Detection of abnormal memory decline in mild cases of Alzheimer's disease using CERAD neuropsychological measures

The present study was designed to determine which of the memory tasks included in the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuropsychological battery best differentiate patients with early Alzheimer's disease from cognitively normal elderly control subjects and also best distinguish between the various levels of severity of the dementia process. A sample of CERAD patients with Alzheimer's disease was stratified by disease severity into those with mild, moderate, or severe dementia and matched with control subjects for sex, age, and education. Using multivariate procedures and cutting scores, the efficacy of each memory measure in distinguishing between these groups and control subjects was determined. The test for delayed recall was found to be the best overall discriminatory measure. The other tests of memory, ie, immediate recall, intrusion errors, and recognition memory, had poor overall discriminability. None of the CERAD memory measures were found to be particularly powerful in staging the severity of dementia. These findings suggest that tests for delayed recall may be particularly useful in the early detection of Alzheimer's disease and should be considered in screening batteries for dementia in community surveys.     

The impact of the CERAD-NP on diagnosis of cognitive deficiencies in late onset depression and Alzheimer's disease

OBJECTIVES: To identify the most appropriate test combination for distinguishing between late onset depression (LOD) and Alzheimer's disease (AD). To achieve this objective, the Consortium to Establish a Register for Alzheimer's Disease-Neuropsychological Battery (CERAD-NP) data of patients diagnosed with these two conditions were analyzed using multiple regression analysis. METHODS: In the first regression analysis, the following CERAD-NP subtests were included: verbal fluency, Boston naming test, word list learning, constructional praxis, word list recall, and constructional praxis recall. In a second regression analysis, only CERAD-NP memory parameters were included: word list learning, word list recall, word list intrusions, word list savings, word list recognition, word list false positive errors, constructional praxis recall, and constructional praxis savings. RESULTS: The combination of word list recall and constructional praxis recall best distinguished between LOD and AD, with a ROC of 0.91. In the stepwise regression of memory measures, word list recall, word list savings, and constructional praxis recall was the best combination, resulting in a ROC of 0.92. CONCLUSION: The most efficacious combination of the CERAD-NP battery for discriminating between LOD and AD consisted of word list recall and constructional praxis recall. Of the CERAD-NP memory measures, word list recall, word list savings, and constructional praxis recall represented the best diagnostic combination.     

CERAD test performances in amnestic mild cognitive impairment and Alzheimer's disease

OBJECTIVES: The aim of the study was to examine the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test performances cross-sectionally in patients suffering from amnestic mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Moreover, we wanted to determine the sensitivity to amnestic MCI and mild AD, as well as the specificity of different CERAD subtests in our study groups. MATERIAL AND METHODS: Fifteen healthy elderly individuals, 15 amnestic MCI patients and 15 probable AD patients suffering from mild dementia were tested with the CERAD neurocognitive dementia screening test. RESULTS: Significant differences were found in all CERAD tests except Constructional praxis (copy) and Clock drawing between the controls and the AD group. The MCI group was differentiated from the controls only in the Wordlist learning test. In the language tests the sensitivity to MCI and AD was quite low and the specificity very high. In the savings scores the sensitivity to AD was high, but the specificity rather low. The Wordlist recognition test screened no false positives using the current cut-off score and the sensitivity to AD was 0.6, but only one MCI patient was detected using the current cut-off score. Raising the cut-off score also raised the sensitivity to MCI without dramatic loss of specificity. Cut-off scores for the Wordlist learning test and Wordlist delayed recall, which have been found to differentiate normal aging from dementia, are lacking in the Finnish CERAD. The current data indicates that the Wordlist learning test might be relatively sensitive to MCI. CONCLUSIONS: The results indicate that the Finnish CERAD test battery with its current cut-off scores has low sensitivity to MCI, and using it as a sole cognitive screening instrument for MCI and preclinical dementia might result in false negatives.     

Performance on the CERAD neuropsychology battery of two samples of Japanese-American elders: norms for persons with and without dementia.

Norms for cognitive measures used to assess dementia are scant for minority groups, in particular for older Japanese Americans. Using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychology Battery, we compared the baseline performance of demented and nondemented Japanese Americans. Participants came from two harmonized epidemiological studies of dementia which were examined separately: the Kame Project, Seattle (350 men and women; 201 nondemented), age 65 and older; Honolulu-Asia Aging Study (HAAS), Hawaii (418 men; 120 nondemented), age 71 and older. The measures examined were Verbal Fluency; abbreviated Boston Naming; constructional praxis; and Word List Learning, Recall, and Recognition. Within each study, the CERAD measures distinguished between nondemented participants and those with mild cognitive impairment. Among persons with dementia, average level of performance decreased as severity of dementia increased. Determinants of score (age, education, language of administration, stage of dementia) varied between the two studies. Among Japanese Americans, the CERAD Neuropsychology Battery distinguished nondemented persons from those with dementia, but was less consistent in distinguishing levels of severity of dementia. This battery is useful for comparative epidemiological studies of dementia in minority populations.     

Performance of chronic schizophrenic patients on cognitive neuropsychological measures sensitive to dementia

Although many chronic schizophrenic patients manifest substantial global cognitive impairment, it is not clear as to whether this impairment should be characterized as dementia. Since many degenerative dementias have a characteristic signature of cognitive impairment and a specific pattern of cognitive decline, examination of schizophrenic patients on these measures can provide information about the qualitative similarity of their cognitive impairment to these other conditions. Three hundred and two chronically hospitalized schizophrenic patients ranging in age from 26 to 98 were examined with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery, as well as a more global measure of cognitive impairment, the Mini-Mental State Examination (MMSE). This assessment was repeated twice, with a 1-year follow-up interval. The CERAD battery measures the prototypical cognitive deficits of Alzheimer's disease, including word list learning and delayed recall, naming and praxis. In contrast to Alzheimer's disease, all aspects of cognitive impairment were linearly associated with MMSE scores and there were no qualitatively different patterns of deficits associated with MMSE scores in different ranges of severity. There was no change in performance on any measure across the follow-up period, regardless of the MMSE scores of the patients at baseline. These data suggest that the specific patterns of deficit in chronic schizophrenic patients with severe cognitive deficits differ from Alzheimer's disease in both course and profile of impairment.     

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed brief, comprehensive, and reliable batteries of clinical and neuropsychological tests for assessment of patients with the clinical diagnosis of Alzheimer's disease (AD). We administered these batteries in a standardized manner to more than 350 subjects with a diagnosis of AD and 275 control subjects who were enrolled in a nationwide registry by a consortium of 16 university medical centers. The tests selected for this study measured the primary cognitive manifestations of AD across a range of severity of the disorder, and discriminated between normal subjects and those with mild and moderate dementia. The batteries also detected deterioration of language, memory, praxis, and general intellectual status in subjects returning for reassessment 1 year later. Interrater and test-retest reliabilities were substantial. Long-term observations of this cohort are in progress in an effort to validate the clinical and neuropsychological assessments and to confirm the diagnosis by postmortem examinations. Although information on validation is limited thus far, the CERAD batteries appear to fill a need for a standardized, easily administered, and reliable instrument for evaluating persons with AD in multicenter research studies as well as in clinical practice.     

Neuropsychological study of familial Alzheimer's disease caused by mutation E280A in the presenilin 1 gene

In Antioquia, Colombia, investigators have recently discovered the largest family with the E280A mutation in the presenilin 1 gene that causes one type of familial Alzheimer's disease (FAD). The current study compares two groups within this family: those diagnosed with Alzheimer's disease (AD) in its early stage (nine subjects) and relatives (carriers) who did not show any signs of dementia (nine subjects). A battery of the following neuropsychological tests was administered to subjects in both groups: the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), a Phonological Verbal Fluency test, the Visual "A" Cancellation Test, memory of three phrases, the Rey-Osterrieth Complex Figure, and the Trail Making Test Part A. Statistical analyses of the average test scores of each group showed that the AD group scored significantly (p < 0.01 or p < 0.05) lower on 29 of the 43 neuropsychological variables measured (67 percent). Therefore, this specific battery was useful in discriminating subjects with AD from their healthy relatives who are carriers of the disease. The AD group as a whole presented slight dementia with predominant deficits in memory, language, praxis, and attention. This profile is similar to those reported in subjects with sporadic AD in its early stage and confirms the findings found in other neuropsychological studies of subjects with FAD linked to mutations in chromosome 14.     

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease

The Neuropathology Task Force of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed a practical and standardized neuropathology protocol for the postmortem assessment of dementia and control subjects. The protocol provides neuropathologic definitions of such terms as "definite Alzheimer's disease" (AD), "probable AD," "possible AD," and "normal brain" to indicate levels of diagnostic certainty, reduce subjective interpretation, and assure common language. To pretest the protocol, neuropathologists from 15 participating centers entered information on autopsy brains from 142 demented patients clinically diagnosed as probable AD and on eight nondemented patients. Eighty-four percent of the dementia cases fulfilled CERAD neuropathologic criteria for definite AD. As increasingly large numbers of prospectively studied dementia and control subjects are autopsied, the CERAD neuropathology protocol will help to refine diagnostic criteria, assess overlapping pathology, and lead to a better understanding of early subclinical changes of AD and normal aging.     

Cognitive impairment and functional status in elderly institutionalized patients with schizophrenia.

OBJECTIVE: The relationship of cognitive impairment to functional status in older adults with schizophrenia was investigated. PATIENTS: Ninety-three psychiatric inpatients with schizophrenia between the ages of 65 and 88 years. Two subsets of this sample, consisting of 48 and 24 patients, were studied with a greater number of assessment instruments. MEASURES: The Mini-Mental State Examination (MMSE) was used for brief assessment of overall cognitive functioning, and the Psychogeriatric Dependency Rating Scale (PGDRS) was administered to assess functional status. The cognitive test battery from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and/or an expanded neuropsychological battery, was given to a subset of the patients. RESULTS: In the overall sample, patients with greater global cognitive impairment had higher levels of rated impairment on the individual items that comprised the Orientation and Physical, but not Behavior, subscales of the PGDRS. Furthermore, in the two subsamples, specific neuropsychological measures of problem-solving, word list learning, naming and constructional praxis were related to overall measures of outcome. CONCLUSIONS: Neuropsychological deficit and psychosocial outcome are multi-dimensional entities that relate to one another in complex ways.     

Neuropsychological comparison of Alzheimer's disease and dementia with lewy bodies

BACKGROUND/AIMS: The present study examined the patterns of memory and cognitive performance associated with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). METHODS: A battery of standardized neuropsychological tests was administered to individuals with these disorders as well as to a group of cognitively intact controls. The battery included measures of memory (learning, recall and recognition), language, visuospatial ability, psychomotor speed, executive functioning and mood. All subjects (n = 115) were evaluated at a memory disorder clinic and were diagnosed based on published criteria. RESULTS: The controls outperformed both dementia groups on all cognitive measures. With respect to memory, the DLB group scored significantly higher than the AD group on measures of word list free recall and recognition (p < or = 0.001). In other cognitive domains, the AD group performed significantly better than the DLB group on constructional praxis, sustained attention, phonemic fluency, spatial judgment, psychomotor speed and working memory (all p < or = 0.01). CONCLUSION: These findings support the usefulness of memory and other cognitive test score patterns as in distinguishing AD from DLB, particularly in mild to moderately demented populations that may not present with hallmark symptomology.     

Factor structure of the CERAD neuropsychological battery.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery was developed to evaluate cognitive impairments associated with Alzheimer's disease (AD). Previous studies have suggested that the battery is multi-dimensional, represented by either 3 or 5 dimensions. In this study a principal factor analysis was conducted using contemporary quantitative methods for determining the number of factors. Exploratory factor analysis of the CERAD battery and MMSE was conducted using one-half of the CERAD database (total N = 969). Glorfeld's modification of Horn's parallel analysis method suggested that there was 1 common factor in the variable matrix. Characterization of patterns of deficits in AD requires supplementation of measures derived from the CERAD and MMSE with other tests.     

Memory testing in dementia: how much is enough?

Analyses of eight widely used memory measures (Word List Acquisition and Recall used in the Alzheimer's Disease Assessment Scale and the Consortium to Establish a Registry for Alzheimer's Disease neuropsychology battery, Wechsler Memory Scale-Revised [WMS-R] Logical Memory I and II, WMS-R Visual Reproduction I and II, the memory scores from the Neurobehavioral Cognitive Status Examination [NCSE], memory scores from the Mini-Mental State Examination [MMSE]), and the MMSE total score showed each to have moderate predictive power in differentiating between patients with mild dementia and healthy normal controls. When these instruments were combined in a logistic regression analysis, three of them had substantial predictive power. Together, the Word List Acquisition, WMS-R Logical Memory II, and WMS-R Visual Reproduction II were 97.26% accurate (100% sensitive and 94.59% specific) in distinguishing these two groups. The Word List Acquisition is a brief test that alone had high accuracy (92%). These memory tests are highly useful in the diagnosis of mild dementia.     

Clinical diagnosis and course of Alzheimer's disease

Alzheimer's disease can be accurately diagnosed by clinical methods alone in about 90% of cases. The adoption of uniform diagnostic criteria and assessment procedures, such as those developed by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), will likely improve the characterization of the disease across a variety of clinical settings. In general, Alzheimer's disease is a relentlessly progressive disorder; however, it also is clinically heterogeneous. This is underscored by its diverse cognitive deficits, neurologic features, behavioral pathology, and rates of progression.     

Performance of elderly Native Americans and Caucasians on the CERAD Neuropsychological Battery

The performance of 40 elderly Native Americans and 40 demographically similar Caucasians clinically diagnosed with Alzheimer disease were compared on the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB). The purpose was to determine whether performance on the CERAD-NB, a cognitive screening battery used to evaluate dementia in the elderly, is affected by cultural differences between these two groups, after controlling for age, education, and gender. All subjects were administered the CERAD-NB as part of a standard diagnostic evaluation. Statistical analyses revealed no significant differences between the two groups on any measures from the CERAD-NB. Thus, the CERAD-NB appears to be an efficient cognitive screening assessment in English-speaking Native Americans with known or suspected dementing illness and it appears that special norms may not be necessary in this population. However, additional studies of larger samples are needed for confirmation and to explore factors such as education, acculturation, and degree of Native American heritage, which may influence cognitive test performance.     

CERAD-neuropsychological battery in screening mild Alzheimer's disease

Sotaniemi M, Pulliainen V, Hokkanen L, Pirttilä T, Hallikainen I, Soininen H, Hänninen T. CERAD‐neuropsychological battery in screening mild Alzheimer’s disease.
Acta Neurol Scand: 2012: 125: 16–23.
© 2011 John Wiley & Sons A/S. Objectives – The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery (nb) is used as an evaluation tool for dementia. In Finland, CERAD‐nb was introduced in 1999 and has been proposed to be used in primary health care. However, some of its parts need reassessment and focusing. The goal of this study was to examine the sensitivity and specificity of the subtests and their cut‐off points most appropriate for identifying mild Alzheimer’s disease (AD). Materials and Methods – The study population consisted of 171 patients with mild AD and 315 cognitively normal elderly. Both groups underwent CERAD‐nb investigation as a part of a wider examination procedure. Results – The most efficient subtests to discriminate patients with mild AD from the normal elderly were Wordlist delayed recall and savings, Wordlist learning and Wordlist recognition and a new variable of Total recall. Optimal cut‐off points for each subtest are suggested. The sensitivities of the verbal memory subtests varied between 0.75 and 0.94, the specificities between 0.80 and 0.93 and the areas under the receiver operating characteristics curve between 0.89 and 0.96. Conclusions – The CERAD‐nb is capable of differentiating cases with mild AD from normal elderly individuals particularly with its verbal memory subtests. New cut‐off scores for CERAD’s subtests validated in the study further enhance the differentiating power, and with these clarifications, CERAD‐nb is considered appropriate to be used as a screening tool for AD even in primary health care.     

Neuropathological substrates of psychiatric symptoms in prospectively studied patients with autopsy-confirmed dementia with lewy bodies

OBJECTIVE: This investigation was undertaken to clarify the neuropathological substrates of key psychiatric symptoms in dementia with Lewy bodies. METHOD: The authors studied 112 autopsy-confirmed cases of dementia with Lewy bodies in patients who had had annual standardized clinical evaluations until their death. The relationships of persistent psychiatric symptoms (visual hallucinations, delusions, depression) to plaques (Consortium to Establish a Registry for Alzheimer's Disease protocol), tangles (Braak staging), and Lewy bodies (consensus Lewy body staging) were evaluated. In addition, symptom frequency and persistent symptoms were compared in the patients with Lewy body dementia and 90 patients with autopsy-confirmed Alzheimer's disease studied prospectively during life. RESULTS: The main neuropathological correlate of persistent visual hallucinations was the presence of less severe tangle pathology, but there was no significant association between tangle pathology and persistent delusions. Lewy body staging was associated with the presence of persistent visual hallucinations and persistent delusions. All baseline psychiatric features were significantly more frequent in dementia with Lewy bodies than in Alzheimer's disease, as were persistent visual hallucinations, but patients who had dementia with Lewy bodies and severe tangle pathology had a clinical symptom profile more similar to that of Alzheimer's disease patients and were less likely to have neocortical Lewy bodies. CONCLUSIONS: The modest proportion of patients with Lewy body dementia and more severe tangle pathology resembled Alzheimer's disease patients clinically. Unlike Alzheimer's disease, dementia with Lewy bodies showed a significant inverse association between tangle burden and psychosis.     

Prevalence of amyloid-beta deposition in the cerebral cortex in Parkinson's disease.

The pathological basis for the dementia which occurs in 20 to 40% of patients with idiopathic Parkinson's disease (PD) remains uncertain. In the present postmortem study, we compared the prevalence and severity of parenchymal and vascular amyloid-beta (Abeta) deposition in the cerebral cortex in a group of 57 PD brains, including 13 cases with dementia, and in 100 control brains. A higher proportion of PD brains had vascular Abeta deposition, whereas the proportions and severity of parenchymal Abeta were similar in the PD and control groups. There was a poor correlation between Abeta deposition and neurofibrillary tangles which were present in only small numbers in a minority of cases. Cortical Abeta deposition was present in only 6 of the 13 cases with dementia and only 3 fulfilled the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for definite Alzheimer's disease. The present findings confirm that dementia in PD is only infrequently due to fully established Alzheimer's disease. However, vascular and parenchymal Abeta deposition could still contribute to dementia and cognitive decline when combined with other changes such as alpha-synuclein deposition in the cerebral cortex and cortical Lewy bodies.     

Norms and the effects of demographic variables on a neuropsychological battery for use in healthy ageing Australian populations.

OBJECTIVE: The current study examined the performance of a healthy ageing population on the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery in order to determine norms for use in an Australian setting. The effects of age, education, gender and mood on cognitive performance in healthy older individuals were also explored. METHOD: The CERAD neuropsychological battery was administered to a sample of healthy elderly subjects (n = 243). Subjects also completed an anxiety inventory and a depression scale. Means and standard deviations of different age, gender and education groups are reported as normative data. A Principal Components Analysis (PCA) was also calculated. Linear regression was applied to the five factors extracted from the PCA using age, education, gender and mood as independent variables. RESULTS: All recorded means were within 1 SD of those reported in the original CERAD normative study. Five factors that loaded on measures of memory and learning, language, praxis and executive function were extracted. The independent variables age, education and gender all had significant effects on cognitive performance. However, mood had no such effect. CONCLUSIONS: Risk factors for cognitive decline indicated by the CERAD battery include age, education and gender. Anxiety and depression are not associated with CERAD cognitive performance. The CERAD battery is a valid and reliable neuropsychological tool that may assist in the detection and diagnosis of Alzheimer's disease in Australian populations.     

Clinical utility of CERAD neuropsychological battery in elderly Jamaicans.

Information on the clinical utility of neuropsychological tests in non-North-American samples is limited. We examined the diagnostic efficacy of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery in Jamaican men and women age 65 and older. A total of 72 elders were diagnosed as normal and 12 were demented based on history, physical, and neurological examination. Independent of this medical examination, participants were tested with the CERAD battery. Normal controls scored significantly better than dementia patients on all tests in the CERAD battery. A discriminant function found that a combination of Word List Learning Sum Recall and Boston Naming Test correctly classified a total of 81% of the cases (83% of the dements and 81% of the normal controls). This study is the first to demonstrate the clinical utility of the CERAD neuropsychological battery in the differential diagnosis of memory disorders of the aged in a non-North-American sample.     

Patterns of cognitive decline in presymptomatic Alzheimer disease: a prospective community study.

BACKGROUND: Specific patterns of decline over time were evaluated across a spectrum of cognitive measures in presymptomatic Alzheimer disease (AD) within a community sample. METHODS: A total of 551 individuals completed a battery of standard cognitive tests 3.5 and 1.5 years before outcome (clinical onset of AD vs continued nondemented status) within a prospective community-based study of AD. Test score changes in 68 cases (who subsequently developed symptomatic AD) and 483 controls (who remained nondemented) on each of 15 cognitive measures were transformed into z scores adjusted for age, sex, and education. A case-control rate ratio of the proportions of individuals who showed "cognitive decline" on each test was calculated, representing the relative magnitude of cognitive decline on each test in presymptomatic AD compared with normal aging. RESULTS: Declines in Trail-Making Tests A and B and Word List delayed recognition of originals and third immediate learning trial had the highest rate ratios, larger than 3.0 (P<.01). These were followed by Word List delayed recognition of foils and delayed recall, Consortium to Establish a Registry for Alzheimer's Disease Praxis, Clock Drawing, the Boston Naming Test, and Orientation, with rate ratios between 1.7 and 3.0 (P<.05). CONCLUSIONS: Memory and executive dysfunction showed the greatest decline over time in individuals who would clinically manifest AD 1.5 years later. These findings might help us understand the underlying evolution of the early neurodegenerative process. They highlight the importance of executive dysfunction early in the disease process and might facilitate early detection of AD.