Decline In Mini-Mental State Examination Score Research Articles

Dosimetric predictors of toxicity in a randomized study of short-course vs conventional radiotherapy for glioblastoma

PurposeThere is no consensus on appropriate organ at risk (OAR) constraints for short-course radiotherapy for patients with glioblastoma. Using dosimetry and prospectively-collected toxicity data from a trial of short-course radiotherapy for glioblastoma, this study aims to empirically examine the OAR constraints, with particular attention to left hippocampus dosimetry and impact on neuro-cognitive decline. Methods and MaterialsData was taken from a randomized control trial of 133 adults (age 18–70 years; ECOG performance score 0–2) with newly diagnosed glioblastoma treated with 60 Gy in 30 (conventional arm) versus 20 (short-course arm) fractions of adjuvant chemoradiotherapy (ClinicalTrials.gov Identifier: NCT02206230). The delivered plan’s dosimetry to the OARs was correlated to prospective-collected toxicity and Mini-Mental State Examination (MMSE) data. ResultsToxicity events were not significantly increased in the short-course arm versus the conventional arm. Across all OARs, delivered radiation doses within protocol-allowable maximum doses correlated with lack of grade ≥ 2 toxicities in both arms (p < 0.001), while patients with OAR doses at or above protocol limits correlated with increased grade ≥ 2 toxicities across all examined OARs in both arms (p-values 0.063–0.250). Mean left hippocampus dose was significantly associated with post-radiotherapy decline in MMSE scores (p = 0.005), while the right hippocampus mean dose did not reach statistical significance (p = 0.277). Compared to the original clinical plan, RapidPlan left hippocampus sparing model decreased left hippocampus mean dose by 43 % (p < 0.001), without compromising planning target volume coverage. ConclusionsIn this trial, protocol OAR constraints were appropriate for limiting grade ≥ 2 toxicities in conventional and short-course adjuvant chemoradiotherapy for glioblastoma. Higher left hippocampal mean doses were predictive for neuro-cognitive decline post-radiotherapy. Routine contouring and use of dose constraints to limit hippocampal dose is recommended to minimize neuro-cognitive decline in patients with glioblastoma treated with chemoradiotherapy.

Associations of sleep timing and time in bed with dementia and cognitive decline among Chinese older adults: A cohort study.

The longitudinal associations of sleep timing and time in bed (TIB) with dementia and cognitive decline in older adults are unclear. This population-based cohort study used data from 1982 participants who were aged ≥60 years, free of dementia, and living in rural communities in western Shandong, China. At the baseline (2014) and follow-up (2018) examinations, sleep parameters were assessed using standard questionnaires. Cognitive function was measured using the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the DSM-IV criteria, and the NIA-AA criteria for Alzheimer disease (AD). Data were analyzed using restricted cubic splines, Cox proportional-hazards models, and general linear models. During the mean follow-up of 3.7 years, dementia was diagnosed in 97 participants (68 with AD). Restricted cubic spline curves showed J-shaped associations of sleep duration, TIB, and rise time with dementia risk, and a reverse J-shaped association with mid-sleep time. When sleep parameters were categorized into tertiles, the multivariable-adjusted hazard ratio (HR) of incident dementia was 1.69 (95%CI 1.01-2.83) for baseline sleep duration >8 hours (vs. 7-8 h), 2.17 (1.22-3.87) for bedtime before 9 p.m. (vs. 10 p.m. or later), and 2.00 (1.23-3.24) for mid-sleep time before 1 a.m. (vs. 1-1.5 a.m.). Early bedtime and mid-sleep time were significantly associated with incident AD (HR range: 2.25-2.51; p < 0.05). Among individuals who were free of dementia at follow-up, baseline long TIB, early bedtime and mid-sleep time, early and late rise time, and prolonged TIB and advanced bedtime and mid-sleep time from baseline to follow-up were associated with a greater decline in MMSE score (p < 0.05). These associations with cognitive decline were statistically evident mainly among men or participants who were aged 60-74 years. Long TIB and early sleep timing are associated with an increased risk of dementia, and the associations with greater cognitive decline are evident only among older people aged 60-74 years and men.

Association between depression tendency and cognitive trajectory in the elderly in rural area in China

Objective: To explore cognitive trajectory and its association with depression tendency in the elderly in rural area in China. Methods: Based on the data of the rural elderly aged ≥65 years in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2011 to 2018, unconditional and conditional latent variable growth curve models were constructed to analyze the mini-mental state examination (MMSE) score trajectory and its association with depression tendency in the elderly. Results: A total of 1 788 elderly persons were included, and 19.1% of them had a depression tendency. The average MMSE score of those with and without a depression tendency at baseline survey were 26.62±3.54 and 27.59±3.17 respectively. The rate of MMSE score decline was 0.52 points (P<0.05). Before and after controlling covariates, the initial score was 0.84 points lower (P<0.05) and 0.81 points lower (P<0.05) in those with depressive tendency than in those without depressive tendency respectively, furthermore, the decline rate of MMSE score was 0.33 points lower (P<0.05) and 0.40 points lower (P<0.05) in those with depressive tendency than in those without respectively. Conclusions: The depression tendency in the elderly in rural area in China was associated with the cognitive function change trajectory, with those with depression tendency had lower-level trajectory. Attention should be paid to the mental health of the elderly in rural area to prevent dementia and slow its development.

Association of Enlarged Perivascular Spaces With Amyloid Burden and Cognitive Decline in Alzheimer Disease Continuum.

To investigate the effects of enlarged perivascular space (EPVS) on amyloid burden and cognitive function in Alzheimer disease (AD) continuum. We retrospectively reviewed 208 patients with AD across the cognitive continuum (preclinical, prodromal, and AD dementia) who showed amyloid deposition on 18F-florbetaben PET scans and 82 healthy controls. EPVSs were counted for each patient in the basal ganglia (BG), centrum semiovale (CSO), and hippocampus (HP) on axial T2-weighted images. Patients were then classified according to the number of EPVSs into the EPVS+ (>10 EPVSs) and EPVS- (0-10 EPVSs) groups for the BG and CSO, respectively. In terms of HP-EPVS, equal or more than 7 EPVSs on bilateral hemisphere were regarded as the presence of HP-EPVS. After adjusting for markers of small vessel disease (SVD), multiple linear regression analyses were performed to determine the intergroup differences in global and regional amyloid deposition and cognitive function at the time of diagnosis of AD continuum. A linear mixed model was used to assess the effects of EPVSs on the longitudinal changes in the Mini-Mental State Examination (MMSE) scores. Amyloid burden at the time of diagnosis of AD continuum was not associated with the degree of BG-, CSO-, or HP-EPVS. BG-EPVS affected language and frontal/executive function via SVD markers, and HP-EPVS was associated with general cognition via SVD markers. However, CSO-EPVS was not associated with baseline cognition. A higher number of CSO-EPVS was significantly associated with a more rapid decline in MMSE scores (β = -0.58, standard error = 0.23, p = 0.011) independent of the amyloid burden. In terms of BG and HP, there was no difference between the EPVS+ and EPVS- groups in the rate of longitudinal decreases in MMSE scores. Our findings suggest that BG-, CSO-, and HP-EPVS are not associated with baseline β-amyloid burden or cognitive function independently of SVD at the diagnosis of AD continuum. However, CSO-EPVS appears to be associated with the progression of cognitive decline in an amyloid-independent manner. Further studies are needed to investigate whether CSO-EPVS is a potential therapeutic target in patients with AD continuum.

Trajectories of cognitive and physical performance after accidental falls in nursing home residents: A prospective study

This prospective study evaluated cognitive and physical trajectories of nursing home (NH) residents after fall occurrence and their predictors. In 167 residents aged ≥60, we considered the closest pre-fall assessment and up to the first three post-fall assessments of cognitive and physical functions performed through Mini-Mental State Examination (MMSE) and Tinetti tests. Mixture models identified three post-fall cognitive and physical trajectories: stability, slow decline, and rapid decline. At logistic regression, older age, fewer informal visits, and falls within one month from institutionalization increased the probability of experiencing a decline in MMSE and Tinetti scores. Worse pre-fall cognitive function increased the likelihood of cognitive and physical decline, while worse pre-fall Tinetti score negatively impacted only physical decline.In conclusion, the impact of falls on the cognitive and physical health of NH residents may be modulated by their pre-fall cognitive function and some modifiable factors, such as social interactions and physical function.

Association between gait features assessed by artificial intelligent system and cognitive function decline in patients with silent cerebrovascular disease: study protocol of a multicenter prospective cohort study (ACCURATE-2)

BackgroundGait disturbances may appear prior to cognitive dysfunction in the early stage of silent cerebrovascular disease (SCD). Subtle changes in gait characteristics may provide an early warning of later cognitive decline. Our team has proposed a vision-based artificial intelligent gait analyzer for the rapid detection of spatiotemporal parameters and walking pattern based on videos of the Timed Up and Go (TUG) test. The primary objective of this study is to investigate the relationship between gait features assessed by our artificial intelligent gait analyzer and cognitive function changes in patients with SCD.MethodsThis will be a multicenter prospective cohort study involving a total of 14 hospitals from Shanghai and Guizhou. One thousand and six hundred patients with SCD aged 60–85 years will be consecutively recruited. Eligible patients will undergo the intelligent gait assessment and neuropsychological evaluation at baseline and at 1-year follow-up. The intelligent gait analyzer will divide participant into normal gait group and abnormal gait group according to their walking performance in the TUG videos at baseline. All participants will be naturally observed during 1-year follow-up period. Primary outcome are the changes in Mini-Mental State Examination (MMSE) score. Secondary outcomes include the changes in intelligent gait spatiotemporal parameters (step length, gait speed, step frequency, step width, standing up time, and turning back time), the changes in scores on other neuropsychological tests (Montreal Cognitive Assessment, the Stroop Color Word Test, and Digit Span Test), falls events, and cerebrovascular events. We hypothesize that both groups will show a decline in MMSE score, but the decrease of MMSE score in the abnormal gait group will be more significant.ConclusionThis study will be the first to explore the relationship between gait features assessed by an artificial intelligent gait analyzer and cognitive decline in patients with SCD. It will demonstrate whether subtle gait abnormalities detected by the artificial intelligent gait analyzer can act as a cognitive-related marker for patients with SCD.Trial registrationThis trial was registered at ClinicalTrials.gov (NCT04456348; 2 July 2020).

166 EFFECT OF ANTIMUSCARINIC DRUGS ON COGNITIVE FUNCTIONS IN THE MANAGEMENT OF OVERACTIVE BLADDER IN ELDERLY

Background: overactive bladder (OAB) affects 17-41% older adults in community dwelled setting. For several years, antimuscarinics have been validated as the first-line medical treatment for OAB. Despite abundant data obtained from clinical trials provisions the use of antimuscarinics, investigation about the effect of this drug on cognitive function in elderly remains scarce. The objective of this study is to investigate the effect of antimuscarinics therapy on cognitive functions in OAB geriatric patients. Methods: this study design is a systematic review and meta-analysis. Studies were collected using several search engines; those were PubMed, Science Direct, Cochrane, and EBSCOhost using predetermined MeSH keywords with Boolean operators. Selection of studies was done by three reviewers. Studies which fulfilled the inclusion and exclusion criteria underwent full-text review. For every selected full text, we extracted the following data if available: patients demographics, types of antimuscarinics used, placebo, dose, follow-up period, and Mini-Mental State Examination (MMSE) total score. Results: a total of 8 studies from an initial 146 publications were selected. There were 8 antimuscarinic agents evaluated in the studies, including Oxybutynin, Darifenacin, Tolterodine, Trospium, Imidafenacin, Propiverine hydrochloride, Fesoterodine, and Solifenacin. Oxybutynin was shown to have largest effect towards the decline of MMSE score [Mean difference: -2.90; 95% CI: -4.07, -1.73]. Darifenacin and Tolterodine were also shown to be significant in the decline of total MMSE score, although still inferior to Oxybutynin. Conclusion: the use of most antimuscarinics medication has little to no effect towards the cognitive function in the management of overactive bladder in elderly patients. However, Oxybutynin, Darifenacin, and Tolterodine was shown to have significant decrease in cognitive functions, as shown in the decline of total MMSE score.

Blood pressure mediated the effects of cognitive function impairment related to aluminum exposure in Chinese aluminum smelting workers

ObjectivesThe aim of this study is to investigate the effects that the Al on blood pressure and the effect of hypertension in aluminum-induced cognitive impairment in electrolytic aluminum worker. MethodsThe study was conducted 392 male aluminum electrolytic workers in an aluminum plant of China. The concentration of alumina dust in the air of the electrolytic aluminum workshop is 1.07 mg/m3–2.13 mg/m3. According to the Permissible concentration-Time Weighted Average of alumina dust is 4 mg/m3, which does not exceed the standard. The blood pressure of the workers was measured. The plasma aluminum concentration of workers was determined by ICP-MS (Inductively Coupled Plasma Mass Spectrometry). Cognitive functions were measured using MMSE (Mini-Mental State Examination), VFT (Verbal Fluency Test), ATIME (Average Reaction Time), FOM (Fuld Object Memory Evaluation), DST (Digit Span Test), CDT (Clock Drawing Test) scales. Modified Poisson regression was used to analyze the risk of hypertension and cognitive impairment with different plasma aluminum concentrations. Generalized linear regression model was used to analyze the relationship between aluminum and cognitive function, blood pressure and cognitive function. Causal Mediation Analysis was used to analyze the mediation effect of blood press in aluminum-induced cognitive impairment. ResultsPlasma aluminum appeared to be a risk factor for hypertension (PR (prevalence ratio) = 1.630, 95 %-CI (confidence interval): 1.103–2.407), systolic blood pressure (PR = 1.578, 95 %-CI: 1.038–2.399) and diastolic blood pressure (PR = 1.842, 95 %-CI: 1.153–2.944). And plasma aluminum increased by e-fold, the scores of MMSE and VFT decreased by 0.630 and 2.231 units respectively and the time of ATIME increased by 0.029 units. In addition, generalized linear regression model showed that blood press was negatively correlated with the scores of MMSE and VFT. Finally, causal Mediation Analysis showed that hypertension was a part of the mediating factors of aluminum-induced decline in MMSE score, and the mediating effects was 16.300 % (7.100 %, 33.200 %). In addition, hypertension was a part of the mediating factors of aluminum-induced decline in VFT score, and the mediating effects was 9.400 % (2.600 %, 29.000 %) ConclusionOccupational aluminum exposure increases the risk of hypertension and cognitive impairment. And hypertension may be a mediating factor of cognitive impairment caused by aluminum exposure.

The effect of China's Clean Air Act on cognitive function in older adults: a population-based, quasi-experimental study

SummaryBackgroundAir pollution might accelerate cognitive ageing; it is unclear whether large-scale interventions, such as China’s Clean Air Act (CCAA), can mitigate cognitive deterioration. We aimed to evaluate the effect of CCAA on changes in cognitive function in older adults.MethodsIn this population-based, quasi-experimental study, we did a difference-in-differences analysis of the data collected during the 2014 and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). The study design used a counterfactual analysis feature by dividing CLHLS participants into two groups. The intervention group included participants who lived in areas where the provincial government set a target of reducing particulate matter (PM) by at least 5% annually from 2014 onward, whereas the control group consisted of individuals who lived in areas without a PM reduction target. Global cognitive function was measured using the Mini-Mental State Examination (MMSE). We used fixed-effects models to examine the between-group differences in MMSE score changes before and after CCAA implementation. We associated longitudinal changes in MMSE scores with changes in concentrations of PM with a diameter of less than 2·5 μm (PM2·5) concentration and other regulated pollutants. We used alternative models and sensitivity analyses to evaluate the robustness of the results from the main models.Findings2812 individuals participated in the 2014 and 2018 surveys (mean age 81·0 years [SD 9·3] in 2014; 1408 [50·1%] female and 1404 [49·9%] male). 2251 (80·0%) were included in the intervention group and 561 (20·0%) in the control group. After controlling for potential confounders, the intervention group had a significantly smaller decline in MMSE scores from 2014 to 2018 compared with the control group: the mean between-group difference was 2·45 points (95% CI 1·32–3·57). Interquartile increases in PM2·5 were associated with a significant MMSE score decline of 0·83 points (95% CI 0·24–1·42); similarly, increases in SO2 were also associated with a significant MMSE score decline of 0·80 points (0·32–1·29).InterpretationImplementing stringent clean air policies might mitigate the risk of air pollutant-associated cognitive ageing in older people.FundingNational Natural Sciences Foundation of China, National Key R&D Program of China, China Postdoctoral Science Foundation funded project, the Duke/Duke-National University of Singapore Collaboration Pilot Project, the National Institute on Aging and Peking University-Baidu Fund, Energy Foundation, and the Fundamental Research Funds for the Central Universities.

Primary age-related tauopathy in a Finnish population-based study of the oldest old (Vantaa 85+).

AimsFew studies have investigated primary age‐related tauopathy (PART) in a population‐based setting. Here, we assessed its prevalence, genetic background, comorbidities and features of cognitive decline in an unselected elderly population.MethodsThe population‐based Vantaa 85+ study includes all 601 inhabitants of Vantaa aged ≥ 85 years in 1991. Neuropathological assessment was possible in 301. Dementia (DSM IIIR criteria) and Mini‐Mental State Examination (MMSE) scores were assessed at the baseline of the study and follow‐ups. PART subjects were identified according to the criteria by Crary et al and were compared with subjects with mild and severe Alzheimer's disease (AD) neuropathological changes. The effects of other neuropathologies were taken into account using multivariate and sensitivity assays. Genetic analyses included APOE genotypes and 29 polymorphisms of the MAPT 3′ untranslated region (3′UTR region).ResultsThe frequency of PART was 20% (n = 61/301, definite PART 5%). When PART subjects were compared with those with severe AD pathology, dementia was less common, its age at onset was higher and duration shorter. No such differences were seen when compared with those with milder AD pathology. However, both AD groups showed a steeper decline in MMSE scores in follow‐ups compared with PART. APOE ε4 frequency was lower, and APOE ε2 frequency higher in the PART group compared with each AD group. The detected nominally significant associations between PART and two MAPT 3′UTR polymorphisms and haplotypes did not survive Bonferroni correction.ConclusionsPART is common among very elderly. PART subjects differ from individuals with AD‐type changes in the pattern of cognitive decline, associated genetic and neuropathological features.

Rates of Cognitive Decline in 100 Patients With Alzheimer Disease.

Background: In the state of Louisiana, the prevalence of Alzheimer disease (AD) is projected to increase 26.4% by 2025 because of the rapidly increasing geriatric population. While significant research is available on risk factors for developing AD, less data are available regarding AD progression and the rate of change among patients with the disease. To date, no research has established the baseline cognitive decline of patients with AD residing in New Orleans, Louisiana.Methods: We evaluated 100 patients in the Ochsner Health system from September 2013 to December 2019 who had a diagnosis of AD and repeated Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA) scores to determine annual rates of decline. Associated variables that were analyzed included race, age at diagnosis, social factors, and comorbidities.Results: The average annual rates of decline for MMSE and MoCA scores were 2.43 (SD 2.82) points and 2.39 (SD 1.88) points, respectively. Our results were significant for a faster rate of decline in MMSE scores among smokers (3.50 points, SD 3.20) vs nonsmokers (1.54 points, SD 2.07). We found no significant difference in MoCA scores for smokers vs nonsmokers, in addition to other demographic and lifestyle variables.Conclusion: The rate of decline seen in an urban population of patients with AD is lower than the average rate of decline reported in the literature, a finding that can help inform future interventional studies that use rate of decline as a primary outcome.

Amyloid‐tau‐neurodegeneration (ATN) profiles and influence of age‐of‐onset on cognitive trajectories in a Southeast Asian cohort: SYNC project

AbstractBackgroundThe amyloid‐tau‐neurodegeneration (ATN) scheme enables unbiased biomarker‐based diagnoses, independent of cognitive status and temporal ordering of AD pathogenic mechanisms [Jack et al.,2016]. ATN profiles in the diverse Southeast‐Asian region will provide important insights into the ATN framework and its association with cognition [Hilal et al.,2017; Knopman et al., 2018]. We examined the effect of amyloid‐beta status on longitudinal cognitive trajectory in young and late‐onset patients as well as impact of ATN categories on longitudinal cognition in a Southeast‐Asian cohort. We hypothesized that age of onset would differentially influence the association between amyloid status and longitudinal cognition.MethodWe studied 92 patients with cognitive impairment from the Singapore YouNg Dementia Cohort. Patients underwent structural‐MRI and lumbar puncture for cerebrospinal fluid amyloid‐beta (1–42), phosphorylated‐tau (p‐tau) and total‐tau (t‐tau) to assess biomarker positivity [Blennow et al., 2020]. A cut‐off age of 60 years was used to define young‐onset cognitive impairment. Separately, ATN profiles were assigned based on cerebrospinal fluid biomarker levels: normal biomarker profile (A‐T‐N‐), suspected non‐Alzheimer’s pathology (SNAP: A‐T±N±) and Alzheimer’s continuum (A+T±N±). Linear mixed effects models assessed longitudinal group differences in mini‐mental state examination (MMSE) trajectory.ResultYoung (&lt;60yrs) sporadic amyloid‐positive, patients demonstrated significantly greater decline in longitudinal MMSE scores (AmyloidStatus*AgeOfOnset*Time: β=2.82, p=0.0193; Fig. 1) compared to older (≥60yrs) amyloid‐positive counterparts. Across the three ATN categories, there were no differences in baseline age, sex, white matter hyperintensities, medial temporal atrophy or APOE4 status (Table 1). Patients along the Alzheimer’s continuum showed a greater decline in MMSE scores over time compared to both normal biomarker A‐T‐N‐ (β=−2.23, p=0.001; Fig. 2‐3) and SNAP patients (β=−2.05, p=0.004; Fig. 2‐3). MMSE decline did not differ between SNAP and A‐T‐N‐ groups.ConclusionWe show steeper MMSE decline in young amyloid‐positive patients than their amyloid‐positive older counterparts. Additionally, Alzheimer’s continuum patients showed steeper MMSE decline than A‐T‐N‐ and SNAP patients. These findings provide insights into mechanisms for the more aggressive cognitive decline frequently observed in younger patients.

The association of antidiabetic medications and Mini-Mental State Examination scores in patients with diabetes and dementia

BackgroundThe effect of antidiabetic medication on cognitive function is unclear. We analyzed the association between five antidiabetic drugs and change in Mini-Mental State Examination (MMSE) scores in patients with diabetes and dementia.MethodsUsing the Swedish Dementia Registry and four supplementary Swedish registers/databases, we identified 1873 patients (4732 observations) with diagnosis of type 2 diabetes (diabetes) and Alzheimer’s disease or mixed-pathology dementia who were followed up at least once after dementia diagnosis. Use of metformin, insulin, sulfonylurea, thiazolidinediones (TZD), and dipeptidyl-peptidase-4 inhibitors (DPP-4i) was identified at baseline. Prevalent-user, incident-user, and drug-drug cohorts were sampled, and propensity-score matching was used to analyze comparable subjects. Beta coefficients with 95% confidence intervals (CI) from the random intercept and slope linear mixed-effects models determined the association between the use of antidiabetic medications and decline in MMSE score points between the follow-ups. Inverse-probability weighting was used to account for patient dropout.ResultsCompared to non-users, prevalent users of metformin (beta 0.89, 95% CI 0.44; 1.33) and DPP-4i (0.72, 0.06; 1.37) experienced a slower cognitive decline with time. Secondly, compared to DPP-4i, the use of insulin (−1.00, −1.95; −0.04) and sulfonylureas (−1.19; −2.33; −0.04) was associated with larger point-wise decrements in MMSE with annual intervals.ConclusionsIn this large cohort of patients with diabetes and dementia, the use of metformin and DPP-4i was associated with a slower decline in MMSE scores. Further examination of the cognitive effects of metformin and incretin-based medications is warranted.

CNTN5 is associated with disease risk and pathology throughout the Alzheimer's disease continuum.

Contactins are a family of molecules that are involved in neuronal development. Contactin 5 (CNTN5) is a neuronal membrane protein that contributes to axonal targeting, synaptic formation and plasticity. A GWAS performed in a population isolate from Eastern Canada identified a polymorphism in the CNTN5 gene (rs1461684_G) which is associated with increased risk of developing Alzheimer's disease (AD). In order to further characterize the role of CNTN5 in AD, we used two cohorts (the "at-risk" pre-symptomatic PREVENT-AD and the symptomatic ROSMAP) to examine the association of CNTN5 genotype and protein levels with pathological hallmarks and clinical manifestations of AD. In the PREVENT-AD cohort, [18F]-AV1451 PET was used to measure Tau burden, Olink's primer extension assay was used to measure CNTN5 in plasma and CSF and ELISAs were used for Tau, Phospho Tau, and amyloid CSF levels. Participants were followed for at least 4 years. In the autopsied-confirmed ROSMAP cohort, Aß load and NFT density in the cortex were measured with immunocytochemistry, and cognition was assessed with the Mini-Mental State Examination (MMSE). In the ROSMAP cohort participants were followed throughout most of their adult life, until death. Homozigotes CNTN5 G variant had a 58% lower chance of developing cognitive decline than non-carriers and heterozygous subjects (p=0.033) (Fig 1a). Carriers of the GG variant showed less decline in MMSE scores compared to the other genotypes (p=0.042) (Fig 1b). CSF CNTN5 levels were higher in follow-up visits 12 (p=0.018), 24 (p=0.013) and 48 (p<0.001) months compared to baseline (Fig 2) and, were significantly higher in Controls compared to AD subjects (p<0.001) (Fig 3). CSF CNTN5 was positively correlated with PET TAU burden in the entorhinal cortex (p=0.029), with CSF Total Tau (p<0.001), Phospho Tau (p<0.001), Aß1-42(p=0.018) and Aß 1-40 (p=0.002) (Fig 4). There was no correlation between Plasma and CSF CNTN5 levels (p =0.37). There are no association between CNTN5 genotype and CERAD or Braak stages. These results show that the rs146168 variant of CNTN5 plays a role in the risk of developing AD and that CNTN5 CSF levels are strongly correlated with AD pathology, especially in the pre-symptomatic phase of the disease.

Association between intra-individual changes in social network diversity and global cognition in older adults: Does closeness to network members make a difference?

ObjectiveAlthough qualitative aspects of interpersonal networks, such as diversity or closeness, can protect the health of older adults, their association with cognitive health remains unclear. This study examined the concurrent and time-lagged association between intra-individual changes in global cognition and social network diversity, while considering emotional closeness. MethodsIn this 10-year study, we obtained six-wave, biennial data from the National Institute for Longevity Sciences, Longitudinal Study of Aging. Data from 808 community-dwelling, cognitively intact adults aged 65 or older at baseline were analyzed. Global cognition was assessed using the Mini-Mental State Examination (MMSE). Social network diversity scores were assessed using a social convoy model, comprising three closeness levels: inner (closest), middle (second closest), and outer (least close). ResultsThe mean age of the respondents was 72.0 ± 4.4 years at baseline, and 50.1% were male. A fixed-effects model showed that intra-individual change in total (coefficients, B: 0.10; standard error [SE]: 0.05; p = .042) and inner (B: 0.25; SE: 0.07; p < .001) social network diversity was significantly associated with MMSE score decline, even after adjusting for covariates. Yet, in time-lagged models, diversity and MMSE score changes were not significantly associated during the subsequent two years. ConclusionOlder adults' global cognition declined when the diversity of their closest social network decreased. This may be a promising marker for early cognitive decline in older adults. Indeed, their closest networks are relatively unlikely to decline as part of normal aging or diseases except dementia.

The relationship between aortic calcification on chest radiograph and neurocognitive impairment after coronary artery bypass grafting.

Background In this study, we aimed to investigate the possible relationship between aortic calcification as detected by preoperative chest radiography and postoperative neurocognitive impairment in patients undergoing coronary artery bypass grafting. Methods A total of 124 patients (101 males, 23 females; mean age: 59.9±8.8 years; range, 34 to 84 years) who underwent coronary artery bypass grafting in our clinic between January 2019 and July 2019 were included. Of these patients, 35 whose preoperative chest radiography revealed aortic calcification in the aortic knuckle were included as the patient group. The control group consisted of 89 patients without aortic calcification. The patients with aortic calcification underwent additional imaging with thoracic computed tomography angiography and ascending aorta and aortic arch calcium scores were calculated. Neurocognitive dysfunction was assessed using the Standardized Mini-Mental State Examination. Postoperative delirium was evaluated by confusion assessment method in the intensive care unit. Both groups were compared for demographic, operative and postoperative data. Results Of all patients included in the study, the overall cerebrovascular event incidence was 3.2%. Although not statistically significant, the number of patients with neurocognitive decline was higher in the patient group than the control group (48.6% vs. 34.8%, respectively; p=0.157). Both Standardized Mini-Mental State Examination score decline and percentage decline were significantly higher in the patients with high aortic arch calcium scores (>2,250 AU). Carotid artery stenosis was 3.2 times higher in the patient group. In the patients with carotid artery stenosis, the aortic arch calcium scores were also higher (p=0.042). Conclusion Aortic calcification detectable on chest radiography with high calcium scores may be associated with neurocognitive impairment and carotid artery stenosis in patients undergoing coronary artery bypass grafting.

Clinical Application of the Vestibular Stimulation Effect on Balance Disorders with Dementia.

In a previous study on Alzheimer's disease (AD), we showed that vestibular dysfunction derived from cerebral disorders contributes to balance disorders. No previous clinical study has attempted to prevent the progression of balance disorders in dementia patients through vestibular stimulation using an air caloric device. The purpose of this pilot study was to delay the progression of balance disorders by inducing vestibular compensation, specifically by utilizing the effect of vestibular stimulation to activate the cerebrum. Fifteen individuals were randomized and classified into a stimulation group or a nonstimulation group. Eight AD patients underwent vestibular stimulation every 2 weeks for 6 months in the stimulation group. Seven AD patients participated in the nonstimulation group (the control group). Both groups were subsequently evaluated using a Mini-Mental State Examination (MMSE), stepping test, caloric test, and smooth pursuit eye movement test just before starting the study and 6 months later. For balance parameters, the various tests did not show any significant differences between the two groups. However, in the stepping test, the decline rate tended to be higher in the nonstimulation group than in the stimulation group. The stimulation group's rate of decline in MMSE scores was lower than that of the nonstimulation group (p=0.015). No adverse events were tracked during the present study. Repeated vestibular stimulation might help patients retain greater balance and higher function. To prove these effects, the future clinical application will require an increased number of cases and longer periods of vestibular stimulation. This study showed that vestibular stimulation by air caloric device is safe and tolerable in patients with AD.

Eating Alone and Cognitive Decline in Korean Older Adults: A 3-Year Prospective Study.

BackgroundEating alone is a critical factor in nutritional risk screening among older adults. We investigated whether changes in eating status (eating alone or with others) in late-life affected cognitive decline in community-dwelling older adults. MethodsWe used data from the Survey of the Living Conditions and Welfare Needs of Korean Older Persons. Nutritional risk, including eating status, was assessed using seven questions from the Nutrition Screening Initiative checklist, and cognitive function was measured using the Mini-Mental State Examination (MMSE). On the basis of changes in eating status between baseline (2008) and the 3-year follow-up (2011), the subjects were divided into four groups: group 1 (eating with others at both surveys), group 2 (eating alone in 2008 and eating with others in 2011), group 3 (eating with others in 2008 and eating alone in 2011), and group 4 (eating alone at both surveys). Generalized linear models were used to compare the changes in MMSE scores over the 3-year period among the four groups. ResultsAmong older women, group 2 had the least decline in MMSE scores (-0.55±0.46), whereas group 3 had the greatest decline (-1.76±0.37) (p=0.034). We observed no difference in the change in MMSE scores among the four eating groups in older men. Conclusion Deprivation of mealtime partners in late life showed significant cognitive decline compared with gaining mealtime partners. Eating alone may be a risk factor for cognitive impairment; thus, meal programs reinforcing social integration might help preserve cognitive function.

Assessment of Plasma Amyloid-β42/40 and Cognitive Decline Among Community-Dwelling Older Adults

Plasma measurement of amyloid-β (Aβ) peptides has been associated with cognitive function, but evidence of its ability to identify cognitive decline is still scarce. To investigate the associations between plasma Aβ42/40 and cognitive decline over time among community-dwelling older adults with subjective memory concerns. This multicenter cohort study used data from volunteers in the 5-year study Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or older and observed for a median (interquartile range) of 3.9 (2.0-4.0) years. Recruitment of participants started in May 2008 and ended in February 2011. Follow-up ended in April 2016. Data analysis was conducted from April to October 2020. Plasma Aβ42 and Aβ40 were measured at 12 months for 448 participants (92.8%) and at 24 months for the rest. The moment of Aβ assessment was defined as the baseline for this study. Cognitive function was assessed at 12, 24, 36, 48, and 60 months by a composite cognitive score based on 4 tests; Mini Mental State Examination (MMSE); Clinical Dementia Rating, sum of boxes; and Alzheimer Disease Cooperative Study-Activities of Daily Living. Mixed-effect linear regressions were performed. A total of 483 participants (median [IQR] age, 76.0 [73.0-80.0]; 286 [59.2%] women) were analyzed. Of them, 161 (33.3%) were classified as low plasma Aβ42/40 (≤0.107). After adjusting for age, sex, education, body mass index, Geriatric Depression Scale score, apolipoprotein E ε4 genotype, and MAPT intervention groups, low plasma Aβ42/40 was associated with more pronounced decline in composite cognitive score (adjusted between-group mean difference: -0.20, 95% CI, -0.34 to -0.07; P = .004) and decline in MMSE score (adjusted between-group mean difference: -0.59; 95% CI, -1.07 to -0.11; P = .02) during the follow-up period compared with the group with an Aβ42/40 ratio greater than 0.107. In this study, low plasma Aβ42/40 was associated with more pronounced decline in cognitive function (measured by multiple outcomes) over time. Findings suggest that plasma Aβ42/40 may be used to identify people at risk of cognitive decline, being an alternative to more complex and expensive measures, such as positron emission tomography imaging or cerebrospinal fluid measurement.

Olfactory Dysfunction Predicts Disease Progression in Parkinson's Disease: A Longitudinal Study.

Background and Objective:Olfactory dysfunction (hyposmia) is an important non-motor symptom of Parkinson’s disease (PD). To investigate the potential prognostic value of hyposmia as a marker for disease progression, we prospectively assessed clinical manifestations and longitudinal changes of hyposmic PD patients and normosmic ones.MethodsOlfactory function was evaluated with the Sniffin’ Sticks in PD patients at baseline. One hundred five hyposmic PD patients and 59 normosmic PD patients were enrolled and followed up for 2 years. They were subsequently evaluated at baseline and during follow-up periods with neurological and neuropsychological assessments. Clinical manifestations and disease progressions were compared between hyposmic and normosmic patients. In addition, the relationship between disease progressions and olfactory function was analyzed.ResultsOur study suggested that hyposmic PD patients and normosmic ones were similar in gender, age, education levels, age of onset, disease duration, and clinical features at baseline. Hyposmic PD patients exhibited more severe Unified Parkinson’s Disease Rating Scale Part II–III (UPDRS II-III) scores, higher levodopa equivalent dose (LED) needs, and poorer Mini-Mental State Examination (MMSE) score at follow-up visits compared to those in normosmic PD patients. Hyposmia also showed greater rates in the increase of LED needs, improvement of UPDRS III score, and deterioration of MMSE score. Both improvement of UPDRS III score and decline of MMSE score were associated with poorer odor identification.ConclusionOur prospective study demonstrated that hyposmic PD patients showed a relatively worse clinical course compared with normosmic patients. Olfactory dysfunction is a useful predictor of disease progression.