Mean Mini-Mental State Examination Research Articles

Long-term follow-up study of SWEDD patients with mild parkinsonian signs

BackgroundWhether scan without evidence of dopaminergic deficit (SWEDD) can be a reliable indication of a clinical entity of Parkinson’s disease (PD) is controversial.ObjectiveTo evaluate the proportion of SWEDD patients with...

Adapted problem adaptation therapy for depression in mild to moderate Alzheimer's disease dementia: A randomized controlled trial.

Trials of effectiveness of treatment options for depression in dementia are an important priority. Randomized controlled trial to assess adapted Problem Adaptation Therapy (PATH) for depression in mild/moderate dementia caused by Alzheimer's disease. Three hundred thirty-six participants with mild or moderate dementia, >7 on Cornell Scale for Depression in Dementia (CSDD), randomized to adapted PATH or treatment as usual. Mean age 77.0years, 39.0% males, mean Mini-Mental State Examination 21.6, mean CSDD 12.9. For primary outcome (CSDD at 6 months), no statistically significant benefit with adapted PATH on the CSDD (6 months: -0.58; 95% CI -1.71 to 0.54). The CSDD at 3 months showed a small benefit with adapted PATH (-1.38; 95% CI -2.54 to -0.21) as did the EQ-5D (-4.97; 95% CI -9.46 to -0.48). An eight-session course of adapted PATH plus two booster sessions administered within NHS dementia services was not effective treatment for depression in people with mild and moderate dementia. Future studies should examine the effect of more intensive and longer-term therapy.

Donepezil for dementia with Lewy bodies: meta-analysis of multicentre, randomised, double-blind, placebo-controlled phase II, III, and, IV studies.

Current evidence for the management of symptoms associated with dementia with Lewy bodies (DLB) using donepezil is limited. We conducted a meta-analysis of three randomised controlled trials of donepezil in patients with DLB to investigate the overall efficacy of donepezil on Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), and Clinician's Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus). A meta-analysis was performed using the data of 312 patients administered placebo or 10 mg donepezil. Overall mean score differences for MMSE, NPI-2, and NPI-10 from baseline to week 12 and their 95% confidence intervals (CI) were estimated. For CIBIC-plus, which was transformed from a seven-point grade to a dichotomous outcome (improvements/no improvements), odds ratio (OR) and its 95% CI were estimated. Random-effects models were used, and heterogeneity was evaluated using the Cochrane's Q test and I2 statistic. Heterogeneity was suspected for NPI-2 (P < 0.05; I2  = 87.2%) and NPI-10 (P < 0.05; I2  = 67.7%) while it was not suspected for MMSE (P = 0.23; I2  = 32.4%) and CIBIC-plus (P = 0.26; I2  = 19.8%). The overall mean MMSE score difference (mean difference: 1.50; 95% CI, 0.67-2.34) and the overall odds of improving CIBIC-plus (OR: 2.20; 95% CI, 1.13-4.26) from baseline to week 12 were higher in the donepezil group than in the placebo group. Results of our meta-analysis indicated overall efficacy of donepezil on cognitive impairment and global clinical status in patients with DLB.

Efficacy and safety of donepezil in patients with dementia with Lewy bodies: results from a 12-week multicentre, randomised, double-blind, and placebo-controlled phase IV study.

Donepezil has been approved in Japan for the treatment of dementia with Lewy bodies (DLB) based on clinical trials showing its beneficial effects on cognitive impairment. This phase IV study evaluated the efficacy of donepezil by focusing on global clinical status during a 12-week double-blind phase. Patients with probable DLB were randomly assigned to the placebo (n = 79) or 10 mg donepezil (n = 81) groups. The primary endpoint was changes in global clinical status, assessed using the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). We also assessed four CIBIC-plus domains (general condition, cognitive function, behaviour, and activities of daily living) and changes in cognitive impairment and behavioural and neuropsychiatric symptoms measured using the Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI), respectively. Although donepezil's superiority was not shown in the global clinical status, a significant favourable effect was detected in the cognitive domain (P = 0.006). MMSE scores improved in the donepezil group after adjustments in post hoc analysis (MMSE mean difference, 1.4 (95% confidence interval (CI), 0.42-2.30), P = 0.004). Improvements in NPIs were similar between the groups (NPI-2: -0.2 (95% CI, -1.48 to 1.01), P = 0.710; NPI-10: 0.1 (95% CI, -3.28 to 3.55), P = 0.937). The results support the observation that the efficacy of 10 mg donepezil in improving cognitive function is clinically meaningful in DLB patients. The evaluation of global clinical status might be affected by mild to moderate DLB patients enrolled in this study. No new safety concerns were detected.

Noninvasive assessment of glymphatic dysfunction in idiopathic normal pressure hydrocephalus with diffusion tensor imaging.

Diffusion tensor imaging (DTI) along the perivascular space (ALPS) (DTI-ALPS)-by calculating the ALPS index, a ratio accentuating water diffusion in the perivascular space-has been proposed as a noninvasive, indirect MRI method for assessing glymphatic function. The main aim of this study was to investigate whether DTI-ALPS would reveal glymphatic dysfunction in idiopathic normal pressure hydrocephalus (iNPH) and whether the ALPS index was associated with disease severity. Thirty iNPH patients (13 men; median age 77 years) and 27 healthy controls (10 men; median age 73 years) underwent MRI and clinical assessment with the Timed Up and Go test (TUG) and Mini-Mental State Examination (MMSE); only the patients were evaluated with the Hellström iNPH scale. MRI data were analyzed with the DTI-ALPS method and Radscale screening tool. iNPH patients showed significantly lower mean ALPS index scores compared with healthy controls (median [interquartile range] 1.09 [1.00-1.15] vs 1.49 [1.36-1.59], p < 0.001). Female healthy controls showed significantly higher ALPS index scores than males in both hemispheres (e.g., right hemisphere 1.62 [1.47-1.67] vs 1.33 [1.14-1.41], p = 0.001). This sex difference was not seen in iNPH patients. The authors found a moderate exponential correlation between mean ALPS index score and motor function as measured with time required to complete TUG (r = -0.644, p < 0.001), number of steps to complete TUG (r = -0.571, p < 0.001), 10-m walk time (r = -0.637, p < 0.001), and 10-m walk steps (r = -0.588, p < 0.001). The authors also found a positive linear correlation between mean ALPS index score and MMSE score (r = 0.416, p = 0.001). Simple linear regression showed a significant effect of diagnosis (B = -0.39, p < 0.001, R2 = 0.459), female sex (B = 0.232, p = 0.002, R2 = 0.157), and Evans index (B = -4.151, p < 0.001, R2 = 0.559) on ALPS index. Multiple linear regression, including diagnosis, sex, and Evans index score, showed a higher predictive value (R2 = 0.626) than analysis of each of these factors alone. The ALPS index, which was significantly decreased in iNPH patients, could serve as a marker of disease severity, both clinically and in terms of neuroimaging. However, it is important to consider the significant influence of biological sex and ventriculomegaly on the ALPS index, which raises the question of whether the ALPS index solely reflects glymphatic function or if it also encompasses other types of injury. Future studies are needed to address potential confounding factors and further validate the ALPS method.

The outcomes of treatment for homebound adults with complex medical conditions in a hospital-at-home unit in the southern district of Israel

BackgroundA model of hospital-at-home services called the Home Care Unit (“the unit”) has been implemented in the southern region of the Clalit Healthcare Services in Israel. The aim of the present study was to characterize this service model.MethodsA retrospective cross-over study. included homebound patients 65 years of age and above who were treated for at least one month in the framework of the unit, between 2013 and 2020. We compared the hospitalization rate, the number of hospital days, the number of emergency room visits, and the cost of hospitalization for the six-month period prior to admission to the unit, the period of treatment in the unit, and the six-month period following discharge from the unit.ResultsThe study included 623 patients with a mean age of 83.7 ± 9.2 years with a mean Mini-mental State Examination (MMSE) score of 12.0 ± 10.2, a mean Charlson Comorbidity Index (CCI) of 3.7 ± 2.2 and a Barthel Index score of 23.9 ± 25.1. The main indications for admission to the unit were various geriatric syndromes (56.7%), acute functional decline (21.2%), and heart failure (12%). 22.8% died during the treatment period and 63.4% were discharged to ongoing treatment by their family doctor after their condition stabilized. Compared to the six months prior to admission to the unit there was a significant decrease (per patient per month) in the treatment period in the number of days of hospitalization (2.84 ± 4.35 vs. 1.7 ± 3.8 days, p < 0.001) and in the cost of hospitalization (1606 ± 2170 vs. 1066 ± 2082 USD, p < 0.001).ConclusionsTreatment of homebound adults with a high disease burden in the setting of a hospital-at-home unit can significantly reduce the number of hospital days and the cost of hospitalization. This model of service for homebound patients with multiple medical problems maintained a high level of care while reducing costs. The results support the widespread adoption of this service in the community to enable the healthcare system to respond to the growing population of elderly patients with medical complexity.

Impact of cat-assisted therapy (Ca-AT) among elderly patients with Alzheimer’s disease at home: a case study

Purpose This study aims to explore the effects of cat-assisted therapy (Ca-AT) on a patient in their homes, specifically investigating the effects on patient’s memory, behavioral pathology and ability to perform activities of daily living, independently. Design/methodology/approach A case study design was used in patient’s homes using three measuring scales, namely, Mini-Mental State Examination (MMSE), Barthel index (BI) and Behavioral Pathology in Alzheimer’s Disease (AD) Rating Scale. Findings The MMSE and BI mean scores were increased, whereas the Behavioral Pathology mean score was decreased. Patient negative behaviors were improved specifically, aggressiveness, anxieties, phobias, and caregiver burden was decreased. Practical implications Patients with AD could significantly benefit from Ca-AT in their own homes, and it could decrease caregiving burden. Originality/value Ca-AT is a newly developed type of animal-assisted therapy that uses cats to treat patients, especially elderly people with AD, in their homes.

Shifting the Paradigm of Nursing Home Care for People with Dementia: The Italian Experience of Il Paese Ritrovato and the Impact of SARS-CoV-2.

Il Paese Ritrovato is an Italian nursing home founded in 2018, it is based on the Alzheimer village model and admits people with mild-to-moderate dementia. Describe the impact of the SARS-CoV-2 pandemic on people living at Il Paese Ritrovato through a Comprehensive Geriatric Assessment (CGA) regularly administered prior to and during the pandemic. We explored the effects of a person-centered approach. We assessed 64 subjects (enrolled and followed between June 2018 and December 2020), who underwent at least 18 months of observation prior to the pandemic. Each subject was evaluated using a CGA on admission time (T0) and at defined time-points: T6, T12, T18. One last CGA evaluation was performed during the SARS-CoV-2 pandemic (TCovid-19). Temporal trends during T0-T18, and differences between T18 and TCovid-19 were calculated. The mean age was 82 years with a prevalence for females (77.0%) and Alzheimer's disease diagnosis (60%). Psychiatric and behavioral disorders were the most common conditions (80%). We utilized a nonpharmacological approach aimed at promoting the residents' overall wellbeing and observed satisfactory performance during the first 18 months. In comparison with the pre-pandemic period, TCovid-19 enlightened +11.7% use of antidepressants and a decline of Mini-Mental State Examination mean values (not statistically significant), while engagement in activities dropped. The pandemic may have disrupted the existing model of care, but at the same time, it confirmed that the Il Paese Ritrovato approach, which encompasses symptoms improvement and multicomponent support, is in fact beneficial.

Changes in dementia treatment patterns associated with changes in the National Policy in South Korea among patients with newly diagnosed Alzheimer’s disease between 2011 and 2017: results from the multicenter, retrospective CAPTAIN study

BackgroundThe South Korean government has been actively involved in plans to combat dementia, implementing a series of national strategies and plans since 2008. In July 2014, eligibility for mandatory long-term care insurance (LTCI) was extended to people with dementia enabling access to appropriate long-term care including the cognitive function training program and home nursing service. This study aimed to investigate changes in treatment patterns for Alzheimer’s disease (AD) between July 2011 and June 2017 which spanned the 2014 revision.MethodsThis multicenter, retrospective, observational study of patients with newly diagnosed AD analyzed electronic medical records from 17 general hospitals across South Korea. Based on their time of AD diagnosis, subjects were categorized into Cohort 1 (1 July 2011 to 30 June 2014) and Cohort 2 (1 July 2014 to 30 June 2017).ResultsSubjects (N=3,997) divided into Cohorts 1 (n=1,998) and 2 (n=1,999), were mostly female (66.4%) with a mean age of 84.4 years. Cohort 1 subjects were significantly older (P<0.0001) and had a lower number of comorbidities (P=0.002) compared with Cohort 2. Mean Mini-Mental State Examination (MMSE) scores in Cohorts 1 and 2 at the time of AD diagnosis or start of initial treatment were 16.9 and 17.1, respectively (P=0.2790). At 1 year, mean MMSE scores in Cohorts 1 and 2 increased to 17.9 and 17.4, respectively (P=0.1524). Donepezil was the most frequently administered medication overall (75.0%), with comparable rates between cohorts. Rates of medication persistence were ≥98% for acetylcholinesterase inhibitor or memantine therapy. Discontinuation and switch treatment rates were significantly lower (49.7% vs. 58.0%; P<0.0001), and mean duration of initial treatment significantly longer, in Cohort 2 vs. 1 (349.3 vs. 300.2 days; P<0.0001).ConclusionsComparison of cohorts before and after revision of the national LTCI system for dementia patients found no significant difference in mean MMSE scores at the time of AD diagnosis or start of initial treatment. The reduction in the proportion of patients who discontinued or changed their initial treatment, and the significant increase in mean duration of treatment, were observed following revision of the LTCI policy which enabled increased patient access to long-term care.

An Interplay between Health Equity and Disparity in Cognitive Decline

AbstractBackgroundCognitive decline may be an early indicator of Alzheimer diseases and related dementia (ADRD). To identify the intervention targets that ameliorate disparities in ADRD, it is critical to employ disparity measures that account for health equity. We aimed to investigate disparity estimates in cognitive decline built on three health equity measures.MethodThe study sample (n = 451) was derived from the bi‐ethnic community‐dwelling San Antonio Longitudinal Study of Aging (SALSA). The latent variable mixture model classified cognitive function trajectory strata based on four repeated measures of the Mini Mental Status Examination (MMSE) over 8.5±1.3 years of follow‐up. Three risk adjustments were employed to optimize equity in social determinants of health (SDoH: income, education, social interactions) between Hispanics and non‐Hispanics. 1) Average constrained regression adjustment minimized the impact of SDoH for Hispanics. 2) Covariance constrained adjustment derived estimates with a near independence between the residuals with ethnicity. 3) Net compensation penalized regression imposed a penalty for excess lower MMSE among Hispanics. Inverse propensity score weighting (IPSW) estimates of disparity further adjusted away confounding due to covariates (demographics, disease burdens) between ethnic groups.ResultTable 1 contrasted baseline characteristics of the study sample between Hispanics and non‐Hispanics. Two MMSE trajectory strata were identified: cognitive decline stratum (38%) with mean MMSE decreased from 23.9 to 21.2; and stable cognitive function stratum (62%) with mean MMSE around 28 throughout. Average constrained and covariance constrained risk adjustments attained optimal SDoH equity across three fairness metrics: predictive ratios, fair covariance, and net compensation (Table 2). Ethnic disparity in cognitive decline (Table 3) was strong conditioned on SDoH equity alone (log(aOR) = 4.27, p&lt;0.001). Balancing covariates alone via IPSW without equity in SDoH also fell short for parity (aOR = 1.16, p&lt;0.001). Parity in cognitive decline could be achievable under both SDoH equity and balanced covariates between ethnic groups (aOR = 0.85, p = 0.21).ConclusionOur study suggested that integrating equity metrices in ADRD disparity research could guide the paths to improve equity and reduce disparity. The field would be better served by identifying the causal drivers of disparities through the advancement in equity metrices and mediation analyses that delineate intricate interactions between SDoH and ADRD risk factors.

Catalan Early Onset Dementia Network 2021 Report

AbstractBackgroundThe Catalan Early Onset Neurodegenerative Dementia Network is a multicenter project launched in 2020 with the aim of understanding the epidemiology and clinical care of people with early‐onset neurodegenerative dementia and their caregivers.MethodsNeurologists and geriatricians visiting patients with cognitive impairment in Catalonia were invited to prospectively collect demographical and clinical data from patients with age at onset (AAO) less than 65 years visited during the year 2021.ResultWe registered information of 1221 subjects from 14 centers. Mean age was 56,2 years (SD 8.7), 64% were woman. Mean age at symptom onset was 53,9 years (SD 9.1). The most frequent cognitive symptoms at onset were memory impairment (72,9%) and dysexecutive difficulties (21,8%). Mean Mini Mental State Examination (MMSE) score was 26,7 (range 7‐30). Initial clinical diagnose was a non‐neurodegenerative disorder in 81,4% of cases and a neurodegenerative disorder in 17,81%. Genetic counseling accounted for 0,8% of visits. The suspected non‐neurodegenerative and neurodegenerative patients were studied with a neuropsychological test (85,5% vs 86,7%, respectively), magnetic resonance imaging (MRI) (39,9% vs 55,6%), computerized tomography (CT) scan (33,2% vs 34,4%), fluorodeoxyglucose positron emission tomography (FDG‐PET) (6,8% vs 39,0%), amyloid‐PET (3,9% vs 34,4%) and lumbar puncture (7,1%, vs 44,8%). 16,6% of participants had a final diagnose of a neurodegenerative cognitive disorder (10,9% Alzheimer’s disease, 2,3% frontotemporal lobular degeneration, 2,1% MCI of suspected neurodegenerative etiology, 0,58% other neurodegenerative dementias); 83,4% were diagnosed with a non‐degenerative disorder (28,4% subjective cognitive decline (SCD), 25,0% mild cognitive impairment of non‐neurodegenerative etiology, 19,8% cognitive impairment after Covid‐19, 10,2% other dementias). Diagnostic delay was higher for neurodegenerative disorders (17 months: median 12 months (interquartile range (IQR) 19) between AAO and first visit +5 months (IQR 8) between first visit and diagnose) than non‐degenerative disorders (12 months: 9 months (IQR 19,6) + 3 months (IQR 7) respectively).ConclusionOf 1221 patients under 65 years old visited in cognitive disorders units, only 16,6% had a final diagnose of neurodegenerative cognitive disorder. More than a quarter of subjects were diagnosed as SCD and a fifth as cognitive impairment after Covid‐19. In 2021, diagnosis delay was higher in neurodegenerative disorders (median 17 months).

Visual Cognitive Assessment Test (VCAT): Utility in detecting early dementia in diverse language cohorts

AbstractBackgroundCognitive tests play a crucial role in evaluating mild cognitive impairment (MCI) and dementia. As most tests are originally developed in English‐speaking cohorts, their application in multilingual populations will need to be translated and may affect the test psychometrics. Therefore, the VCAT was developed as a language‐neutral visual‐based assessment to mitigate this issue. Although the VCAT has been validated in Southeast Asian countries, its performance in wider language cohorts remains unclear. Here, we aim to compare the utility of VCAT with established screening tests, Montreal Cognitive Assessment (MoCA) and Mini‐Mental State Examination (MMSE), in distinguishing MCI and dementia from cognitively normal (CN) individuals in a multinational study.MethodThis collaboration between Canada, China, India, Korea and Singapore recruited 614 participants (306 CN, 212 MCI, 94 Dementia). The administration of the cognitive tests were standardized across all study sites. Participants underwent the MMSE, MoCA, and VCAT on the same day, with their scores and demographic data (age, gender, years of education, ethnicity, primary written and spoken language) collected in the centers respectively. The performance of VCAT in distinguishing MCI and dementia from CN were assessed within each sites using the area under the curve (AUC).ResultBaseline demographics of the participants in each site were summarized in Table 1. The mean (SD) MMSE, MoCA and VCAT scores in each diagnostic group across all countries were summarized in Table 2. The mean (SD) VCAT scores across all countries for CN, MCI and dementia were 25.91 (3.14); 21.00 (5.36) and 11.91 (4.79) respectively. Corresponding scores for MoCA were 26.09 (2.76); 22.62 (4.43); 14.02 (5.17) and corresponding scores for MMSE were 28.34 (1.79); 26.55 (2.90); 18.91 (4.81). The AUC of VCAT in detecting cognitive impairment (MCI+Dementia) was found to be 0.83 (95%CI 0.80 to 0.86), which is comparable to the MoCA 0.82 (95%CI 0.78 to 0.85) and the MMSE 0.78 (95%CI 0.74 to 0.81).ConclusionVCAT was comparable to the MoCA and MMSE in distinguishing cognitive impairment from CN in a multinational, multilingual population. Further studies with wider language populations are needed to further validate the utility of VCAT globally.

Association of individual and multiple comorbid neuropathologies with cognitive decline in the oldest‐old: Results from The 90+ Study

AbstractBackgroundAge‐related neuropathologies are common in the oldest‐old and associated with cognitive decline. In this study, we examined the associations of individual and multiple comorbid neuropathologies with cognitive decline in participants who had normal cognition in at least one in‐person visit during their time in The 90+ Study.MethodOur study included 251 individuals from The 90+ Study‐ a longitudinal study on aging, who had at least 2 in‐person visits, had normal cognition in at least one of them and had autopsy data. We used longitudinal Mini Mental State Examination (MMSE) scores to assess cognitive trajectories. For the first part of our analysis, we examined individual neuropathologies that were evaluated as: Alzheimer’s Disease neuropathologic change (ADNC) (intermediate/high), presence of Cerebral amyloid angiopathy (CAA), Microinfarcts (2+), atherosclerosis, arteriolosclerosis, Lewy body disease (LBD), Hippocampal sclerosis (HS), Limbic‐predominant age‐related TDP‐43 encephalopathy neuropathological change (LATE‐NC), and Age‐related tau astrogliopathy (ARTAG). For the second part of our analysis, we examined multiple comorbid neuropathologies. For this analysis we recoded each neuropathology as: 0 for absent/negligible levels, 0.4 for intermediate, or 1 for severe. These recoded scores were added to create four summary indices: all pathology index (total of all individual neuropathologies), vascular index (CAA, Microinfarcts, atherosclerosis, and arteriolosclerosis), neurodegenerative index (ADNC, LB, HS, and LATE‐NC) and non‐AD neurodegenerative index (LB, HS, and LATE‐NC). We used linear mixed effects models to examine the associations of individual neuropathologies and the pathology indices with cognitive decline.ResultAt baseline, participants had a mean age of 93 years and a mean MMSE score of 27.6. Mean follow up time was 5.1 years (Table1). Presence of LBD (ß = ‐0.20; p = 0.07), and HS (ß = ‐0.24; p = 0.06) trends toward to an association with faster cognitive decline (Table2). All pathology index (ß = ‐0.10; p = 0.01), neurodegenerative index (ß = ‐0.17; p = 0.003) and non‐AD neurodegenerative index (ß = ‐0.16; p = 0.02) were significantly associated with faster cognitive decline (Table3).ConclusionIn individuals who maintain normal cognition until age 90+ and then start declining, the rate of cognitive decline is related to the burden of neuropathologies, particularly neurodegenerative neuropathologies. Therefore, multiple comorbid neuropathologies need to be targeted for preventing cognitive decline in the oldest‐old.

Insight into impaired social functioning in dementia

Background:People with dementia commonly have impaired social functioning and may not recognise this. This lack of insight may result in worse outcomes for the person and their family carers. We aimed to characterise insight into social functioning in dementia, and describe its association with dementia severity.Methods:Observational cross-sectional study of people aged &gt;65 years with clinically diagnosed dementia and their family informants recruited from three sites in Germany, Japan and the United Kingdom. We used the Social Functioning in Dementia scale (SF-DEM), which assesses three domains: “spending time with other people” (domain 1), “communicating with other people” (domain 2), and “sensitivity to other people” (domain 3). We calculated lack of insight into social functioning as the discrepancy between the ratings of the participants with dementia and their informant. We described this discrepancy and the proportion of people with dementia whose rating was overestimated, congruent or underestimated compared to their family informant. We calculated the association between SF-DEM discrepancy score and total mini-mental status examination (MMSE) score and recall and attention/concentration subdomains.Results:In 108 participants with dementia (50.9% women), mean age = 78.9 (standard deviation, SD 6.5) years, and mean MMSE score = 22.7 (SD 3.7). Ratings of patients and informants for domain 1 did not differ, but patient-rating was higher than carer-rating for domain 2 (patient-rated score 11.2 (2.5), carer-rated score 10.1 (3.4); p = 0.003) and domain 3 (patient-rated score 9.7 (2.4), carer-rated score 8.1 (2.8); p &lt; 0.001). Sixty (55.6%) people with dementia overestimated their overall social functioning, 30 (27.8%) underestimated, and 18 (16.7%) gave ratings congruent with their family informant. Performance on the MMSE, and its sub-domains was not associated with SF-DEM discrepancy score.Conclusions:We found that insight varies according to subdomains of social functioning, with people with dementia rating their communication and sensitivity differently, and usually higher than their carers. Researchers and clinicians should consider insight into social functioning in dementia as a multidimensional, rather than a unified, concept. Clinicians should help family members understand and adapt by explaining their relative with dementia’s lack of insight about aspects of their social functioning.

Associations among depressive symptoms, hippocampal volume and cognition in community‐dwelling older Latinos

AbstractBackgroundLatinos are the fastest growing subpopulation of older adults in the U.S. and have a higher risk for dementia than non‐Latino Whites. Depressive symptoms are prevalent among US Latinos. However, these symptoms often go undiagnosed and are undertreated. Depressive symptoms may be early manifestations of Alzheimer’s Disease (AD) before the onset of mild cognitive impairment and dementia. It’s unclear whether depressive symptoms in the presence of incipient neurodegeneration are associated with cognitive function in older Latino adults. Here, we examined the associations among depressive symptoms, cognition and hippocampal volume in older Latinos.MethodA total of 65 Spanish‐speaking Latinos enrolled in the Boston Latino Aging Study (BLAST) and the Harvard Aging Brain Study (HABS) were included. Depressive symptoms were assessed with the 30‐item‐Geriatric Depression Scale (GDS) and cognition with the Preclinical Alzheimer’s Cognitive Composite (PACC5), which includes the Mini‐Mental State Examination (MMSE), Digit Symbol Coding, Free and Cued Selective Reminding Test, Category Fluency (animals) and Logical Memory Delayed Recall (NEUROPSI Stories for BLAST participants). A subset of 34 participants also underwent a structural brain MRI on a 3T scanner. Spearman correlations were used to determine cross‐sectional associations among depressive symptoms, hippocampal volume, and cognition. Models were adjusted for age and education.ResultsParticipants had a mean age of 66 +/‐ 7.2 years, a mean education of 12.9 +/‐ 5.1 years, and 74% were female. They had a mean MMSE score of 26.7 +/‐ 2.8, a mean GDS score of 6.1 +/‐ 5.5 and a mean adjusted hippocampal volume of 7836.5 +/ = 630.9 mm3. Correlation analyses revealed that higher depressive symptoms were associated with lower years of education (r = ‐0.39, p&lt;0.001), worse performance on cognitive measures (r = ‐0.33, p = 0.009) and smaller hippocampal volume (r = ‐0.61, p = &lt;0.001).ConclusionsPreliminary results of this ongoing biomarker study suggest that depressive symptoms in older Latinos are associated with markers of neurodegeneration (i.e., hippocampal volume) and worse cognition. Future work will focus on investigating predictors of long‐term emotional and cognitive functioning in Spanish‐speaking, older Latino populations.

Concurrent validity of clinical balance tests for older adults with cognitive impairment

Older adults with cognitive impairment frequently have reduced balance and are at high risk for falling.  We investigated the concurrent validity of the Physiological Profile Assessment (PPA) and the Timed Up and Go (TUG) test with computerised posturography in 13 older adults (mean (SD) age 80 (8) years) with mild-to-moderate cognitive impairment (mean (SD) Mini-Mental State Examination score, 19 (9)). Spearman’s rho demonstrated: moderately good positive correlation between  PPA (muscle strength) and posturography rising index (rs = 0.699, p = 0.01) and posturography mediolateral sway during eyes open standing on a foam surface (rs = 0.604, p = 0.04); good negative correlations between PPA anteroposterior sway (eyes closed) and posturography sway velocity (eyes open) standing on foam (rs = –0.745, p = 0.01) and Romberg ratios of PPA and posturography (rs = –0.698, p = 0.02); moderately good positive correlations between TUG and posturography (left step quick turn time; left turn sway; rs = 0.548, p = 0.04; 0.646, p = 0.02) and good-to-excellent negative correlation between TUG and posturography (rising index rs = –0.719, p = 0.01). Both tests appear valid measures of balance in older adults with mild-to-moderate cognitive impairment; however, we suggest both are used.

CTNI-48. SURVIVAL, TOXICITY, AND PATIENT REPORTED QOL OUTCOMES FOLLOWING PULSED REDUCED DOSE RATE RE-IRRADIATION WITH CONCURRENT BEVACIZUMAB FOR RECURRENT GRADE 4 GLIOMAS: RESULTS OF A PHASE II STUDY

Abstract Grade 4 gliomas are aggressive primary brain tumors with dismal prognosis despite maximal treatment. Recurrent disease is typically found within the prior radiation treatment field, complicating reirradiation. Pulsed reduced dose rate (PRDR) radiation is a treatment technique that reduces effective dose rate and increases treatment time allowing for intrafraction repair. Bevacizumab is a systemic VEGF inhibitor with efficacy in treating gliomas. We conducted a phase 2 prospective trial combining PRDR radiation with biweekly bevacizumab (10 mg/kg) in patients with recurrent grade 4 gliomas. Radiation was delivered with reduced dose rate delivered in 20 cGy pulses every 3 minutes in 2 Gy daily fractions to a total dose of 54 Gy. Kaplan Meier analysis was utilized to calculate progression free survival (PFS) and overall survival (OS). Toxicities were evaluated based on Common Terminology Criteria for Adverse Event v5.0 criteria. Mini Mental Status Examination (MMSE), as well as FACT-Brain, and FACIT-Fatigue patient reported quality of life (QoL) surveys were collected at baseline and follow up visits. Minimal important difference scores were calculated using by ½ standard deviation method. A total of 36 patients were enrolled, with 77% having previously received additional therapy for recurrent disease prior to study enrollment. Median PFS was 4.9 months and median OS was 6.9 months. No grade 4+ toxicity was observed. Two patients had grade 3 treatment related toxicity (seizure and radiation necrosis, both PRDR related). Treatment related grade 2 toxicity was seen in 44% of patients, primarily fatigue (30%). Clinically significant decrease in mean MMSE score, and FACT-BR QoL metrics across all sub-domains were noted in follow up. No clinically significant difference in mean FACIT-Fatigue QoL metric was observed. In this prospective phase 2 trial, PRDR with concurrent bevacizumab resulted in encouraging survival outcomes with acceptable toxicity in patients with recurrent grade 4 gliomas.

66 An Examination of Racial Disparities on Dementia Types in the Black Community

Objective:There is limited and inconsistent research exploring diagnosis, treatment, and prevention of dementias amongst Black Indigenous People of Color (BIPOC). By 2050, it is suspected that the White population will significantly decrease and BIPOC groups will comprise the majority of the US population yet BIPOC are historically underrepresented in dementia research. Prior research indicates apolipoprotein 4 allele (APOE-4) status is associated with a greater risk of developing Alzheimer’s disease in Black individuals when compared to non-Hispanic Whites. Investigating the racial disparities in dementia will expand our knowledgebase of risk for dementia types in the Black community to better meet the evergrowing population needs. The current study explored the impact of racial identity on global cognitive functioning, independent of age, education, and APOE e4 status.Participants and Methods:Participants were drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study and consisted of five pairs of Black and White individuals (n = 10) matched based on age, education, and APOE status. Global cognitive performance was measured by the total Mini Mental Status Examination (MMSE) score. Notably, only five Black individuals in phase 1 of ADNI met inclusion criteria. It was hypothesized Black individuals would be more cognitively impaired than their White counterparts. A matched pairs t-test was utilized to examine the relationship between global cognitive performance and race.Results:Black and White individuals’ MMSE scores did not significantly differ (p &gt; .05). The mean MMSE performance of White participants (26.40) was less robust than Black participants (27.80). Findings are inconsistent with current research, indicating that BIPOC individuals are disproportionately impacted by AD, with increased severity of cognitive impairment. There is a profound need for more research in preventative interventions and recruitment of BIPOC individuals who have been historically marginalized in cognitive research trials to help better understand diagnosis, treatment, and prevention of AD in BIPOC.Conclusions:The observed commensurate global cognitive functioning performance between matched Black and White individuals is not consistent with prior research findings demonstrating increased risk of developing dementia amongst BIPOC. This study’s small sample size reflects a significant barrier to detecting clinically meaningful differences. Efforts to address the recruitment crisis, underreporting, cultural influences, and overall mistrust of research among BIPOC is warranted. Inclusive research is critical to dismantling health disparities.

Progression of brain cholinergic dysfunction in patients with isolated rapid eye movement sleep behavior disorder.

Reduced cortical acetylcholinesterase activity, as measured by 11 C-donepezil positron emission tomography (PET), has been reported in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD). However, its progression and clinical implications have not been fully investigated. Here, we explored the relationship between longitudinal changes in brain acetylcholinesterase activity and cognitive function in iRBD. Twelve iRBD patients underwent 11 C-donepezil PET at baseline and after 3 years. PET images were interrogated with statistical parametric mapping (SPM) and a regions of interest (ROI) approach. Clinical progression was assessed with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III). Cognitive function was rated using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). From baseline to follow-up, the mean 11 C-donepezil distribution volume ratio (DVR) decreased in the cortex (p = 0.006), thalamus (p = 0.013), and caudate (p = 0.013) ROI. Despite no significant changes in the group mean MMSE or MoCA scores being observed, individually, seven patients showed a decline in their scores on these cognitive tests. Subgroup analysis showed that only the subgroup of patients with a decline in cognitive scores had a significant reduction in mean cortical 11 C-donepezil DVR. Our results show that severity of brain cholinergic dysfunction in iRBD patients increases significantly over 3 years, and those changes are more severe in those with a decline in cognitive test scores.

ASSESSMENT OF COGNITIVE FUNCTIONS AMONG SUBJECTS WITH SUBCLINICAL HYPOTHYROIDISM

Objective: The consequences of overt hypothyroidism on CNS are well known. In contrast, there is less evidence regarding the effects of subclinical hypothyroidism (SCH) on cognitive functions. Studies have shown a variable association between SCH and cognitive dysfunction. This study was done to assess the prevalence of cognitive impairment among subjects with SCH. Methods: The participants were 100 subjects (aged 40-60 years) with SCH and similar number of age-matched euthyroid controls. Subclinical hypothyroidism was defined as serum TSH level &gt; 4.5 mIU/L with normal FT3 and FT4. Participants were interviewed by a single observer. Cognitive function was assessed by mini mental state examination (MMSE) and clock drawing test (CDT). MMSE scores ≤24 is indicative of cognitive impairment. For CDT a score of ≥3 represents a cognitive deficit, while a score of 1 or 2 was considered normal. Results: The mean age of patient group was 47.4 years, and BMI of 26.1kg/m2 which were comparable to controls who had a mean age of 46.1 years (P=0.16) and mean BMI of 25.9 kg/m2 (P=0.25). All other baseline variables including sex ratio, co-morbidities, family history of dementia, smoking, alcohol use, education and exercise were also comparable in both groups. The mean TSH was 7.8 mIU/L in patients and 2.7 mIU/L in controls (P&lt; 0.05). The mean MMSE score was 26.1 in patient group and 27.7 in controls (P=0.31) The patients had mean CDT of 2.32 and controls 2.44 (P=0.61). Cognitive impairment by MMSE (score ≤24) was found in 22.0% of patients and in 16.0% of controls (P=0.14), also the cognitive impairment by CDT (score of ≥3) was present in 27.0% of patients and 25.0% of controls (P=0.29). Conclusion: In the present study we have found that the prevalence of cognitive impairment in subjects with SCH is similar to the age matched controls. Therefore the potential benefit of levothyroxine therapy if used with an aim of improving cognitive functions becomes doubtful.