Clinical Dementia Rating Sum Of Boxes Scores Research Articles

Hippocampal volume and CDR-SB can predict conversion to dementia in MCI patients

To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB) and hippocampal volume (HV) as predictors of conversion from mild cognitive impairment (MCI) to dementia. Twenty-eight individuals (9 normal and 19 with MCI) were classified according to their CDR sum of boxes scores into 3 groups. The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy.

Progression of Alzheimer’s disease as measured by Clinical Dementia Rating Sum of Boxes scores

BackgroundThis study examined rates of dementia progression as ascertained by the Clinical Dementia Rating Sum of Boxes (CDR-SB) for symptomatic Alzheimer’s disease (sAD), and assessed participant characteristics as predictors of CDR-SB progression. MethodsParticipants (n = 792) were enrolled in longitudinal studies at an Alzheimer’s Disease Research Center, received a diagnosis of sAD with a global CDR of 0.5 (n = 466) or 1 (n = 326), and had at least one follow-up assessment. Progression in CDR-SB over time as a function of baseline global CDR was examined. ResultsA longitudinal increase (P < .0001) in CDR-SB was observed. The annual rate of change in CDR-SB scores was 1.43 (standard error [SE] = 0.05) in the CDR 0.5 sample and 1.91 (SE = 0.07) in the CDR 1 sample. For participants followed from the beginning of the CDR stage, time to progression to a higher global CDR was longer for individuals who were CDR 0.5 (3.75 years; 95% confidence interval [CI]: 3.18–4.33) than those who were CDR 1 at baseline (2.98 years; 95% CI: 2.75–3.22). In the total CDR 0.5 sample, the significant predictors of progression to the next global CDR stage (P < .01) were age at first sAD diagnosis and apolipoprotein E4 genotype. ConclusionsThe study findings are relevant to sAD clinical trial design and accurate, reliable ascertainment of the effect of disease-modifying treatments.

A 1-Year Randomized Controlled Trial Comparing Mind Body Exercise (Tai Chi) With Stretching and Toning Exercise on Cognitive Function in Older Chinese Adults at Risk of Cognitive Decline

To compare the effectiveness of Chinese-style mind-body exercise (24 forms simplified Tai Chi) versus stretching and toning exercise in the maintenance of cognitive abilities in Chinese elders at risk of cognitive decline. A 1-year single-blind cluster randomized controlled trial. Community centers and residential homes for elders in Hong Kong. A total of 389 subjects at risk of cognitive decline (Clinical Dementia Rating, CDR 0.5 or amnestic-MCI) participated in an exercise intervention program. A total of 171 subjects were trained with Tai Chi (Intervention [I]) and 218 were trained with stretching and toning exercise (Control [C]). Cognitive and functional performance were assessed at the baseline, and at 5, 9, and 12 months. Data were analyzed using multilevel mixed models. Primary outcomes included progression to clinical dementia as diagnosed by DSM-IV criteria, and change of cognitive and functional scores. Secondary outcomes included postural balance measured by the Berg Balance Scale neuropsychiatric and mood symptoms measured by the Neuropsychiatric Inventory, and Cornell Scale for Depression in Dementia. At 1 year, 92 (54%) and 169 (78%) participants of the I and C groups completed the intervention. Multilevel logistic regression with completers-only analyses controlled for baseline differences in education revealed that the I group had a trend for lower risk of developing dementia at 1 year (odds ratio 0.21, 95% CI 0.05-0.92, P = .04). The I group had better preservation of CDR sum of boxes scores than the C group in both intention-to-treat (P = .04) and completers-only analyses (P = .004). In completers-only analyses, the I group had greater improvement in delay recall (P = .05) and Cornell Scale for Depression in Dementia scores (P = .02). Regular exercise, especially mind-body exercise with integrated cognitive and motor coordination, may help with preservation of global ability in elders at risk of cognitive decline; however, logistics to promote long-term practice and optimize adherence needs to be revisited.

CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease

Measures of neuronal damage/dysfunction are likely good surrogates for disease progression in Alzheimer disease (AD). CSF markers of neuronal injury may offer utility in predicting disease progression and guiding prognostic and outcome assessments in therapeutic trials. Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury. We here investigate the utility of VILIP-1 and VILIP-1/Aβ42 in predicting rates of cognitive decline in early AD. Individuals with a clinical diagnosis of very mild or mild AD (n = 60) and baseline CSF measures of VILIP-1, tau, p-tau181, and Aβ42 were followed longitudinally for an average of 2.6 years. Annual assessments included the Clinical Dementia Rating (CDR), CDR-sum of boxes (CDR-SB), and global composite scores. Mixed linear models assessed the ability of CSF biomarker measures to predict rates of cognitive decline over time. Baseline CSF VILIP-1 and VILIP-1/Aβ42 levels predicted rates of future decline in CDR-SB and global composite scores over the follow-up period. Individuals with CSF VILIP-1 ≥560 pg/mL (corresponding to the upper tercile) progressed much more rapidly in CDR-SB (1.61 boxes/year; p = 0.0077) and global scores (-0.53 points/year; p = 0.0002) than individuals with lower values (0.85 boxes/year and -0.15 points/year, respectively) over the follow-up period. CSF tau, p-tau181, tau/Aβ42, and p-tau181/Aβ42 also predicted more rapid cognitive decline in CDR-SB and global scores over time. These findings suggest that CSF VILIP-1 and VILIP-1/Aβ42 predict rates of global cognitive decline similarly to tau and tau/Aβ42, and may be useful CSF surrogates for neurodegeneration in early AD.

Pre-MCI and MCI: Neuropsychological, Clinical, and Imaging Features and Progression Rates

To compare clinical, imaging, and neuropsychological characteristics and longitudinal course of subjects with pre-mild cognitive impairment (pre-MCI), who exhibit features of MCI on clinical examination but lack impairment on neuropsychological examination, to subjects with no cognitive impairment (NCI), nonamnestic MCI (naMCI), amnestic MCI (aMCI), and mild dementia. For 369 subjects, clinical dementia rating sum of boxes (CDR-SB), ApoE genotyping, cardiovascular risk factors, parkinsonism (UPDRS) scores, structural brain MRIs, and neuropsychological testing were obtained at baseline, whereas 275 of these subjects received an annual follow-up for 2-3 years. At baseline, pre-MCI subjects showed impairment on tests of executive function and language, higher apathy scores, and lower left hippocampal volumes (HPCV) in comparison to NCI subjects. Pre-MCI subjects showed less impairment on at least one memory measure, CDR-SB and UPDRS scores, in comparison to naMCI, aMCI and mild dementia subjects. Follow-up over 2-3 years showed 28.6% of pre-MCI subjects, but less than 5% of NCI subjects progressed to MCI or dementia. Progression rates to dementia were equivalent between naMCI (22.2%) and aMCI (34.5%) groups, but greater than for the pre-MCI group (2.4%). Progression to dementia was best predicted by the CDR-SB, a list learning and executive function test. This study demonstrates that clinically defined pre-MCI has cognitive, functional, motor, behavioral and imaging features that are intermediate between NCI and MCI states at baseline. Pre-MCI subjects showed accelerated rates of progression to MCI as compared to NCI subjects, but slower rates of progression to dementia than MCI subjects.

PL‐03‐02: Evaluating semagacestat, a gamma‐secretase inhibitor, in a phase III trial

PL‐03‐02: Evaluating semagacestat, a gamma‐secretase inhibitor, in a phase III trial

Interim follow‐up of a randomized controlled trial comparing Chinese style mind body (Tai Chi) and stretching exercises on cognitive function in subjects at risk of progressive cognitive decline

We reported the interim findings of a randomized controlled trial (RCT) to examine the effects of a mind body physical exercise (Tai Chi) on cognitive function in Chinese subjects at risk of cognitive decline. 389 Chinese older persons with either a Clinical Dementia Rating (CDR 0.5) or amnestic-MCI participated in an exercise program. The exercise intervention lasted for 1 year; 171 subjects were trained with 24 forms simplified Tai Chi (Intervention, I) and 218 were trained with stretching and toning exercise (Control, C). The exercise comprised of advised exercise sessions of at least three times per week. At 5th months (2 months after completion of training), both I and C subjects showed an improvement in global cognitive function, delayed recall and subjective cognitive complaints (paired t-tests, p < 0.05). Improvements in visual spans and CDR sum of boxes scores were observed in I group (paired t-tests, p < 0.001). Three (2.2%) and 21(10.8%) subjects from the I and C groups progressed to dementia (Pearson chi square = 8.71, OR = 5.34, 95% CI 1.56-18.29). Logistic regression analysis controlled for baseline group differences in education and cognitive function suggested I group was associated with stable CDR (OR = 0.14, 95%CI = 0.03-0.71, p = 0.02). Our interim findings showed that Chinese style mind body (Tai Chi) exercise may offer specific benefits to cognition, potential clinical interests should be further explored with longer observation period.

Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease

Docosahexaenoic acid (DHA) is the most abundant long-chain polyunsaturated fatty acid in the brain. Epidemiological studies suggest that consumption of DHA is associated with a reduced incidence of Alzheimer disease. Animal studies demonstrate that oral intake of DHA reduces Alzheimer-like brain pathology. To determine if supplementation with DHA slows cognitive and functional decline in individuals with Alzheimer disease. A randomized, double-blind, placebo-controlled trial of DHA supplementation in individuals with mild to moderate Alzheimer disease (Mini-Mental State Examination scores, 14-26) was conducted between November 2007 and May 2009 at 51 US clinical research sites of the Alzheimer's Disease Cooperative Study. Participants were randomly assigned to algal DHA at a dose of 2 g/d or to identical placebo (60% were assigned to DHA and 40% were assigned to placebo). Duration of treatment was 18 months. Change in the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) and change in the Clinical Dementia Rating (CDR) sum of boxes. Rate of brain atrophy was also determined by volumetric magnetic resonance imaging in a subsample of participants (n = 102). A total of 402 individuals were randomized and a total of 295 participants completed the trial while taking study medication (DHA: 171; placebo: 124). Supplementation with DHA had no beneficial effect on rate of change on ADAS-cog score, which increased by a mean of 7.98 points (95% confidence interval [CI], 6.51-9.45 points) for the DHA group during 18 months vs 8.27 points (95% CI, 6.72-9.82 points) for the placebo group (linear mixed-effects model: P = .41). The CDR sum of boxes score increased by 2.87 points (95% CI, 2.44-3.30 points) for the DHA group during 18 months compared with 2.93 points (95% CI, 2.44-3.42 points) for the placebo group (linear mixed-effects model: P = .68). In the subpopulation of participants (DHA: 53; placebo: 49), the rate of brain atrophy was not affected by treatment with DHA. Individuals in the DHA group had a mean decline in total brain volume of 24.7 cm(3) (95% CI, 21.4-28.0 cm(3)) during 18 months and a 1.32% (95% CI, 1.14%-1.50%) volume decline per year compared with 24.0 cm(3) (95% CI, 20-28 cm(3)) for the placebo group during 18 months and a 1.29% (95% CI, 1.07%-1.51%) volume decline per year (P = .79). Supplementation with DHA compared with placebo did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer disease. clinicaltrials.gov Identifier: NCT00440050.

Cerebrospinal Fluid Biomarkers and Rate of Cognitive Decline in Very Mild Dementia of the Alzheimer Type

Cerebrospinal fluid (CSF) levels of Abeta peptide 1-42 (Abeta 42), tau, and phosphorylated tau (ptau) are potential biomarkers of Alzheimer disease. To determine whether Abeta 42, tau, and ptau predict the rate of cognitive change in individuals with very mild dementia of the Alzheimer type (DAT). Retrospective analysis of CSF biomarkers and clinical data. An academic Alzheimer disease research center. Research volunteers in a longitudinal study of aging and cognition. Participants (n = 49) had a clinical diagnosis of very mild DAT with a Clinical Dementia Rating (CDR) of 0.5 at the time of lumbar puncture. All the participants had at least 1 follow-up assessment (mean [SD] follow-up, 3.5 [1.8] years). Baseline CSF levels of Abeta 42, Abeta 40, tau, and ptau at threonine 181 (ptau181) and the rate of dementia progression as measured using the CDR sum of boxes (CDR-SB) score and psychometric performance. The rate of dementia progression was significantly more rapid in individuals with lower baseline CSF Abeta 42 levels, higher tau or ptau181 levels, or high tau: Abeta 42 ratios. For example, the annual change in the CDR-SB score was 1.1 for the lowest 2 tertiles of Abeta 42 values and 0.3 for the highest tertile of Abeta 42 values. In individuals with very mild DAT, lower CSF Abeta 42 levels, high tau or ptau181 levels, or high tau:Abeta 42 ratios quantitatively predict more rapid progression of cognitive deficits and dementia. Biomarkers of CSF may be useful prognostically and to identify individuals who are more likely to progress for participation in therapeutic clinical trials.

The prevalence of cognitive impairment with no dementia in older people: The seoul study

This study aimed to estimate prevalence of cognitive impairment with no dementia (CIND) in older people. It was conducted in an urban area of Korea, Seoul, and employed a two-stage design for case identification. Overall 643 persons aged 65 years and older participated and 217 persons sampled from the three levels of performance of MMSE underwent a second stage clinical evaluation. CIND was diagnosed when the global Clinical Dementia Rating (CDR) index was 0.5 and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition diagnostic features of dementia were not satisfied. CIND cases without any apparent causes were classified as CIND of unidentified cause (CIND(uc)). CIND prevalence ranged from 26.3% in persons aged 65-69 to 46.5% in persons aged 85 years and older. The age-standardized prevalence for overall CIND was 31.9% and for CIND(uc) 19.2%. The prevalences of CIND for the three severity grade were 15.8%, 9.7%, and 6.2% for CDR sum of boxes scores of 0.5, 1-1.5, and >or=2, respectively. The prevalence of CIND in community-residing elderly is probably higher than previously reported. The results of this study are useful for assessments of present and future demands for healthcare services.

P3-029: The usefulness of an autobiographical memory task in assessing dementia severity

Background: Deficits in episodic memory are useful diagnostic indicators in assessing the presence of Alzheimer’s disease and one of the most sensitive to the earliest signs of the disease. Episodic memory is typically assessed clinically by using standardized memory tasks, such as recall of a story or word lists presented during evaluation. An additional method used at the Washington University Alzheimer Disease Research Center involves querying participants about the details of recent personal events. This project tested whether the outcomes of the autobiographical memory query or the brief episodic memory tasks described below are more highly correlated with the clinicians’ final dementia severity rating. Methods: In the autobiographical memory task, participants (N 852) aged 60 years with no, very mild, or mild dementia were asked to recall two personal events, one occurring over the past week and one over the past month, that had been related to the clinician by an informant. The clinician scored the recounting of each event as largely correct, partially correct, or largely incorrect, and scores for the two events were combined. Brief measures of episodic memory examined were the number of errors on recall of the John Brown phrase from the Short Blessed Test (SBT), and the number incorrect on the MMSE 3-item recall. Spearman rank-order correlations were used to examine associations between scores on the memory tasks and dementia severity, as reflected in the Clinical Dementia Rating (CDR) Sum of Boxes. Results: Scores on the autobiographical recall task were more highly correlated with CDR Sum of Boxes than were scores on the John Brown phrase (p .0001) or MMSE 3-item recall (p .0001). Correlation coefficients (95%CI) with the CDR Sum of Boxes score were .76 ( .74 to .79) for the autobiographical recall scores, .68 ( .64 to .71) for the SBT John Brown phrase, and .65 ( .61 to .69) for MMSE 3-item recall. The correlation coefficients of the two brief episodic memory tasks with Sum of Boxes did not differ from each other (p .1822). Conclusions: Clinicians’ CDR ratings reflect a greater level of agreement with the results of the autobiographical memory task compared to brief episodic memory tasks.

Voxel-based morphometry to detect brain atrophy in progressive mild cognitive impairment

Recent research has shown an increased rate of conversion to dementia in subjects with mild cognitive impairment (MCI) compared to controls. However, there are no specific methods to predict who will later develop dementia. In the present study, 22 controls and 56 MCI subjects were followed on average for 37 months (max. 60 months) and studied with magnetic resonance imaging (MRI) at baseline to assess changes in brain structure associated to later progression to dementia. Voxel-based morphometry (VBM) was used to investigate gray matter atrophy. During the follow-up, 13 subjects progressed to dementia. At baseline, no differences were detected in age or education between the control and MCI subjects, but they differed by several neuropsychological tests. The stable and progressive MCI subjects differed only by CDR sum of boxes scores and delayed verbal recall, which were also significant predictors of conversion to dementia. At the baseline imaging, the MCI subjects showed reduced gray matter density in medial temporal, temporoparietal as well as in frontal cortical areas compared to controls. Interestingly, the progressive MCI subjects showed atrophy in the left temporoparietal and posterior cingulate cortices and in the precuneus bilaterally, and a trend for hippocampal atrophy when compared to the stable MCI subjects. We conclude that widespread cortical atrophy is present already two and a half years before a clinical diagnosis of dementia can be set.

Longitudinal change in cognitive performance among individuals with mild cognitive impairment.

The authors used mixed-effects growth models to examine longitudinal change in neuropsychological performance over a 4-year period among 197 individuals who were either normal or had mild cognitive impairment (MCI) at baseline. At follow-up, the participants were divided into 4 groups: (a) controls: participants who were normal at both baseline and follow-up (n = 33), (b) stables: participants with MCI whose Clinical Dementia Rating-Sum of Boxes (CDR-SB) score did not differ between the first and last evaluations (n = 22), (c) decliners: participants with MCI whose CDR-SB score declined between the first and last evaluations (n = 95), and (d) converters: participants who received a clinical diagnosis of Alzheimer's disease during the follow-up period (n = 47). Only the Episodic Memory factor showed a significantly greater rate of decline over the follow-up period among the converters. Two other factors were significantly lower in converters at baseline in comparison with other groups (the executive function factor and the general knowledge factor), but the rate of decline over time did not differ. Individuals with an APOE epsilon4 allele scored lower on the episodic memory and executive function factors at baseline.

A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment

Inflammatory mechanisms have been implicated in Alzheimer's disease (AD) and might be mediated via the COX-2 enzyme. Previous studies with the selective COX-2 inhibitors, rofecoxib and celecoxib, have shown that they do not alter the progression of AD. We conducted a double-blind study to investigate whether rofecoxib could delay a diagnosis of AD in patients with mild cognitive impairment (MCI), a group with an expected annual AD diagnosis rate of 10-15%. MCI patients > or =65 years were randomized to rofecoxib 25 mg (N=725) or placebo (N=732) daily for up to 4 years. The primary end point was the percentage of patients with a clinical diagnosis of AD. The estimated annual AD diagnosis rate was lower than the anticipated 10-15%: 6.4% in the rofecoxib group vs 4.5% in the placebo group (rofecoxib : placebo hazard ratio=1.46 (95% CI: 1.09, 1.94), p=0.011). Analyses of secondary end points, including measures of cognition (eg the cognitive subscale of the AD Assessment Scale (ADAS-Cog)) and global function (eg the Clinical Dementia Rating (CDR)), did not demonstrate differences between treatment groups. There was also no consistent evidence that rofecoxib differed from placebo in post hoc analyses comparing ADAS-Cog and CDR-sum of boxes scores in overlapping subgroups of patients who had Mini Mental State Exam scores of 24-26 in the present MCI study and in a previous AD treatment study with a similar design. The results from this MCI study did not support the hypothesis that rofecoxib would delay a diagnosis of AD. In conjunction with the lack of effects observed in previous AD studies, the findings suggest that inhibition of COX-2 is not a useful therapeutic approach in AD.