Consortium To Establish A Registry For Alzheimer's Disease Total Score Research Articles

Go4cognition: Evaluation of a Newly Developed Multicomponent Intervention in Mild Cognitive Impairment.

Cognitive training and physical exercise show positive effects on cognitive decline in subjects with mild cognitive impairment (MCI). Multimodal interventions for MCI patients, combining physical and cognitive training in a social context seem to slow down cognitive decline. Based on a previous study, a new mobile gamification tool (go4cognition; https://www.ontaris.de/go4cognition) has been developed to train cognitive and physical functions simultaneously in a group setting. It involves tasks targeting various cognitive functions (short-term memory, working memory, executive functions). The computer-based setup allows for individual performance analysis. This study evaluated the effects of this tool. 30 participants with MCI, as defined by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) cut-off-score, aged between 66 and 89 years, trained for one hour two days a week for twelve weeks. Additionally, standard neuropsychological assessment of memory and attention was carried out before and after the intervention. The go4cognition device is highly effective in improving various cognitive functions. A significant improvement in the CERAD total score resulting in re-classification of 70% of former MCI patients into non-MCI patients was found. Additionally, an improvement of verbal fluency, verbal memory, spatial memory, and attention was observed. Furthermore, the CERAD total score was significantly correlated with performance in the go4cognition tool. The results of the intervention support the idea of the effectiveness of a combined cognitive and motor intervention by incorporating neuropsychological paradigms in a group setting and suggest a close relation between combined cognitive and physical exercise and cognitive performance.

Oxidative Stress Mediates the Association Between Dietary Fat Intake and Cognition in US Older Adults

OBJECTIVEDietary fat intake was considered as a modifiable factor influencing cognitive performance. The objective was to 1) examine the associations between different types of dietary fat intakes and cognitive outcomes among elder adults (≥60 years old); 2) assess whether peripheral oxidative stress and antioxidant biomarkers are potential mediators of dietary fat intake and cognitive impairment relationship. METHODSUsing data from National Health and Nutrition Examination Survey 2011-2014, total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), cholesterol, ω-3 and ω-6 fatty acids were used to evaluate dietary fat intakes. Cognitive outcomes were assessed by word learning and recall modules from the consortium to establish a registry for Alzheimer's Disease (CERAD), animal fluency test, and digit symbol substitution test (DSST). Antioxidant biomarkers were assessed by gamma glutamyl transpeptidase (GGT), bilirubin, uric acid, and vitamin D levels. Linear regression models and causal mediation analysis were applied to quantify the associations. RESULTSA total of 2,253 elder adults were included in the data analyses. Dietary intake of PUFA and ω-6 fatty acid were positively associated with DSST [β (95% CI): 0.06 (0.01,0.10), t statistic = 2.39, df= 2238, p = 0.02; β (95% CI): 0.06 (0.01,0.11), t statistic = 2.54, df= 2238, p = 0.01, respectively]. GGT was negatively associated with DSST [β (95% CI): -0.04 (-0.07, -0.01), t statistic = -2.73, df= 2239, p = 0.01], whereas uric acid was positively associated with CERAD total score [β (95% CI): 0.04 (0.00,0.08), t statistic = 2.03, df= 2233, p = 0.04]. The association between dietary intake of PUFA/ω -3/ω -6 and DSST performance was partially mediated by GGT level. CONCLUSIONOur findings support that PUFAs in dietary sources were associated with lower risks for cognitive impairment partially via lowering oxidative stress. Dietary PUFA supplementation may potentially reduce risk of cognitive impairment via antioxidative mechanism.

A new CERAD total score with equally weighted z-scores and additional executive and non-amnestic „CERAD-Plus“ tests enhances cognitive diagnosis in patients with Parkinson's disease: Evidence from the LANDSCAPE study

IntroductionThe Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is a renowned cognitive test battery, which has been extended in its German version to the CERAD-Plus including tests of executive functions and processing speed. The most commonly used total score (TS) is based on the restricted CERAD version and reflects the sum of selected raw-values (Chandler et al., 2005). The CERAD-Plus extensions might be of particular diagnostic utility for cognitive assessments in Parkinson's Disease (PD), as executive functions and processing speed belong to the most vulnerable domains in PD. ObjectiveThe aim was to develop a CERAD-TS based on the extended CERAD-Plus' age-, gender-, and education-corrected z-scores and to evaluate its diagnostic accuracy compared to the established CERAD-Chandler-TS. MethodsBaseline data of n = 679 patients with PD (69% male, n = 277 PD without cognitive impairment, n = 307 PD-MCI, n = 95 PD-D) from the multicenter, prospective DEMPARK/LANDSCAPE study were analyzed. ROC-analyses were conducted for four different TS that were either based on the original CERAD or CERAD-Plus, on raw-values or z-scores, and equally-weighted or based on factor scores. AUC-comparisons were conducted to determine the best yet most parsimonious TS. ResultsThe newly designed CERAD-Plus-TS based on equally-weighted z-scores outperformed both the CERAD-Chandler-TS and cognitive screening instruments when differentiating between individuals with PD of varying cognitive impairment (0.78 ≤ AUC ≤ 0.98). ConclusionResults suggest a high relevance of non-amnestic subscales for the cognitive assessment in PD populations. The proposed CERAD-Plus-TS needs further validation. The extensions might offer diagnostic potential for non-PD populations as well.

Exercise, diet, and cognition in a 4-year randomized controlled trial: Dose-Responses to Exercise Training (DR’s EXTRA)

ABSTRACTBackgroundEvidence for the effects of exercise and dietary interventions on cognition from long-term randomized controlled trials (RCTs) in large general populations remains insufficient.ObjectiveThe objective of our study was to investigate the independent and combined effects of resistance and aerobic exercise and dietary interventions on cognition in a population sample of middle-aged and older individuals.MethodsWe conducted a 4-y RCT in 1401 men and women aged 57–78 y at baseline. The participants were randomly assigned to the resistance exercise, aerobic exercise, diet, combined resistance exercise and diet, combined aerobic exercise and diet, or control group. Exercise goals were at least moderate-intensity resistance exercise ≥2 times/wk and at least moderate-intensity aerobic exercise ≥5 times/wk. Dietary goals were ≥400 g/d of vegetables, fruit, and berries; ≥2 servings of fish/wk; ≥14 g fiber/1000 kcal; and ≤10% of energy of daily energy intake from SFAs. The primary outcome was the change in global cognition measured by the total score of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological tests [CERAD total score (CERAD-TS)]. The data were analyzed using the intention-to-treat principle and linear mixed-effects models.ResultsThere was a trend toward improved CERAD-TS over 4 y in the combined aerobic exercise and diet group compared with the control group (net increase: 1.4 points; 95% CI: 0.1, 2.7; P = 0.06) adjusted for age, sex, years of education, symptoms of depression, and waist circumference at baseline. No other differences in CERAD-TS changes were found across the 6 study groups. Diet did not potentiate the effect of aerobic or resistance exercise on CERAD-TS.ConclusionsA combination of at least moderate-intensity aerobic exercise and a healthy diet may improve cognition in older individuals over 4 y, but there was no effect of either of these interventions alone, resistance training alone, or resistance exercise with a healthy diet on cognition.

Genome-wide screen to identify genetic loci associated with cognitive decline in late-life depression.

This study sought to conduct a comprehensive search for genetic risk of cognitive decline in the context of geriatric depression. A genome-wide association study (GWAS) analysis in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study. Longitudinal, naturalistic follow-up study. Older depressed adults, both outpatients and inpatients, receiving care at an academic medical center. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery was administered to the study participants at baseline and a minimum of twice within a subsequent 3-year period in order to measure cognitive decline. A GWAS analysis was conducted to identify genetic variation that is associated with baseline and change in the CERAD Total Score (CERAD-TS) in NCODE. The GWAS of baseline CERAD-TS revealed a significant association with an intergenic single-nucleotide polymorphism (SNP) on chromosome 6, rs17662598, that surpassed adjustment for multiple testing (p = 3.7 × 10-7; false discovery rate q = 0.0371). For each additional G allele, average baseline CERAD-TS decreased by 8.656 points. The most significant SNP that lies within a gene was rs11666579 in SLC27A1 (p = 1.1 × 10-5). Each additional copy of the G allele was associated with an average decrease of baseline CERAD-TS of 4.829 points. SLC27A1 is involved with processing docosahexaenoic acid (DHA), an endogenous neuroprotective compound in the brain. Decreased levels of DHA have been associated with the development of Alzheimer's disease. The most significant SNP associated with CERAD-TS decline over time was rs73240021 in GRXCR1 (p = 1.1 × 10-6), a gene previously linked with deafness. However, none of the associations within genes survived adjustment for multiple testing. Our GWAS of cognitive function and decline among individuals with late-life depression (LLD) has identified promising candidate genes that, upon replication in other cohorts of LLD, may be potential biomarkers for cognitive decline and suggests DHA supplementation as a possible therapy of interest.

In Thai Nationals, the ApoE4 Allele Affects Multiple Domains of Neuropsychological, Biobehavioral, and Social Functioning Thereby Contributing to Alzheimer's Disorder, while the ApoE3 Allele Protects Against Neuropsychiatric Symptoms and Psychosocial Deficits.

The apolipoprotein E epsilon 4 (ApoE4) allele is the strongest genetic risk factor for Alzheimer's disorder (AD) and is associated with semantic and episodic memory deficits. The aim of this study was to examine the associations between ApoE alleles (E2, E3, E4) and genotypes and neuropsychological tests, behavioral functions, and dementia symptoms as assessed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD). This study included 60 patients with Alzheimer's disorder (AD), 60 with mild cognitive disorder (MCI), and 62 normal volunteers. ApoE4 carriers and individuals with E3/E4 and E4/E4 genotypes show an increased incidence of AD, but not MCI. ApoE4 carriers and especially E4/E4 homozygotes show a worse outcome on the CERAD total score, Blessed Dementia Scale, and Short Blessed Test and lower scores on the Verbal Fluency Test, Boston Naming Test, Constructional Praxis Recall, and Word List Memory, Recall, and Recognition. ApoE4 carriers and E4/E3 heterozygotes show higher scores on the Clock Drawing Test. ApoE4 carriers show a worse outcome on the CERAD clinical history scores of memory, language, personality, ADL, orientation, and social skills, while allele AopE3 carriers show better scores on activities of daily living (ADL) and social skills. ApoE3 carriers show lower total weighted, irritability/aggression, and behavioral dysregulation scores on the Behavior Rating Scale for Dementia. The results show that in Thai individuals, the presence of ApoE4 allele is accompanied by a multifarious decline in neurocognitive functions and behavioral features and that ApoE3 may convey protection against neuropsychiatric symptoms and a decline in social skills. ApoE4 and especially the E4/E4 genotype may affect multiple domains of cognitive, biobehavioral, and social functioning thereby contributing to AD phenomenology.

Diagnostic accuracy of CERAD total score in a Colombian cohort with mild cognitive impairment and Alzheimer's disease affected by E280A mutation on presenilin-1 gene.

This study aimed to determine Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychological Assessment Battery total score diagnostic accuracy in the diagnosis of mild cognitive impairment (MCI) and dementia in familial Alzheimer's disease (FAD) with E280A mutation on presenilin-1 gene (PSEN1). A cross-sectional study was conducted in a cohort of PSEN1 E280A carriers and non-carriers assessed between January 1995 and February 2013. During the first neuropsychological assessment, 76 were having dementia, 46 had MCI, and 1,576 were asymptomatic. CERAD cut-off points were established for MCI and dementia using a Receiver Operating Characteristics (ROC) analysis, and were further analyzed according to education level in two groups: low education level (eight years or less), and high education level (over eight years). The area under curve-ROC CERAD total score for dementia was 0.994 (95% CI = 0.989-0.999), and that for MCI was 0.862 (95% CI = 0.816-0.908). The dementia diagnosis cut-off point for the low education group was 54, (98.4% sensitivity, 92.6% specificity), and that for the high education group was 67 (100% sensitivity, 94.1% specificity). The MCI diagnosis cut-off point for the low education group was 66 (91.2% sensitivity, 56.4% specificity), and that for the high education group was 72 (91.7% sensitivity, 76.3% specificity). The CERAD total score is a useful screening tool for dementia and MCI in a population at risk of FAD.

The Nordic diet and cognition--The DR's EXTRA Study.

The rapid increase in the prevalence of dementia associated with ageing populations has stimulated interest in identifying modifiable lifestyle factors that could prevent cognitive impairment. One such potential preventive lifestyle factor is the Nordic diet that has been shown to reduce the risk of CVD; however, its effect on cognition has not been studied. The aim of the present study was to estimate the cross-sectional and longitudinal associations of the baseline Nordic diet with cognitive function at baseline and after a 4-year follow-up in a population-based random sample (n 1140 women and men, age 57-78 years) as secondary analyses of the Finnish Dose-Responses to Exercise Training study. The Nordic diet score was created based on reported dietary components in 4-d food records. Cognition was assessed by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery and the Mini-mental State Examination (MMSE). The baseline Nordic diet score had been positively associated with Verbal Fluency (β 0.08 (95% CI 0.00, 0.16), P = 0.039) and Word List Learning (β 0.06 (95% CI 0.01, 0.10), P = 0.022) at 4 years but not with the Consortium to Establish a Registry for Alzheimer's Disease total score (CERAD-TS) or MMSE at 4 years, after adjustment for baseline cognitive scores, demographic factors and health-related factors. After excluding individuals with impaired cognition at baseline, the baseline Nordic diet score had also been positively associated with the CERAD-TS (β 0.10 (95% CI 0.00, 0.20), P = 0.042) and MMSE (β 0.03 (95% CI 0.00, 0.06), P = 0.039) at 4 years. These associations disappeared after further adjustment for energy intake. In conclusion, the Nordic diet might have a positive association with cognition in individuals with normal cognition.

The CERAD Neuropsychologic Battery Total Score and the Progression of Alzheimer Disease

To establish the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychologic battery as a valid measure of cognitive progression in Alzheimer disease (AD) by deriving annualized CERAD Total Change Scores and corresponding confidence intervals in AD and controls from which to define clinically meaningful change. Subjects included 383 normal control (NC) and 655 AD subjects with serial data from the CERAD registry database. Annualized CERAD Total Change Scores were derived and Reliable Change Indexes (RCIs) calculated to establish statistically reliable change values. CERAD Change Scores were compared with annualized change scores from the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR) Sum of Boxes, and Blessed Dementia Rating Scale (BDRS). For the CERAD Total Score, the AD sample showed significantly greater decline than the NC sample over the 4-year interval, with AD subjects declining an average of 22.2 points compared with the NCs' improving an average 2.8 points from baseline to last visit [Group x Time interaction [F(4,1031)=246.08, P<0.001)]. By Visit 3, the majority of AD subjects (65.2%) showed a degree of cognitive decline that fell outside the RCI. CERAD Change Scores significantly correlated (P<0.001) with MMSE (r=-0.66), CDR (r=-0.42), and BDRS (r=-0.38) change scores. Results support the utility of the CERAD Total Score as a measure of AD progression and provide comparative data for annualized change in CERAD Total Score and other summary measures.

Cognitive performance and informant reports in the diagnosis of cognitive impairment and dementia in African Americans and whites

Background The diagnosis of cognitive impairment and dementia must reflect an increasingly diverse and aging United States population. This study compared direct testing and informant reports of cognition with clinical diagnoses of cognitive impairment and dementia between African Americans and whites. Methods Participants in the Aging, Demographics, and Memory Study completed in-person dementia evaluations, and were assigned clinical diagnoses (by a consensus panel of dementia experts) of normal; cognitive impairment, not demented (CIND); and dementia. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were used to assess cognitive performance and reported cognitive decline. Results A higher CERAD total score was associated with lower odds of CIND and dementia, at comparable ratios between African Americans and whites. Higher IQCODE scores were associated with increased odds of dementia in both African Americans and whites. Higher IQCODE scores were associated with increased odds of CIND among whites, but not among African Americans. Conclusions Cultural differences may influence informant reports of prevalent CIND and dementia. Our findings also highlight the need for more comparative research to establish the cultural validity of measures used to diagnose these conditions.

The association of cognitive dysfunction and osteoporosis in old age

Little is known about the association between osteoporosis and cognitive dysfunction in the elderly. The aim of the study was to explore the correlation between the bone mineral density (BMD) and cognitive function in the elderly Korean. A population-based study was performed for a total of 720 elderly Korean, from the Ansan Geriatric Study (AGE study). Dual-energy x-ray absorptiometry (DXA) was performed on L1~L4 lumbar spine for evaluation of osteoporosis state. The cognitive function was evaluated by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery and the CERAD total score was tested. The distributions of CERAD total score were 57.86±13.40 in the elderly with osteoporosis, 62.72±12.39 in osteopenia, and 65.10±14.71 in normal (F=13.94, P<0.001). The distributin of MMSE score were 25.19±4.21 in the elderly with osteoporosis, 25.93±3.67 in osteopenia, and 26.34±4.21 in normal. The cognitive dysfunction was correlated with BMD (r=0.159, P<0.01). Osteoporosis was associated with cognitive dysfunction in the elderly. Additional studies are needed to confirm this correlation.

A total score for the CERAD neuropsychological battery

To develop a total or composite score for the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery. CERAD total scores were obtained by summing scores from the individual CERAD subtests (excluding the Mini-Mental State Examination [MMSE]) into a total composite (maximum score = 100). The method of tabulating the total score was constructed using normal controls (NCs; n = 424) and patients with AD (n = 835) from the CERAD registry database. The utility of the total score was further tested in independent samples of mild AD (n = 95), mild cognitive impairment (MCI; n = 60), and NC (n = 95) subjects. The CERAD total score was highly accurate in differentiating NC and AD subjects in the CERAD registry. Age, gender, and education effects were observed, and demographic correction scores were derived through multiple regression analysis. Demographically corrected CERAD total scores showed excellent test-retest reliability across samples (r = 0.95) and were highly correlated with the MMSE (r = 0.89) and Clinical Dementia Rating Scale (r = -0.83) in mixed AD and NC samples and with the Blessed Dementia Rating Scale in an AD sample (r = -0.40). The CERAD total score was highly accurate in differentiating independent samples of NC, MCI, and AD subjects. Results provide support for the validity of a Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score that can be used along with the normative data to provide an index of overall level of cognitive functioning from the CERAD neuropsychological battery.