Domains Of Cognitive Function Research Articles

Challenges in Cognitive Domain Performance for Laboratory-Embedded Electrical Engineering Courses

Challenges in Cognitive Domain Performance for Laboratory-Embedded Electrical Engineering Courses

Anticholinergic Medication Burden and Cognitive Subtypes in Parkinson's Disease without Dementia.

Cognitive changes are heterogeneous in Parkinson's disease (PD). This study compared whether anticholinergic burden drives differences in cognitive domain performance and empirically-derived PD-cognitive phenotypes. A retrospective chart review contained participants (n = 493) who had idiopathic PD without dementia. Participants' medications were scored (0-3) and summed based on the anticholinergic cognitive burden scale (ACBS). We examined the ACBS' relationship to five cognitive domain composites (normative z-scores) and three (K-means clustering based) cognitive phenotypes: cognitively intact, low executive function (EF), and predominately impaired EF/memory. Analyses included Spearman correlations, analysis of covariance, and Pearson chi-squared test. Overall, phenotypes did not differ in anticholinergic burden, and (after false-discovery-rate corrections) no cognitive domains related. When comparing those above and below the clinically relevant ACBS cutoff (i.e., score ≥3), no significant phenotype or domain differences were found. Anticholinergic medication usage did not drive cognitive performance in a large clinical sample of idiopathic PD without dementia.

#235 Quality of sleep and the quality of life in chronic kidney disease patients undergoing hemodialysis in a tertiary hospital in the Philippines

Abstract Background and Aims Sleep quality and quality of life are critical aspects of health and well-being, particularly for individuals undergoing hemodialysis. Hemodialysis is a life-sustaining treatment for individuals with end-stage kidney disease (ESKD), but it can significantly impact various dimensions of their health, including sleep quality and overall quality of life. Understanding the relationship between sleep and quality of life in hemodialysis patients is essential for developing effective interventions to improve their overall well-being. Studies have shown that hemodialysis patients often experience poor sleep quality, characterized by difficulty falling asleep, frequent awakenings during the night, and early morning awakening. Moreover, sleep disturbances experienced by hemodialysis patients can also affect their ability to perform daily activities which can have a negative impact on their overall quality of life. Factors that have been shown to be associated with quality of sleep and quality of life in hemodialysis patients include age, sex, comorbidity, mode and schedule of hemodialysis, hemoglobin, phosphorus and albumin. Physicians can provide patient-centered care more effectively when they have a better grasp of the quality of life. However, the quality of life is not thoroughly studied in individuals with chronic kidney disease, particularly those undergoing hemodialysis. To address these issues, it is essential to prioritize sleep quality and quality of life in hemodialysis patients. The aims of this study were to determine the prevalence of ‘poor sleepers’ in patients undergoing hemodialysis using a validated sleep quality questionnaire and to examine the relationship between patients’ sleep quality with the quality of life using a validated kidney-disease specific quality of life questionnaire. Method This was a descriptive cross-sectional study conducted at The Medical City Ortigas from May to July 2023. The subjects recruited were adult hemodialysis patients enrolled in The Medical City Ortigas. To get a 95% confidence level, a minimum population of 80 patients should be included based on 71% prevalence from the study of Iliescu in 2003. This study evaluated a total of 85 patients through random selection. Patients excluded were those <18 years of age, had been on dialysis for less than 3 months, were not competent to give informed consent, and those with diagnosed sleeping disorder prior to having chronic kidney disease. Quality of sleep and quality of life were measured using validated self-administered questionnaires; the Pittsburgh Sleep Quality Index (PSQI) and the Kidney Disease Quality of Life-Short Form v1.3 (KDQOL) respectively. Results Among the respondents 67 (78.82%) were found to be poor sleepers (PSQI >5) with a mean global PSQI of 9.25. Age appeared to be a significant factor as the percentage of bad sleepers belong to the 46-65 and >65 age groups. In contrast, sex, marital status, 150 employment, hemodialysis shift, BMI, kt/V, hemodialysis type, albumin, phosphorus, and hemoglobin levels did not have significant association with quality of sleep. There is significantly a greater number of bad sleepers that have a lower functioning due to symptoms experienced (50.65 bad sleepers vs 62.85 good sleepers). Bad sleepers also have worse quality of life in domains of cognitive function (66.67 vs 55.22), sleep (56.67 vs 46.9), patient satisfaction (57.41 vs 45.27) overall health (54.44 vs 43.28) and general health (40.83 vs 32.16). Correlations between the global PSQI score and the domains of KDQOL computed via Pearson r coefficient showing an inverse correlation between PSQI and the mental (-.392) and physical (-0.320) component summaries. Conclusion Poor sleep is common in hemodialysis patients and is associated with poorer quality of life.

The impact of incident stroke on cognitive trajectories in later life

BackgroundCognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals.Methods19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test–Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke.ResultsDuring a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants.ConclusionsThese findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention.

The association between physical frailty and cognitive performance in older adults aged 60-96 years. Data from the "Good Aging in Skåne" (GÅS) Swedish population study.

The association between physical frailty and performance in different cognitive domains in the absence of cognitive disorders is poorly understood. Hence, we aimed to explore the associations between frailty levels based on the Fried Physical Frailty Phenotype and performance of different cognitive domains. We also aimed to examine the associations between cognitive function and each criterion in the Fried Frailty Scale using the same cognitive domains in a non-dementia population aged 60-96 years. This cross-sectional study included 4,329 participants aged 60-93 years, drawn from the "Good Aging in Skåne" population study. Frailty indices included handgrip strength, physical endurance, body mass index (BMI), physical activity, and walking speed. Cognitive function was assessed across eight domains: episodic memory, processing speed, semantic memory, verbal fluency, working memory, attention, executive function, and visual perception. We constructed adjusted multiple linear regression models for each cognitive domain, with the frailty levels as the independent variable. Likewise, we constructed linear regression models with each cognitive domain as the dependent variable and frailty criteria as independent variables. Physical frailty was associated with poor performance in episodic memory, processing speed, semantic memory, verbal fluency, working memory, attention, and executive functions (p < 0.001 for all associations). Weaker hand grip strength was independently associated with poorer performance in all cognitive domains (p < 0.001-0.015). Higher levels of frailty were associated with poorer performance in all cognitive domains except visual perception. Describing frailty by considering cognitive functioning may provide a better understanding of frailty.

Changes in cognitive function after a 12-week POWER rehabilitation in older adults with schizophrenia and frailty.

The effectiveness of isolated resistance training (RT) on cognitive function among older adults with schizophrenia is insufficiently investigated. This study investigated the effectiveness of 12-weeks POWER rehabilitation, a novel RT regimen, on cognitive function among older patients with schizophrenia and frailty. Thirty-two older adults with schizophrenia and frailty were enrolled and randomized to receive either a 12-week, twice weekly POWER rehabilitation, or without add-on training. Cognitive functioning was assessed using mini-mental state examination (MMSE), digit symbol substitution test, color trail task (CTT), and digit span task (DST). Physical performance was assessed by walking speed and hand grip strength. The generalized estimating equations was used to compare pre- and post-training outcome measure between groups. Between-group analysis revealed significant improvement in CTT1 and hand grip strength in the intervention group compared to the controls. Subgroup analyses showed CTT1 performance significantly improved after 12 weeks of POWER rehabilitation in the intervention group (time, p < .001), independent of age, educational level, global cognition, depressive symptoms, and psychotropic medication use. Increased hand grip strength was significantly associated with improved performance in MMSE, CTT1, and DST forward at study endpoint. A 12-week POWER rehabilitation for older patients with schizophrenia and frailty is safe and feasible, and may benefit physical and some domains of cognitive functioning.

Apathy and Depression Among People Aging With Traumatic Brain Injury: Relationships to Cognitive Performance and Psychosocial Functioning.

Apathy and depression are both common after moderate to severe traumatic brain injury (TBI) and may be especially important to distinguish in older adults with TBI. The authors examined apathy and depression in relation to cognitive performance domains and their potentially unique contribution to psychosocial functioning in this patient population. A total of 106 participants (mean±SD age=64±8 years) with chronic moderate to severe TBI (≥1 year) completed questionnaires assessing severity of apathy (Frontal Systems Behavior Scale-apathy subscale) and depression (Geriatric Depression Scale-15) symptoms, health-related quality of life (HRQoL), and societal participation. Participants also completed neuropsychological tests of episodic memory, processing speed, and executive functioning. Apathy symptom severity was significantly associated with all cognitive performances in correlations adjusted for the familywise error rate; a relationship with executive functioning remained after controlling for demographic and injury variables. Depression symptom severity was not significantly associated with cognition after statistical correction. Both symptomatologies uniquely contributed to HRQoL. Only depression symptoms contributed to societal participation. On the basis of clinical cutoffs, half the sample had neither depression nor apathy, approximately 25% met criteria for only apathy, and 25% had both apathy and depression. The combined presence of clinical depression and apathy was associated with worse HRQoL and societal participation. This is the first study to examine apathy and depression in relation to cognition and psychosocial functioning in an older sample with a history of TBI. Findings suggest that the two syndromes can be dissociated in clinically meaningful ways, which may help to refine psychiatric and behavioral interventions in this vulnerable population.

Modeling the effects of treatment resistance and anticholinergic burden on cognitive function domains in patients with schizophrenia

The contribution of anticholinergic burden to cognitive function in patients with treatment resistant schizophrenia (TRS) is uncertain. This case-control study of patients aims to comprehensively examine the association between treatment resistance and cognitive functions and the contribution of anticholinergic burden. Anticholinergic burden of all patients was calculated using the Anticholinergic Cognitive Burden scale. Exploratory Factor Analysis of 11 cognitive assessments identified four cognitive domains: verbal memory, attention and general cognitive functions, visual memory and processing speed, and executive function. Two structural equation models (SEM) examined the relationship of TRS and these cognitive functions with, and without considering anticholinergic burden. A total of 288 participants were included (TRS N=111, non-TRS N=177). Patients with TRS performed poorer than the non-TRS group only in the executive function domain. Anticholinergic burden contributed significantly to the attention and general cognitive functions, visual memory and processing speed, and executive function. The impact of TRS on executive function was no longer significant after adding anticholinergic burden to the SEM. Results suggested that anticholinergic burden contributes to a wide range of cognitive function impairment in patients with schizophrenia and is likely to be part of the apparent differences of cognitive function between TRS and non-TRS.

The effects of radiofrequency exposure on cognition: A systematic review and meta-analysis of human observational studies

BackgroundWe aimed to assess evidence of long-term effects of exposure to radiofrequency (RF) electromagnetic fields (EMF) on indicators of cognition, including domains of learning and memory, executive function, complex attention, language, perceptual motor ability and social cognition, and of an exposure–response relationship between RF-EMF and cognition. MethodsWe searched PubMed, Embase, PsycInfo and the EMF-Portal on September 30, 2022 without limiting by date or language of publication. We included cohort or case-control studies that evaluated the effects of RF exposure on cognitive function in one or more of the cognitive domains. Studies were rated for risk of bias using the OHAT tool and synthesised using fixed effects meta-analysis. We assessed the certainty of the evidence using the GRADE approach and considered modification by OHAT for assessing evidence of exposures. ResultsWe included 5 studies that reported analyses of data from 4 cohorts with 4639 participants consisting of 2808 adults and 1831 children across three countries (Australia, Singapore and Switzerland) conducted between 2006 and 2017. The main source of RF-EMF exposure was mobile (cell) phone use measured as calls per week or minutes per day.For mobile phone use in children, two studies (615 participants) that compared an increase in mobile phone use to a decrease or no change were included in meta-analyses. Learning and memory. There was little effect on accuracy (mean difference, MD −0.03; 95% CI −0.07 to 0.02) or response time (MD −0.01; 95% CI −0.04 to 0.02) on the one-back memory task; and accuracy (MD −0.02; 95%CI −0.04 to 0.00) or response time (MD −0.01; 95%CI −0.04 to 0.03) on the one card learning task (low certainty evidence for all outcomes). Executive function. There was little to no effect on the Stroop test for the time ratio ((B-A)/A) response (MD 0.02; 95% CI −0.01 to 0.04, very low certainty) or the time ratio ((D-C)/C) response (MD 0.00; 95% CI −0.06 to 0.05, very low certainty), with both tests measuring susceptibility to interference effects. Complex attention. There was little to no effect on detection task accuracy (MD 0.02; 95% CI −0.04 to 0.08), or response time (MD 0.02;95% CI 0.01 to 0.03), and little to no effect on identification task accuracy (MD 0.00; 95% CI −0.04 to 0.05) or response time (MD 0.00;95% CI −0.01 to 0.02) (low certainty evidence for all outcomes). No other cognitive domains were investigated in children.A single study among elderly people provided very low certainty evidence that more frequent mobile phone use may have little to no effect on the odds of a decline in global cognitive function (odds ratio, OR 0.81; 95% CI 0.42 to 1.58, 649 participants) or a decline in executive function (OR 1.07; 95% CI 0.37 to 3.05, 146 participants), and may lead to a small, probably unimportant, reduction in the odds of a decline in complex attention (OR 0.67;95%CI 0.27 to 1.68, 159 participants) and a decline in learning and memory (OR 0.75; 95% CI 0.29 to 1.99, 159 participants). An exposure–response relationship was not identified for any of the cognitive outcomes. DiscussionThis systematic review and meta-analysis found only a few studies that provided very low to low certainty evidence of little to no association between RF-EMF exposure and learning and memory, executive function and complex attention. None of the studies among children reported on global cognitive function or other domains of cognition. Only one study reported a lack of an effect for all domains in elderly persons but this was of very low certainty evidence. Further studies are needed to address all types of populations, exposures and cognitive outcomes, particularly studies investigating environmental and occupational exposure in adults. Future studies also need to address uncertainties in the assessment of exposure and standardise testing of specific domains of cognitive function to enable synthesis across studies and increase the certainty of the evidence. OtherThis review was partially funded by the WHO radioprotection programme and prospectively registered on PROSPERO CRD42021257548.

“Discharge Doesn’t Mean the End” Exploring Success in Discharge to Community Self-management For Young Adults Living with Chronic Pain: A Qualitative Study

Background Living with chronic pain as a young adult (YA) can impact the physical, emotional, social, cognitive, and role function domains of life. Once YAs receive care for their specialist chronic pain care they are expected to self-navigate a complex healthcare system to transition to community-based care (i.e. primary care). Inadequate discharge planning may increase the unique difficulties YAs face in self-management, which may lead to adverse health outcomes, suboptimal discharge, and a need to re-access care. Aims The purpose of this qualitative study is to explore how YAs with chronic pain define a successful discharge transition from a health service delivery model of specialized chronic pain services setting to self-management in a community setting (i.e. primary care) and contextual factors that promote discharge success. Methods This qualitative study included young adults with chronic pain. Data were obtained through semi-structured interviews which were transcribed verbatim and analyed using inductive content analysis.. Results Ten participants identified that successful discharge includes the following consideration, 1) acknowledging the tension between moving forward and looking back, 2) a collaborative discharge process, and 3) the need for ongoing, relevant resources and support. Conclusion This study provided a deeper understanding of how YAs with chronic pain characterize success in the discharge transition from specialized chronic pain services to community self-management. Our findings highlighted the importance of provider-patient collaboration during the discharge planning process to develop a patient centered self-management plan that incorporates community resources tailored to the needs of the individual to promote an optimal discharge.

Neighborhood disadvantage is associated with working memory and hippocampal volumes among older adults

ABSTRACT It is not well understood how neighborhood disadvantage is associated with specific domains of cognitive function and underlying brain health within older adults. Thus, the objective was to examine associations between neighborhood disadvantage, brain health, and cognitive performance, and examine whether associations were more pronounced among women. The study included 136 older adults who underwent cognitive testing and MRI. Neighborhood disadvantage was characterized using the Area Deprivation Index (ADI). Descriptive statistics, bivariate correlations, and multiple regressions were run. Multiple regressions, adjusted for age, sex, education, and depression, showed that higher ADI state rankings (greater disadvantage) were associated with poorer working memory performance (p < .01) and lower hippocampal volumes (p < .01), but not total, frontal, and white matter lesion volumes, nor visual and verbal memory performance. There were no significant sex interactions. Findings suggest that greater neighborhood disadvantage may play a role in working memory and underlying brain structure.

Subjective sleep more predictive of global cognitive function than objective sleep in older adults: A specification curve analysis

ObjectivesSleep is associated with cognitive function in older adults. In the current study, we examined this relationship from subjective and objective perspectives, and determined the robustness and dimensional specificity of the associations using a comprehensive modelling approach. MethodsMultiple dimensions of subjective (sleep quality and daytime sleepiness) and objective sleep (sleep stages, sleep parameters, sleep spindles, and slow oscillations), as well as subjectively reported and objectively measured cognitive function were collected from 55 older adults. Specification curve analysis was used to examine the robustness of correlations for the effects of sleep on cognitive function. ResultsRobust associations were found between sleep and objectively measured cognitive function, but not with subjective cognitive complaints. In addition, subjective sleep showed robust and consistent associations with global cognitive function, whereas objective sleep showed a more domain-specific association with episodic memory. Specifically, subjective sleep quality and daytime sleepiness correlated with global cognitive function, and objective sleep parameters correlated with episodic memory. ConclusionsOverall, associations between sleep and cognitive function in older adults depend on how they are measured and which specific dimensions of sleep and domains of cognitive function are considered. It highlights the importance of focusing on specific associations to ameliorate the detrimental effects of sleep disturbance on cognitive function in later life.

Cardiovascular Health, Race, and Decline in Cognitive Function in Midlife Women: The Study of Women's Health Across the Nation.

Cognitive decline may progress for decades before dementia onset. Better cardiovascular health (CVH) has been related to less cognitive decline, but it is unclear whether this begins early, for all racial subgroups, and all domains of cognitive function. The purpose of this study was to determine the impact of CVH on decline in the 2 domains of cognition that decline first in White and Black women at midlife. Subjects were 363 Black and 402 White women, similar in baseline age (mean±SD, 46.6±3.0 years) and education (15.7±2.0 years), from the Chicago site of the Study of Women's Health Across the Nation. Cognition, measured as processing speed and working memory, was assessed annually or biennially over a maximum of 20 years (mean±SD, 9.8±6.7 years). CVH was measured as Life's Essential 8 (blood pressure, body mass index, glucose, non-high-density lipoprotein cholesterol, smoking, physical activity, diet, sleep). Hierarchical linear mixed models identified predictors of cognitive decline with progressive levels of adjustment. There was a decline in processing speed that was explained by race, age, and the 3-way interaction of race, CVH, and time (F1,4308=8.8, P=0.003). CVH was unrelated to decline in White women but in Black women poorer CVH was associated with greater decline. Working memory did not decline in the total cohort, by race, or by CVH. In midlife Black women, CVH promotion may be a target for preventing the beginnings of cognitive decline, thereby enhancing independent living with aging.

Comparison of time to clinically meaningful improvement in quality of life in neurological disorders in patients treated with natalizumab versus ocrelizumab.

Aim: To assess time to improvement in Quality of Life in Neurological Disorders (Neuro-QoL) domains for patients treated with natalizumab versus ocrelizumab. Methods: Patients enrolled in the MS PATHS network who initiated treatment with either natalizumab or ocrelizumab rated the Neuro-QoL domains of physical function, symptoms, emotional health, cognitive function and social ability. Results: Time to clinically meaningful improvement was significantly shorter with natalizumab versus ocrelizumab for cognitive function (event time ratio [95% CI]: 0.37 [0.24-0.57]; p<0.001), sleep disturbance (0.45 [0.28-0.72]; p=0.001), social role participation (0.37 [0.21-0.66]; p=0.001) and social role satisfaction (0.5 [0.31-0.8]; p=0.004). Conclusion: Natalizumab had shorter time to clinically meaningful improvement in cognitive, sleep, and social role Neuro-QoL domains versus ocrelizumab.

Depressive symptoms and cognitive decline in older adults.

Few studies have examined the impact of late-life depression trajectories on specific domains of cognitive function. This study aims to delineate how different depressive symptom trajectories specifically affect cognitive function in older adults. Prospective longitudinal cohort study. Australia and the United States of America. In total, 11,035 community-dwelling older adults with a mean age of 75 years. Depressive trajectories were modelled from depressive symptoms according to annual Centre for Epidemiological Studies Depression Scale 10 (CES-D-10) surveys. Four trajectories of depressive symptoms were identified: low ("nondepressed"), consistently mild ("subthreshold depression"), consistently moderate ("persistent depression"), and initially low but increasing ("emerging depression"). Global cognition (Modified Mini-Mental State Examination [3MS]), verbal fluency (Controlled Oral Word Association Test [COWAT]), processing speed (Symbol Digit Modalities Test [SDMT]), episodic memory (Hopkins Verbal Learning Test - Revised [HVLT-R]), and a composite z-score were assessed over a subsequent median 2 years. Subthreshold depression predicted impaired performance on the SDMT (Cohen's d -0.04) and composite score (-0.03); emerging depression predicted impaired performance on the SDMT (-0.13), HVLT-R (-0.09), 3 MS (-0.08) and composite score (-0.09); and persistent depression predicted impaired performance on the SDMT (-0.08), 3 MS (-0.11), and composite score (-0.09). Depressive symptoms are associated with later impaired processing speed. These effects are small. Diverse depression trajectories have different impacts on cognitive function.

Associations between physical activity, sedentary behaviour and cognitive domain performance of people living with mild cognitive impairment in the community.

Physical activity is known to positively influence cognitive performance. For adults with mild cognitive impairment (MCI), the relationship between physical activity levels and cognitive performance is unknown. This cross-sectional study aimed to determine if cognitive performance [as measured by the Montreal Cognitive Assessment (MoCA)] of people living in the community with MCI is associated with their physical activity levels or sedentary behaviour. ActivPAL™ accelerometers were used to objectively measure physical activity and sedentary behaviour for seven full days. Cognitive performance was measured using the MoCA. No involvement other than as research participants RESULTS: Eighty-two participants from the Balance on the Brain randomised controlled trial were included. Most participants were retired (88%), with 33 (40%) reporting a fall in the last year. The median MoCA score was 24 (IQR 22-26). Participants achieved a mean of 6296 (±2420) steps per day and were sedentary for 10.6 (±2) hours per day. The only physical activity outcomes that had a fair, positive correlation were moderate- to vigorous-intensity physical activity measures of total stepping time and total number of steps (with a cadence of ≥100 steps/min) with the orientation MoCA domain score (r(82) =0.36, p≤0.001 and r(82) =0.37, p≤0.001, respectively). Higher total sedentary time had a weak, positive correlation with better visuospatial/executive performance (r(82) =0.23, p= 0.041). The orientation outcomes remained significant when analysed in an adjusted logistic regression model. This study found that performance in the MoCA orientation domain had a fair-positive correlation with moderate-intensity physical activity (i.e., stepping time and step count with a cadence of ≥100 steps/min) as measured by a thigh-worn accelerometer for community-dwelling older adults with MCI. When considering the relationship between cognitive domains and sedentary behaviour, consideration may be needed regarding whether cognitive enhancing activities (such as crosswords and other brain games) are being performed, which may confound this relationship. Further investigation is required to confirm these results.

A preliminary study on the neurocognitive deficits associated with loneliness in young adults.

The experience of loneliness is universal and may have an adverse effect on neurocognitive functioning even at a younger age. Using a comprehensive neurocognitive functioning test (NCFT) battery, we examined the possible negative effects of loneliness on neurocognitive functioning in young adults. The high-loneliness and low-loneliness groups were screened using the UCLA Loneliness Scale v. 3, and measures pertaining to the domains of intelligence, attention, memory, executive function, and psychomotor functioning were tested and compared. As depression and anxiety were significantly higher in the high-loneliness group, an analysis of covariance was conducted. As a result, the high-loneliness group showed significantly poor performance on measures of executive function and attention prior to controlling for depression and anxiety, and executive function retained its significance even after controlling for these variables. Additional analysis showed that depression and anxiety did not significantly mediate the relationship between loneliness and neurocognitive functioning. Such results suggest that loneliness is likely to negatively affect executive functioning and attention in early adulthood and then progressively spread to other domains of cognitive functioning, as reported in the older adult population. The limitations and implications of the present study were considered and addressed.

Large-scale whole-exome sequencing of neuropsychiatric diseases and traits in 350,770 adults.

While numerous genomic loci have been identified for neuropsychiatric conditions, the contribution of protein-coding variants has yet to be determined. Here we conducted a large-scale whole-exome-sequencing study to interrogate the impact of protein-coding variants on 46 neuropsychiatric diseases and 23 traits in 350,770 adults from the UK Biobank. Twenty new genes were associated with neuropsychiatric diseases through coding variants, among which 16 genes had impacts on the longitudinal risks of diseases. Thirty new genes were associated with neuropsychiatric traits, with SYNGAP1 showing pleiotropic effects across cognitive function domains. Pairwise estimation of genetic correlations at the coding-variant level highlighted shared genetic associations among pairs of neurodegenerative diseases and mental disorders. Lastly, a comprehensive multi-omics analysis suggested that alterations in brain structures, blood proteins and inflammation potentially contribute to the gene-phenotype linkages. Overall, our findings characterized a compendium of protein-coding variants for future research on the biology and therapeutics of neuropsychiatric phenotypes.

Cognitive Effects of Reducing First-Generation Antipsychotic Dose Compared to Switching to Ziprasidone in Long-Stay Patients with Schizophrenia.

Background: Cognitive impairment is a core symptom of schizophrenia and is associated with functional outcomes. Improving cognitive function is an important treatment goal. Studies have reported beneficial cognitive effects of the second-generation antipsychotic (SGA) ziprasidone. Reducing the dose of first-generation antipsychotics (FGA) might also improve cognitive function. This study compared the cognitive effects in long-stay patients who were randomized to groups who underwent FGA dose reduction or switched to ziprasidone. Methods: High-dose FGA was reduced to an equivalent of 5 mg of haloperidol in 10 patients (FGA-DR-condition), and 13 patients switched to ziprasidone 80 mg b.i.d. (ZIPRA condition). Five domains of cognitive function were assessed before dose reduction or switching (T0) and after 1 year (T1). This study was approved by the ethics committee of the Open Ankh (CCMO number 338) and registered at the Netherlands Trial Register (code 5864). Results: Non-significant deterioration was seen in all cognitive domains studied in the FGA-DR condition, whereas there was a non-significant improvement in all cognitive domains in the ZIPRA condition. The most robust difference between conditions, in favor of ziprasidone, was in executive function. Conclusions: In patients with severe chronic schizophrenia, ziprasidone had a non-significant and very modest beneficial effect on cognitive function compared with FGA dose reduction. Larger trials are needed to further investigate this effect.

The mediating role of neuroimaging-derived biological brain age in the association between risk factors for dementia and cognitive decline in middle-aged and older individuals without cognitive impairment: a cohort study

Neuroimaging-based brain-age delta has been shown to be a mediator linking cardiovascular risk factors to cognitive function. We aimed to assess the mediating role of brain-age delta in the association between modifiable risk factors of dementia and longitudinal cognitive decline in middle-aged and older individuals who are asymptomatic, stratified by Alzheimer's disease pathology. We also explored whether the mediation effect is specific to cognitive domain. In this cohort study, we included participants from the ALFA+ cohort aged between 45 years and 65 years who were cognitively unimpaired and who had available structural MRI, cerebrospinal fluid β-amyloid (Aβ)42 and Aβ40 measurements obtained within 1 year of each other, modifiable risk factors assessment, and cognitive evaluation over 3 years. Participants were recruited from the Barcelonaβeta Brain Research Center (Barcelona, Spain). Included individuals underwent a first assessment between Oct 25, 2016, and Jan 28, 2020, and a follow-up cognitive assessment 3·28 (SD 0·27) years later. We computed brain-age delta and composites of different cognitive function domains (preclinical Alzheimer's cognitive composite [PACC], attention, executive function, episodic memory, visual processing, and language). We used partial least squares path modelling to explore mediation effects in the associations between modifiable risk factors (including cardiovascular, mental health, mood, metabolic or endocrine history, and alcohol use) and changes in cognitive composites. To assess the role of Alzheimer's disease pathology, we computed separate models for Aβ-negative and Aβ-positive individuals. Of the 419 participants enrolled in ALFA+, 302 met our inclusion criteria, of which 108 participants were classified as Aβ-positive and 194 as Aβ-negative. In Aβ-positive individuals, brain-age delta partially mediated (percent mediation proportion 15·73% [95% CI 14·22-16·66]) the association between modifiable risk factors and decline in overall cognition (across cognitive domains). Brain-age delta fully mediated (mediation proportion 28·03% [26·25-29·21]) the effect of modifiable risk factors on the PACC, wherein increased values for risk factors correlated with an older brain-age delta, and, consequently, an older brain-age delta was linked to greater PACC decline. This effect appears to be primarily driven by memory decline. Mediation was not significant in Aβ-negative individuals (3·52% [0·072-4·17]) on PACC, although path coefficients were not significantly different from those in the Aβ-positive group. Our findings suggest that brain-age delta captures the association between modifiable risk factors and longitudinal cognitive decline in middle-aged and older people. In asymptomatic middle-aged and older individuals who are Aβ-positive, the pathology might be the strongest driver of cognitive decline, whereas the effect of risk factors is smaller. Our results highlight the potential of brain-age delta as an objective outcome measure for preventive lifestyle interventions targeting cognitive decline. La Caixa Foundation, the TriBEKa Imaging Platform, and the Universities and Research Secretariat of the Catalan Government. For the Spanish translation of the abstract see Supplementary Materials section.