Aberrant brain structural-functional connectivity coupling associated with cognitive dysfunction in different cerebral small vessel disease burdens.

AIMS: Emerging evidence suggests that cerebral small vessel disease (CSVD) pathology changes brain structural connectivity (SC) and functional connectivity (FC) networks. Although network-level SC and FC are closely coupled in the healthy population, how SC-FC coupling correlates with neurocognitive outcomes in patients with different CSVD burdens remains largely unknown. METHODS: Using multimodal MRI, we reconstructed whole-brain SC and FC networks for 54 patients with severe CSVD burden (CSVD-s), 106 patients with mild CSVD burden (CSVD-m), and 79 healthy controls. We then investigated the aberrant SC-FC coupling and functional network topology in CSVD and their correlations with cognitive dysfunction. RESULTS: Compared with controls, the CSVD-m patients showed no significant change in any SC-FC coupling, but the CSVD-s patients exhibited significantly decreased whole-brain (p = 0.014), auditory/motor (p = 0.033), and limbic modular (p = 0.011) SC-FC coupling. For functional network topology, despite no change in global efficiency, CSVD-s patients exhibited significantly reduced nodal efficiency of the bilateral amygdala (p = 0.024 and 0.035) and heschl gyrus (p = 0.001 and 0.005). Notably, for the CSVD-s patients, whole-brain SC-FC coupling showed a significantly positive correlation with MoCA (r = 0.327, p = 0.020) and SDMT (r = 0.373, p = 0.008) scores, limbic/subcortical modular SC-FC coupling showed a negative correlation (r = -0.316, p = 0.025) with SCWT score, and global/local efficiency (r = 0.367, p = 0.009 and r = 0.353, p = 0.012) showed a positive correlation with AVLT score. For the CSVD-m group, whole-brain and auditory/motor modular SC-FC couplings showed significantly positive correlations with SCWT (r = 0.217, p = 0.028 and r = 0.219, p = 0.027) and TMT (r = 0.324, p = 0.001 and r = 0.245, p = 0.013) scores, and global/local efficiency showed positive correlations with AVLT (r = 0.230, p = 0.020 and r = 0.248, p = 0.012) and SDMT (r = 0.263, p = 0.008 and r = 0.263, p = 0.007) scores. CONCLUSION: Our findings demonstrated that decreased whole-brain and module-dependent SC-FC coupling associated with reduced functional efficiency might underlie more severe burden and worse cognitive decline in CSVD. SC-FC coupling might serve as a more sensitive neuroimaging biomarker of CSVD burden and provided new insights into the pathophysiologic mechanisms of clinical development of CSVD.

Cognitive Impairment in Liver Tranplant Recipients: A Cross-Sectional Study.

OBJECTIVES: The proportion of older transplant recipients has increased. Cognitive impairment is not rare after kidney transplant, but data on this issue in liver transplant recipients are scarse. MATERIALS AND METHODS: In this cross-sectional study, we evaluated all liver transplant recipients from a single center in Brazil from July 2018 to June 2020 in terms of cognitive performance to determine the prevalence of neurocognitive disorder. We compared liver transplant recipients with neurocognitive disorder with liver transplant recipients without neurocognitive disorder. We also compared those with an alcoholic cause of liver transplant with other patients. The presence of depressive symptoms was assessed. We performed correlations of clinical data with cognitive scores. RESULTS: In a sample of 100 recipients with median age of 62 years (interquartile range, 56.2-69 y), neurocognitive disorder was present in 21% of the group. Patients with cognitive impairment were older (68 y [61-72] vs 61 y [52-68]; P = .019) and had a trend to higher proportion of persistent kidney injury (33.3% vs 13.9%; P = .055) versus patients without cognitive impairment. Recipients with alcoholic cause of liver transplant exhibited worse cognitive performance in the Mini-Mental State Examination (score of 26 [23.7-28.2] vs 28 [26-29]; P = .024) and the Alzheimer Disease Assessment Scale-cognitive (score of 10.4 [8.6-14.2] vs 8 [6.3-10]; P = .008) than other patients. Weak negative correlations were shown in cognitive performance scores versus recipient age (Semantic Verbal Fluency test, r = -0.334 [P = .001]; Clock Drawing test, r = -0.209 [P = .037]; Alzheimer Disease Assessment Scale-cognitive, r = -0.323 [P = .001]). CONCLUSIONS: Neurocognitive disorder was common in liver transplant recipients, in part due to increased age. This study also suggested a role for alcoholic cause of liver transplant and persistent kidney injury in the development of cognitive impairment.

Validity and reliability of the Pain Assessment in Impaired Cognition 15 (PAIC15) observation scale in persons with aphasia.

BACKGROUND: The use of self-report pain scales in persons with aphasia can be challenging due to communication and cognitive problems, while for assessing pain self-report pain is considered the gold standard (Harrison RA, Field TS. Post stroke pain: identification, assessment, and therapy. Cerebrovasc Dis. 2015;39(3-4):190-201.). An observational scale may be used as an alternative. This study examines the validity and reliability of the observational Pain Assessment in Impaired Cognition (PAIC15) scale in persons with aphasia. METHODS: Persons with aphasia were observed during rest and transfer by two observers using the PAIC15. The PAIC15 comprises 15 items covering the three domains of facial expressions, body movements, and vocalizations. When able, the participant completed four self-report pain scales after each observation. The observations were repeated within one week. For criterion validity, correlations between the PAIC15 and self-report pain scales were calculated and for construct validity, three hypotheses were tested. Reliability was determined by assessing internal consistency, and intra- and interobserver agreement. RESULTS: PAIC15 observations were obtained for 71 persons (mean age 75.5 years) with aphasia. Fair positive correlations (rest: 0.35-0.50; transfer: 0.38-0.43) were reported between PAIC15 and almost all self-report pain scales. Results show that significantly more pain was observed in persons with aphasia during transfer than during rest. No differences were found for observed pain between persons with aphasia who use pain medication and those without, or persons who have joint diseases compared to those without. Results showed acceptable internal consistency. Intra- and interobserver agreement was high for most PAIC15 items, particularly for the domains body movements and vocalizations during rest and transfer. CONCLUSIONS: Recognition of pain in persons aphasia using the PAIC15 showed mixed yet promising results.

Effects of Virtual Reality Motor-Cognitive Training for Older People With Cognitive Frailty: Multicentered Randomized Controlled Trial.

BACKGROUND: Cognitive frailty refers to a clinical syndrome in which physical frailty and mild cognitive impairment coexist. Motor-cognitive training and virtual reality (VR) have been used to launch various therapeutic modalities to promote health in older people. The literature advocates that motor-cognitive training and VR are effective in promoting the cognitive and physical function of older people. However, the effects on older people with cognitive frailty are unclear. OBJECTIVE: This study examined the effects of VR motor-cognitive training (VRMCT) on global cognitive function, physical frailty, walking speed, visual short-term memory, inhibition of cognitive interference, and executive function in older people with cognitive frailty. METHODS: This study used a multicentered, assessor-blinded, 2-parallel-group randomized controlled trial design. Participants were recruited face-to-face in 8 older adult community centers. Eligible participants were aged ≥60 years, were community dwelling, lived with cognitive frailty, had no dementia, and were not mobility restricted. In the intervention group, participants received VRMCT led by interventionists with 16 one-hour training sessions delivered twice per week for 8 weeks. In the control group, participants received the usual care provided by the older adult community centers that the investigators did not interfere with. The primary outcome was global cognitive function. The secondary outcomes included physical frailty, walking speed, verbal short-term memory, inhibition of cognitive interference, and executive function. Data were collected at baseline (T0) and the week after the intervention (T1). Generalized estimating equations were used to examine the group, time, and interaction (time × group) effects on the outcomes. RESULTS: In total, 293 eligible participants enrolled in the study. The mean age of the participants was 74.5 (SD 6.8) years. Most participants were female (229/293, 78.2%), had completed primary education (152/293, 52.1%), were married (167/293, 57.2%), lived with friends (127/293, 43.3%), and had no VR experience (232/293, 79.5%). In the intervention group, 81.6% (119/146) of participants attended >80% (13/16, 81%) of the total number of sessions. A negligible number of participants experienced VR sickness symptoms (1/146, 0.7% to 5/146, 3%). VRMCT was effective in promoting global cognitive function (interaction effect: P=.03), marginally promoting executive function (interaction effect: P=.07), and reducing frailty (interaction effect: P=.03). The effects were not statistically significant on other outcomes. CONCLUSIONS: VRMCT is effective in promoting cognitive functions and reducing physical frailty and is well tolerated and accepted by older people with cognitive frailty, as evidenced by its high attendance rate and negligible VR sickness symptoms. Further studies should examine the efficacy of the intervention components (eg, VR vs non-VR or dual task vs single task) on health outcomes, the effect of using technology on intervention adherence, and the long-term effects of the intervention on older people with cognitive frailty at the level of daily living. TRIAL REGISTRATION: ClinicalTrials.gov NCT04730817; https://clinicaltrials.gov/study/NCT04730817.

Predicting Adherence to Computer-Based Cognitive Training Programs Among Older Adults: Study of Domain Adaptation and Deep Learning.

Background: Cognitive impairment and dementia pose a significant challenge to the aging population, impacting the well-being, quality of life, and autonomy of affected individuals. As the population ages, this will place enormous strain on health care and economic systems. While computerized cognitive training programs have demonstrated some promise in addressing cognitive decline, adherence to these interventions can be challenging. Objective: The objective of this study is to improve the accuracy of predicting adherence lapses to ultimately develop tailored adherence support systems to promote engagement with cognitive training among older adults. Methods: Data from 2 previously conducted cognitive training intervention studies were used to forecast adherence levels among older participants. Deep convolutional neural networks were used to leverage their feature learning capabilities and predict adherence patterns based on past behavior. Domain adaptation (DA) was used to address the challenge of limited training data for each participant, by using data from other participants with similar playing patterns. Time series data were converted into image format using Gramian angular fields, to facilitate clustering of participants during DA. To the best of our knowledge, this is the first effort to use DA techniques to predict older adults' daily adherence to cognitive training programs. Results: Our results demonstrated the promise and potential of deep neural networks and DA for predicting adherence lapses. In all 3 studies, using 2 independent datasets, DA consistently produced the best accuracy values. Conclusions: Our findings highlight that deep learning and DA techniques can aid in the development of adherence support systems for computerized cognitive training, as well as for other interventions aimed at improving health, cognition, and well-being. These techniques can improve engagement and maximize the benefits of such interventions, ultimately enhancing the quality of life of individuals at risk for cognitive impairments. This research informs the development of more effective interventions, benefiting individuals and society by improving conditions associated with aging.

Addressing Long COVID Sequelae and Neurocovid: Neuropsychological Scenarios and Neuroimaging Findings.

In the face of increasing reports of CNS involvement in COVID-19 cases, it is likely that the current epidemic may be accompanied by a significant increase in the prevalence of neurological sequelae, cognitive dysfunction, and long-term behavioural alterations affecting quality of life and autonomy in daily life. This is consequential to the neuroinvasion and multi-organ dysfunction, but also to the psychological distress and socioeconomic changes that occur. Long COVID and neurocovid are now an established concept worldwide. However, the clinical features of these two entities are still debated. The chapter provides information about the nosographic framing, associated pathophysiological mechanisms, alterations in the central and peripheral nervous systems, and the associated neurocognitive profile, indications about predictor and clinical evaluation according to a patient-centred multidimensional immuno-behavioural approach.

Investigating Acoustic and Psycholinguistic Predictors of Cognitive Impairment in Older Adults: Modeling Study.

BACKGROUND: About one-third of older adults aged 65 years and older often have mild cognitive impairment or dementia. Acoustic and psycho-linguistic features derived from conversation may be of great diagnostic value because speech involves verbal memory and cognitive and neuromuscular processes. The relative decline in these processes, however, may not be linear and remains understudied. OBJECTIVE: This study aims to establish associations between cognitive abilities and various attributes of speech and natural language production. To date, the majority of research has been cross-sectional, relying mostly on data from structured interactions and restricted to textual versus acoustic analyses. METHODS: In a sample of 71 older (mean age 83.3, SD 7.0 years) community-dwelling adults who completed qualitative interviews and cognitive testing, we investigated the performance of both acoustic and psycholinguistic features associated with cognitive deficits contemporaneously and at a 1-2 years follow up (mean follow-up time 512.3, SD 84.5 days). RESULTS: Combined acoustic and psycholinguistic features achieved high performance (F1-scores 0.73-0.86) and sensitivity (up to 0.90) in estimating cognitive deficits across multiple domains. Performance remained high when acoustic and psycholinguistic features were used to predict follow-up cognitive performance. The psycholinguistic features that were most successful at classifying high cognitive impairment reflected vocabulary richness, the quantity of speech produced, and the fragmentation of speech, whereas the analogous top-ranked acoustic features reflected breathing and nonverbal vocalizations such as giggles or laughter. CONCLUSIONS: These results suggest that both acoustic and psycholinguistic features extracted from qualitative interviews may be reliable markers of cognitive deficits in late life.

The Relationship Between Anxiety, Depression and Cognitive Functioning in Older Adults: An Exploratory Cross-Sectional Analysis of Wave 1 Lothian Birth Cohort 1936 Data.

OBJECTIVES: To explore the strength of the association between cognitive functioning and depression and anxiety in older people without dementia. METHODS: An exploratory, cross-sectional analysis of Wave 1 (2004-2007) data from the Lothian Birth Cohort 1936 dataset. Three subgroups were based on Hospital Anxiety and Depression Scale (HADS) subscales: no probable anxiety or depression (N = 592), probable anxiety no depression (N = 122), probable depression with/without anxiety (depression) (N = 30). Regression analyses determined relationships between subgroups and identified cognitive test variables. RESULTS: Participants were 744 individuals (male = 385 [51.5%]; mean [M] age = 69.5 years [Standard deviation = 0.83]); characteristics for subgroups were similar. Participants with probable depression had slower simple reaction time scores than those with no anxiety or depression (regression slope [ß] on the log10 scale = 0.05, 95% Confidence Interval [0.03, 0.08], p ≤ 0.001). Those with probable anxiety had significantly worse scores on other tests: Spatial span (ß = -0.80 [-1.36, -0.25], p ≤ 0.005), Symbol Search (ß = -1.67 [-2.90, -0.45], p ≤ 0.01), Matrix Reasoning (ß = -1.58 [-2.55, -0.60], p ≤ 0.005) and Block Design (ß = -3.33 [-5.29, -1.37], p ≤ 0.001), than those without probable anxiety or depression. CONCLUSION: Probable depression and anxiety were found to be associated with lower cognitive function in those without evidence of dementia. People with probable anxiety showed poorer performance in tests that concerned making decisions. People with probable depression showed slower processing speed.

Limbic Network Derangement Mediates Unawareness of Apathy in Mild Cognitive Impairment due to Alzheimer's Disease: Clues from [18F]FDG PET Voxel-Wise Analysis.

Background: Discrepancy between caregiver and patient assessments of apathy in mild cognitive impairment (MCI) is considered an index of apathy unawareness, independently predicting progression to AD dementia. However, its neural underpinning are uninvestigated. Objective: To explore the [18F]FDG PET-based metabolic correlates of apathy unawareness measured through the discrepancy between caregiver and patient self-report, in patients diagnosed with MCI. Methods: We retrospectively studied 28 patients with an intermediate or high likelihood of MCI-AD, progressed to dementia over an average of two years, whose degree of apathy was evaluated by means of the Apathy Evaluation Scale (AES) for both patients (PT-AES) and caregivers (CG-AES). Voxel-based analysis at baseline was used to obtain distinct volumes of interest (VOIs) correlated with PT-AES, CG-AES, or their absolute difference (DISCR-AES). The resulting DISCR-AES VOI count densities were used as covariates in an inter-regional correlation analysis (IRCA) in MCI-AD patients and a group of matched healthy controls (HC). Results: DISCR-AES negatively correlated with metabolism in bilateral parahippocampal gyrus, posterior cingulate cortex, and thalamus, PT-AES score with frontal and anterior cingulate areas, while there was no significant correlation between CG-AES and brain metabolism. IRCA revealed that MCI-AD patients exhibited reduced metabolic/functional correlations of the DISCR-AES VOI with the right cingulate gyrus and its anterior projections compared to HC. Conclusions: Apathy unawareness entails early disruption of the limbic circuitry rather than the classical frontal-subcortical pathways typically associated with apathy. This reaffirms apathy unawareness as an early and independent measure in MCI-AD, marked by distinct pathophysiological alterations.

Association between widowhood and cognitive function among Chinese older adults with hearing impairment: the moderating effect of social support and participation.

BACKGROUND: Older adults with hearing impairments are vulnerable to cognitive impairment. Although previous reports suggest a correlation between widowhood and cognitive impairment, further investigation is needed to elucidate the effect of widowhood on cognitive function and the moderating effects of social support and participation on widowhood-related cognitive impairment in this vulnerable demographic. METHODS: The study's data were sourced from the nationally representative Chinese Longitudinal Healthy Longevity Survey (CLHLS) for the years 2011, 2014, and 2018. Multiple linear regression was used to analyze the association between widowhood and cognitive function among older adults. Multivariate logistic regression examined the effect of widowhood on the likelihood of experiencing various levels of cognitive impairment in older adults with hearing impairments. A moderating effect model explored the roles of social support and participation in mitigating widowhood-related cognitive impairment. RESULTS: The cognitive function of older adults with hearing impairment was found to be lower than that of those without hearing impairment. Widowhood was significantly negatively correlated with Mini-Mental State Examination (MMSE) scores in older adults, both with (Coef. = -0.898) and without (Coef.: = -0.680) hearing impairments. A stronger association was observed between widowhood and declining cognitive function among older adults with hearing impairment. Specifically, widowhood may be more likely to significantly increase the likelihood of moderate and severe cognitive impairment (RRR = 1.326, 1.538) among older adults with hearing impairments. Social support and social participation significantly moderated the cognitive impairment associated with widowhood among hearing-impaired older adults. These forms of support and engagement are buffers against the risk of widowhood-related cognitive impairment among this demographic. CONCLUSIONS: Our findings indicate that widowhood is significantly associated with cognitive impairment in older adults with hearing impairment. Social support and participation help mitigate this risk. Strategies should prioritize early screening, specialized cognitive rehabilitation, comprehensive care, and enhancing social support and participation to maintain cognitive health in this vulnerable population following widowhood.

Meta-analysis of the effect of exercise intervention on cognitive function in elderly patients with type 2 diabetes mellitus.

OBJECTIVE: Cognitive dysfunction is a common complication of diabetes after central nervous system involvement. The impact of exercise, as an important non-pharmacological intervention strategy, on cognitive function remains controversial. Thus, we conducted a meta-analysis to assess the impact of exercise on cognitive function of elderly patients with type2 diabetes mellitus (T2DM). METHODS: We computer searched PubMed, Web of Science, Embase, CINAHL, Cochrane Library, CNKI, Wanfang date, and VIP, and traced back the references included in the literature from 1974 to July 2024. We used RevMan5.4 software for data analysis, and also conducted sensitivity, subgroup, and publication bias analyses. RESULTS: Eight eligible studies with a combined total of 747 elderly patients with T2DM were included. Meta-analysis showed that the combined effect size of exercise intervention on cognitive improvement in elderly patients with T2DM was significant [SMD = 0.65, 95% CI (0.48, 0.82), P < 0.01]. The following three factors had significant effects on the overall cognitive function of participants: subgroups (MoCA group [MD = 2.22 95% CI (1.26, 3.18), P < 0.01] and MMSE group [MD = 1.81, 95% CI (0.71,2.90), P = 0.001]); intervention times (3-month intervention [MD = 3.14, 95% CI (2.50, 3.78), P < 0.01], 6-month intervention [SMD = 0.32, 95% CI (0.12. 0.52), P = 0.002], and > 6 month intervention [SMD = 0.21, 95% CI (0.45, 0.81), P < 0.01]); intervention forms (single exercise [SMD = 0.21, 95% CI (0.45, 0.81), P < 0.01] and multiple exercise [SMD = 0.86, 95% CI ( 0.39,1.33), P < 0.0001]). CONCLUSION: Exercise intervention may improve cognitive function in elderly patients with T2DM.

Association between apathy and caregiver burden in patients with amyotrophic lateral sclerosis: a cross-sectional study.

OBJECTIVES: To investigate the relationship among patients' apathy, cognitive impairment, depression, anxiety, and caregiver burden in amyotrophic lateral sclerosis (ALS). DESIGN: A cross-sectional study design was used. SETTING: The study was conducted at a tertiary hospital in Wuhan, Hubei, China. PARTICIPANTS: A total of 109 patients with ALS and their caregivers were included. OUTCOME MEASURES: Patients with ALS were screened using the Edinburgh Cognitive and Behavioural Screen, Beck Depression Inventory-II, Generalised Anxiety Disorder-7 and Apathy Scale to assess their cognition, depression, anxiety and apathy, respectively. The primary caregivers completed the Zarit Burden Interview. The association between apathy, cognitive impairment, depression, anxiety and caregiver burden was analysed using logistic regression. Mediation models were employed to investigate the mediating effect of patients' apathy on the relationship between depression/anxiety and caregiver burden. RESULTS: Patients in the high caregiver burden group exhibited significantly higher levels of depression, anxiety and apathy compared with those in the low caregiver burden group (p<0.05). There was a positive association observed between caregiver burden and disease course (rs=0.198, p<0.05), depression (rs=0.189, p<0.05), anxiety (rs=0.257, p<0.05) and apathy (rs=0.388, p<0.05). There was a negative association between caregiver burden and the Revised ALS Functional Rating Scale (rs=-0.275, p<0.05). Apathy was an independent risk factor for higher caregiver burden (OR 1.121, 95% CI 1.041 to 1.206, p<0.05). Apathy fully mediated the relationship between depression and caregiver burden (ß=0.35, 95% CI 0.16 to 0.54, p<0.05) while partially mediating the relationship between anxiety and caregiver burden (ß=0.34, 95% CI 0.16 to 0.52, p<0.05). CONCLUSIONS: Apathy, depression and anxiety exerted a detrimental impact on caregiver burden in individuals with ALS. Apathy played a mediating role in the relationship between depression and caregiver burden and between anxiety and caregiver burden. These findings underscore the importance of identifying apathy and developing interventions for its management within the context of ALS.

[Neurological long-term consequences of COVID-19]. / Neurologische Langzeitfolgen von COVID-19.

The COVID-19 pandemic faced the public health sector with unprecedented challenges. While the immediate impact on society seems to diminish, reports of long-term health consequences persist. Among the most frequently reported symptoms are neurological complaints such as persistent fatigue and cognitive impairments. Scientific understanding is evolving rapidly, and first therapeutic approaches are emerging. However, many questions still remain unanswered.

Depressive symptoms mediate the longitudinal relationships between sleep quality and cognitive functions among older adults with mild cognitive impairment: A cross-lagged modeling analysis.

Although it is generally recognized that sleep quality, depressive symptoms, and cognitive functions are related respectively, the main ambiguity comes from difficulties in determining their cause-effect relationships. The present study aimed to explore the longitudinal causation relationships among sleep quality, depressive symptoms, and cognitive functions in older people with mild cognitive impairment (MCI). A total of 134 patients from 24 communities in Ningbo City, Zhejiang Province, China with MCI were interviewed at baseline, while 124 of them were re-interviewed 2 months later, and 122 were re-interviewed 4 months later. The Patient Health Questionnaire-9, the Pittsburgh Sleep Quality Index and the Montreal Cognitive Assessment Scale were assessed in the interview. Cross-lagged models were tested to disentangle the relationships among sleep quality, depressive symptoms, and cognitive functions using structural equation modeling with latent variables on the four-mouth longitudinal data. The correlation coefficients between sleep quality and depressive symptoms were significant showing the stability across time points of assessment, while the correlation coefficient of cognitive function was not significant (r = 0.159, p > 0.05). The results of index of model fit indicated that the cross-lagged model was acceptable (CFI = 0.934, TLI = 0.899, RMSEA = 0.075, χ2/df = 1.684). The results of cross-lagged model analysis supported the complete mediating role of depressive symptoms in the association between sleep quality and cognitive functions, where worse sleep quality may lead to more severe depressive symptoms, which in turn leads to more severe cognitive decline. In Conclusion, sleep quality is significantly correlated with cognitive functions in patients with mild cognitive impairment, which association is fully mediated by depressive symptoms. Approaches addressing sleep quality and depressive symptoms are recommended and hold promise for the management of mild cognitive impairment.

Objective and subjective experiences of childhood maltreatment and their relationships with cognitive deficits: a cohort study in the USA.

BACKGROUND: Cognitive deficits might contribute to the elevated risk of life-course psychopathology observed in maltreated children. Leading theories about the links between childhood maltreatment and cognitive deficits focus on documented exposures (objective experience), but empirical research has largely relied on retrospective self-reports of these experiences (subjective experience), and the two measures identify largely non-overlapping groups. We aimed to test the associations of objective and subjective measures of maltreatment with cognitive abilities within the same individuals. METHODS: We studied a cohort of individuals from the US Midwest with both objective, court-documented evidence of childhood maltreatment and subjective self-reports of individuals' histories at age 29 years. Between the ages of 29 years and 41 years, participants were assessed with a comprehensive set of cognitive tests, including tests of general verbal intelligence (Quick Test and Wide Range Achievement Test-Revised [WRAT]), non-verbal intelligence (Matrix Reasoning Test [MRT]), executive function (Stroop Test and Trail Making Test Part B [TMT-B]), and processing speed (Trail Making Test Part A [TMT-A]). Participants were also assessed for psychopathology (Center for Epidemiologic Studies Depression Scale and Beck Anxiety Inventory). We tested the associations between objective or subjective measures of childhood maltreatment with cognitive functions using ordinary least squares regression. To test whether cognitive deficits could explain previously described associations between different measures of maltreatment and subsequent psychopathology, we re-ran the analyses accounting for group differences in the Quick Test. People with lived experience were not involved in the research or writing process. FINDINGS: The cohort included 1196 individuals (582 [48·7%] female, 614 [51·3%] male; 752 [62·9%] White, 417 [34·9%] Black, 36 [3·8%] Hispanic) who were assessed between 1989 and 2005. Of the 1179 participants with available data, 173 had objective-only measures of childhood maltreatment, 492 had objective and subjective measures, 252 had subjective-only measures, and 262 had no measures of childhood maltreatment. Participants with objective measures of childhood maltreatment showed pervasive cognitive deficits compared with those without objective measures (Quick Test: ß=-7·97 [95% CI -9·63 to -6·30]; WRAT: ß=-7·41 [-9·09 to -5·74]; MRT: ß=-3·86 [-5·86 to -1·87]; Stroop Test: ß=-1·69 [-3·57 to 0·20]; TMT-B: ß=3·66 [1·67 to 5·66]; TMT-A: ß=2·92 [0·86 to 4·98]). The associations with cognitive deficits were specific to objective measures of neglect. In contrast, participants with subjective measures of childhood maltreatment did not differ from those without subjective measures (Quick Test: ß=1·73 [95% CI -0·05 to 3·50]; WRAT: ß=1·62 [-0·17 to 3·40]; MRT: ß=0·19 [-1·87 to 2·24]; Stroop Test: ß=-1·41 [-3·35 to 0·52]; TMT-B: ß=-0·57 [-2·69 to 1·55]; TMT-A: ß=-0·36 [-2·38 to 1·67]). Furthermore, cognitive deficits did not explain associations between different measures of maltreatment and subsequent psychopathology. INTERPRETATION: Previous studies based on retrospective reports of childhood maltreatment have probably grossly underestimated the extent of cognitive deficits in individuals with documented experiences of childhood maltreatment, particularly neglect. Psychopathology associated with maltreatment is unlikely to emerge because of cognitive deficits, but might instead be driven by individual appraisals, autobiographical memories, and associated schemas. FUNDING: National Institute of Justice, National Institute of Mental Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute on Aging, Doris Duke Charitable Foundation, and National Institute for Health and Care Research.

Housing status is protective of neuropsychiatric symptoms among dementia-free multi-ethnic Asian elderly.

BACKGROUND: Housing has been associated with dementia risk and disability, but associations of housing with differential patterns of neuropsychiatric symptoms (NPS) among dementia-free older adults remain to be explored. The present study sought to explore the contribution of housing status on NPS and subsyndromes associated with cognitive dysfunction in community-dwelling dementia-free elderly in Singapore. METHODS: A total of 839 dementia-free elderly from the Epidemiology of Dementia in Singapore (EDIS) study aged ≥ 60 were enrolled in the current study. All participants underwent clinical, cognitive, and neuropsychiatric inventory (NPI) assessments. The housing status was divided into three categories according to housing type. Cognitive function was measured by a comprehensive neuropsychological battery. The NPS were assessed using 12-term NPI and were grouped into four clinical subsyndromes: psychosis, hyperactivity, affective, and apathy. Associations of housing with composite and domain-specific Z-scores, as well as NPI scores, were assessed using generalized linear models (GLM). Binary logistic regression models analysed the association of housing with the presence of NPS and significant NPS (NPI total scores ≥ 4). RESULTS: Better housing status (5-room executive apartments, condominium, or private housing) was associated with better NPS (OR = 0.49, 95%CI = 0.24 to 0.98, P < 0.05) and significant NPS profile (OR = 0.20, 95%CI = 0.08 to 0.46, P < 0.01), after controlling for demographics, risk factors, and cognitive performance. Compared with those living in 1-2 room apartments, older adults in better housing had lower total NPI scores (ß=-0.50, 95%CI=-0.95 to -0.04, P = 0.032) and lower psychosis scores (ß=-0.36, 95%CI=-0.66 to -0.05, P = 0.025), after controlling for socioeconomic status (SES) indexes. Subgroup analysis indicated a significant correlation between housing type and NPS in females, those of Malay ethnicity, the more educated, those with lower income, and those diagnosed with cognitive impairment, no dementia (CIND). CONCLUSIONS: Our study showed a protective effect of better housing arrangements on NPS, especially psychosis in a multi-ethnic Asian geriatric population without dementia. The protective effect of housing on NPS was independent of SES and might have other pathogenic mechanisms. Improving housing could be an effective way to prevent neuropsychiatric disturbance among the elderly.

Trajectories of pain and their associations with long-term cognitive decline in older adults: evidence from two longitudinal cohorts.

BACKGROUND: Pain is a dynamic experience that varies over time, but it remains unknown whether trajectories of pain are associated with subsequent cognitive decline. The purpose of this study was to identify distinct trajectories of pain presence and activity-limiting pain and investigate their longitudinal associations with the rate of subsequent cognitive decline in older adults. METHODS: A total of 5685 participants from the English Longitudinal Study of Ageing (ELSA) and 7619 participants from the Health and Retirement Study (HRS) were included. Pain presence trajectories were identified over eight years in the ELSA and 10 years in the HRS, while trajectories of activity-limiting pain were identified over 10 years in the HRS. We utilised linear mixed-effects models to investigate the long-term relationship between pain trajectories and the rate of cognitive decline across various domains, including memory, orientation, executive function and global cognition. RESULTS: Three pain presence trajectories were identified. Moderate-increasing and high-stable groups exhibited steeper declines in global cognition than the low-stable group. Furthermore, individuals in the moderate-increasing group experienced a more rapid decline in executive function, while the high-stable group showed a faster decline in orientation function. Two trajectories of activity-limiting pain were identified, with the moderate-increasing group experiencing a faster decline in orientation function and global cognition. CONCLUSIONS: The trajectories of both pain presence and activity-limiting pain are linked to the rate of subsequent cognitive decline among older people. Interventions for specific pain trajectories might help to delay the decline rate of cognition in specific domains.

On the Clinimetrics of the Montreal Cognitive Assessment: Cutoff Analysis in Patients with Mild Cognitive Impairment due to Alzheimer's Disease.

Background: In the era of disease-modifying therapies, empowering the clinical neuropsychologist's toolkit for timely identification of mild cognitive impairment (MCI) is crucial. Objective: Here we examine the clinimetric properties of the Montreal Cognitive Assessment (MoCA) for the early diagnosis of MCI due to Alzheimer's disease (MCI-AD). Methods: Data from 48 patients with MCI-AD and 47 healthy controls were retrospectively analyzed. Raw MoCA scores were corrected according to the conventional Nasreddine's 1-point correction and demographic adjustments derived from three normative studies. Optimal cutoffs were determined while previously established cutoffs were diagnostically reevaluated. Results: The original Nasreddine's cutoff of 26 and normative cutoffs (non-parametric outer tolerance limit on the 5th percentile of demographically-adjusted score distributions) were overly imbalanced in terms of Sensitivity (Se) and Specificity (Sp). The optimal cutoff for Nasreddine's adjustment showed adequate clinimetric properties (≤23.50, Se = 0.75, Sp = 0.70). However, the optimal cutoff for Santangelo's adjustment (≤22.85, Se = 0.65, Sp = 0.87) proved to be the most effective for both screening and diagnostic purposes according to Larner's metrics. The results of post-probability analyses revealed that an individual testing positive using Santangelo's adjustment combined with a cutoff of 22.85 would have 84% post-test probability of receiving a diagnosis of MCI-AD (LR+ = 5.06). Conclusions: We found a common (mal)practice of bypassing the applicability of normative cutoffs in diagnosis-oriented clinical practice. In this study, we identified optimal cutoffs for MoCA to be allocated in secondary care settings for supporting MCI-AD diagnosis. Methodological and psychometric issues are discussed.

The Role of Functional Deficits, Depression, and Cognitive Symptoms in the Perceived Loneliness of Older Adults in Mexico City.

The world is aging and experiencing loneliness. Functional impairment in instrumental activities of daily living (IADL) in older people (OP) with mild neurocognitive disorder (MNCD) predicts loneliness. After the pandemic, there was an increase in perceived loneliness. We explored the association between loneliness, depression, deficits in IADL, and cognitive symptoms among OP. From February to December 2023, using a cross-sectional design, we interviewed probable cases with mild cognitive impairment and caregivers in two public facilities. We administered the UCLA Loneliness Scale v3, Lawton IADL Scale, Mini-Mental State Examination (MMSE), and Yesavage's Geriatric Depression Scale. Samples were matched: 85 per group, 82.4% were women, married (52.95%), and mean age of 69.17 (±6.93) years. In our study, 30% displayed moderate to high levels of perceived loneliness. Multivariate analysis showed loneliness was associated with depression, low levels of IADL, and older age, but not with cognitive symptoms, which explained 22% of the total variance (F 165) = 16.99, (p < 0.001). Targeting symptoms and behaviors that could be modified (i.e., depression and functionality) can improve feelings of perceived loneliness and have an impact on morbidity and mortality with which it is associated.