Lower Mini-Mental State Examination Scores Research Articles

Late Menarche, Not Reproductive Period, Is Associated with Poor Cognitive Function in Postmenopausal Women in Taiwan.

Female sex hormones such as estrogen and progesterone play an important role in the regulation of a woman’s body, including cognition and neurogenesis. However, the effects of age at menarche and reproductive period on cognitive function are still controversial. The aim of this study was to investigate the relationships between age at menarche and reproductive period with cognitive impairment. Data were obtained from the Taiwan Biobank. Cognitive function was assessed using the Mini Mental State Examination (MMSE) and its five subdomains. Multivariable linear regression analysis revealed that an old age at menarche (per one year; coefficient β, −0.189; p = 0.020) was significantly associated with a low total MMSE score, whereas reproductive period (p = 0.733) was not significantly associated with total MMSE score. Furthermore, an old age at menarche was significantly associated with low MMSE G2 (registration) (per one year; coefficient β, −0.022; p = 0.035) and G5 (language, construction and obey) scores (per one year; coefficient β, −0.054; p = 0.047). However, age at menarche was not significantly associated with MMSE G1 (orientation), G3 (attention and calculation) and G4 (recall) scores. In addition, reproductive period was not significantly associated with any MMSE subscores. Late menarche was associated with poor cognitive function, including low total MMSE score and low MMSE G2 and G5 scores. However, reproductive period was not associated with cognitive function in postmenopausal women.

Tumor metabolism and neurocognition in CNS lymphoma.

The mechanistic basis for neurocognitive deficits in central nervous system (CNS) lymphoma and other brain tumors is incompletely understood. We tested the hypothesis that tumor metabolism impairs neurotransmitter pathways and neurocognitive function. We performed serial cerebrospinal fluid (CSF) metabolomic analyses using liquid chromatography-electrospray tandem mass spectrometry to evaluate changes in the tumor microenvironment in 14 patients with recurrent CNS lymphoma, focusing on 18 metabolites involved in neurotransmission and bioenergetics. These were paired with serial mini-mental state examination (MMSE) and MRI studies for tumor volumetric analyses. Patients were analyzed in the setting of the phase I trial of lenalidomide/rituximab. Associations were assessed by Pearson and Spearman correlation coefficient. Generalized estimating equation (GEE) models were also established, adjusting for within-subject repeated measures. Of 18 metabolites, elevated CSF lactate correlated most strongly with lower MMSE score (P < 8E-8, ρ = -0.67). High lactate was associated with lower gamma-aminobutyric acid (GABA), higher glutamate/GABA ratio, and dopamine. Conversely, high succinate correlated with higher MMSE scores. Serial analysis demonstrated a reproducible, time-dependent, reciprocal correlation between changes in lactate and GABA concentrations. While high lactate and low GABA correlated with tumor contrast-enhancing volume, they correlated more significantly with lower MMSE scores than tumor volumes. We provide evidence that lactate production and Warburg metabolism may impact neurotransmitter dysregulation and neurocognition in CNS lymphomas. We identify novel metabolomic biomarkers that may be applied in future studies of neurocognition in CNS lymphomas. Elucidation of mechanistic interactions between lymphoma metabolism, neurotransmitter imbalance, and neurocognition may promote interventions that preserve cognitive function.

Cognitive, physical and disability trajectories in community-dwelling elderly people

Backgrounds and aimsHealth trajectories in aging, rather than single time-point assessments, could be early indicators of the onset of conditions such as dementia. The aim of this study was to identify different aging trajectories and to investigate their influence on the cumulative incidence of dementia.MethodsWe evaluated data referring to 993 elders from the InveCe.Ab study cohort. All subjects were free from dementia at baseline and re-assessed on at least one other occasion thereafter. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), physical function using the Walking Speed Test (WST), and disability on the basis of the Activities of Daily Living (ADL) score. To describe the different courses of the three outcomes combined, the Group-Based Trajectory Model (GBTM) method was applied. We looked for differences in age, gender, education, ApoE-e4 carrier status and obesity, and then investigated the influence of the observed trajectories on the incidence of dementia.ResultsThree trajectories were identified: a “good” scenario was observed in 703 (70.2%) individuals, who showed substantially stable cognitive and physical function and no disability; an “intermediate” scenario in 248 subjects (25.5%), who recorded a longer walking time, lower MMSE score, and a one-point higher ADL score; and a “severe” scenario in 42 elders (4.3%), who recorded declines in all the outcomes. Female gender, obesity and low education were most represented in the “severe” group. ApoE-e4 carrier status showed no difference between groups. The estimated cumulative incidence of dementia was higher in the “severe” (37%) than in the “intermediate” (7%) and “good” (< 1%) scenarios.ConclusionsUsing simple measurements, we built different aging trajectories, and observed that the worst performers had the highest incidence of dementia. Better knowledge of trajectories of aging would be useful for preventive interventions aimed at promoting healthier aging.

Transient Cognitive Impairment and White Matter Hyperintensities in Severely Depressed Older Patients Treated With Electroconvulsive Therapy

Although electroconvulsive therapy (ECT) is a safe and effective treatment for patients with severe late life depression (LLD), transient cognitive impairment can be a reason to discontinue the treatment. The aim of the current study was to evaluate the association between structural brain characteristics and general cognitive function during and after ECT. A total of 80 patients with LLD from the prospective naturalistic follow-up Mood Disorders in Elderly treated with Electroconvulsive Therapy study were examined. Magnetic resonance imaging scans were acquired before ECT. Overall brain morphology (white and grey matter) was evaluated using visual rating scales. Cognitive functioning before, during, and after ECT was measured using the Mini Mental State Examination (MMSE). A linear mixed-model analysis was performed to analyze the association between structural brain alterations and cognitive functioning over time. Patients with moderate to severe white matter hyperintensities (WMH) showed significantly lower MMSE scores than patients without severe WMH (F(1,75.54) = 5.42, p = 0.02) before, during, and post-ECT, however their trajectory of cognitive functioning was similar as no time × WMH interaction effect was observed (F(4,65.85) = 1.9, p = 0.25). Transient cognitive impairment was not associated with medial temporal or global cortical atrophy (MTA, GCA). All patients showed a significant drop in cognitive functioning during ECT, which however recovered above baseline levels post-ECT and remained stable until at least 6 months post-ECT, independently of severity of WMH, GCA, or MTA. Therefore, clinicians should not be reluctant to start or continue ECT in patients with severe structural brain alterations.

β-Amyloid PET and 123I-FP-CIT SPECT in Mild Cognitive Impairment at Risk for Lewy Body Dementia.

ObjectiveTo determine the clinical phenotypes associated with the β-amyloid PET and dopamine transporter imaging (123I-FP-CIT SPECT) findings in mild cognitive impairment (MCI) with the core clinical features of dementia with Lewy bodies (DLB; MCI-LB).MethodsPatients with MCI who had at least 1 core clinical feature of DLB (n = 34) were grouped into β-amyloid A+ or A− and 123I-FP-CIT SPECT D+ or D− groups based on previously established abnormality cut points for A+ with Pittsburgh compound B PET standardized uptake value ratio (PiB SUVR) ≥1.48 and D+ with putamen z score with DaTQUANT <−0.82 on 123I-FP-CIT SPECT. Individual patients with MCI-LB fell into 1 of 4 groups: A+D+, A+D−, A−D+, or A−D−. Log-transformed PiB SUVR and putamen z score were tested for associations with patient characteristics.ResultsThe A−D+ biomarker profile was most common (38.2%), followed by A+D+ (26.5%) and A−D− (26.5%). The least common was the A+D- biomarker profile (8.8%). The A+ group was older, had a higher frequency of APOE ε4 carriers, and had a lower Mini-Mental State Examination score than the A− group. The D+ group was more likely to have probable REM sleep behavior disorder. Lower putamen DaTQUANT z scores and lower PiB SUVRs were independently associated with higher Unified Parkinson’s Disease Rating Scale-III scores.ConclusionsA majority of patients with MCI-LB are characterized by low β-amyloid deposition and reduced dopaminergic activity. β-Amyloid PET and 123I-FP-CIT SPECT are complementary in characterizing clinical phenotypes of patients with MCI-LB.

Change in cognitive function according to cholinesterase inhibitor use and amyloid PET positivity in patients with mild cognitive impairment

BackgroundCholinesterase inhibitors (ChEIs) are an FDA-approved symptomatic treatment for patients with Alzheimer’s disease (AD). Its efficacy in patients with mild cognitive impairment (MCI), however, is controversial. Nonetheless, ChEIs have often been used in patients with MCI. From the perspective that ChEIs were developed based on the pathomechanism of AD, the effect of ChEIs in MCI patients could be different depending on the amyloid burden. In this retrospective observational study, we aimed to investigate the influence of ChEIs and amyloid burden on cognitive change for 1 year in patients with MCI.MethodsWe included 111 patients with MCI with a Clinical Dementia Rating (CDR) score of 0.5, a 1-year follow-up cognitive assessment, and amyloid positron emission tomography (PET) performed within 6 months before or after the baseline cognitive assessment (73 ChEI users and 38 ChEI non-users) from the Neurocognitive Behavior Center of Seoul National University Bundang Hospital. Additionally, those who had a positive amyloid PET scan more than 6 months before the baseline cognitive assessment and those who had a negative amyloid PET scan more than 6 months after the 1-year follow-up cognitive assessment were also included. Among the total 111 patients, 25 ChEI users and 25 ChEI non-users were matched by baseline Mini-Mental State Examination (MMSE) score, age, educational level, CDR Sum of Boxes, and amyloid PET positivity using propensity score matching. Multiple linear regression analysis was performed to assess the influence of ChEI use and amyloid PET positivity on cognitive change for 1 year. Univariate and multivariate logistic regression analyses were performed to evaluate the association between ChEI use and disease progression to CDR 1 at the 1-year follow-up visit.ResultsChEI use or non-use was not associated with cognitive change for 1 year. Amyloid PET positivity or negativity did not change this non-association. Furthermore, progression to CDR 1 was related to low baseline MMSE score (OR 0.606, CI 0.381–0.873), but not with ChEI use or non-use, and not with amyloid PET result.ConclusionChEI use or non-use was not related to cognitive change at a 1-year follow-up visit in patients with or without amyloid burden. In addition, ChEI use or non-use could not predict disease progression to CDR 1 at 1-year follow-up visit.

Detecting Lower MMSE Scores in Older Adults Using Cross-Trial Features From a Dual-Task With Gait and Arithmetic

The Mini-Mental State Examination (MMSE) is widely used in clinics to screen for low cognitive status. However, it is limited in that it requires examiners to be present; and has fixed questions that constrain its repeated use. Thus, the MMSE cannot be used as a daily assessment to facilitate early detection of cognitive impairment. To address this issue, we developed an automated system to detect older adults with lower MMSE scores by analyzing performance during a dual task involving stepping and calculation, which can be used repeatedly because its questions were randomly created. Leveraging this advantage, this paper proposes a learning-based method to detect subjects with lower MMSE scores using multiple trials with the dual-task system. We investigated various patterns for effectively combining the features acquired during multiple continuous trials, and analyzed the sensitivity of the number $N$ of trials on detection performance to find the optimal $N$ via experiments. We compared our approach with previous methods and demonstrated the superiority of our strategy. Using the cross-trial feature, our approach achieved an overall performance (sensitivity + specificity) as high as 1.79 for detecting older adults whose MMSE score is equal to or less than 23 (indicate a relatively high probability of dementia), and 1.75 for detecting older adults whose MMSE score is equal to or less than 27 (indicative of a relatively high probability of mild cognitive impairment (MCI)).

Association between self‐reported night sleep duration and cognitive function among older adults with intact global cognition

The purpose of this study was to clarify the association between self-reported night sleep duration and cognitive functions such as word memory, story memory, attention, executive function, and processing speed of older adults with normal global cognitive function. A total of 241 functionally independent older adults (mean age, 75.5 ± 6.4 years) participated in this study. No participants had a history of dementia diagnosis, and each had a Mini-Mental State Examination (MMSE) score ≥ 24. Participants were evaluated for self-reported sleep duration and cognitive function using the National Center for Geriatrics and Gerontology-Functional Assessment Tool (NCGG-FAT). The longest sleep duration group (≥9 h) had lower MMSE scores (p = 0.010), Z-score of word list memory II (delayed recall; p = 0.001), and Z-score of story memory II (delayed recognition; p = 0.002) than the medium sleep duration group (7-8 h). Longest and long sleep duration (8-9 h) was significantly associated with impairment of story memory II (longest sleep duration: adjusted odds ratio [OR] = 3.58, 95% confidence interval [CI] = 1.13-11.37, long sleep duration: adjusted OR = 4.30, 95% CI = 1.34-13.82) with reference to medium sleep duration, but no impairment of MMSE according to multiple logistic regression analysis. Furthermore, short sleep duration (<7 h) was not associated with cognitive impairment. This study suggests that long sleep duration is associated with cognitive impairment, especially of story memory (delayed recognition) in older adults with normal global cognitive function.

Depressive symptoms are associated with hippocampal neurodegeneration in preclinical autosomal dominant Alzheimer’s disease

AbstractBackgroundIncreasing evidence suggests that depressive symptoms may be among early behavioral changes in Alzheimer’s Disease (AD). However, the neurobiology of these symptoms in the preclinical stages of AD remains unclear, particularly in relation to markers of neurodegeneration. Studying depression in individuals who carry mutations for autosomal dominant AD (ADAD) is a compelling way to characterize depressive symptoms in preclinical AD, as virtually all ADAD mutation carriers develop dementia and have a well‐characterized trajectory from pre‐symptomatic to clinical disease stages.MethodWe evaluated cross‐sectional associations between the 15‐item Geriatric Depression Scale (GDS) and neurodegeneration of the hippocampus, one of the most vulnerable brain regions in ADAD and depression, in 27 cognitively unimpaired PSEN1 E280A mutation carriers and 26 matched non‐carrier family members of a Colombian kindred with ADAD. Global cognition was measured by the Mini‐Mental State Examination (MMSE); hippocampal volume was assessed by structural MRI. A general linear model with dependent variable GDS, predictor hippocampal volume, and covariates, age, sex, MMSE, and intracranial volume (ICV), was employed.Result PSEN1 E280A carriers and non‐carriers did not differ in GDS (carriers:2.2±2.6, non‐carriers:2.9±3.5; p=0.64), sex (carriers:70% females, non‐carriers:88% females; p=0.24), age (carriers:35.9±8.2 years, non‐carriers:37.0±6.5; p=0.56), ICV (carriers:1.4 x106 ±1.1 x 105 mm3, non‐carriers:1.4 x 106 ±1.3 x 105 mm3; p=0.16), or hippocampal volume (carriers: 3867±569 mm3, non‐carriers: 4090±371 mm3; p=0.20). Compared to non‐carriers, carriers had lower MMSE scores (carriers: 28.3±2.9, non‐carriers: 29.7±0.5; p=0.03). In carriers, GDS was negatively associated with hippocampal volume (β= ‐0.71, t= ‐2.6, p=0.02), but not with age, sex, MMSE, or ICV. This association between GDS and hippocampal volume was not observed in non‐carriers (β= ‐0.26, t= ‐1.2, p=0.25).ConclusionDepressive symptoms in cognitively‐unimpaired carriers of an ADAD mutation are significantly associated with early hippocampal neurodegeneration, years before the estimated onset of dementia. This provides some of the first evidence of a region‐specific neurodegenerative basis of depressive symptoms in preclinical ADAD. Future longitudinal investigation is needed to characterize the temporal sequence of depressive symptoms in relation to markers of brain pathology and cognitive decline in AD. Findings may have implications for early interventions to reduce depressive symptoms in individuals who have AD risk factors.

The anticholinergic effect on cognition (AEC) scale: Associations with mortality, hospitalisation and cognitive decline following dementia diagnosis

AbstractObjectivesTo investigate associations between central anticholinergic burden (using the AEC scale), and mortality, hospitalisation and cognitive decline in patients with dementia.MethodsThe South London and Maudsley NHS Foundation Trust (SLaM) Clinical Records Interactive Search (CRIS) application was used to identify patients 65 years or older at their first recorded diagnosis of dementia. Data were linked to national mortality and hospitalisation sources, and serially recorded Mini‐Mental State Examination (MMSE) scores were used to investigate cognitive decline over the 36 months after diagnosis in mixed models.ResultsPatients for whom a review of their medication was indicated (AEC score ≥ 2 for any individual drug or total AEC score ≥ 3) had an increased risk of mortality (hazard ratio 1.07; 95% CI 1.01‐1.15) and emergency hospitalisation (1.10; 95% CI 1.04‐1.17), but there were no associations with duration of hospitalisation. Cognitive trajectory analyses showed that this exposure group had lower MMSE scores at diagnosis and a sharper increase in MMSE scores over the subsequent 6 months, but similar slopes for the 6‐36 months period to the remainder of the sample.ConclusionsPatients with dementia receiving medication with high central anticholinergic activity (as measured on the AEC scale), appear to have worse prognosis in terms of mortality and hospitalisation risk, but have primarily acutely impaired cognitive function, rather than longer term differences in cognitive decline.

The association of marital status with cognitive function and the role of gender in Chinese community-dwelling older adults: a cross-sectional study.

Evidence of the association between marital status and cognitive function in Chinese older adults is limited. To examine the relationship between marital status and cognitive function and to explore the role of gender amongst older adults from three Chinese communities. A total of 1376 participants aged 60years or over were included in this cross-sectional study. Cognitive function was assessed using the Chinese version of the mini-mental state examination (MMSE). Marital status and other variables were collected using a standardized questionnaire. Multiple linear regression models were used to examine associations between marital statuses and cognitive function amongst the target population. The moderating role of gender in these potential associations has also been explored. In univariate linear regression models, compared to being married, both being widowed (β [95% CI]: -1.46[-2.78 to - 0.13]) and being single (β [95% CI]: - 4.88[-6.43 to - 3.38]) were associated with lower MMSE scores. After adjustment for confounding factors, the significant association of being widowed with MMSE scores disappeared (β [95% CI: - 0.08[- 1.04 to 0.86]), but the association of being single with MMSE scores still existed (β [95% CI]: - 1.87[- 3.17 to - 0.58]). Furthermore, the association of being single with MMSE scores was statistically significant in men (β [95% CI]: - 5.25[- 7.17 to - 3.33]) but not in women (β [95% CI: 0.88[- 0.87 to 2.64]). Being single was associated with poorer cognitive function compared with their married counterparts in older Chinese men but not in women. Morepreventive measurementsshouldbe implemented for single men to reduce or delay cognitive decline. This is particularly important in the context of an aging population in China.

Mild functional decline and driving performance of older drivers without a diagnosed dementia: Study of leukoaraiosis and cognitive function

Motor vehicle collisions involving older drivers have increased and become an important social issue. It is known that the decline of cognitive function, including dementia, affects driving performance. A series of studies using the Mini-Mental State Examination (MMSE) and other tests of dementia have attempted to prevent motor vehicle collisions by identifying as early as possible older drivers who may be unable to maintain their driving performance. Further, the performance of older drivers may deteriorate even if they do not have a diagnosis of dementia. Therefore we focused on the relationship between cognitive functioning assessed by the MMSE and diagnosis of leukoaraiosis (LA), or changes in the cerebral white matter, with different aspects of driving behavior resulting from aging. Qualified driving instructors evaluated participants’ driving behaviors on an outdoor driving course at a driving school. Visual search duration and angle at intersections were obtained by wearable wireless sensors. Vehicle speed and minimum vehicle speed were recorded from vehicle speed pulse signals. Duration of signaling and visual searches at unsignalized intersections were recorded using an in-vehicle camera. We assessed instructors’ evaluations and the scores on two instruments to evaluate the effects of MMSE scores and the grade of LA on driving performance were verified. The results suggest that lower MMSE scores and higher LA grade can predict some aspects of poor driving performance in older drivers before they experience dementia or an evident decline in cognitive functioning. Based on these results, we discuss countermeasures that may prevent motor vehicle collisions involving older drivers.

Correlates of olfactory impairment in middle-aged non-diabetic Caucasian subjects with stage I-II obesity.

This study evaluates among middle-aged subjects with obesity the prevalence of olfactory impairment (OI) with respect to normative values and its correlation with body composition, cognition, sleep quality, and inflammation. In 60 (31 women, 29 men) volunteers with a body mass index ≥ 30 to ≤ 40kg/m2, aged ≥ 50 to ≤ 70years, we assessed olfaction by the Sniffin' Stick test. We measured anthropometrics, body composition and metabolic profiles and evaluated cognition by the MiniMental State Examination (MMSE) and sleep disturbances by the Insomnia Severity Index (ISI). Patients were classified into two groups according to a total olfactory score (odor Threshold, Discrimination, Identification, TDI) below or above the 25th percentile from age and gender-adjusted normative data. Overall, 25 subjects (42%) had OI (TDI < 25th percentile). The largest differences between subjects with and without OI were observed in discrimination and identification scores, with a large overlap in olfactory threshold. Subjects with an abnormal TDI showed significantly higher fat mass index, ISI scores and urinary neopterin and lower MMSE scores than those without OI. By multivariable logistic regression, MMSE, ISI score and urinary neopterin were significantly associated to OI. Among middle-aged subjects with stage I and II obesity, OI is highly prevalent and is independently associated with poor self-reported sleep quality, lower cognition scores and higher levels of the inflammatory marker neopterin.

Homocysteinemia is Associated with the Presence of Microbleeds in Cognitively Impaired Patients

Background & ObjectiveHomocysteine is possibly associated with cerebral small vessel diseases such as leukoaraiosis, silent brain infarction and cerebral microbleeds, which are in turn associated with cognitive dysfunction. We aimed to examine the relationships between cerebral microbleeds (CMBs) and plasma total homocysteine (tHcy) level, methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cognitive function. MethodsA total of 819 patients with memory disturbance who visited a dementia clinic consecutively were included in this study. We retrospectively collected demographic, clinical and laboratory data including tHcy level, MTHFR C677T polymorphism and Mini-Mental State Examination (MMSE). All patients underwent brain MRI including fluid attenuated inversion recovery (FLAIR) image and T2*-weighed gradient-echo (GRE) image. Logistic regression analysis was performed to test the association between risk factors and the presence of microbleeds. ResultsOne hundred and sixty-one (19.7%) patients had CMBs, of whom 88 (54.7%) had CMBs in the lobar region. CMBs were more common in older hypertensive male patients with hyperhomocysteinemia. In multivariable analysis, plasma tHcy remained an independent predictor of the presence of CMBs after adjusting other confounders (OR: 1.035, 95% CI: 1.009-1.062, p = 0.009). Higher plasma tHcy level was also associated with number of CMBs, TT MTHFR genotype, and lower MMSE scores. ConclusionsElevated plasma tHcy level is related to high prevalence of CMBs and cognitive dysfunction. Lowering plasma tHcy could be helpful in cognitively impaired patients who have CMBs or the MTHFR TT genotype.

Bouncing Back from the Burden of Dementia

Abstract. Background: Although there is mounting evidence of dyadic interdependencies between patients with dementia (PWD) and their caregivers, predictors of resilience among PWD and their caregivers are generally regarded in isolation. We therefore investigated how dyadic interdependencies regarding common resilience factors predict subjective notions of individual resilience. Methods: A total of 29 dyads (caregivers: 23 female, 73 ± 7 years; PWD: 6 female, 76 ± 6 years, Mini-Mental State Examination (MMSE) score: 18 ± 6) drawn from two studies answered questions about resilience (Brief Resilience Scale; BRS), partnership quality (Marital Quality Questionnaire; PFB), and depression (Geriatric Depression Scale; GDS-15). Using linear regression models, we predicted BRS scores by linearly combining individual characteristics (intraindividual level), characteristics of the partner (interindividual level), and their dyadic similarity (dyadic level). Results: Intraindividually, higher resilience in caregivers was associated with female sex; interindividually, it was associated with lower MMSE scores and higher PFB scores in PWD. On a dyadic level, the more different the GDS-15 scores were, the higher the resilience of caregivers. For PWD, higher resilience was significantly related to individual lower GDS-15 scores and higher PFB scores, while the characteristics of caregivers did not explain any variance. However, similarity in GDS-15 scores predicted higher resilience in PWD. Discussion: Resilience is affected differently in PWD and caregivers, potentially pointing to different strategies in coping with disease-related changes. Future studies are necessary to examine the mechanisms underlying resilience in PWD and their respective caregiver in order to tailor interventions that address the needs of both parties, from the individual, interindividual, and dyadic perspectives.

Cortical atrophy mediates the accumulating effects of vascular risk factors on cognitive decline in the Alzheimer's disease spectrum.

There are increasing concerns regarding the association of vascular risk factors (VRFs) and cognitive decline in the Alzheimer's disease (AD) spectrum. Currently, we investigated whether the accumulating effects of VRFs influenced gray matter volumes and subsequently led to cognitive decline in the AD spectrum. Mediation analysis was used to explore the association among VRFs, cortical atrophy, and cognition in the AD spectrum. 123 AD spectrum were recruited and VRF scores were constructed. Multivariate linear regression analysis revealed that higher VRF scores were correlated with lower Mini-Mental State Examination scores and higher Alzheimer's Disease Assessment Scale-Cognitive Subscale scores, indicating higher VRF scores lead to severer cognitive decline in the AD spectrum. In addition, subjects with higher VRF scores suffered severe cortical atrophy, especially in medial prefrontal cortex and medial temporal lobe. More importantly, common circuits of VRFs- and cognitive decline associated with gray matter atrophy were identified. Further, using mediation analysis, we demonstrated that cortical atrophy regions significantly mediated the relationship between VRF scores and cognitive decline in the AD spectrum. These findings highlight the importance of accumulating risk in the vascular contribution to AD spectrum, and targeting VRFs may provide new strategies for the therapeutic and prevention of AD.

Value of the Frontal Assessment Battery Tool for Assessing the Frontal Lobe Function in Stroke Patients.

ObjectiveTo examine the correlation between the Frontal Assessment Battery (FAB) test, which is used to assess the frontal lobe function, and anatomical lesions as well as the ability of the test to detect frontal lobe dysfunction.MethodsRecords of stroke patients undergoing a FAB test and Mini-Mental State Examination (MMSE) were retrospectively reviewed. The patients were divided into three groups according to the lesions determined by an imaging study: frontal lobe cortex lesions, frontal subcortical circuit lesions, and other lesions. The FAB scores of the three groups were compared using the Kruskal-Wallis test. The validity of the FAB test to detect frontal lobe dysfunction was assessed by a comparison with the Computerized Neuropsychological Function Test (CNT) using the Spearman correlation coefficient. The correlation coefficients between the FAB test and MMSE were analyzed further based on the MMSE cutoff score.ResultsPatients with frontal cortex lesions had significantly lower total and subtest scores according to the FAB test than the other patients. The FAB test correlated better with the CNT than the MMSE, particularly in the executive function and memory domains. A high MMSE score (r=0.435) indicated a lower correlation with the FAB test score than a low MMSE score (r=0.714).ConclusionThe FAB test could differentiate frontal lobe lesions from others in stroke patients and showed a good correlation with the CNT. Moreover, the FAB test can be used in patients with high MMSE scores to detect frontal lobe dysfunction and determine the treatment strategies for stroke patients.

Moderate-to-Severe Obstructive Sleep Apnea and Cognitive Function Impairment in Patients with COPD.

PurposePrior studies have indicated that patients with chronic obstructive pulmonary disease (COPD) exhibit significant cognitive defects on neuropsychological testing. Obstructive sleep apnea (OSA) is common in patients with COPD and is associated with reduced cognitive function; however, the combined impact of these two conditions on cognitive function is unknown. The aim of the study was to investigate the impact of OSA on cognitive impairment in patients with COPD.MethodsSixty-five stable COPD patients aged over 60 years underwent overnight polysomnography (PSG). Global cognitive functions were evaluated using the Mini-Mental State Examination (MMSE).ResultsCompared to patients with COPD alone, patients with both COPD and OSA performed worse on the MMSE (25.5±2.9 vs 23.5±3.2; p=0.01) and were more likely to be at risk for developing dementia based on the MMSE score (MMSE≤24) (31% vs 66%; p<0.01), independent of key demographic, educational and medical variables known to affect cognitive function in COPD. COPD patients with an apnea hypopnea index (AHI) of ≥30 events/h had lower MMSE scores than those with an AHI of <15 events/h. In addition to age and education level, the severity of nocturnal intermittent hypoxia is an independent predictor of the risk of dementia in patients with COPD (OR=1.24, 95% CI 1.04–1.48, p = 0.02).ConclusionThe current findings indicate that patients with COPD with comorbid OSA may be at greater risk for global cognitive impairment relative to patients with COPD alone. The mechanisms underlying the exaggerated cognitive dysfunction seem to be related to intermittent hypoxia. Further work is needed to understand the impact of OSA on the specific domains of cognitive impairment and the therapeutic implications of OSA in COPD.

The anticholinergic effect on cognition (AEC) scale-Associations with mortality, hospitalisation and cognitive decline following dementia diagnosis.

To investigate associations between central anticholinergic burden (determined through the anticholinergic effect on cognition [AEC] scale) and mortality, hospitalisation and cognitive decline in patients with dementia. The South London and Maudsley NHS Foundation Trust (SLaM) Clinical Records Interactive Search (CRIS) application was used to identify patients with a first diagnosis of dementia. Medication exposure was extracted through a natural language processing algorithm, allowing for calculations and comparisons of AEC scores. Data were linked to national mortality and hospitalisation data sources, and serially recorded Mini-Mental State Examination (MMSE) scores were used to investigate cognitive decline. We identified 14 093 patients with dementia, 60.7% were female and the mean age at diagnosis was 79.8 years. Patients for whom a review of their medication was indicated (AEC score ≥ 2 for any individual drug or total AEC score ≥ 3) had an increased risk of mortality (hazard ratio 1.07; 95% confidence interval [CI]: 1.01-1.15) and emergency hospitalisation (1.10; 95% CI: 1.04-1.17), but there were no associations with duration of hospitalisation. Cognitive trajectory analyses showed that this exposure group had lower MMSE scores at diagnosis and a sharper increase in MMSE scores over the subsequent 6 months, but similar slopes for the 6 to 36 months period compared to the remainder of the sample. Patients with dementia receiving medication with high central anticholinergic activity appear to have worse prognosis in terms of mortality and hospitalisation risk, but have, primarily, acutely impaired cognitive function, rather than longer-term differences in cognitive decline. J Am Geriatr Soc 68:-, 2020.

Use of day services improved cognitive function in patients with Alzheimer's disease.

Day services (DS) are part of the public nursing care system in Japan. The purpose of DS is to help elderly individuals maintain mental and physical functions, eliminate feelings of isolation among homebound users, and reduce the burden of care on family members. However, the relationship between DS and the progression of Alzheimer's disease (AD) remains unclear. We retrospectively analyzed 161 AD patients based on available Mini-Mental State Examination (MMSE) scores. The patients were divided into two groups: those who started to use DS (n = 106) and those who did not use DS (n = 55). We then compared the groups' MMSE scores between the first memory clinic visit and the 6-month point. There were no significant differences between the two groups with regard to sex and the number of family members, but the non-DS group was younger, had more education, and had better MMSE scores at the first visit. At 6 months, we found a significant improvement in the MMSE scores of DS users, reflecting improved cognitive function. In addition, lower MMSE score at the first visit was associated with greater improvement in MMSE score at 6 months. Interestingly, the frequency of DS use had no significant effect on MMSE score. However, after approximately 6 months, DS use significantly improved the cognitive function of AD patients. DS use significantly improved the cognitive function of AD patients. However, most DS users in Japan are older and have severe dementia. Patients who are younger, have more education, or have mild dementia dislike using DS. As a significant difference was found in the MMSE scores between the two groups after 6 months, DS use appears to be a useful non-drug therapy.