The association between serum vitamin d level and cognitive function in older adults: Cooper Center Longitudinal Study.

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.

The Relationship between Cardiorespiratory Fitness and Montreal Cognitive Assessment Scores in Older Adults.

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.

Predictors of Reversion from Mild Cognitive Impairment to Normal Cognition.

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.

Cardiovascular Risk Factors Associated with Smaller Brain Volumes in Regions Identified as Early Predictors of Cognitive Decline.

PURPOSE: To 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 METHODS: The 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. RESULTS: Lower 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. CONCLUSION: Smaller 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.

Atypical multiple system atrophy is a new subtype of frontotemporal lobar degeneration: frontotemporal lobar degeneration associated with α-synuclein.

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).

Molecular neuropsychology: creation of test-specific blood biomarker algorithms.

BACKGROUND: Prior work on the link between blood-based biomarkers and cognitive status has largely been based on dichotomous classifications rather than detailed neuropsychological functioning. The current project was designed to create serum-based biomarker algorithms that predict neuropsychological test performance. METHODS: A battery of neuropsychological measures was administered. Random forest analyses were utilized to create neuropsychological test-specific biomarker risk scores in a training set that were entered into linear regression models predicting the respective test scores in the test set. Serum multiplex biomarker data were analyzed on 108 proteins from 395 participants (197 Alzheimer patients and 198 controls) from the Texas Alzheimer's Research and Care Consortium. RESULTS: The biomarker risk scores were significant predictors (p < 0.05) of scores on all neuropsychological tests. With the exception of premorbid intellectual status (6.6%), the biomarker risk scores alone accounted for a minimum of 12.9% of the variance in neuropsychological scores. Biomarker algorithms (biomarker risk scores and demographics) accounted for substantially more variance in scores. Review of the variable importance plots indicated differential patterns of biomarker significance for each test, suggesting the possibility of domain-specific biomarker algorithms. CONCLUSIONS: Our findings provide proof of concept for a novel area of scientific discovery, which we term 'molecular neuropsychology'.

The association between midlife cardiorespiratory fitness levels and later-life dementia: a cohort study.

BACKGROUND: Primary prevention of Alzheimer disease and other types of dementia (all-cause dementia) is an important public health goal. Evidence to date is insufficient to recommend any lifestyle change to prevent or delay the onset of dementia. OBJECTIVE: To assess the association between objectively measured midlife cardiorespiratory fitness ("fitness") levels and development of all-cause dementia in advanced age. DESIGN: Prospective, observational cohort study. SETTING: Preventive medicine clinic. PATIENTS: 19 458 community-dwelling, nonelderly adults who had a baseline fitness examination. MEASUREMENTS: Fitness levels, assessed using the modified Balke treadmill protocol between 1971 and 2009, and incident all-cause dementia using Medicare Parts A and B claims data from 1999 to 2009. RESULTS: 1659 cases of incident all-cause dementia occurred during 125 700 person-years of Medicare follow-up (median follow-up, 25 years [interquartile range, 19 to 30 years]). After multivariable adjustment, participants in the highest quintile of fitness level had lower hazard of all-cause dementia than those in the lowest quintile (hazard ratio, 0.64 [95% CI, 0.54 to 0.77]). Higher fitness levels were associated with lower hazard of all-cause dementia with previous stroke (hazard ratio, 0.74 [CI, 0.53 to 1.04]) or without previous stroke (hazard ratio, 0.74 [CI, 0.61 to 0.90]). LIMITATIONS: Dementia diagnoses were based on Medicare claims, and participants generally were non-Hispanic white, healthy, and well-educated and had access to preventive health care. This study evaluated fitness levels, so a specific exercise prescription cannot be generated from results and the findings may not be causal. CONCLUSION: Higher midlife fitness levels seem to be associated with lower hazards of developing all-cause dementia later in life. The magnitude and direction of the association were similar with or without previous stroke, suggesting that higher fitness levels earlier in life may lower risk for dementia later in life, independent of cerebrovascular disease. PRIMARY FUNDING SOURCE: The Cooper Institute; University of Texas Southwestern Medical Center; National Heart, Lung, and Blood Institute; and American Heart Association.

Global brain hypoperfusion and oxygenation in amnestic mild cognitive impairment.

BACKGROUND: To determine if global brain hypoperfusion and oxygen hypometabolism occur in patients with amnestic mild cognitive impairment (aMCI). METHODS: Thirty-two aMCI and 21 normal subjects participated. Total cerebral blood flow (TCBF), cerebral metabolic rate of oxygen (CMRO2), and brain tissue volume were measured using color-coded duplex ultrasonography (CDUS), near-infrared spectroscopy (NIRS), and MRI. TCBF was normalized by total brain tissue volume (TBV) for group comparisons (nTCBF). Cerebrovascular resistance (CVR) was calculated as mean arterial pressure divided by TCBF. RESULTS: Reductions in nTCBF by 9%, CMRO2 by 11%, and an increase in CVR by 13% were observed in aMCI relative to normal subjects. No group differences in TBV were observed. nTCBF was correlated with CMRO2 in normal controls, but not in aMCI. CONCLUSIONS: Global brain hypoperfusion, oxygen hypometabolism, and neurovascular decoupling observed in aMCI suggest that changes in cerebral hemodynamics occur early at a prodromal stage of Alzheimer's disease, which can be assessed using low-cost and bedside-available CDUS and NIRS technology.

White matter hyperintensities: use of aortic arch pulse wave velocity to predict volume independent of other cardiovascular risk factors.

PURPOSE: To evaluate the relationship between pulse wave velocity (PWV) from the aortic arch and subsequent cerebral microvascular disease independent of other baseline cardiovascular risk factors among the participants in the multiethnic Dallas Heart Study. MATERIALS AND METHODS: Each subject gave written consent to participate in this HIPAA-compliant, institutional review board-approved prospective study. Aortic arch PWV was measured with phase-contrast magnetic resonance (MR) imaging in a population sample (n = 1270) drawn from the probability-based Dallas Heart Study. Seven years later, the volume of white matter hyperintensities (WMHs) was determined from brain MR images. Linear regression was conducted with aortic arch PWV, 15 other cardiovascular risk factors, and age, sex, and ethnicity included as predictors of WMH. The authors implemented a smoothly clipped absolute deviation-penalized variable selection method to evaluate an optimal predictive risk factor model. RESULTS: Aortic arch PWV helped predict WMH volume independent of the other demographic and cardiovascular risk factors (regression coefficient: 0.29; standard error: 0.06; 95% confidence interval: 0.17, 0.42; P < .0001). The optimal predictor variables of subsequent WMH volume adjusted for sex and ethnicity included aortic arch PWV, age, systolic blood pressure, hypertension treatment, and congestive heart failure. The authors estimated that a 1% increase in aortic arch PWV (in meters per second) is related to a 0.3% increase in subsequent WMH volume (in milliliters) when all other variables in the model are held constant. CONCLUSION: Aortic arch PWV measured with phase-contrast MR imaging is a highly significant independent predictor of subsequent WMH volume, with a higher standardized effect than any other cardiovascular risk factor assessed except for age. In an optimal predictive model of subsequent WMH burden, aortic arch PWV provides a distinct contribution along with systolic blood pressure, hypertension treatment, congestive heart failure, and age.

Regional changes of cortical mean diffusivities with aging after correction of partial volume effects.

Accurately measuring the cortical mean diffusivity (MD) derived from diffusion tensor imaging (DTI) at the comprehensive lobe, gyral and voxel level of young, elderly healthy brains and those with Alzheimer's disease (AD) may provide insights on heterogeneous cortical microstructural changes caused by aging and AD. Due to partial volume effects (PVE), the measurement of cortical MD is overestimated with contamination of cerebrospinal fluid (CSF). The bias is especially severe for aging and AD brains because of significant cortical thinning of these brains. In this study, we aimed to quantitatively characterize the unbiased regional cortical MD changes due to aging and AD and delineate the effects of cortical thinning of elderly healthy and AD groups on MD measurements. DTI and T1-weighted images of 14 young, 15 elderly healthy subjects and 17 AD patients were acquired. With the parcellated cortical gyri and lobes from T1 weighted image transformed to DTI, regional cortical MD of all subjects before and after PVE correction were measured. CSF contamination model was used to correct bias of MD caused by PVE. Compared to cortical MD of young group, significant increases of corrected MD for elderly healthy and AD groups were found only in frontal and limbic regions, respectively, while there were significant increases of uncorrected MD all over the cortex. Uncorrected MD are significantly higher in limbic and temporal gyri in AD group, compared to those in elderly healthy group but higher MD only remained in limbic gyri after PVE correction. Cortical thickness was also measured for all groups. The correlation slopes between cortical MD and thickness for elderly healthy and AD groups were significantly decreased after PVE correction compared to before correction while no significant change of correlation slope was detected for young group. It suggests that the cortical thinning in elderly healthy and AD groups is a significant contributor to the bias of uncorrected cortical MD measurement. The established comprehensive unbiased cortical MD profiles of young, elderly healthy subjects and AD patients at the lobe, gyral and voxel level may serve as clinical references for cortical microstructure.

Leptin and cognition.

BACKGROUND: Leptin has been reported to have positive effects on cognition but has not been studied in a population-based sample or stratified by race or gender. METHODS: Leptin and fat mass were measured in 2,731 subjects, including 50% African Americans. Eight years later, subjects were administered the Montreal Cognitive Assessment (MoCA). Demographic factors and baseline measures, including a deficiency in leptin or levels in excess of what was predicted by fat, were investigated to see which predicted cognitive performance. RESULTS: There was a statistical trend for lower leptin levels to be associated with higher cognitive scores. Once stratified by race and gender, excessive leptin was associated with lower MoCA total scores and delayed recall domain score for black men, but white men demonstrated a reverse relationship. CONCLUSION: Excess leptin appears to have differential effects on delayed recall in black and white men.

The relationship of cardiovascular risk factors to Alzheimer disease in Choctaw Indians.

OBJECTIVES: To test the hypothesis that cardiovascular risk factors (CRFs) influence predisposition to and the clinical course of Alzheimer disease (AD), the authors compared Choctaw Indians, a group with known high CRF with white persons with AD. In addition to CRF history, the authors investigated the frequency of apolipoprotein E4 (apoE4) genotype andplasma homocysteine (HC) levels. METHOD: The authors compared 39 Choctaw Indians with AD and 39 Choctaw Indians without AD to 39 white persons with AD with all groups similar in age. CRF history included diabetes, hypertension, high cholesterol or hypolipidemic agent use, or myocardial infarction. The authors also compared plasma HC concentration and apoE4 allele frequency. RESULTS: Choctaw persons with AD differed significantly from white persons with AD in history of hypertension, diabetes, and in HC values but not from Indians without AD. There was a significantly lower apoE4 allele frequency in Choctaw Indian AD than white persons with AD, and both AD groups had an affected first degree relative significantly more often than Indian controls. There was no relationship between the number of CRF and age at onset among Indians or whites, whereas HC concentration was associated with significantly earlier age of onset for Choctaw Indians but not for whites. CONCLUSIONS: This small study suggests that in Choctaw Indians modifiable risk factors may play more of a role in disease pathogenesis than in whites and that nonmodifiable risk factors such as apoE4 may play less of a role.

Luria's three-step test: what is it and what does it tell us?

BACKGROUND: The purpose of this study is to determine if the three-step Luria test is useful for differentiating between cognitive disorders. METHODS: A retrospective record review of performance on the three-step Luria test was conducted on 383 participants from a university-based dementia clinic. The participants ranged in their diagnosis from frontotemporal dementia (FTD; n = 43), Alzheimer disease (AD; n = 153), mild cognitive impairment (MCI; n = 56), and normal controls (NC; n = 131). Performance of the Luria test was graded as normal or abnormal. RESULTS: An abnormal test occurred in 2.3% of NC, 21.4% of MCI, 69.8% of FTD, and 54.9% of AD subjects. The frequency of abnormal tests in all diagnostic groups increased with functional impairment as assessed by the Clinical Dementia Rating scale (CDR). When CDR = 3 (severe), 100% of the FTD and 72.2% of the AD subjects had abnormal Luria tests. CONCLUSIONS: The three-step Luria test distinguished NC and persons with MCI from FTD and AD, but did not distinguish FTD from AD subjects.

Videoconference diagnosis and management of Choctaw Indian dementia patients.

BACKGROUND: This study reports a 5-year experience using videoconference (VC) technology in diagnosing and treating adult members of the Choctaw Nation with symptoms or complaints of cognitive impairment. METHODS: Patients were given the option of a VC session or a face-to-face evaluation in the clinic. Before their VC session, patients underwent neuropsychological testing, Clinical Dementia Rating, Geriatric Depression Scale and Neuropsychiatric Inventory, brain computed tomography, and routine blood tests. Physical observations made by VC included eyesight, hearing, facial expression, gait and station, coordination, tremor, rapid alternating movements, psychomotor activity, and motor tests of executive function. Cogwheeling and rigidity were tested by our on-site nurse, who also obtained vital signs as indicated. RESULTS: Between January 2005 and March 2010, there were 47 clinics, 171 visits, and 85 unique patients. There were 52 new evaluations and 119 follow-up visits. The number of visits ranged from one to eight and the length of follow-up from 1 month to 4.5 years. The no-show rate for all VC sessions in 2009 was 3%, and only two subjects in 5 years refused further VC visits. CONCLUSION: Once cultural barriers are dealt with, VC-based diagnosis and treatment of adults with cognitive disorders who live in remote areas is feasible and well accepted by patients and families.

FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration.

Through an international consortium, we have collected 37 tau- and TAR DNA-binding protein 43 (TDP-43)-negative frontotemporal lobar degeneration (FTLD) cases, and present here the first comprehensive analysis of these cases in terms of neuropathology, genetics, demographics and clinical data. 92% (34/37) had fused in sarcoma (FUS) protein pathology, indicating that FTLD-FUS is an important FTLD subtype. This FTLD-FUS collection specifically focussed on aFTLD-U cases, one of three recently defined subtypes of FTLD-FUS. The aFTLD-U subtype of FTLD-FUS is characterised clinically by behavioural variant frontotemporal dementia (bvFTD) and has a particularly young age of onset with a mean of 41 years. Further, this subtype had a high prevalence of psychotic symptoms (36% of cases) and low prevalence of motor symptoms (3% of cases). We did not find FUS mutations in any aFTLD-U case. To date, the only subtype of cases reported to have ubiquitin-positive but tau-, TDP-43- and FUS-negative pathology, termed FTLD-UPS, is the result of charged multivesicular body protein 2B gene (CHMP2B) mutation. We identified three FTLD-UPS cases, which are negative for CHMP2B mutation, suggesting that the full complement of FTLD pathologies is yet to be elucidated.

Cross-cultural adaptation and psychometric validation of a Spanish version of the Quality of Life in Late-Stage Dementia Scale.

PURPOSE: The aim of the study was to develop a cross-cultural adaptation and to evaluate the validity and reliability of a Spanish version of the Quality of Life in Late-Stage Dementia (QUALID) scale. METHODS: Observational and cross-sectional validation study. The QUALID was translated according to standardised procedures. Internal consistency was assessed using Cronbach's alpha. The QUALID structure was assessed using a Principal Component Analysis (PCA). Inter-respondent (one rater asking two respondents) and inter-rater (two raters asking one respondent) reliability was assessed using the Intraclass Correlation Coefficient (ICC). The criterion validity (concurrent) was assessed by Spearman's correlation between the QUALID score and the QoL-Visual Analogue Scale (QoL-VAS) score. The construct validity (convergent) was assessed by Spearman's correlations between QUALID score and scores on the Pain-Visual Analogue Scale (Pain-VAS), on the Mini-Mental State Examination (MMSE) and on the Neuropsychiatric Inventory-Nursing Home (NPI-NH). RESULTS: A total of 160 elderly residents and 152 respondents at 8 long-term care centres in the province of Girona (Spain) participated in the study. Results showed satisfactory levels of internal consistency (Cronbach's alpha coefficients 0.74) and evidenced the multidimensionality of the scale. Three factors were identified (behavioural signs of discomfort, behavioural signs of social interaction and signs of negative affective mood). Acceptable inter-respondent reliability (ICC = 0.74) and high inter-rater reliability (ICC = 0.95) were found. The QUALID score was associated with the QoL-VAS score, suggesting a good concurrent criterion validity, and also with the Pain-VAS, the MMSE and the NPI-NH scores, suggesting good construct validity. CONCLUSIONS: Our evaluation of the psychometric properties of the Spanish version of the QUALID indicates that it is a reliable and valid instrument with an adequate capacity to distinguish between different clinical status.

Detection of Mild Cognitive Impairment Among Community-Dwelling African Americans Using the Montreal Cognitive Assessment.

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 (MMCI = 64.76[5.87], MNC = 62.33[6.76]; p = .033) and less educated (MMCI = 13.07[2.37], MNC = 14.36[2.51]; p = .004) and had lower MoCA scores (MMCI=21.26[3.85], MNC = 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.

Clinical criteria for the diagnosis of Alzheimer disease: still good after all these years.

OBJECTIVE: To examine the impact of newer neuropathological techniques on the power of National Institute of Neurological and Communicative Disorders and Stroke-AD and Related Disorders Association criteria for Alzheimer disease (AD) to detect AD at later postmortem study. DESIGN: We examined clinical and postmortem diagnoses of persons evaluated postmortem with thioflavin-S staining for plaques and tangles and immunohistochemical staining techniques for alpha synuclein, uhiquitin, and tau protein. SETTING: Alzheimer Disease Center. PARTICIPANTS: Clinically evaluated persons for whom tissue diagnosis was available. RESULTS: Of 313 evaluees, 166 met criteria for probable AD. An additional 59 subjects had clinical diagnoses that included AD, e.g., possible AD, Lewy body variant of AD, AD and Parkinsonism, and mixed AD and vascular dementia. Of the 166 probable AD cases, 147 of 166 (88.6%) met pathologic criteria for AD. When all five AD groups were combined, 194 of 225 subjects (86.2%) met pathologic criteria for AD. There were five cases diagnosed pathologically as tangle-only dementia, which was considered a variant of AD. A pathologic diagnosis of Lewy body variant of AD was made in 56 (17.9%) of cases, including 44 of 313 (14.1%) cases diagnosed as probable or possible AD. Pure dementia with Lewy bodies was seen in 13 (4.2%). There were 9 (2.9%) cases of mixed AD and vascular dementia, and 37 (11.4%) cases of frontotemporal dementia. CONCLUSIONS: McKhann et al. criteria for probable and possible AD are valid for AD but do not exclude additional Lewy body pathology.

Atherosclerosis risk factors in American Indians with Alzheimer disease: preliminary findings.

Factors predisposing to and associated with atherosclerosis may impact the onset and progression of Alzheimer disease (AD). The high prevalence of atherosclerosis and associated risk factors in American Indians makes them ideal subjects to test this association. We compared frequency of history of hypertension, myocardial infarction, stroke, diabetes, and high cholesterol in 34 American Indians with AD with 34 age-matched American Indian controls, and 34 age-matched whites with probable AD. We also measured waist size, height, and weight, and acquired blood for determination of plasma homocysteine and apolipoprotein E genotype. The 3 groups did not differ significantly in age or sex. History of hypertension and diabetes was significantly more common among American Indian AD patients than Indian controls or whites with AD. The 3 groups did not differ in history of stroke or myocardial infarction. Body mass index was significantly greater in both Indian groups than the white AD group. Plasma homocysteine levels were greater, but not significantly so, in the Indian AD than the Indian control group. Thus, there is preliminary evidence of a modest association between history of hypertension and diabetes and AD in a small sample of American Indians. This suggests that changes in lifestyle factors could influence the expression of AD in American Indians.