Greater Cognitive Impairment Research Articles

Longitudinal clinical decline and baseline predictors in progressive supranuclear palsy

IntroductionProgressive supranuclear palsy (PSP) is associated with several clinical variants defined based on ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction, although little is known about how these features progress over time. We aimed to assess the evolution of these core clinical features across variants and assess baseline clinical and neuroimaging predictors of progression. MethodsNinety-three PSP patients were recruited by the Neurodegenerative Research Group, Mayo Clinic, and underwent two visits 1-year apart, with baseline MRI and [18F]flortaucipir PET. We compared baseline and annualized rates of clinical change on the PSP Rating Scale (total, ocular motor, gait/midline scores) and Montreal Cognitive Assessment, across PSP-Richardson's, PSP-Cortical and PSP-Subcortical variants and assessed relationships between rates of change and baseline regional imaging. ResultsOcular motor scores differed across groups at baseline and follow-up, with lowest scores observed in PSP-subcortical, but no differences were observed in rate of change across groups. PSP Rating Scale total and gait/midline scores differed across groups at follow-up and in rates of change, with PSP-subcortical showing the least impairment and slowest progression. Greatest cognitive impairment was observed in PSP-Cortical. Sample size estimates for treatment trials differed across PSP variants. Greater baseline flortaucipir uptake, but not volume, of midbrain and motor cortex correlated with faster rates of clinical decline. ConclusionThe PSP Rating Scale and its subscores might be useful markers for the prognostic stratification of PSP variants. Flortaucipir imaging at baseline may help predict rate of decline.

FOLLOWING PHYSICIAN’S ADVICE IN LATE LIFE: THE ROLES OF LOCUS OF CONTROL AND HEALTH STATUS

Abstract Adherence to physicians’ recommendations plays an important role in health maintenance in old age (Kravitz, Hays, Sherbourne & DiMatteo,1993). However insufficient attention has been paid to the influence of patients’ mental and physical health and locus of control on adherence to physician’s recommendations. This paper studied subjective health appraisals, chronic illnesses, functional limitations, and cognitive impairment along with internal or external locus of control as influences on adherence to physicians’ recommendations. We explored these associations among 684 older adults (mean age = 80.71 years) living in a retirement community in Florida. Respondents participated in the Elderly Care Research Center successful aging study (Kahana, Kelley-Moore & Kahana 2012). Older patients and those with more functional limitations reported greater adherence to physicians’ recommendations (b=.15, p< 0.05). Those respondents with greater cognitive impairment were less adherent (b=-.1, p< 0.05). Internal locus of control, reflected in beliefs that patients play a major role in health outcomes was associated with less adherence (b=-0.1, p< 0.05). The belief that health professionals influence health outcomes was associated with greater adherence (b=.1, < 0.05). Lower adherence was also associated with the stronger belief that health is a matter of good fortune (b=-.06, p< 0.05). Our findings offer useful insights about the role of internal vs. external influences on health outcome expectations in late life and health behaviors of compliance with medical regimens.

Prevalence of cognitive impairment in patients with rheumatoid arthritis: a cross sectional study.

To explore the role of chronic inflammation in rheumatoid arthritis (RA) on cognition. Six hundred sixty-one men and women aged ≥55 years who fulfilled the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for RA were recruited from three healthcare trusts in the United Kingdom (UK) between May 2018 and March 2020. Study participants took part in interviews which captured sociodemographic information, followed by an assessment of cognition. RA specific clinical characteristics were obtained from hospital medical records. Participants were cognitively assessed using the Montreal Cognitive Assessment (MoCA) and were classified as cognitively impaired if they scored ≤27/30 points. Linear regression analyses were conducted to identify which demographic and clinical variables were potential predictors of cognitive impairment. The average age of participants was 67.6 years and 67% (444/661) were women. 72% (458/634; 95% CI 0.69 to 0.76) of participants were classified as cognitively impaired (MoCA≤27). Greater cognitive impairment was associated with older age (p= .006), being male (p= .041) and higher disease activity score (DAS28) (with moderate (DAS28 > 3.1) (p= 0.008) and high (DAS28 > 5.1) (p= 0.008)) compared to those in remission (DAS28 ≤ 2.6). There was no association between MoCA score and education, disease duration, RF status, anti-cyclic citrullinated peptide (anti-CCP) status, RA medication type or use of glucocorticoids or non-steroidal anti-inflammatory drugs (p> 0.05). This study suggests that cognitive impairment is highly prevalent in older adults with RA. This impairment appears to be associated with higher RA disease activity and supports the concept that chronic systemic inflammation might accelerate cognitive decline. This underlines the importance of controlling the inflammatory response.

White Matter Disease is Associated with Widespread Grey Matter Atrophy in APOE4 non‐carriers with Early‐Stage Dementia

AbstractBackgroundThe APOE‐ε4 (APOE4) allele and cerebrovascular disease (CVD), represented by surrogate MRI measures involving white matter hyperintensities (WMH) are key dementia risk factors [Tosto et al.,2015; Mahley et al.,2006]. They relate to grey matter volume (GMV) and cognitive decline, and demonstrate increased occurrence with lowered age of dementia onset [Boyle et al.,2016; Brickman et al.,2014]. Whether APOE4 is a key effect modifier in the relationship between WMH and GMV needs further exploration. Therefore, we examined independent and interactive effects of WMH and APOE4 on GMV and cognition in cognitively unimpaired (CU) and early‐stage dementia (ESD) participants. We hypothesized that participants with higher WMH load would demonstrate worse GMV atrophy and greater cognitive impairment, especially among APOE4 carriers.MethodWe studied 259 CU and 192 ESD (mild cognitive impairment, mild dementia) from a Singapore research cohort with neuroimaging, APOE genotyping and neuropsychological assessment data (Table 1). We investigated independent and interactive effects of WMH and APOE4 on whole‐brain voxel‐wise GMV using voxel‐based morphometry (uncorrected p<0.001; minimum cluster size=100 voxels). Multiple linear regression models assessed APOE4 and WMH interactive effects on global cognition (mini‐mental state examination–MMSE), memory (Alzheimer’s disease assessment scale‐delayed word recall) and executive function (Color Trails 2) in ESD.ResultHigher WMH load associated with widespread voxel‐wise grey matter atrophy across frontal, parietal, temporal and occipital lobes in CU and ESD (Fig.1). When stratified by APOE4 status, APOE4 carriers showed regions of GM atrophy in frontal, temporal and parietal regions. When examining the interaction between WMH and APOE4 on GMV, contrary to our hypothesis, APOE4 non‐carriers showed more extensive derogatory effects of WMH on GMV than APOE4 carriers (Fig.2). These effects extended into ESD cognitive performance with APOE4 non‐carriers displaying deteriorating global and executive function with increasing WMH load than APOE4 carriers (Fig.3).ConclusionWe illustrate APOE4 status as likely a key moderator in the relationship between WMH and GMV in both preclinical CU and ESD stages. With differential effects of WMH on GMV and cognition between APOE4 carriers and non‐carriers, interventions targeting WMH may need a differential approach depending on the APOE4 status.

The longitudinal relationship between fatigue, mobility, and cognitive function in older adults with chronic stroke: secondary analysis of a randomized controlled trial

AbstractBackgroundFatigue is a common consequence of stroke. Cross‐sectional evidence suggests post‐stroke fatigue is negatively associated with both mobility and cognitive function. We aim to understand the longitudinal relationship between fatigue, mobility, and cognitive function in community‐dwelling adults with chronic stroke (defined as having a stroke = or > 12 months prior to study).MethodsA secondary analysis of data from a 6‐month randomized controlled trial with 120 adults with chronic stroke who were randomized to group‐based, supervised: 1) exercise training; 2) complex social and mental activities; and 2) stretch and balance exercises with general education sessions. We constructed linear regression models to assess the contribution of changes in fatigue to changes in usual gait speed (over 4 meters) and to changes in cognitive function. Cognitive function was measured by the Alzheimer’s Disease Assessment Scale ‐ Cognitive Subscale (ADAS‐Cog) Plus. Higher ADAS‐Cog Plus scores indicate greater cognitive impairment. Fatigue was assessed using: 1) Fatigue Severity Scale; and 2) Visual Analogue Scale. The Fatigue Severity Scale measures fatigue severity and its impact on daily activities global fatigue The Visual Analogue Scale asks individuals to rate their global fatigue. Higher Fatigue Severity Scale and Visual Analogue Scale scores indicate greater severity and degree of fatigue, respectively. In the regression models, we controlled for experimental group, age, and biological sex.ResultsReduced severity of fatigue over the 6 months was associated with improved gait speed (p = 0.02). Reduced global fatigue was associated with improved cognitive function (p = 0.04). Specifically, a reduction of 25 points on the Fatigue Severity Scale was associated with an increase of 0.1 m/s in gait speed (R‐square = 5%). For the Visual Analogue Scale, a reduction of 3.3 points in global fatigue was associated with a reduction of 1 point (i.e., improvement) in the ADAS‐Cog Plus (R‐square = 4%).ConclusionsGiven the prevalence and consequence of fatigue on function in chronic stroke, future work is needed to identify effective interventions.

Potential Savings in Caregiver Time and Societal Costs Associated with Slowing Disease Progression over 36 months in Patients with Early Alzheimer’s Disease: Findings from GERAS‐US

AbstractBackgroundAlzheimer’s disease (AD) is associated with significant costs that increase with disease progression. These analyses describe the relationship between cognitive decline and measures of caregiver time and societal costs and estimate the impact of slowing disease progression over 36 months.MethodsAmyloid positive patients with mild cognitive impairment (MCI) and mild AD dementia (MILD) from the GERAS‐US study1 were included. Assessments included: Mini Mental State Examination (MMSE‐ cognition); Resource Utilization in Dementia (RUD‐ caregiver time, societal costs). The generalized linear model (GLM) with normal distribution was performed for caregiver time and with log link and gamma distribution for total societal cost. The associated outcome savings over 36 months were calculated based on least squares mean change (LSMC) in MMSE and coefficient of MMSE change from baseline to month 36.ResultsTable 1 shows baseline characteristics of 617 patients (300 MCI, 317 MILD, 47.3% male) with a mean (SD) age of 71.0 (7.8) years. MILD vs. MCI patients had greater cognitive impairment, higher caregiver time, and higher monthly societal cost. Over 36 months, MILD patients had significantly greater disease progression compared to MCI (MMSE LSMC 4.1 vs. 2.1). A 2.1‐point worsening in MMSE over 36 months for MCI was associated with an increase of 35.7 hours in total caregiver time and an increase of $8,084 per patient in total societal costs (Table 3). Delaying progression by 20% ‐30% could lead to a savings 7.2 to 10.7 hours for caregiver time and $1,675 to $2,502 in total societal costs. For MILD, a 4.1‐point worsening in MMSE was associated with an increase of 77.3 hours in total caregiver time and $12,807 per patient in total societal costs. Delaying progression by 20%‐30% could save 15.5 to 23.2 hours in caregiver time and $2,665 to $ 3,978 in total societal cost.ConclusionCaregiver time and total societal costs are higher in MILD than in MCI; caregiver time increases over 3 years for both MCI and Mild. Treatments that slow cognitive decline have the potential to keep patients in earlier disease stages longer with a resulting savings in caregiver time and societal cost. 1J Alzheimers Dis. 2019;72(1):279‐292

Different Sides of Depression in the Elderly: An In-depth View on the Role of Aβ Peptides.

Late-onset depression (LOD) is the most common neuropsychiatric disorder associated with Alzheimer's disease (AD), often associated with structural and functional brain changes, neuropsychological impairments and negative family history for affective disorders. LOD could be a risk factor or a prodromal phase of AD; this has led to the investigation of the link between depression and amyloid-β (Aβ) peptides by measuring Aβ levels in plasma, cerebrospinal fluid (CSF) and brains of elderly depressed subjects. This study aims to clarify the complex relationship between depression, Aβ peptides and AD. We evaluated all articles published up to 2019 in PubMed in which Aβ was measured in serum (or plasma), CSF or brain in elderly with Major Depressive Disorder or depressive symptoms evaluated with standard scales. Low plasma Aβ42 levels are strongly associated with depression severity. Plasma Aβ40 levels are higher in younger depressed, drug-resistant and those with more severe symptoms. CSF Aβ42 levels are lower in depressed than controls. PET-detected global and region-specific increases in Aβ deposition are sometimes associated with LOD, cognitive impairment, anxiety but not with Cardiovascular Diseases (CVDs)/CVD risk factors. Elderly depressed with CVDs/CVD risk factors have more frequently high plasma Aβ40 levels and drug-resistance; those without Conclusion: Two specific Aβ profiles emerge in the depressed elderly. One is associated with Aβ42 reductions in plasma and CSF, possibly reflecting increased brain amyloid deposition and prodromal AD. The other one is characterized by high plasma Aβ40 levels, cerebrovascular disease and is clinically associated with increased AD risk.

Computerized Games versus Crosswords Training in Mild Cognitive Impairment

BackgroundMild cognitive impairment (MCI) increases the risk of dementia. The efficacy of cognitive training in patients with MCI is unclear.MethodsIn a two-site, single-blinded, 78-week trial, participants with MCI — stratified by age, severity (early/late MCI), and site — were randomly assigned to 12 weeks of intensive, home-based, computerized training with Web-based cognitive games or Web-based crossword puzzles, followed by six booster sessions. In mixed-model analyses, the primary outcome was change from baseline in the 11-item Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) score, a 70 point scale in which higher scores indicate greater cognitive impairment at 78 weeks, adjusted for baseline. Secondary outcomes included change from baseline in neuropsychological composite score, University of California San Diego Performance-Based Skills Assessment (functional outcome) score, and Functional Activities Questionnaire (functional outcome) score at 78 weeks, adjusted for baseline. Changes in hippocampal volume and cortical thickness on magnetic resonance imaging were assessed.ResultsAmong 107 participants (n=51 [games]; n=56 [crosswords]), ADAS-Cog score worsened slightly for games and improved for crosswords at week 78 (least squares [LS] means difference, −1.44; 95% confidence interval [CI], −2.83 to −0.06; P=0.04). From baseline to week 78, mean ADAS-Cog score worsened for games (9.53 to 9.93) and improved for crosswords (9.59 to 8.61). The late MCI subgroup showed similar results (LS means difference, −2.45; SE, 0.89; 95% CI, −4.21 to −0.70). Among secondary outcomes, the Functional Activities Questionnaire score worsened more with games than with crosswords at week 78 (LS means difference, −1.08; 95% CI, −1.97 to −0.18). Other secondary outcomes showed no differences. Decreases in hippocampal volume and cortical thickness were greater for games than for crosswords (LS means difference, 34.07; SE, 17.12; 95% CI, 0.51 to 67.63 [hippocampal volume]; LS means difference, 0.02; SE, 0.01; 95% CI, 0.00 to 0.04 [cortical thickness]).ConclusionsHome-based computerized training with crosswords demonstrated superior efficacy to games for the primary outcome of baseline-adjusted change in ADAS-Cog score over 78 weeks. (Supported by the National Institutes of Health, National Institute on Aging; ClinicalTrials.gov number, NCT03205709.)

The genetic influence of the DRD3 rs6280 polymorphism (Ser9Gly) on functional connectivity and gray matter volume of the hippocampus in patients with first-episode, drug-naïve schizophrenia

The D3 dopamine receptor (DRD3) plays a major role in cognitive function and is a candidate gene for schizophrenia. DRD3 is widely distributed in the hippocampus, but whether there are potential associations between the rs6280 genotype, the hippocampus, and cognitive function in first-episode, drug-naïve (FES) patients and healthy controls (HCs) is still poorly understood. First, using functional and structural magnetic resonance imaging data, we calculated the gray matter volume (GMV) and functional connectivity (FC) of the hippocampus. Then, we examined the possible interaction effect of the DRD3 genotype and the disease on the FC and GMV of the hippocampus in 52 FES patients and 51 HCs. Finally, the correlation between the FC and GMV in the hippocampus, influenced by rs6280, and the cognitive performance of subjects was analyzed. A significant interaction effect of diagnostic group by genotype of rs6280 on the GMV of the left hippocampus was found, with lower GMV in FES patients that were C carriers compared with TT homozygotes; the opposite pattern was found in the genetic subgroups of HCs. In the FES group, C carriers performed significantly worse on reasoning and problem-solving tests than TT homozygotes. The left hippocampal GMV positively correlated with reasoning and problem-solving performance in TT homozygotes, but this correlation disappeared in FES patients that were C carriers and in genetic subgroups of HCs. Together, these results suggest that FES patients that are C carriers of rs6280 have lower GMV in the hippocampus, resulting in greater cognitive impairment.

Factors related to cognitive function in type-2 diabetes and neuropathic pain patients, the role of mood and sleep disorders in this relationship

To compare cognitive function in patients with diabetes mellitus type-2 (T2DM) both with and without diabetic neuropathic pain (DNP). To analyse the relationship between mood and sleep disorders, quality of life and cognitive function in patients with DNP. Cross-sectional study conducted in patients with T2DM and neuropathy. The presence of DNP, cognitive function, mood status, sleep quality, health-related quality of life, pain intensity and phenotype of pain were measured. Descriptive, bivariate and multivariate analyses were performed. A total of 149 patients (71 with DNP) were included. Patients with and without DNP presented similar scores on the TYM (41.46; SD = 6.70 vs. 41.97; SD = 5.50) and those with DNP had a slightly higher frequency of cognitive impairment (TYM score ≤ 41: 40.8% vs. 43.6%). The patients without DNP performed better in the verbal fluency dimension (mean = 3.53; SD = 0.98 vs. mean = 3.82; SD = 0.66). Being older (B = − 0.258) and under treatment with insulin (B = − 2.919) were related with greater cognitive impairment. Obesity (OR = 17.277) and a longer duration of diabetes (OR = 1.317) were also related to greater risk of cognitive impairment. Impaired cognitive function in patients with DNP is more related to T2DM factors than pain factors. The presence of depression and a worse quality of life were related to a greater risk of cognitive impairment. Identifying and controlling these factors should be an essential intervention for maintaining the cognitive function in patients with T2DM and DNP.

Toxoplasma gondii seropositivity and cognitive function in adults with schizophrenia

Introduction and methodsBased on the limited research focusing on the severity of cognitive deterioration in schizophrenia with preceding toxoplasmosis, we sampled 89 demographically matched paranoid schizophrenia patients (mean age 38.97 years) with (n = 42) and without (n = 47) seroprevalence of IgG type anti T. gondii antibodies as marker of past infection. They underwent examination of verbal memory (10 words Luria test), logical memory and visual memory (BVRT), processing speed (TMT-A/DSST) and executive functions (TMT-B/verbal fluency). We compared the results of both groups, taking into account the normative values for the Bulgarian population where available. We also compared the two groups in terms of clinical severity as evidenced by positive, negative and disorganization sub-scores of the PANSS. ResultsWhile both groups were expectedly under the population norms for verbal and logical memory, seropositive patients showed significantly bigger impairment in verbal memory (Luria Smax = 72.85 vs 78.51; p = 0.029), psychomotor speed (TMT-A 50.98 s vs 44.64 s; p = 0.017), semantic verbal fluency (27.12 vs 30.02; p = 0.011) and literal verbal fluency (17.17 vs 18.78; p = 0.014) compared to the seronegative ones. In addition to that, they gave less correct answers on the BVRT (2.98 vs 4.09; p = 0.006) while making markedly more errors (13.95 vs 10.21; p = 0.002). Despite not reaching statistical significance, past toxoplasmosis was associated with higher score on the PANSS disorganization sub-scale (16.50 points vs 14.72 points) and with lower educational attainment. ConclusionOur results suggest a more profound neuropathological insult(s) resulting in greater cognitive impairment in schizophrenia cases that are exposed to T. gondii infection.

Brain atrophy pattern in de novo Parkinson’s disease with probable RBD associated with cognitive impairment

Rapid eye movement sleep behavior disorder (RBD) is associated with high likelihood of prodromal Parkinson’s disease (PD) and is common in de novo PD. It is associated with greater cognitive impairment and brain atrophy. However, the relation between structural brain characteristics and cognition remains poorly understood. We aimed to investigate subcortical and cortical atrophy in de novo PD with probable RBD (PD-pRBD) and to relate it with cognitive impairment. We analyzed volumetry, cortical thickness, and cognitive measures from 79 PD-pRBD patients, 126 PD without probable RBD patients (PD-non pRBD), and 69 controls from the Parkinson’s Progression Markers Initiative (PPMI). Regression models of cognition were tested using magnetic resonance imaging measures as predictors. We found lower left thalamus volume in PD-pRBD compared with PD-non pRBD. Compared with controls, PD-pRBD group showed atrophy in the bilateral putamen, left hippocampus, left amygdala, and thinning in the right superior temporal gyrus. Specific deep gray matter nuclei volumes were associated with impairment in global cognition, phonemic fluency, processing speed, and visuospatial function in PD-pRBD. In conclusion, cognitive impairment and gray matter atrophy are already present in de novo PD-pRBD. Thalamus, hippocampus, and putamen volumes were mainly associated with these cognitive deficits.

Comparing emergency department use among individuals with varying levels of cognitive impairment

IntroductionAs the population ages, Alzheimer’s disease and related dementias (ADRD) are becoming increasingly common in patients presenting to the emergency department (ED). This study compares the frequency of ED use among a cohort of individuals with well-defined cognitive performance (cognitively intact, mild cognitive impairment (MCI), and ADRD).MethodsWe performed a retrospective cohort study of English-speaking, community-dwelling individuals evaluated at four health system-based multidisciplinary memory clinics from 2014–2016. We obtained demographic and clinical data, including neuropsychological testing results, through chart review and linkage to electronic health record data. We characterized the frequency and quantity of ED use within one year (6 months before and after) of cognitive evaluation and compared ED use between the three groups using bivariate and multivariate approaches.ResultsOf the 779 eligible patients, 89 were diagnosed as cognitively intact, 372 as MCI, and 318 as ADRD. The proportion of subjects with any annual ED use did not increase significantly with greater cognitive impairment: cognitively intact (16.9%), MCI (26.1%), and ADRD (28.9%) (p = 0.072). Average number of ED visits increased similarly: cognitively intact (0.27, SD 0.72), MCI (0.41, SD 0.91), and ADRD (0.55, SD 1.25) (p = 0.059). Multivariate logistic regression results showed that patients with MCI (odds ratio (OR) 1.62; CI = 0.87–3.00) and ADRD (OR 1.84; CI = 0.98–3.46) did not significantly differ from cognitively intact adults in any ED use. Multivariate negative binomial regression found patients with MCI (incidence rate ratio (IRR) 1.38; CI = 0.79–2.41) and ADRD (IRR 1.76, CI = 1.00–3.10) had elevated but non-significant risk of an ED visit compared to cognitively intact individuals.ConclusionThough there was no significant difference in ED use in this small sample from one health system, our estimates are comparable to other published work. Results suggested a trend towards higher utilization among adults with MCI or ADRD compared to those who were cognitively intact. We must confirm our findings in other settings to better understand how to optimize systems of acute illness care for individuals with MCI and ADRD.

Locomotor Adaptation Deficits in Older Individuals With Cognitive Impairments: A Pilot Study.

Gait dysfunction and fall risk have been well documented in people with Alzheimer's Disease (AD) and individuals with mild cognitive impairment (MCI). Normal locomotor adaptation may be an important prerequisite for normal and safe community walking function, especially in older adults with age-related neural, musculoskeletal, or cardiovascular changes and cognitive impairments. The split-belt walking task is a well-studied and robust method to evaluate locomotor adaptation (e.g., the ability to adjust stepping movements to changing environmental demands). Here, we capitalized on the split-belt adaptation task to test our hypothesis that a decreased capacity for locomotor adaptation may be an important contributing factor and indicator of increased fall risk and cognitive decline in older individuals with MCI and AD. The objectives of this study were to (1) compare locomotor adaptation capacity in MCI and AD compared to healthy older adults (HOA) during split-belt treadmill walking, and (2) evaluate associations between locomotor adaptation and cognitive impairments. Our results demonstrated a significant decrease in split-belt locomotor adaptation magnitude in older individuals with MCI and AD compared to HOA. In addition, we found significant correlations between the magnitude of early adaptation and de-adaptation vs. cognitive test scores, demonstrating that individuals with greater cognitive impairment also display a reduced capacity to adapt their walking in response to the split-belt perturbation. Our study takes an important step toward understanding mechanisms underlying locomotor dysfunction in older individuals with cognitive impairment.

Specific metabolic syndrome components predict cognition and social functioning in people with type 2 diabetes mellitus and severe mental disorders.

Obesity and metabolic diseases such as metabolic syndrome (MetS) are more prevalent in people with type 2 diabetes mellitus (T2DM), major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). MetS components might be associated with neurocognitive and functional impairments in these individuals. The predictive and discriminatory validity of MetS and its components regarding those outcomes were assessed from prospective and transdiagnostic perspectives. Metabolic syndrome components and neurocognitive and social functioning were assessed in 165subjects, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28healthy controls (HCs). A posteriori, individuals were classified into two groups. The MetS group consisted of those who met at least three of the following criteria: abdominal obesity (AO), elevated triglycerides (TG), reduced high-density lipoprotein cholesterol (HDL), elevated blood pressure (BP), and elevated fasting glucose (FPG); the remaining participants comprised the No-MetS group. Mixed one-way analysis of covariance and linear and binary logistic regression analyses were performed. Cognitive impairment was significantly greater in the MetS group (n = 82) than in the No-MetS group (n = 83), with small effect sizes (p < 0.05; η²p = 0.02 - 0.03). In both groups, the most robust associations between MetS components and neurocognitive and social functioning were observed with TG and FPG (p < 0.05). There was also evidence for a significant relationship between cognition and BP in the MetS group (p < 0.05). The combination of TG, FPG, elevated systolic BP and HDL best classified individuals with greater cognitive impairment (p < 0.001), and TG was the most accurate (p < 0.0001). Specific MetS components are significantly associated with cognitive impairment across somatic and psychiatric disorders. Our findings provide further evidence on the summative effect of MetS components to predict cognition and social functioning and allow the identification of individuals with worse outcomes. Transdiagnostic, lifestyle-based therapeutic interventions targeted at that group hold the potential to improve health outcomes.

Potentially avoidable causes of hospitalisation in people with dementia: contemporaneous associations by stage of dementia in a South London clinical cohort

ObjectivesTo estimate the frequency of all-cause and ambulatory care sensitive condition (ACSCs)-related hospitalisations among individuals with dementia. In addition, to investigate differences by stage of dementia based on recorded cognitive...

Comorbidity Between Anorexia Nervosa and Depressive Disorder: A Narrative Review.

Objective Anorexia nervosa (AN) is a disorder with a significantly high prevalence. Affective disorders, including depressive disorder (DD), often coexist with this eating disorder (ED). In this review we will focus on its prevalence, associated vulnerability factors, clinical manifestations, possible etiological factors and its prognosis. Methods A bibliographic search was carried out in the PubMed database selecting those articles that approached the subject of comorbidity between AN and DD. The search was limited to articles published from January 1990 to December 2021. Results Of the 1891 abstracts reviewed, 33 studies met inclusion criteria. The prevalence of this comorbidity was extremely variable between studies, which exposed their heterogeneity. As to symptomatology this comorbidity presents itself with more severity, greater expression of psychological traits and greater cognitive impairment. Certain personality traits are postulated as vulnerability factors. Genetic factors such as neurochemicals seem to be involved in its pathogenesis. Conclusion The comorbidity between DD and ED have important influence in its symptomatic expression, severity and prognosis. Some of the analyzed studies provide consistent data, but there are others that are contradictory. It would be necessary to increase the number of studies and use a unified methodology.

Cognitive Remediation Therapy for Participants with Late Life Schizophrenia

<h3>Introduction</h3> Cognitive deficits strongly predict function in schizophrenia, including in late life. Cognitive remediation (CR) improves cognition in schizophrenia, however literature in late-life schizophrenia (LLS) is sparse. Anticholinergic medication burden (ACB) compounds age-related cognitive declines in late-life schizophrenia (LLS). This study examined the effect of CR on cognitive performance in patients with LLS. We also assessed CR tolerability, the interaction between ACB and CR on cognition. <h3>Methods</h3> We adapted CR from our pilot study to a larger group. CR was provided over 12, twice-weekly, therapist-guided group sessions. Computerized drill-and-practice exercise difficulty levels were adjusted automatically based on performance. Participants were assessed at baseline and at study completion using clinical and cognitive measures. <h3>Results</h3> Thirty-four participants were enrolled and 20 (mean (SD) age: 66.0 [5.8]) completed 92.3% (22.14 [1.98]) all CR sessions; the ITT group (N=34) attended 72.9% (17.50 [7.23]) sessions. Global cognition did not improve (completers: p=0.80, ITT: p=0.86) with negligible effect size (completers: d=0.08; ITT d=0.04). There was no significant improvement in executive function (completers: p=0.16; ITT: p=0.33). Medication ACB was inversely associated with total MoCA score, accounting for 8.9% of the variance in final MoCA score (p=0.02). <h3>Conclusions</h3> Overall, CR was well tolerated but did not improve global cognition or executive functioning in this outpatient sample with LLS. A higher ACB was associated with greater cognitive impairment and a poorer response to CR. Future studies need to better characterize potential variables serving to limit the response to CR, including the number and frequency of CR sessions and the role of ACB. <h3>This research was funded by</h3> Funding for this project was provided by the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario

Gestures analysis during a picture description task: Capacity to discriminate between healthy controls, mild cognitive impairment, and Alzheimer's disease

The main objective of this study is to compare the gesticulation of the five study groups that conform the evolution from healthy ageing to a moderate stage of Alzheimer's disease (AD). As a secondary aim we intend to assess the capacity of co-speech gestures to discriminate between the two main groups of amnestic Mild Cognitive Impairment (MCI), executive MCI (ex-MCI) and temporo-medial MCI (tm-MCI), since this last group is the one with the highest rate of progression to AD. 52 participants were divided into five groups, according to their global cognition state (healthy controls, ex-MCI, tm-MCI, mild AD, and moderate AD). They were videotaped during a picture description task and their verbal (speech fluency and lexical diversity measures) and non-verbal communication (gestural production) performances were analysed. Statistical analysis confirmed that the global cognition performance was worse in patients with greater cognitive impairment, and MCI groups differ from each other in delayed recall memory. Concerning verbal communication, time of speech was lower in the healthy control group when compared with the rest of the groups. In the non-verbal communication aspect, a trend toward statistical significance was found in iconic gestures per minute, iconic gestures per word and iconic gestures for word substitution. Pairwise comparison highlighted these variables as potential differentiating factor between ex-MCI, tm-MCI and mild AD groups. As for the first objective, our study results demonstrated there was not a linear progression in gestural production among groups. In relation to the second objective, outcomes pointed to a great value, since iconic gestures variables have been identified as a potential marker for the specific identification of tm-MCI individuals, who are a subgroup of amnestic MCI with a greater predisposition to progress to Alzheimer's disease.

Signature laminar distributions of pathology in frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) with either tau (FTLD-tau) or TDP-43 (FTLD-TDP) inclusions are distinct proteinopathies that frequently cause similar frontotemporal dementia (FTD) clinical syndromes. FTD syndromes often display macroscopic signatures of neurodegeneration at the level of regions and networks, but it is unclear if subregional laminar pathology display patterns unique to proteinopathy or clinical syndrome. We hypothesized that FTLD-tau and FTLD-TDP accumulate pathology in relatively distinct cortical layers independent of clinical syndrome, with greater involvement of lower layers in FTLD-tau. The current study examined 170 patients with either FTLD-tau (n = 73) or FTLD-TDP (n = 97) spanning dementia and motor phenotypes in the FTD spectrum. We digitally measured the percent area occupied by tau and TDP-43 pathology in upper layers (I–III), lower layers (IV–VI), and juxtacortical white matter (WM) from isocortical regions in both hemispheres where available. Linear mixed-effects models compared ratios of upper to lower layer pathology between FTLD groups and investigated relationships with regions, WM pathology, and global cognitive impairment while adjusting for demographics. We found lower ratios of layer pathology in FTLD-tau and higher ratios of layer pathology in FTLD-TDP, reflecting lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology, respectively (p < 0.001). FTLD-tau displayed lower ratios of layer pathology related to greater WM tau pathology (p = 0.002) and to earlier involved/severe pathology regions (p = 0.007). In contrast, FTLD-TDP displayed higher ratios of layer pathology not related to either WM pathology or regional severity. Greater cognitive impairment was associated with higher ratios of layer pathology in FTLD-tau (p = 0.018), but was not related to ratios of layer pathology in FTLD-TDP. Lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology are proteinopathy-specific, regardless of clinical syndromes or regional networks that define these syndromes. Thus, patterns of laminar change may provide a useful anatomical framework for investigating how degeneration of select cells and corresponding laminar circuits influence large-scale networks and clinical symptomology in FTLD.