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.

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.

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.

Plasma 24S-hydroxycholesterol and other oxysterols in acute closed head injury.

PRIMARY OBJECTIVE: To determine if plasma levels of 24S-hydroxycholesterol, the primary catabolite of brain cholesterol, provide a measure of axonal damage in acute brain trauma. RESEARCH DESIGN: Determination of plasma 24S-hydroxycholesterol in a series of persons admitted to an intensive care unit for treatment of closed head injury. METHODS AND PROCEDURES: Levels of 24-S-hydroxycholesterol, 27-hydroxycholesterol, lathosterol and total cholesterol were measured in peripheral blood from 38 persons from 14-55 years of age treated by craniotomy and ventriculostomy for intractable intracerebral hypertension. Severity of brain injury was estimated by the Glasgow Coma Scale (range = 3-13, median = 6 points) and overall injury by the Injury Severity Scale (range = 10-48, median = 29). All subjects were intubated and anaesthetized with intravenous propofol. Plasma sterol levels were compared with those of age-matched control subjects. OUTCOMES AND RESULTS: There was no significant increase in plasma 24-S-hydroxycholesterol in subjects with head injury, but measures of peripheral cholesterol synthesis were markedly reduced as compared with values for age-matched normal control subjects. CONCLUSION: Plasma 24S-hydroxycholesterol levels do not change with severe closed head injury.

High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial.

CONTEXT: Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B(6) and B(12). Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline. OBJECTIVE: To determine the efficacy and safety of B vitamin supplementation in the treatment of AD. DESIGN, SETTING, AND PATIENTS: A multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B(6), and vitamin B(12) supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B(12), and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States. INTERVENTION: Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B(6), 1 mg/d of vitamin B(12)] and 40% treated with identical placebo); duration of treatment was 18 months. MAIN OUTCOME MEASURE: Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). RESULTS: A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], -2.42 [3.35] in active treatment group vs -0.86 [2.59] in placebo group; P < .001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-cog score during 18 months (0.372 points per month for placebo group vs 0.401 points per month for active treatment group, P = .52; 95% confidence interval of rate difference, -0.06 to 0.12; based on the intention-to-treat generalized estimating equations model), or on any secondary measures. A higher quantity of adverse events involving depression was observed in the group treated with vitamin supplements. CONCLUSION: This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056225.

Perspective on race and ethnicity in Alzheimer's disease research.

There are adequate scientific, public health, and ethical justifications for studying Alzheimer's disease (AD) in persons of varying race and ethnicity, but to be meaningful variables, race and ethnicity must be examined in context. The complex interactions between race, ethnicity, lifestyle, and environmental factors, such as climate and diet, require that future studies of AD in specific racial or ethnic groups attend to measures of racial/ethnic homogeneity and the assessment of the environment and the elements that comprise the ethnicity of groups under study. Instead of arbitrarily selecting specific racial or ethnic groups in the hope of finding important differences, it may be in the long run less costly and more efficient to recruit families with highly positive (or negative) family histories, to search within these groups for possible racial or ethnic differences, and to investigate the possible racial or ethnic reasons for those differences.

Disease-modifying therapies in Alzheimer's disease.

Alzheimer's disease (AD) is a chronic, progressive, neurodegenerative disorder that places a substantial burden on patients, their families, and society. The disease affects approximately 5 million individuals in the United States, with an annual cost of care greater than $100 billion. During the past dozen years, several agents have been approved that enhance cognition and global function of AD patients, and recent advances in understanding AD pathogenesis has led to the development of numerous compounds that might modify the disease process. A wide array of antiamyloid and neuroprotective therapeutic approaches are under investigation on the basis of the hypothesis that amyloid beta (A beta) protein plays a pivotal role in disease onset and progression and that secondary consequences of A beta generation and deposition, including tau hyperphosphorylation and neurofibrillary tangle formation, oxidation, inflammation, and excitotoxicity, contribute to the disease process. Interventions in these processes with agents that reduce amyloid production, limit aggregation, or increase removal might block the cascade of events comprising AD pathogenesis. Reducing tau hyperphosphorylation, limiting oxidation and excitotoxicity, and controlling inflammation might be beneficial disease-modifying strategies. Potentially neuroprotective and restorative treatments such as neurotrophins, neurotrophic factor enhancers, and stem cell-related approaches are also under investigation.

Validity of Teleneuropsychological Assessment in Older Patients with Cognitive Disorders.

OBJECTIVE: The 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. METHODS: The 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. RESULTS: All 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. CONCLUSIONS: Results 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.