Brain network dynamics have been extensively explored in patients with subjective cognitive decline (SCD). However, these studies are susceptible to individual differences, scanning parameters, and other confounding factors. Therefore, how to reveal subtle SCD-related subtle changes remains unclear. Cross-sectional and longitudinal resting-state functional magnetic resonance imaging data from both Chinese and Western populations were analyzed. We proposed a framework of dynamic proportional loss of functional connectivity (DPLFC). After its stability was validated, the optimal parameters were applied for the clinical diagnosis of SCD. DPLFC yielded a relatively high intraclass correlation coefficient. In particular, the DPLFC of the left superior frontal gyrus (SFG) progressively decreased along the Alzheimer’s disease (AD) continuum. Compared with the traditional index, the DPLFC had better classification performance between cognitively normal controls and patients with SCD. Furthermore, DPLFC was related to Aβ deposition and scale scores. Patients with lower DPLFC values had a greater risk of cognitive decline. Decreased DPLFC in the left SFG may be a potential AD-related neuroimaging biomarker at an early stage.

Objective: To establish a cut score for the Montreal Cognitive Assessment (MoCA) that distinguishes mild cognitive impairment (MCI) from normal cognition (NC) in a community-based African American (AA) sample. Methods: A total of 135 AA participants, from a larger aging study, diagnosed MCI (n = 90) or NC (n = 45) via consensus diagnosis using clinical history, Clinical Dementia Rating score, and comprehensive neuropsychological testing. Logistic regression models utilized sex, education, age, and MoCA score to predict MCI versus NC. Receiver operating characteristic (ROC) curve analysis determined a cut score to distinguish MCI from NC based on optimal sensitivity, specificity, diagnostic accuracy, and greatest perpendicular distance above the identity line. ROC results were compared with previously published MoCA cut scores. Results: The MCI group was slightly older (M-MCI = 64.76[5.87], M-NC = 62.33[6.76]; p = .033) and less educated (M-MCI = 13.07[2.37], M-NC = 14.36[2.51]; p = .004) and had lower MoCA scores (M-MCI = 21.26[3.85], M-NC = 25.47[2.13]; p <.001) than the NC group. Demographics were non-significant in regression models. The area under the curve (AUC) was significant (MoCA =.83, p < .01) and an optimal cut score of <24 maximized sensitivity (72%), specificity (84%), and provided 76% diagnostic accuracy. In comparison, the traditional cut score of <26 had higher sensitivity (84%), similar accuracy (76%), but much lower specificity (58%). Conclusions: This study provides a MoCA cut score to help differentiate persons with MCI from NC in a community-dwelling AA sample. A cut score of <24 reduces the likelihood of misclassifying normal AA individuals as impaired than the traditional cut score. This study underscores the importance of culturally appropriate norms to optimize the utility of commonly used cognitive screening measures.

Background: Relatively little is known regarding the association between objective measures of physical function such as cardiorespiratory fitness (CRF) and cognitive function tests in healthy older adults. Objective: To evaluate the relationship between CRF and cognitive function in adults aged 55 and older. Methods: Between 2008 and 2017, 4,931 men and women underwent a comprehensive preventive physical exam at the Cooper Clinic in Dallas, Texas. CRF was determined by duration of a maximal treadmill exercise test. Cognitive function was evaluated with the Montreal Cognitive Assessment (MoCA). In a multivariate model, adjusted odds ratios with 95% confidence intervals for MoCA scores < 26 (i.e., cognitive impairment) were determined by using CRF as both a continuous and a categorical variable. Results: The mean age of the sample was 61.0 +/- 6.0 years; mean maximal MET values were 10.0 +/- 2.2. Mean MoCA scores were 26.9 +/- 2.2; 23.4% of the sample had MoCA scores indicative of cognitive impairment. The odds ratio for cognitive impairment was 0.93 (0.88-0.97) per 1-MET increment in CRF. When examined as a categorical variable, and using the lowest CRF quintile as the referent, there was a significantly reduced likelihood for cognitive impairment across the remaining ordered CRF categories (p trend = 0.004). Conclusion: The association between CRF and MoCA score in older adults suggests that meeting or exceeding public health guidelines for physical activity is likely to increase CRF in low fit individuals, maintain CRF in those with a moderate to high level of CRF, and thereby help to maintain cognitive function in healthy older adults. (C) 2018 S. Karger AG, Basel

Low blood level of vitamin D and low physical activity have been linked to the development of cognitive impairment in older adults. The purpose of the present study was to examine the relationship between serum vitamin D and cognition as measured via the Montreal Cognitive Assessment (MoCA) in a healthy, older population. The study sample consisted of 4358 patients from the Cooper Clinic in Dallas, TX. All participants underwent a maximal graded exercise test to determine cardiorespiratory fitness (CRF). Cognitive impairment was defined as a MoCA score < 25. Low vitamin D status was defined as serum 25-hydroxyvitamin D < 30 ng/mL. Multivariable logistic regression analysis was employed to evaluate the association between vitamin D blood level and MoCA score. A low MoCA score was directly associated with higher age (OR: 1.75, 95% CI: 1.53, 1.99), and inversely associated with female sex (OR: 0.63, 95% CI: 0.51, 0.77), and years of education (OR: 0.87, 95% CI: 0.84, 0.91). When controlling for significant predictors (age, sex, and education), the low vitamin D group had a significantly greater likelihood of having a low MoCA score (OR: 1.26, 95% CI: 1.04, 1.51). The vitamin D effect remained significant when CRF was added to the model (OR: 1.23, 95% CI: 1.02, 1.48). In conclusion, low vitamin D was shown to be associated with cognitive impairment. Therefore, preventive measures such as vitamin D supplementation may play a protective role in memory loss and/or age-associated cognitive decline.

ObjectiveThe feasibility and reliability of neuropsychological assessment at a distance have been demonstrated, but the validity of this testing medium has not been adequately demonstrated. The purpose of this study was to determine the ability of video teleconferencing administration of neuropsychological measures (teleneuropsychology) in discriminating cognitively impaired from non-impaired groups of older adults. It was predicted that measures administered via video teleconference would distinguish groups and that the magnitude of differences between impaired and non-impaired groups would be similar to group differences achieved in traditional administration.MethodsThe sample consisted of 197 older subjects, separated into two groups, with and without cognitive impairment. The cognitive impairment group included 78 individuals with clinical diagnoses of mild cognitive impairment or Alzheimer's disease. All participants completed counterbalanced neuropsychological testing using alternate test forms in both a teleneuropsychology and a traditional face-to-face (FTF) administration condition. Tests were selected based upon their common use in dementia evaluations, brevity, and assessment of multiple cognitive domains. Results from FTF and teleneuropsychology test conditions were compared using individual repeated measures ANCOVA, controlling for age, education, gender, and depression scores.ResultsAll ANCOVA models revealed significant main effects of group and a non-significant interaction between group and administration condition. All ANCOVA models revealed non-significant main effects for administration condition, except category fluency.ConclusionsResults derived from teleneuropsychologically administered tests can distinguish between cognitively impaired and non-impaired individuals similar to traditional FTF assessment. This adds to the growing teleneuropsychology literature by supporting the validity of remote assessments in aging populations.

This study explored the utility of the Montreal Cognitive Assessment (MoCA) in the detection of cognitive change over time in a community sample (age ranging from 58 to 77 years). The MoCA was administered twice approximately 3.5 years apart (n = 139). Participants were classified as mild cognitive impairment (MCI) or cognitively intact at follow-up based on multidisciplinary consensus. We excluded 33 participants who endorsed cognitive complaints at baseline. The MCI group (n = 53) showed a significant decrease in MoCA scores (M = −1.83, p < .001, d = 0.64). When accounting for age and education, the MCI group showed a decline of 1.7 points, while cognitively intact participants remained stable. Using Reliable Change Indices established by cognitively intact group, 42% of MCI participants demonstrated a decline in MoCA scores. Results suggest that the MoCA can detect cognitive change in MCI over a 3.5-year period and preliminarily supports the utility of the MoCA as a repeatable brief cognitive screening measure.

OBJECTIVE:To report descriptive and normative data for the Montreal Cognitive Assessment (MoCA) in a population-based African American sample.METHOD:The MoCA was administered to 1,419 African American participants (mean age 49.89 years, range 18-75, 64% female). After excluding those with subjective cognitive complaints (n = 301), normative data were generated by education and overlapping age ranges (n = 1,118). Pearson correlations and analysis of variance were used to examine the relationship to demographic variables, and frequency of missed items was reviewed.RESULTS:Total MoCA scores (mean 22.3, SD 3.9) were lower than previously published normative data derived from an elderly Caucasian Canadian population with 80% falling below the suggested cutoff (<26) for impairment. Several MoCA items were missed by a large portion of the sample, including cube drawing (72%), delayed free recall (66% <4/5 words), sentence repetition (63%), and abstraction items (45%).CONCLUSION:This is the first study to examine normative performance on the MoCA specific to community-dwelling African Americans. Findings suggest that certain aspects of this measure and previously established cutoff scores may not be well-suited for some populations.

Background/Aims: Few studies have examined predictors of reversion from mild cognitive impairment (MCI) to normal cognition. We sought to identify baseline predictors of reversion, using the National Alzheimer's Coordinating Center Uniform Data Set, by comparing MCI individuals who reverted to normal cognition to those who progressed to dementia. Methods: Participants (n = 1,208) meeting MCI criteria were evaluated at the baseline visit and 3 subsequent annual visits. Clusters of baseline predictors of MCI reversion included demographic/genetic data, global functioning, neuropsychological functioning, medical health/dementia risk score, and neuropsychiatric symptoms. Stepwise logistic regression models identified predictors of MCI reversion per cluster, which were then entered into a final comprehensive model to find overall predictor(s). Results: At 2 years, 175 (14%) reverted to normal cognition, 612 (51%) remained MCI, and 421 (35%) progressed to dementia, with sustained diagnoses at 3 years. Significant variables associated with MCI reversion were younger age, being unmarried, absence of APOE ε4 allele, lower CDR-SOB score, and higher memory/language test scores. Conclusion: A relatively sizable proportion of MCI individuals reverted to normal cognition, which is associated with multiple factors previously noted. Findings may enhance MCI prognostic accuracy and increase precision of early intervention studies of dementia.

Cognitive decline in late adulthood might be partially mediated by subclinical generalized vascular disease. If so, atherogenic factors such as pro-inflammatory cytokines might be mid-life targets for prevention or treatment. Dallas Heart Study subjects (n = 997; mean age = 42.94 ± 10.2 yrs) underwent blood assays of pro-inflammatory biomarkers associated with atherosclerosis and 8 years later completed a cognitive outcome measure, the Montreal Cognitive Assessment (MoCA). Markers included C-reactive protein (CRP), Interleukin-18 (IL-18), Lipoprotein-associated phospholipase (LP-PLA2), and Monocyte Chemoattractant Protein (MCP-1), with Apolipoprotein E4 (ApoE4) as a potential modifier. We found weak evidence for LP-PLA2 and CRP as predictors of cognitive scores. No relationship was found between elevated MCP-1, IL-18 and cognition. Presence of the ApoE4 allele did not impact the relationship between biomarkers and cognitive function. Levels of atherogenesis-related pro-inflammatory blood biomarkers did not predict cognitive function in middle-aged adults after an interval of 8 years.

Objective: To determine the feasibility and reliability of a brief battery of standard neuropsychological tests administered via video teleconference (VTC) to a sample of rural American Indians compared with traditional face-to-face administration.Methods: The sample consisted of 84 participants from the Choctaw Nation in Oklahoma, including 53 females and 31 males [M age = 64.89 (SD = 9.73), M education = 12.58 (SD = 2.35)]. Of these, 29 had a diagnosis of mild cognitive impairment or dementia, and 55 were cognitively normal. Tests included the MMSE, Clock Drawing, Digit Span Forward and Backward, Oral Trails, Hopkins Verbal Learning Test-Revised, Letter and Category Fluency, and a short form Boston Naming Test. Alternative forms of tests were administered in counterbalanced fashion in both face-to-face and VTC conditions. Intraclass correlation coefficients (ICCs) were used to compare test scores between test conditions across the entire sample.Results: All ICCs were significant (p < .0001) and ranged from 0.65 (Clock Drawing) to 0.93 (Boston Naming Test), with a mean ICC of 0.82.Conclusion: Results add to the expanding literature supporting the feasibility and reliability of remote videoconference-based neuropsychological test administration and extend findings to American Indians.

摘要目的明确在多民族群体中心血管遗传危险因素与海马、楔前叶和后扣带回的关系,以及与无临床先兆的年轻及50岁以上病人的认知功能的关系。材料与方法机构伦理委员会批准了该项研究并且所有参与者均提供书面知情同意书。该项研究由1 629名[男700名,女929名,年龄（50±10.2）岁]参与者组成,其参与者符合以人群为基础的达沃斯

the general population. Another possible weakness in our study is the use of retrospective self-report, possibly decreasing the report of lifetime depression prevalence. In conclusion, we found a significant difference of incidence and lifetime prevalence of depression in autopsy-diagnosed LBD and AD patients and a preponderance of men in the LBD group. Thus, a history of past depressive episodes and the development of depression after the initial visit in a male should raise the suspicion of LBD alone or as a co-morbidity.

Teleneuropsychology applications are growing, but a limited number of assessment tools have been studied in this context. The present investigation was designed to determine the feasibility and reliability of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) administration by comparing video teleconference (VTC) with face-to-face (FF) test conditions. Eighteen adult subjects over age 55 with and without cognitive impairment were administered Forms A and B of the RBANS in VTC and FF settings in counterbalanced fashion. Similar RBANS scores were obtained in both test conditions, with generally high correlations between administration methods. Results support the feasibility and reliability of remote administration of the RBANS via VTC.

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease clinically characterized by cerebellar signs, parkinsonism, and autonomic dysfunction. Pathologically, MSA is an α-synucleinopathy affecting striatonigral and olivopontocerebellar systems, while neocortical and limbic involvement is usually minimal. In this study, we describe four patients with atypical MSA with clinical features consistent with frontotemporal dementia (FTD), including two with corticobasal syndrome, one with progressive non-fluent aphasia, and one with behavioral variant FTD. None had autonomic dysfunction. All had frontotemporal atrophy and severe limbic α-synuclein neuronal pathology. The neuronal inclusions were heterogeneous, but included Pick body-like inclusions. The latter were strongly associated with neuronal loss in the hippocampus and amygdala. Unlike typical Pick bodies, the neuronal inclusions were positive on Gallyas silver stain and negative on tau immunohistochemistry. In comparison to 34 typical MSA cases, atypical MSA had significantly more neuronal inclusions in anteromedial temporal lobe and limbic structures. While uncommon, our findings suggest that MSA may present clinically and pathologically as a frontotemporal lobar degeneration (FTLD). We suggest that this may represent a novel subtype of FTLD associated with α-synuclein (FTLD-synuclein).

Objective: The Montreal Cognitive Assessment (MoCA) is a cognitive screening instrument growing in popularity, but few studies have conducted psychometric item analyses or attempted to develop abbreviated forms. We sought to derive and validate a short-form MoCA (SF-MoCA) and compare its classification accuracy to the standard MoCA and Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI), Alzheimer disease (AD), and normal aging. Methods: 408 subjects (MCI n=169, AD n=87, and normal n=152) were randomly divided into derivation and validation samples. Item analysis in the derivation sample identified most sensitive MoCA items. Receiver Operating Characteristic (ROC) analyses were used to develop cut-off scores and evaluate the classification accuracy of the SF-MoCA, standard MoCA, and MMSE. Net Reclassification Improvement (NRI) analyses and comparison of ROC curves were used to compare classification accuracy of the three measures. Results: Serial subtraction (Cramer's V=.408), delayed recall (Cramer's V=.702), and orientation items (Cramer's V=.832) were included in the SF-MoCA based on largest effect sizes in item analyses. Results revealed 72.6% classification accuracy of the SF-MoCA, compared with 71.9% for the standard MoCA and 67.4% for the MMSE. Results of NRI analyses and ROC curve comparisons revealed that classification accuracy of the SF-MoCA was comparable to the standard version and generally superior to the MMSE. Conclusions: Findings suggest the SF-MoCA could be an effective brief tool in detecting cognitive impairment.

Clinical differentiation of Lewy body disease (LBD) from Alzheimer disease (AD) is still problematic. Many persons with LBD lack the cardinal features of visual hallucinations, fluctuations in cognition, and mild Parkinsonism proposed by McKeith et al. (2005). Some studies suggest that history or presence of depression may help distinguish LBD from AD, but this is confounded because many clinically diagnosed LBD patients have significant co-morbid AD pathology and vice versa (Ranginwala et al. , 2008). We aimed to clarify whether history or symptoms of depression differentiate LBD from AD, in autopsy-confirmed patients, excluding patients with mixed AD and LBD pathology.

IMPORTANCE Understanding the relationships between age-related changes in brain structure and cognitive function has been limited by inconsistent methods for assessing brain imaging, small sample sizes, and racially/ethnically homogeneous cohorts with biased selection based on risk factors. These limitations have prevented the generalizability of results from brain morphology studies. OBJECTIVE To determine the association of 3.0-T structural brain magnetic resonance (MR) imaging measurements with cognitive function in the multiracial/multiethnic, population-based Dallas Heart Study. DESIGN, SETTING, AND PARTICIPANTS Whole-brain, 2-dimensional, fluid-attenuated inversion recovery and 3-dimensional, magnetization-prepared, rapid acquisition with gradient echo MR imaging at 3.0 T was performed in 1645 Dallas Heart Study participants (mean [SD] age, 49.9 [10.5] years; age range, 19-85 years) who received both brain MR imaging and cognitive screening with the Montreal Cognitive Assessment between September 18, 2007, and December 28, 2009. Measurements were obtained for white matter hyperintensity volume, total brain volume, gray matter volume, white matter volume, cerebrospinal fluid volume, and hippocampal volume. Linear regression and a best predictive model were developed to determine the association of MR imaging biomarkers with the Montreal Cognitive Assessment total score and domain-specific questions. MAIN OUTCOMES AND MEASURES High-resolution anatomical MR imaging was used to quantify brain volumes. Scores on the screening Montreal Cognitive Assessment were used for cognitive assessment in participants. RESULTS After adjustment for demographic variables, total brain volume (P < .0001, standardized estimate [SE] = .1069), gray matter volume (P < .0001, SE = .1156), white matter volume (P = .008, SE = .0687), cerebrospinal fluid volume (P = .012, SE = -.0667), and hippocampal volume (P < .0001) were significantly associated with cognitive performance. A best predictive model identified gray matter volume (P < .001, SE = .0021), cerebrospinal fluid volume (P = .01, SE = .0024), and hippocampal volume (P = .004, SE = .1017) as 3 brain MR imaging biomarkers significantly associated with the Montreal Cognitive Assessment total score. Questions specific to the visuospatial domain were associated with the most brain MR imaging biomarkers (total brain volume, gray matter volume, white matter volume, cerebrospinal fluid volume, and hippocampal volume), while questions specific to the orientation domain were associated with the least brain MR imaging biomarkers (only hippocampal volume). CONCLUSIONS AND RELEVANCE Brain MR imaging volumes, including total brain volume, gray matter volume, cerebrospinal fluid volume, and hippocampal volume, were independently associated with cognitive function and may be important early biomarkers of risk for cognitive insult in a young multiracial/multiethnic population. A best predictive model indicated that a combination of multiple neuroimaging biomarkers may be more effective than a single brain MR imaging volume measurement.

PURPOSETo determine in a large multiethnic cohort the cardiovascular and genetic risk factors associated with smaller volume in the hippocampus, precuneus, and posterior cingulate, and their association with preclinical deficits in cognitive performance in patients younger and older than 50 years.MATERIALS AND METHODSThe institutional review board approved the study and all participants provided written informed consent. Eligible for this study were 1629 participants (700 men and 929 women; mean age, 50.0 years ± 10.2 [standard deviation]) drawn from the population-based Dallas Heart Study who underwent laboratory and clinical analysis in an initial baseline visit and approximately 7 years later underwent brain magnetic resonance imaging with automated volumetry and cognitive assessment with the Montreal Cognitive Assessment (MoCA). Regression analysis showed associations between risk factors and segmental volumes, and associations between these volumes with cognitive performance in participants younger and older than 50 years.RESULTSLower hippocampal volume was associated with previous alcohol consumption (standardized estimate, -0.04; P = .039) and smoking (standardized estimate, -0.04; P = .048). Several risk factors correlated with lower total brain, posterior cingulate, and precuneus volumes. Higher total (standardized estimate, 0.06; P = .050), high-density lipoprotein (standardized estimate, 0.07; P = .003), and low-density lipoprotein (standardized estimate, 0.04; P = .037) cholesterol levels were associated with larger posterior cingulate volume, and higher triglyceride levels (standardized estimate, 0.06; P = .004) were associated with larger precuneus volume. Total MoCA score was associated with posterior cingulate volume (standardized estimate, 0.13; P = .001) in younger individuals and with hippocampal (standardized estimate, 0.06; P < .05) and precuneus (standardized estimate, 0.08; P < .023) volumes in older adults.CONCLUSIONSmaller volumes in specific brain regions considered to be early markers of dementia risk were associated with specific cardiovascular disease risk factors and cognitive deficits in a predominantly midlife multiethnic population-based sample. Additionally, the risk factors most associated with these brain volumes differed in participants younger and older than 50 years, as did the association between brain volume and MoCA score.

Objective: To examine the relationship between measures of subclinical atherosclerosis and subsequent cognitive function.Method: Participants from the Dallas Heart Study (DHS), a population-based multiethnic study of cardiovascular disease pathogenesis, were re-examined 8 years later (DHS-2) with the Montreal Cognitive Assessment (MoCA); N=1904, mean age=42.9, range 8-65. Associations of baseline measures of subclinical atherosclerosis (coronary artery calcium, abdominal aortic plaque, and abdominal aortic wall thickness) with MoCA scores measured at follow-up were examined in the group as a whole and in relation to age and ApoE4 status.Results: A significant linear trend of successively lower MoCA scores with increasing numbers of atherosclerotic indicators was observed (F(3, 1150)=5.918, p=.001). CAC was weakly correlated with MoCA scores (p=.047) and MoCA scores were significantly different between participants with and without CAC (M=22.35 vs 23.69, p=0.038). With the exception of a small association between abdominal AWT and MoCA in subjects over age 50, abdominal AWT and abdominal aortic plaque did not correlate with MoCA total score (p >=.052). Cognitive scores and atherosclerosis measures were not impacted by ApoE4 status (p >=.455).Conclusion: In this ethnically diverse population-based sample, subclinical atherosclerosis was minimally associated with later cognitive function in middle-aged adults. (C) 2015 Elsevier Ireland Ltd. All rights reserved.