among PWH. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Development, reliability, validity, and acceptability of the remote administration of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).

BACKGROUND: ALS clinical care and research has changed dramatically since the COVID-19 pandemic, accelerating the need for cognitive assessments to be adapted for remote use. OBJECTIVES: To develop the remote administration method of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), and determine its reliability and validity. Methods: The validation process consisted of: (1) Two versions of the ECAS (A and B) were administered, one in-person and one remotely via video call in a randomized order to 27 people without ALS; (2) The ECAS was administered remotely to 24 pwALS, with a second rater independently scoring performance; and (3) Acceptability was assessed by gathering feedback from 17 pwALS and 19 clinicians and researchers about their experience of using the ECAS remotely. RESULTS: In the group without ALS, the remote and in-person ECAS total scores were found to be equivalent, and a Bland-Altman plot showed good agreement between the two administration methods. In pwALS, there was excellent agreement between two raters (ICC = 0.99). Positive feedback was gained from pwALS, researchers and clinicians with regards to ease of process, convenience, time, and the environment. CONCLUSIONS: These findings provide evidence of the reliability and validity of the remote administration of the ECAS for pwALS, with clinicians, researchers and pwALS viewing it as a good alternative to face-to-face administration.

Domain-specific cognitive impairment 6 months after stroke: The value of early cognitive screening.

BACKGROUND: Cognitive screening following stroke is widely recommended, yet few studies have considered the prognostic value of acute domain-specific function for longer-term cognitive outcome. Identifying which post-stroke cognitive impairments more commonly occur, recover, and persist, and which impairments hold prognostic value, could inform care planning, and resource allocation. AIMS: This study aimed to determine the prevalence of domain-specific impairment acutely and at 6 months, assess the proportion of change in cognitive performance, and examine the prognostic value of acute domain-specific cognitive screening. METHODS: A prospective stroke cohort completed the Oxford Cognitive Screen acutely (⩽2 weeks) and 6 months post-stroke. We determined the prevalence of acute and 6-month domain-specific impairment and proportion of change in performance from acute to 6 months. Hierarchical multivariable regression was used to predict global and domain-specific cognitive impairment at 6 months adjusted for demographic/vascular factors, stroke severity, and lesion volume. RESULTS: A total of 430 stroke survivors (mean/SD age 73.9/12.5 years, 46.5% female, median/interquartile range (IQR) National Institute of Health Stroke Scale (NIHSS) 5/2-10) completed 6-month follow-up. Acutely, domain-specific impairments were highly prevalent ranging from 26.7% (n = 112) in praxis to 46.8% (n = 183) in attention. At 6 months, the proportion of domain-specific recovery was highest in praxis (n = 73, 71%) and lowest in language (n = 89, 46%) and memory (n = 82, 48%). Severity of 6-month cognitive impairment was best predicted by the addition of acute cognitive impairment (adj R2 = 0.298, p < 0.0001) over demographic and clinical factors alone (adj R2 = 0.105, p < 0.0001). Acute cognitive function was the strongest predictor of 6-month cognitive performance (p < 0.0001). Acute domain-specific impairments in memory (p < 0.0001), language (p < 0.0001), and praxis (p < 0.0001) significantly predicted overall severity of cognitive impairment at 6 months. CONCLUSION: Post-stroke cognitive impairment is highly prevalent across all domains acutely, while impairments in language, memory, and attention predominate at 6 months. Early domain-specific screening can provide valuable prognostic information for longer-term cognitive outcomes.

Cannabis use may attenuate neurocognitive performance deficits resulting from methamphetamine use disorder.

OBJECTIVE: Methamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders. METHOD: 423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M-/M+) and/or cannabis (C-/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition. RESULTS: Globally, M+C+ performed worse than M-C- but better than M+C-. M+C+ outperformed M+C- on measures of verbal fluency, information processing speed, learning, memory, and working memory. M-C+ did not display lower performance than M-C- globally or on any domain measures, and M-C+ even performed better than M-C- on measures of learning, memory, and working memory. CONCLUSIONS: Our findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.

Disparate Dementia Risk Factors Are Associated with Cognitive Impairment and Rates of Decline in African Americans.

OBJECTIVE: This study was undertaken to evaluate the frequency of modifiable dementia risk factors and their association with cognitive impairment and rate of decline in diverse participants engaged in studies of memory and aging. METHODS: Modifiable dementia risk factors and their associations with cognitive impairment and cognitive decline were determined in community-dwelling African American (AA; n = 261) and non-Hispanic White (nHW; n = 193) participants who completed ≥2 visits at the Mayo Clinic Alzheimer Disease Research Center in Jacksonville, Florida. Risk factors and their associations with cognitive impairment (global Clinical Dementia Rating [CDR] ≥ 0.5) and rates of decline (CDR Sum of Boxes) in impaired participants were compared in AA and nHW participants, controlling for demographics, APOE ɛ4 status, and Area Deprivation Index. RESULTS: Hypertension, hypercholesterolemia, obesity, and diabetes were overrepresented in AA participants, but were not associated with cognitive impairment. Depression was associated with increased odds of cognitive impairment in AA (odds ratio [OR] = 4.30, 95% confidence interval [CI] = 2.13-8.67) and nHW participants (OR = 2.79, 95% CI = 1.21-6.44) but uniquely associated with faster decline in AA participants (ß = 1.71, 95% CI = 0.69-2.73, p = 0.001). Fewer AA participants reported antidepressant use (9/49, 18%) than nHW counterparts (57/78, 73%, p < 0.001). Vitamin B12 deficiency was also associated with an increased rate of cognitive decline in AA participants (ß = 2.65, 95% CI = 0.38-4.91, p = 0.023). INTERPRETATION: Modifiable dementia risk factors are common in AA and nHW participants, representing important risk mitigation targets. Depression was associated with dementia in AA and nHW participants, and with accelerated declines in cognitive function in AA participants. Optimizing depression screening and treatment may improve cognitive trajectories and outcomes in AA participants. ANN NEUROL 2024;95:518-529.