Lower Mini-Mental State Examination Scores Research Articles

Inflammation and Cognitive Functioning in Depressed Older Adults Treated With Electroconvulsive Therapy: A Prospective Cohort Study.

Objective: Despite the effectiveness of electroconvulsive therapy (ECT), patients and practitioners are often reluctant to start it due to the risk of transient cognitive side effects, particularly in older patients. Inflammatory processes may be associated with the occurrence of these effects. This study assessed whether inflammatory markers prior to ECT are associated with cognitive functioning in depressed patients treated with ECT.Methods: Between 2011 and 2013, 97 older patients (mean [SD] age = 73.1 [8.1] years) with severe unipolar depression (according to DSM-IV) referred for ECT were included. Mini-Mental State Examination (MMSE) scores were used to determine cognitive functioning prior to, weekly during, and in the first week after a course of ECT. Serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) were assessed prior to ECT.Results: In fully adjusted models, there was an association between TNF-α and cognitive functioning (β = -1.05; 95% CI, -2.04 to -0.06; f2 = 0.06). An association was also found between baseline levels of IL-10 and TNF-α and lower MMSE scores during ECT (IL-10: β = -2.08; 95% CI, -3.22 to -0.95; TNF-α: β = -0.65; 95% CI, -1.07 to -0.22). In addition, an association was found between baseline CRP and lower MMSE scores directly after a course of ECT (β = -0.51; 95% CI, -0.93 to -0.09; f2 = 0.10). Associations with IL-6 did not reach significance.Conclusions: This study suggests that inflammatory processes are associated with lower cognitive functioning prior to ECT and predispose for further cognitive dysfunction during and after a course of ECT.Trial registration: ClinicalTrials.gov identifier: NCT02667353.

Impact of C-Reactive Protein on Cognition and Alzheimer Disease Biomarkers in Homozygous APOE ɛ4 Carriers.

Previous research has shown that elevated blood C-reactive protein (CRP) is associated with increased Alzheimer disease (AD) risk only in APOE ε4 allele carriers; the objective of this study was to examine the interactive effects of plasma CRP and APOE genotype on cognition and AD biomarkers. Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed, including APOE genotype; plasma CRP concentrations; diagnostic status (i.e., mild cognitive impairment and dementia due to AD); Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Dementia Staging Instrument scores; CSF concentrations of β-amyloid peptide (Aβ42), total tau (t-Tau) and phosphorylated tau (p-Tau); and amyloid (AV45) PET imaging. Multivariable regression analyses tested the associations between plasma CRP and APOE on cognitive and biomarker outcomes. Among 566 ADNI participants, 274 (48.4%) had no, 222 (39.2%) had 1, and 70 (12.4%) had 2 APOE ε4 alleles. Among only participants who had 2 APOE ε4 alleles, elevated CRP was associated with lower MMSE score at baseline (β [95% confidence interval] -0.52 [-1.01, -0.12]) and 12-month follow-up (β -1.09 [-1.88, -0.17]) after adjustment for sex, age, and education. The interaction of 2 APOE ε4 alleles and elevated plasma CRP was associated with increased CSF levels of t-Tau (β = 11.21, SE 3.37, p < 0.001) and p-Tau (β = +2.74, SE 1.14, p < 0.01). Among those who had no APOE ε4 alleles, elevated CRP was associated with decreased CSF t-Tau and p-Tau. These effects were stronger at the 12-month follow-up. CRP released during peripheral inflammation could be a mediator in APOE ε4-related AD neurodegeneration and serve as a drug target for AD.

Association of central obesity and high body mass index with function and cognition in older adults.

ObjectiveTo investigate the association of normal BMI with central obesity (CO), high BMI with CO, high BMI without CO, and normal BMI without CO, with function and cognition in older adults.MethodsCross-sectional study involving 754 participants ≥ 65 years. Data collected include demographics, cognition, and physical measurements.ResultsFemales had a higher prevalence of high BMI with CO and a lower prevalence of high BMI without CO than males (61.0% vs 44.6% and 4.6% vs 15.0%, respectively). Within gender, CO groups, regardless of BMI, had lower mini-mental state examination (MMSE), handgrip strength (HGS), and longer timed-up-and-go (TUG) scores. Overall, the high BMI without CO group had the highest MMSE scores, HGS, and shortest TUG. Amongst males, HGS was significantly lower in the normal BMI with CO group (B −3.28, 95% CI −6.32 to −0.23, P = 0.04). CO, regardless of normal/high BMI, had significantly longer TUG time (B 2.65, 95% CI 0.45 to 4.84, P = 0.02; B 1.07, 95% CI 0.25 to 1.88, P = 0.01, respectively) than normal BMI without CO group. CO was associated with lower MMSE scores in both genders but significant only in males with normal BMI and CO (B −1.60, 95% CI −3.15 to −0.06, P = 0.04).ConclusionCO may be a better predictor of obesity and adverse outcomes in older adults. High BMI without CO was associated with better outcomes especially in males but require further validation. Prospective longitudinal studies are needed to ascertain the impact of BMI and/or CO on function, cognition, mortality, and gender differences.

High-density lipoprotein cholesterol and brain aging amongst rural-dwelling older adults: a population-based magnetic resonance imaging study.

Current evidence supports the involvement of lipids in brain aging. A range of serum lipids is explored in association with brain structure and cognitive function amongst rural-dwelling older adults. This population-based cross-sectional study included 184 rural-dwelling adults (age≥65years, 39.1% women) in Shandong, China. In 2014-2016, data on demographics, lifestyle, health conditions and serum lipids were collected. Volumes of gray matter, white matter, ventricles, hippocampus and white matter hyperintensity were automatically estimated on brain magnetic resonance imaging. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE), and mild cognitive impairment (MCI) was defined according to Petersen's criteria. Data were analyzed using the general linear regression, logistic regression and mediation models. Of the 184 participants, 47 were defined with MCI. Low high-density lipoprotein cholesterol (HDL-C; <1.55 vs. ≥1.55mmol/l) was significantly associated with reduced volumes of total white matter (multi-adjusted β=-9.77, 95% confidence interval -19.48-0.06) and hippocampus (-0.23, -0.46-0.01), a lower MMSE score (-1.49, -2.67-0.31) and a higher likelihood of MCI (multi-adjusted odds ratio3.21, 95% confidence interval 1.42-7.29). The mediation effects of structural brain measures on the associations between a low level of HDL-C and MMSE score or MCI were not statistically significant (p>0.05). This study suggests that low HDL-C may be involved in structural brain aging and cognitive dysfunction amongst rural-dwelling older adults in China, but the association of low HDL-C with cognitive aging phenotypes appears not to be mediated by brain structure.

Factors Associated With Frailty in Patients Undergoing Cardiac Surgery: A Longitudinal Study.

Frailty may increase the risk of complications and mortality in patients undergoing cardiac surgery. Few studies on frailty and its associated factors have been conducted in these patients. The aim of this study was to explore frailty and related factors in patients undergoing cardiac surgery. A total of 154 patients undergoing cardiac surgery in northern Taiwan were recruited using a longitudinal study design and interviewed using structured questionnaires assessing physical activity, anxiety and depression, and social support before surgery and at 1 month and 3 months after surgery. The prevalence of frailty in patients undergoing cardiac surgery was 16.2%, 20.5%, and 16.6% before surgery and at 1 month and 3 months after surgery, respectively. Frail and prefrail patients undergoing cardiac surgery were more likely to be unemployed, have gout, have a higher New York Heart Association class, have preoperative dysrhythmia, undergo cardiopulmonary bypass, have a lower functional ability, have a higher European System for Cardiac Operative Risk Evaluation score, have a longer anesthesia time, have longer endotracheal tube and extracorporeal circulation times, have longer intensive care unit and hospital stays, have lower hemoglobin and albumin levels, have higher anxiety and depression levels, and have lower Mini-Mental State Examination scores. The significant predictors of prefrailty and frailty included unemployment, the presence of gout, higher New York Heart Association classes, less independence in activities of daily living, lower hemoglobin levels, and higher levels of depression. Frailty was associated with patients' functional status, perioperative conditions and psychosocial factors. Preoperative assessments of frailty and appropriate interventions are needed to improve frailty in patients undergoing cardiac surgery.

Sex Difference in Network Topology and Education Correlated With Sex Difference in Cognition During the Disease Process of Alzheimer.

Background: Alzheimer’s disease (AD) manifests differently in males and females. However, the neuro-mechanism and influence factors are still unknown.Objective: To explore sex differences in brain network topology during AD disease progression and its association with cognition and possible influencing factors.Methods: Resting-state functional magnetic resonance imaging (MRI) data and cognitive scores were collected from 82 AD patients (50 females), 56 amnestic mildly cognitive impaired patients (29 females), and 63 healthy controls (38 females). Global and regional topological network metrics and modular architecture were calculated. Two-way ANOVA was performed to explore group and sex interactions and their main effects. Mediation analysis was used to explore the relationship among education, inter/intra-network connectivity, and the Mini-Mental State Examination (MMSE) score.Results: Lower levels of education, lower MMSE scores, and a positive correlation between the level of education and MMSE scores were found in female AD patients (p = 0.024, r = 0.319). Significantly lower connectivity strength within the sensorimotor network, dorsal attention network, ventral attention network (VAN), and between the sensorimotor and VAN were observed in male AD patients (p = 0.006, 0.028, 0.046, and 0.013, respectively). Group and sex interactions were also found in nodal properties, mainly in the frontal lobe, temporal lobe, middle cingulum, precuneus, and postcentral gyrus. Several of the altered brain network properties were associated with cognitive behavior in male AD patients. Education regulated the MMSE score through the mediation of connection strength between the default mode and limbic networks (LN) in the patient group (aMCI and AD combined).Conclusion: Our results demonstrate that sex differences exist at the brain network level in AD. Sex differences in network topology and education are correlated with sex differences in cognition during AD progression.

Relationship Between Cerebrovascular Reactivity and Cognition Among People With Risk of Cognitive Decline.

Vascular risk factors (e.g., obesity and hypertension) are associated with cerebral small vessel disease, Alzheimer’s disease (AD) pathology, and dementia. Reduced perfusion may reflect the impaired ability of blood vessels to regulate blood flow in reaction to varying circumstances such as hypercapnia (increased end-tidal partial pressures of CO2). It has been shown that cerebrovascular reactivity (CVR) measured with blood-oxygen-level-dependent (BOLD) MRI is correlated with cognitive performance and alterations of CVR may be an indicator of vascular disfunction leading to cognitive decline. However, the underlying mechanism of CVR alterations in BOLD signal may not be straight-forward because BOLD signal is affected by multiple physiological parameters, such as cerebral blood flow (CBF), cerebral blood volume, and oxygen metabolism. Arterial spin labeling (ASL) MRI quantitatively measures blood flow in the brain providing images of local CBF. Therefore, in this study, we measured CBF and its changes using a dynamic ASL technique during a hypercapnia challenge and tested if CBF or CVR was related to cognitive performance using the Mini-mental state examination (MMSE) score. Seventy-eight participants underwent cognitive testing and MRI including ASL during a hypercapnia challenge with a RespirAct computer-controlled gas blender, targeting 10 mmHg higher end-tidal CO2 level than the baseline while end-tidal O2 level was maintained. Pseudo-continuous ASL (PCASL) was collected during a 2-min baseline and a 2-min hypercapnic period. CVR was obtained by calculating a percent change of CBF per the end-tidal CO2 elevation in mmHg between the baseline and the hypercapnic challenge. Multivariate regression analyses demonstrated that baseline resting CBF has no significant relationship with MMSE, while lower CVR in the whole brain gray matter (β = 0.689, p = 0.005) and white matter (β = 0.578, p = 0.016) are related to lower MMSE score. In addition, region of interest (ROI) based analysis showed positive relationships between MMSE score and CVR in 26 out of 122 gray matter ROIs.

The Impact of Intrinsic Capacity on Adverse Outcomes in Older Hospitalized Patients: A One-Year Follow-Up Study

Background: Intrinsic capacity (IC) is a novel view focusing on healthy aging. The effect of IC on adverse outcomes in older hospitalized Chinese adults is rarely studied. Objectives: This study focused on investigating the impact of IC domains on the adverse health outcomes including new activities of daily living (ADL) dependency, new instrumental activities of daily living (IADL) dependency, and mortality over a 1-year follow-up. Methods: In a retrospective observational population-based study, a total of 329 older hospitalized patients from Zhejiang Hospital in China were enrolled and completed 1-year follow-up. The 5 domains of IC including cognition, locomotion, sensory, vitality, and psychological capacity were assessed at admission. The IC composite score was calculated based on these domains, and the higher IC composite score indicated the greater amount of functional capacities reserved. Multivariate logistic regression models were used to explore the association between IC at baseline and 1-year adverse outcomes. Results: During the 1-year follow-up, 69 patients (22.5%) experienced new ADL dependency, 103 patients (33.6%) suffered from new IADL dependency, and 22 patients (6.7%) died. After adjusting for age, sex, education level, comorbidities, and polypharmacy, low Mini-Mental State Examination (MMSE) scores at admission predicted 1-year new ADL dependency (odds ratio [OR] = 2.31, 95% confidence interval [CI]: 1.12–4.78) and new IADL dependency (OR = 2.15, 95% CI: 1.14–4.04) among older hospitalized patients, but no significance was obtained between IC domains and mortality. Higher IC composite score at admission was associated with decreased risks of 1-year new ADL dependency (OR = 0.53, 95% CI: 0.40–0.70) and new IADL dependency (OR = 0.76, 95% CI: 0.61–0.95), and 1-year mortality (OR = 0.48, 95% CI: 0.31–0.74) after adjustment for the possible confounders. Conclusions: Loss of ICs at admission predicted adverse health outcomes including new ADL and IADL dependency and mortality 1 year after discharge among older hospitalized patients.

Associations of Vascular Risk Factors, APOE and TOMM40 Polymorphisms With Cognitive Function in Dementia-Free Chinese Older Adults: A Community-Based Study.

Objective: The associations of vascular risk factors (VRFs), apolipoprotein E (APOE), and translocase of outer mitochondrial membrane 40 (TOMM40) with cognitive function have been investigated mostly in western societies. In the present study, we sought to examine the associations of VRFs [i.e., current smoking, current drinking, physical inactivity, obesity, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), diabetes, and hypertension] and variants located in APOE (ε2/3/4) and TOMM40 (rs2075650) with global cognitive function in Chinese older adults, with a focus on their potential interactions.Methods: This is a cross-sectional study that included 422 permanent residents (mean age 69.2 years, 54.3% female) living in Beijing, who were free of dementia. Data were collected through interviews, clinical examinations, and laboratory tests. The two genetic polymorphisms were genotyped, and participants were dichotomized as carriers vs. non-carriers of APOE ε4 or TOMM40 G. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Data were analyzed with multivariable linear regression models.Results: Physical inactivity and diabetes were independently associated with a lower MMSE score (all p < 0.05). When four putative VRFs (i.e., current smoking, physical inactivity, high LDL-C, and diabetes) were aggregated, an increasing number of having these factors was associated with a decreasing MMSE score in a dose–response manner (p = 0.001). TOMM40 polymorphisms, independent of the APOE ε4 allele, interacted with aggregated VRFs to influence cognitive performance, such that having one or more of these VRFs was particularly detrimental to the cognition of TOMM40 carriers. Further analyses revealed interactions of the TOMM40 polymorphism with (i) physical inactivity and (ii) diabetes, such that having either physical inactivity or diabetes in combination with carrying a TOMM40 G allele, compared to having neither, was significantly associated with a markedly lower MMSE score (all p < 0.05).Conclusion: This study provides some evidence supporting the association of vascular risk factors with poor cognitive performance among dementia-free Chinese older adults and further revealed their interactions with the TOMM40 polymorphism. The results underscore the vulnerability of global cognitive function to VRFs, which could be reinforced by carrying the TOMM40 rs2075650 G allele. These findings have potential implications for developing tailored intervention programs to maintain cognitive function.

Milk and Dairy Products Intake Is Related to Cognitive Impairment at Baseline in Predimed Plus Trial.

To examine the association between milk and dairy products intake and the prevalence of cognitive decline among Spanish individuals at high cardiovascular risk. Cross-sectional analyses are performed on baseline data from 6744 adults (aged 55-75 years old). Intake of milk and dairy products is estimated using a food frequency questionnaire grouped into quartiles. The risk of developing cognitive impairment is based on the Mini-Mental State Examination (MMSE). A higher prevalence of cognitive decline was found in subjects who consumed more grams. Patients with worse MMSE score (10-24) consumed a mean of 395.14±12.21g, while patients with better MMSE score (27-30) consumed a mean of 341.23±2.73g (p<0.05). Those subjects with the lower milk consumption (<220g/day) had a higher MMSE score (28.35±0.045). Higher intake of fermented dairy products was observed in participants with a lower MMSE score (OR 1.340, p=0.003). A positive correlation was found between the consumption of whole milk and the MMSE score (r=0.066, p<0.001). These findings suggest that greater consumption of milk and dairy products could be associated with greater cognitive decline according to MMSE. Conversely, consumption of whole-fat milk could be linked with less cognitive impairment in the cross-sectional study.

Poor Cognitive Function Is Associated with Obstructive Lung Diseases in Taiwanese Adults.

Previous studies have reported an association between the impairment of cognitive performance and lung diseases. However, whether obstructive or restrictive lung diseases have an impact on cognitive function is still inconclusive. We aimed to investigate the association between cognitive function and obstructive or restrictive lung diseases in Taiwanese adults using the Mini-Mental State Examination (MMSE). In this study, we used data from the Taiwan Biobank. Cognitive function was evaluated using the MMSE. Spirometry measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained to assess lung function. Participants were classified into three groups according to lung function, namely, normal, restrictive, and obstructive lung function. In total, 683 patients enrolled, of whom 357 participants had normal lung function (52.3%), 95 had restrictive lung function (13.9%), and 231 had obstructive lung function (33.8%). Compared to the normal lung function group, the obstructive lung function group was associated with a higher percentage of cognitive impairment (MMSE < 24). In multivariable analysis, a low MMSE score was significantly associated with low FVC, low FEV1, and low FEV1/FVC. Furthermore, a low MMSE score was significantly associated with low FEV1 in the participants with FEV1/FVC < 70%, whereas MMSE was not significantly associated with FVC in the participants with FEV1/FVC ≥ 70%. Our results showed that a low MMSE score was associated with low FEV1, low FVC and low FEV1/FVC. Furthermore, a low MMSE score was associated with obstructive lung diseases but not with restrictive lung diseases.

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.

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.