Differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognitive function between untreated major depressive disorder and schizophrenia with depressive mood patients.

BACKGROUND: Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to investigate differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognition in untreated MDD and SZDM patients. METHODS: The study included 42 untreated MDD cases, 30 SZDM patients, and 46 healthy controls (HC). Cognitive assessment utilized the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted, and data were processed using fALFF in slow-4 and slow-5 bands. RESULTS: Significant fALFF changes were observed in four brain regions across MDD, SZDM, and HC groups for both slow-4 and slow-5 fALFF. Compared to SZDM, the MDD group showed increased slow-5 fALFF in the right gyrus rectus (RGR). Relative to HC, SZDM exhibited decreased slow-5 fALFF in the left gyrus rectus (LGR) and increased slow-5 fALFF in the right putamen. Changes in slow-5 fALFF in both RGR and LGR were negatively correlated with RBANS scores. No significant correlations were found between remaining fALFF (slow-4 and slow-5 bands) and RBANS scores in MDD or SZDM groups. CONCLUSIONS: Alterations in slow-5 fALFF in RGR may serve as potential biomarkers for distinguishing MDD from SZDM, providing preliminary insights into the neural mechanisms of cognitive function in schizophrenia.

Estudios normativos españoles (Proyecto NEURONORMA Plus): normas para las pruebas Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Tests (CTT) y Dual Task (DT) / Spanish normative studies (NEURONORMA-Plus project): norms for the Delis Kaplan-Design Fluency Test, Color Trails Test, and Dual Task

Introducción Las tareas de atención compleja y fluencia no verbal se utilizan en las valoraciones neuropsicológicas con el objetivo de explorar subdominios de las funciones ejecutivas. El objetivo de este estudio es proporcionar datos normativos ajustados por edad, escolaridad y género de las pruebas Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Tests (CTT) y Dual Task (DT) como parte del Proyecto NEURONORMA-Plus. Método Se incluyeron 308 individuos sin deterioro cognitivo de entre 18 y 92 años de edad. Se convirtieron las puntuaciones brutas en puntuaciones escalares ajustadas por edad y se realizaron ajustes por escolaridad y género aplicando regresiones lineales estratificando en dos grupos de edad (< 50 y ≥ 50 años). Resultados Globalmente la edad tuvo un impacto negativo en el DK-DFT y el CTT. La escolaridad mostró un efecto positivo en las puntuaciones del DK-DFT sólo en el grupo de mayor edad (≥ 50 años) y se halló un rendimiento discretamente superior en los hombres más jóvenes en la condición básica de esta prueba. La escolaridad se asoció positivamente con todas las puntuaciones de CTT en ambos grupos de edad, excepto en la subprueba CTT-1 en el grupo de adultos jóvenes. La edad y la escolaridad no mostraron influencia sobre el rendimiento en el DT, a diferencia del género, ya que las mujeres jóvenes tuvieron un rendimiento ligeramente superior. Conclusión Estos datos normativos pueden resultar útiles para la interpretación de las evaluaciones neuropsicológicas en población española. (AU)

Introduction Complex attention and non-verbal fluency tasks are used in neuropsychological assessments with the aim of exploring subdomains of executive function. The purpose of this study is to provide norms and age-, education-, and sex-adjusted data for the Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Test (CTT), and Dual Task (DT) as part of the NEURONORMA-Plus project. Methods The sample included 308 cognitively healthy individuals aged between 18 and 92 years. Raw scores were converted to age-adjusted scaled scores. These were further converted into education- and sex-adjusted scaled scores by applying linear regression, with 2 age groups (< 50 and ≥ 50 years). Results Overall, age had a negative impact on DK-DFT and CTT performance. We observed a positive effect of education on DK-DFT scores only in the older group (≥ 50 years). Moreover, younger men performed slightly better in the basic condition of this test. Education was positively associated with all CTT scores in both age groups, with the exception of the CTT-1 subtest in the younger group. Age and education did not influence DT performance, whereas sex did, with young women performing slightly better. Conclusions These normative data may be useful in the interpretation of neuropsychological assessments in the Spanish population. (AU)

Traumatic Brain Injury Characteristics Are Not Related to Neurocognitive Decline in Older Adults: A Nationwide Longitudinal Cohort Study.

OBJECTIVE: Evaluate whether traumatic brain injury (TBI) characteristics, age of injury, or recency of injury predicts the course of neurocognitive decline and/or increases conversion rates to mild cognitive impairment (MCI) or dementia. METHODS: Data were obtained from the National Alzheimer's Coordinating Center for participants 50-85 years old with 3-5 visits from 2015 to 2022, with or without TBI history (TBI+ = 508; TBI- = 2,382). Groups were stratified by self-reported TBI history (i.e., single TBI without loss of consciousness [LOC], single TBI with LOC, multiple TBI without LOC, and multiple TBI with LOC), age of most recent TBI, and recency of TBI. Mixed linear models compared neuropsychological composite trajectories (executive functioning/attention/speed, language, memory, and global), co-varying for age, gender, education, apolipoprotein E4 status, race/ethnicity, and baseline diagnosis (normal aging n = 1,720, MCI n = 749, or dementia n = 417). Logistic binary regression examined MCI/dementia conversion rates. RESULTS: There was a slightly higher frequency of MCI/dementia in those with multiple TBIs (50% to 60% with and without LOC, compared to 39% with no TBI) at baseline, but longitudinal trajectories were similar. TBI history, age of injury, or recency of injury did not impact neurocognitive trajectories or conversion rates to MCI/dementia (all p's > .01). CONCLUSIONS: TBI history, regardless of injury characteristics, age of injury, or recency of injury, did not worsen neurocognitive decline or MCI/dementia conversion. Additional longitudinal research in more diverse cohorts with a wider range of TBI severity is needed to evaluate the specific factors and possible mechanisms in which TBI may increase dementia risk.

Tabla de la normalidad de las pruebas psicométricas para el diagnóstico de encefalopatía hepática subclínica en la población Dominicana / Score of normality psychometric tests for the diagnosis of subclinical hepatic encephalopathy in the Dominican Population

Introducción: La encefalopatía hepática mínima (EHM), es una enfermedad definida por la existencia de varias alteraciones neurofisiológicas, indetectables a la exploración neurológica y el examen clínico. Dentro de las estrategias diagnosticas para la EHM se contemplan las pruebas psicométricas (PHE), pero para su aplicación es indispensable la estandarización previamente en la población de estudio. Objetivo: El estudio se propuso determinar la tabla de la normalidad de las PHE para diagnosticar la encefalopatía hepática subclínica en una muestra de la población dominicana. Método: Se realizó un estudio descriptivo, prospectivo y transversal en un hospital de referencia nacional. Se analizaron 134 personas clasificados por grupos de edades (18-70 años de edad) y años de escolaridad. Se diseñó una tabla de 5x5. Se estudió la influencia de la edad, sexo, uso de espejuelo y de los años de escolarización en el rendimiento de cada uno de las PHE, para lo cual se utilizaron las siguientes pruebas estadísticas: análisis de varianza (ANOVA), prueba t de Student y regresión lineal. Resultado: La escolaridad y la edad fueron variables determinantes en el desempeño de las 5 pruebas psicométricas. Pero, la correlación univariable de la edad con el desempeño de la prueba TMS no hubo diferencias intra e inter grupos estadísticamente significativas (p>0.171). Conclusión: se confecciono la fórmula de predicción de resultados de los test psicométricos. Ninguno sobrepasó el punto de corte de la puntuación que oscila entre los -4 y los +2 puntos.

Introduction: Minimal hepatic encephalopathy (MHE) is a disease defined by the existence of several neurophysiological alterations, undetectable by neurological examination and clinical examination. Among the diagnostic strategies for EHM, psychometric tests (PHE) are contemplated, but for their application, prior standardization in the study population is essential. Objective: The study will need to determine the normality table of PHE to detect subclinical hepatic encephalopathy in a sample of the Dominican population. Method: A descriptive, prospective and cross-sectional study was carried out in a national reference hospital. 134 people classified by age groups (18-70 years of age) and years of schooling were analyzed. A 5x5 board is recommended. The influence of age, sex, use of glasses and years of schooling on the performance of each one of the PHEs was studied, for which the following statistical tests were used: analysis of variance (ANOVA), Student's t test and linear regression. Result: Schooling and age were determining variables in the performance of the 5 psychometric tests. But, the univariate coincidence of age with the performance of the TMS test, there were no statistically significant intra and inter group differences (p>0.171). Conclusion: the formula for predicting the results of the psychometric tests was made. None exceeded the cut-off point of the score that oscillates between -4 and +2 points.

Signatures of Neuropsychological Test Results in the Long Life Family Study: A Cluster Analysis.

BACKGROUND: Discovering patterns of cognitive domains and characterizing how these patterns associate with other risk factors and biomarkers can improve our understanding of the determinants of cognitive aging. OBJECTIVE: To discover patterns of cognitive domains using neuropsychological test results in Long Life Family Study (LLFS) and characterize how these patterns associate with aging markers. METHODS: 5,086 LLFS participants were administered neuropsychological tests at enrollment. We performed a cluster analysis of six baseline neuropsychological test scores and tested the association between the identified clusters and various clinical variables, biomarkers, and polygenic risk scores using generalized estimating equations and the Chi-square test. We used Cox regression to correlate the clusters with the hazard of various medical events. We investigated whether the cluster information could enhance the prediction of cognitive decline using Bayesian beta regression. RESULTS: We identified 12 clusters with different cognitive signatures that represent profiles of performance across multiple neuropsychological tests. These signatures significantly correlated with 26 variables including polygenic risk scores, physical and pulmonary functions, and blood biomarkers and were associated with the hazard of mortality (p < 0.01), cardiovascular disease (p = 0.03), dementia (p = 0.01), and skin cancer (p = 0.03). CONCLUSION: The identified cognitive signatures capture multiple domains simultaneously and provide a holistic vision of cognitive function, showing that different patterns of cognitive function can coexist in aging individuals. Such patterns can be used for clinical intervention and primary care.

Feasibility and Validity of Cambridge Neuropsychological Test Automated Battery in Mild Cognitive Impairment Screening for Patients with Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with the worsening of cognitive function. Strategies that are both convenient and reliable for cognitive screening of AF patients remain underdeveloped. We aimed to analyze the sensitivity and specificity of computerized cognitive screening strategies using subtests from Cambridge Neuropsychological Test Automated Battery (CANTAB) in AF patients. METHODS: The Multitasking Test (MTT), Rapid Visual Information Processing (RVP), and Paired Associates Learning (PAL) subtests from CANTAB were performed in 105 AF patients. Traditional standard neuropsychological tests were used as a reference standard. Cognitive screening models using different CANTAB subtests were established using multivariable logistic regression. Further stepwise regression using the Akaike Information Criterion (AIC) was applied to optimize the models. Receiver operating characteristic curve analyses were used to study the sensitivity and specificity of these models. RESULTS: Fifty-eight (55%) patients were diagnosed with mild cognitive impairment (MCI). MTT alone had reasonable sensitivity (82.8%) and specificity (74.5%) for MCI screening, while RVP (sensitivity 72.4%, specificity 70.2%) and PAL (sensitivity 70.7%, specificity 57.4%) were less effective. Stepwise regression of all available variables revealed that a combination of MTT and RVP brought about higher specificity (sensitivity 82.8%, specificity 85.8%), while PAL was not included in the optimal model. Moreover, adding education to the models did not result in improved validity for MCI screening. CONCLUSION: The CANTAB subtests are feasible and effective strategies for MCI screening among AF patients independent of patients' education levels. Hence, they are practical for cardiologists or general practitioners.

Substance Use-Related Cognitive Decline in Families with Autosomal Dominant Alzheimer's Disease: A Cohort Study.

BACKGROUND: Cigarette smoking is a known risk factor for Alzheimer's disease (AD). However, the association between neurodegeneration and other substances has not been fully determined. It is of vital importance to evaluate this relationship in populations at high risk of dementia. Since substance use possibly modifies the progression rate of cognitive decline, we studied this association in a unique and well-phenotyped cohort from the University of Antioquia: carriers of the PSEN1-E280A genetic variant. OBJECTIVE: To determine the association between substance use and cognitive decline in carriers of the PSEN1-E280A genetic variant. METHODS: A retrospective cohort study was conducted with 94 carriers and 69 noncarriers recruited between January 2019 and April 2020. A psychiatrist interviewed the participants using the Consumption of Alcohol, Cigarettes and other Substances questionnaire. The participants were also submitted to cognitive evaluation. The relationship between cognitive decline and substance use was explored through a mixed effects regression model. RESULTS: There was an association between cigarettes and better performance on tasks related to perceptual organization, verbal fluency, and memory in carriers. Alcohol had a positive or negative effect on memory according to the type of alcoholic beverage. Results on marijuana use were no conclusive. Coffee was associated with progressive improvements in executive function and verbal fluency. CONCLUSION: Cigarette and alcohol were associated with an improvement of some cognitive assessments, possibly by a survival bias. In addition, coffee was related to improvements in executive function and language; therefore, its short-term neuroprotective potential should be studied.

Utility of Machine Learning Approach with Neuropsychological Tests in Predicting Functional Impairment of Alzheimer's Disease.

BACKGROUND: In assessing the levels of clinical impairment in dementia, a summary index of neuropsychological batteries has been widely used in describing the overall functional status. OBJECTIVE: It remains unexamined how complex patterns of the test performances can be utilized to have specific predictive meaning when the machine learning approach is applied. METHODS: In this study, the neuropsychological battery (CERAD-K) and assessment of functioning level (Clinical Dementia Rating scale and Instrumental Activities of Daily Living) were administered to 2,642 older adults with no impairment (n = 285), mild cognitive impairment (n = 1,057), and Alzheimer's disease (n = 1,300). Predictive accuracy on functional impairment level with the linear models of the single total score or multiple subtest scores (Model 1, 2) and support vector regression with low or high complexity (Model 3, 4) were compared across different sample sizes. RESULTS: The linear models (Model 1, 2) showed superior performance with relatively smaller sample size, while nonlinear models with low and high complexity (Model 3, 4) showed an improved accuracy with a larger dataset. Unlike linear models, the nonlinear models showed a gradual increase in the predictive accuracy with a larger sample size (n > 500), especially when the model training is allowed to exploit complex patterns of the dataset. CONCLUSION: Our finding suggests that nonlinear models can predict levels of functional impairment with a sufficient dataset. The summary index of the neuropsychological battery can be augmented for specific purposes, especially in estimating the functional status of dementia.

Treatment-resistant schizophrenia: Addressing white matter integrity, intracortical glutamate levels, clinical and cognitive profiles between early- and adult-onset patients.

BACKGROUND: Treatment-resistance in schizophrenia is 30-40%. Its neurobiology remains unclear; to explore it, we conducted a combined spectrometry/tractography/cognitive battery and psychopathological rating study on patients with treatment-resistant schizophrenia (TRS), dividing the sample into early-onset (N = 21) and adult-onset TRS (N = 20). Previous studies did not differentiate between early- (onset 13-18 years) and adult-onset (>18 years at formal diagnosis of schizophrenia) TRS. METHODS: We evaluated cross-sectionally 41 TRS patients (26 male and 15 female) and 20 matched healthy controls (HCs) with psychopathological and cognitive testing prior to participating in brain imaging scanning using magnetic resonance spectroscopy and diffusion tensor imaging to determine the relationship between their symptoms and their glutamate levels and white matter integrity. RESULTS: TRS patients scored lower than HCs on all cognitive domains; early-onset patients performed better than adult-onset patients only on the Symbol Coding domain. TRS correlated with symptom severity, especially negative symptoms. Glutamate levels and glutamate/creatine were increased in anterior cingulate cortex. Diffusion tensor imaging showed low fractional anisotropy in TRS patients in specific white matter tracts compared to HCs (bilateral anterior thalamic radiation, cortico-spinal tract, forceps minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and right uncinate fasciculus). CONCLUSIONS: We identified specific magnetic resonance spectroscopy and diffusion tensor imaging alterations in TRS patients. Adult-onset TRS differed little from early-onset TRS on most measures; this points to alterations being present since the outset of schizophrenia and may constitute a biological signature of treatment-resistance.

Impact of polygenic risk for coronary artery disease and cardiovascular medication burden on cognitive impairment in psychotic disorders.

BACKGROUND: Cognitive impairment is a core deficit across psychotic disorders, the causes and therapeutics of which remain unclear. Epidemiological observations have suggested associations between cognitive dysfunction in psychotic disorders and cardiovascular risk factors, but an underlying etiology has not been established. METHODS: Neuropsychological performance using the Brief Assessment of Cognition in Schizophrenia (BACS) was assessed in 616 individuals of European ancestry (403 psychosis, 213 controls). Polygenic risk scores for coronary artery disease (PRSCAD) were quantified for each participant across 13 p-value thresholds (PT 0.5-5e-8). Cardiovascular and psychotropic medications were categorized for association analyses. Each PRSCAD was examined in relation to the BACS and the optimized PT was confirmed with five-fold cross-validation and independent validation. Functional enrichment analyses were used to identify biological mechanisms linked to PRSCAD-cognition associations. Multiple regression analyses examined PRSCAD under the optimal PT and medication burden in relation to the BACS composite and subtest scores. RESULTS: Higher PRSCAD was associated with lower BACS composite scores (p = 0.001) in the psychosis group, primarily driven by the Verbal Memory subtest (p < 0.001). Genes linked to multiple nervous system related processes and pathways were significantly enriched in PRSCAD. After controlling for PRSCAD, a greater number of cardiovascular medications was also correlated with worse BACS performance in patients with psychotic disorders (p = 0.029). CONCLUSIONS: Higher PRSCAD and taking more cardiovascular medications were both significantly associated with cognitive impairment in psychosis. These findings indicate that cardiovascular factors may increase the risk for cognitive dysfunction and related functional outcomes among individuals with psychotic disorders.

Associations between smoking and accelerated brain ageing.

Smoking accelerates the ageing of multiple organs. However, few studies have quantified the association between smoking, especially smoking cessation, and brain ageing. Using structural magnetic resonance imaging data from the UK Biobank (n = 33,293), a brain age predictor was trained using a machine learning technique in the non-smoker group (n = 14,667) and then tested in the smoker group (n = 18,626) to determine the relationships between BrainAge Gap (predicted age - true age) and smoking parameters. Further, we examined whether smoking was associated with poorer cognition and whether this relationship was mediated by brain age. The predictor achieved an appreciable performance in training data (r = 0.712, mean-absolute-error [MAE] = 4.220) and test data (r = 0.725, MAE = 4.160). On average, smokers showed a larger BrainAge Gap (+0.304 years, Cohens'd = 0.083) than controls, more explicitly, the extents vary depending on their smoking characteristic that active regular smokers had the largest BrainAge Gap (+1.190 years, Cohens'd = 0.321), and light smokers had a moderate BrainAge Gap (+0.478, Cohens'd = 0.129). The increased smoking amount was associated with a larger BrainAge Gap (ß = 0.035, p = 1.72 × 10-20) while a longer duration of quitting smoking in ex-smokers was associated with a smaller BrainAge Gap (ß = -0.015, p = 2.14 × 10-05). Furthermore, smoking was associated with poorer cognition, and this relationship was partially mediated by BrainAge Gap. The study provides insight into the association between smoking, brain ageing, and cognition, which provide more publicly acceptable propaganda against smoking.

A Comparison of Behavioral and Psychological Symptoms of Dementia (BPSD) and BPSD Sub-Syndromes in Early-Onset and Late-Onset Alzheimer's Disease.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) have a large impact on the quality of life of patients with Alzheimer's disease (AD). Few studies have compared BPSD between early-onset (EOAD) and late-onset (LOAD) patients, finding conflicting results. OBJECTIVE: The aims of this study were to: 1) characterize the presence, overall prevalence, and time of occurrence of BPSD in EOAD versus LOAD; 2) estimate the prevalence over time and severity of each BPSD in EOAD versus LOAD in three stages: pre-T0 (before the onset of the disease), T0 (from onset to 5 years), and T1 (from 5 years onwards); 3) track the manifestation of BPSD sub-syndromes (i.e., hyperactivity, psychosis, affective, and apathy) in EOAD versus LOAD at T0 and T1. METHODS: The sample includes 1,538 LOAD and 387 EOAD diagnosed from 1996 to 2018. Comprehensive assessment batteries, including the Neuropsychiatric Inventory (NPI), were administered at the first medical assessment and at different follow-up period. RESULTS: The overall prevalence for the most of BPSD was significantly higher in EOAD compared to LOAD whereas most BPSD appeared significantly later in EOAD patients. Between the two groups, from pre-T0 to T1 we recorded a different pattern of BPSD prevalence over time as well as for BPSD sub-syndromes at T0 and T1. Results on severity of BPSD did not show significant differences. CONCLUSION: EOAD and LOAD represent two different forms of a single entity not only from a neuropathological, cognitive, and functional level but also from a psychiatric point of view.

Integrated Cognitive-Behavioral Social Skills Training and Compensatory Cognitive Training for Negative Symptoms of Psychosis: Effects in a Pilot Randomized Controlled Trial.

OBJECTIVE: Negative symptoms and cognitive impairment in schizophrenia (SZ) remain unmet treatment needs as they are highly prevalent, associated with poor functional outcomes, and resistant to pharmacologic treatment. The current pilot randomized controlled trial examined the efficacy of an integrated Cognitive-Behavioral Social Skills Training and Compensatory Cognitive Training (CBSST-CCT) intervention compared to Goal-focused Supportive Contact (SC) on negative symptoms and cognitive performance. METHODS: Fifty-five adults with SZ or schizoaffective disorder with moderate-to-severe negative symptoms were randomized to receive 25 twice-weekly, 1-h manualized group sessions (12.5 weeks total duration) of either CBSST-CCT or SC delivered by master's level clinicians in five community settings. Assessments of negative symptom severity (primary outcomes) and neuropsychological performance, functional capacity, social skills performance, and self-reported functional ability/everyday functioning, psychiatric symptom severity, and motivation (secondary outcomes) were administered at baseline, mid-treatment, post-treatment, and 6-month follow-up. RESULTS: Mixed-effects models using baseline, mid-treatment, and post-treatment data demonstrated significant CBSST-CCT-associated effects on negative symptom severity, as assessed by the Scale for the Assessment of Negative Symptoms (p = .049, r = 0.22), with improvements in diminished motivation driving this effect (p = .037, r = 0.24). The CBSST-CCT group also demonstrated improved verbal learning compared to SC participants (p = .026, r = 0.36). The effects of CBSST-CCT appeared to be durable at 6-month follow-up. CONCLUSIONS: CBSST-CCT improved negative symptom severity and verbal learning in high-negative-symptom individuals relative to SC. CBSST-CCT warrants larger investigations to examine its efficacy in treating negative symptoms, along with other symptoms, cognition, and, ultimately, real-world functional outcomes. Clinical Trial registration number NCT02170051.

Body Mass Index and Leptin Are Related to Cognitive Performance Over 10 Years in Women With and Without HIV Infection.

CONTEXT: It is not yet understood whether people living with HIV infection have an increased risk of Alzheimers Disease and Related Dementias due to enhanced survivorship with highly effective antiretroviral therapies and/or increasing adiposity with aging. OBJECTIVE: This work aimed to determine whether body mass index (BMI) and leptin were longitudinally associated over 10 years with neuropsychological performance (NP) among middle-aged women with HIV (WWH) vs without HIV. METHODS: Women's Interagency HIV Study (WIHS) participants (301 WWH, 113 women without HIV from Brooklyn, New York City, and Chicago had baseline and 10-year BMI and fasting plasma leptin levels using commercial enzyme-linked immunosorbent assay (ng/mL); and demographically adjusted NP T scores (attention/working memory, executive function [EF], processing speed, memory, learning, verbal fluency, motor function, global) at 10-year follow-up. Multivariable linear regression analyses, stratified by HIV serostatus, examined associations between BMI, leptin, and NP. RESULTS: Over 10 years, women (baseline age 39.8 ±â€…9.2 years, 73% Black, 73% WWH) transitioned from average overweight (29.1 ±â€…7.9) to obese (30.5 ±â€…7.9) BMI. Leptin increased 11.4 ±â€…26.4 ng/mL (P < .001). Higher baseline BMI and leptin predicted poorer 10-year EF among all women (BMI ß = -6.97, 95% CI (-11.5 to -2.45) P = .003; leptin ß = -1.90, 95% CI (-3.03 to -0.76), P = .001); higher baseline BMI predicted better memory performance (ß = 6.35, 95% CI (1.96-10.7), P = .005). Greater 10-year leptin increase predicted poorer EF (P = .004), speed (P = .03), and verbal (P = .02) and global (P = 0.005) performance among all women, and WWH. Greater 10-year BMI increase predicted slower processing speed (P = .043) among all women; and among WWH, poorer EF (P = .01) and global (P = .04) performance. CONCLUSION: In middle-aged WIHS participants, 10-year increases in BMI and leptin were associated with poorer performance across multiple NP domains among all women and WWH. Trajectories of adiposity measures over time may provide insight into the role of adipose tissue in brain health with aging.

Repetitive Transcranial Magnetic Stimulation as a Treatment for Veterans with Cognitive Impairment and Multiple Comorbidities.

BACKGROUND: Despite decades of research efforts, current treatments for Alzheimer's disease (AD) are of limited effectiveness and do not halt the progression of the disease and associated cognitive decline. Studies have shown that repetitive transcranial magnetic stimulation (rTMS) may improve cognition. OBJECTIVE: We conducted a pilot study to investigate the effect of rTMS on cognitive function in Veterans with numerous medical comorbidities. METHODS: Participants underwent 20 sessions, over the course of approximately 4 weeks, of 10 Hz rTMS at the left dorsolateral prefrontal cortex with intensity of 120% resting motor threshold. Outcome measures including memory, language, verbal fluency, and executive functions were acquired at baseline, end of treatment, and 4 months after the last rTMS session. Twenty-six Veterans completed the study (13 in the active rTMS group, 13 in the sham rTMS group). RESULTS: The study protocol was well-tolerated. Active, compared to sham, rTMS showed improved auditory-verbal memory at the end of treatment and at 4-month follow-up. However, the active rTMS group demonstrated a trend in decreased semantic verbal fluency at the end of treatment and at 4-month follow up. CONCLUSION: These preliminary results show rTMS is safe in general in this elderly Veteran population with multiple co-morbidities. Patients in the sham group showed an expected, slight decline in the California Verbal Learning Test scores over the course of the study, whereas the active treatment group showed a slight improvement at the 4-month post-treatment follow up. These effects need to be confirmed by studies of larger sample sizes.

Associations Between Midlife Functional Limitations and Self-Reported Health and Cognitive Status: Results from the 1998-2016 Health and Retirement Study.

BACKGROUND: Life-course approaches to identify and help improve modifiable risk factors, particularly in midlife, may mitigate cognitive aging. OBJECTIVE: We examined how midlife self-rated physical functioning and health may predict cognitive health in older age. METHODS: We used data from the Health and Retirement Study (1998-2016; unweighted-N = 4,685). We used survey multinomial logistic regression and latent growth curve models to examine how midlife (age 50-64 years) activities of daily living (ADL), physical function, and self-reported health affect cognitive trajectories and cognitive impairment not dementia (CIND) and dementia status 18 years later. Then, we tested for sex and racial/ethnic modifications. RESULTS: After covariates-adjustment, worse instrumental ADL (IADL) functioning, mobility, and self-reported health were associated with both CIND and dementia. Hispanics were more likely to meet criteria for dementia than non-Hispanic Whites given increasing IADL impairment. CONCLUSION: Midlife health, activities limitations, and difficulties with mobility are predictive of dementia in later life. Hispanics may be more susceptible to dementia in the presence of midlife IADLs. Assessing midlife physical function and general health with brief questionnaires may be useful for predicting cognitive impairment and dementia in later life.

Exploration of the Mechanism Underlying the Association of Incident Microinfarct and Motor Deficit: A Preliminary Functional MRI Study.

BACKGROUND: Cerebral microinfarcts (CMIs) might cause measurable disruption to brain connections and are associated with cognitive decline, but the association between CMIs and motor impairment is still unclear. OBJECTIVE: To assess the CMIs effect on motor function in vivo and explore the potential neuropathological mechanism based on graph-based network method. METHODS: We identified 133 non-demented middle-aged and elderly participants who underwent MRI scanning, cognitive, and motor assessment. The short physical performance battery (SPPB) assessed motor function, including balance, walking speed, and chair stand. We grouped participants into 34 incident CMIs carriers and 99 non-CMIs carriers as controls, depending on diffusion-weighted imaging. Then we assessed the independent CMIs effects on motor function and explored neural mechanisms of CMIs on motor impairment via mapping of degree centrality (DC) and eigenvector centrality (EC). RESULTS: CMIs carriers had worse motor function than non-carriers. Linear regression analyses showed that CMIs independently contributed to motor function. CMIs carriers had decreased EC in the precuneus, while increased DC and EC in the middle temporal gyrus and increased DC in the inferior frontal gyrus compared to controls (p < 0.05, corrected). Correlation analyses showed that EC of precuneus was related to SPPB (r = 0.25) and balance (r = 0.27); however, DC (r = -0.25) and EC (r = -0.25) of middle temporal gyrus was related with SPPB in all participants (p < 0.05, corrected). CONCLUSION: CMIs represent an independent risk factor for motor dysfunction. The relationship between CMIs and motor function may be attributed to suppression of functional hub region and compensatory activation of motor-related regions.

Prevalence, Incidence, and Progression of Cognitive Impairment, No Dementia Among Rural-Dwelling Chinese Older Adults.

BACKGROUND: Few studies have examined occurrence and progression of cognitive impairment, no dementia (CIND) in rural China. OBJECTIVE: To determine the prevalence and incidence of CIND in rural-dwelling Chinese older adults, and to examine risk and protective factors associated with progression to CIND and dementia. METHODS: This population-based study included 2,781 dementia-free participants (age≥65 years) who were examined at baseline (2014) and followed in 2018. Demographic, epidemiological, clinical, and neuropsychological data were collected following a structured questionnaire. We defined CIND according to subjective cognitive complaints and the age- and education-specific Mini-Mental State Examination (MMSE) score. Data were analyzed with the multinomial logistic regression models. RESULTS: The overall prevalence of CIND was 10.54% and the incidence was 28.26 per 1,000 person-years. CIND at baseline was associated with the multi-adjusted odds ratio (OR) of 2.06 (95% confidence interval = 1.23-3.47) for incident dementia. Multinomial logistic regression analysis suggested that compared with no CIND, the multi-adjusted OR of incident CIND was 2.21 (1.51-3.23) for women and 0.62 (0.38-0.99) for high social support, whereas the multi-adjusted OR of incident dementia was 1.14 (1.09-1.18) for older age, 0.29 (0.16-0.53) for high education, and 2.91 (1.47-5.74) for having a stroke history. CONCLUSION: CIND affects over one-tenth of older adults living in rural communities of western Shandong province. People with CIND are twice as likely to progress to dementia as people without CIND. Female sex, low education, stroke history, and low social support are associated with an increased risk of progression from normal cognition to CIND or dementia.

Neuropsychiatric Symptoms in Patients with Neurocognitive Disorder and Their Performance Between Mild and Major Stages.

BACKGROUND: The neuropsychiatric symptoms (NPS) in patients with neurocognitive disorders (NCD) increases the risk of exhibiting significant cognitive and functional decline. However, to the best of our knowledge, few studies have evaluated to what extent the presence of chronic and early NPS impacts cognition and functionality in patients with minor or major stages of NCD. OBJECTIVE: We aimed to assess the interplay between early and chronic NPS and cognitive and functional presentation of patients with mild and major forms of NCD. METHODS: We used two NPS tools tracking early and late NPS and assessed to what extent they determine cognitive and functional outcomes in patients with mild and major forms of NCD. RESULTS: We found an inverse relationship between the presence of NPS, as measured by the Neuropsychiatric Inventory and Mild Behavioral Impairment Checklist (MBI-C), and cognitive and functional variables in major forms of NCD. In contrast, the minor stage of NCD was associated with increased MBI-C scores. CONCLUSION: Our results revealed that NPS are associated with cognitive and functional outcomes in mild and chronic forms of NCD. Crucially our results suggest that NPS could be considered as a pathological marker of the clinical course of dementia. Additionally, our study calls to study early and late forms of NPS as both impact cognition and functionality of NCD.

Functional Neural Correlates of Semantic Fluency Task Performance in Mild Cognitive Impairment and Alzheimer's Disease: An FDG-PET Study.

BACKGROUND: Total score (TS) of semantic verbal fluency test (SVFT) is generally used to interpret results, but it is ambiguous as to specific neural functions it reflects. Different SVFT strategy scores reflecting qualitative aspects are proposed to identify specific cognitive functions to overcome limitations of using the TS. OBJECTIVE: Functional neural correlates of the TS as well as the other strategy scores in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia using Fluorine-18-Fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Correlations between various SVFT scores (i.e., TS, mean cluster size, switching (SW), hard switching, cluster switching (CSW)) and cerebral glucose metabolism were explored using voxelwise whole-brain approach. Subgroup analyses were also performed based on the diagnosis and investigated the effects of disease severity on the associations. RESULTS: Significant positive correlation between TS and cerebral glucose metabolism was found in prefrontal, parietal, cingulate, temporal cortex, and subcortical regions. Significantly increased glucose metabolism associated with the SW were found in similar but smaller regions, mainly in the fronto-parieto-temporal regions. CSW was only correlated with the caudate. In the subgroup analysis conducted to assess different contribution of clinical severity, differential associations between the strategy scores and regional glucose metabolism were found. CONCLUSION: SW and CSW may reflect specific language and executive functions better than the TS. The SVFT is influenced by brain dysfunction due to the progression of AD, as demonstrated by the SW with larger involvement of temporal lobe for the AD, and CSW with significant association only for the MCI.