Prediction of all-cause dementia using neuropsychological tests within 10 and 5 years of diagnosis in a community-based sample

While neuropsychological tests have been identified for the early prediction of Alzheimer's disease, this has not been established for prediction of all-cause dementia. This would be helpful for clinicians concerned about the risk of progression to dementia in patients who may present with a variety of medical and neurological conditions. We wanted to determine whether neuropsychological tests could accurately predict incident dementia within 10 and five years of diagnosis in a community-based sample. The Canadian Study of Health and Aging was conducted in three waves over a 10-year period (1991-2002). We studied 1472 non-demented participants who completed neuropsychological testing in 1991 and received a diagnostic assessment for dementia in 2001 (n = 284). We also studied 1231 non-demented participants who completed neuropsychological testing in 1996 and received a diagnostic assessment in 2001 (n = 634). Diagnosticians were blinded to performance on the predictive tests. Age, education, and sex were included as covariates in all regression analysis. Ten-year prediction: 2 tests, Rey Auditory Verbal Learning Test (RAVLT) short delayed verbal recall and Wechsler Adult Intelligence Test Revised (WAIS-R) Digit Symbol, were significant predictors of dementia (sensitivity = 78%, specificity = 72%, positive likelihood ratio = 2.81). Five-year prediction: 4 tests, Wechsler Memory Scale Information, RAVLT short delayed verbal recall, animal fluency, and WAIS-R Digit Symbol, significantly predicted incident dementia (sensitivity = 75%, specificity = 74%, positive likelihood ratio = 2.90). Regression models were supported with bootstrapping estimates. Neuropsychological tests can accurately predict progression to all-cause dementia within 10 years of diagnosis in a large community-based sample of non-demented participants.     

The HIV Dementia Scale: predictive power in mild dementia and HAART

BACKGROUND: HIV-associated dementia (HIV-D) is a subcortical dementia consisting of cognitive and motor symptoms that ultimately affects as many as 20% of patients with AIDS and is associated with significant morbidity and mortality. With the advent of highly active antiretroviral therapy (HAART), the use of sensitive and efficient screening tests for HIV-D continue to be needed for identifying individuals who develop this disorder. OBJECTIVE: The objective of this study was to compare the HIV Dementia Scale (HDS) with comprehensive neuropsychological procedures in detecting both minor cognitive and motor disorder (MCMD) and HIV-D in a population of patients with varying durations of HAART. METHODS: Forty-six HIV-seropositive patients completed both the HDS and a battery of neuropsychological tests as they enrolled in a MRI study. Each person was also assigned a MSK score based on clinical neurological examination. HDS score of 10 were considered cognitively unimpaired. Two separate sensitivity analyses were performed. Global Z scores (NPZ8) averaged from eight individual neuropsychological subtests were compared to the HDS score for each subject. An NPZ8 score -2.0 standard deviations (S.D.) below the mean was used to define HIV-D. Additionally, HIV-D, defined as -2.0 S.D. below the mean on one test or -1.0 S.D. below the mean on two or more tests from the NPZ8, were also compared to the HDS. Finally, performance on these cognitive measures was used to predict duration of HAART in this sample. RESULTS: Using the average NPZ8 score based on American Academy of Neurology consensus criteria yielded a test sensitivity of 30%, a specificity of 0%, a positive predictive value of 0%, and a negative predictive value of 58% when compared to clinical MSK ratings. Comparison of the number of impaired tests with MSK severity yielded a test sensitivity of 43%, a specificity of 91%, a positive predictive value of 83%, and a negative predictive value of 61%. HDS scores were less efficient in predicting the presence of subtle and mild HIV-D in this sample. CONCLUSION: While the HDS is a useful bedside test that a physician may quickly administer to HIV seropositive patients to assist in diagnosing suspected cases of frank HIV-D, the HDS, as a screen, is not as accurate in detecting HIV-D as a more thorough neuropsychological examination. With an increasing prevalence of HIV-D and minor cognitive/motor disorder (MCMD) following the introduction of HAART, the development of more sensitive bedside measures is essential in order to identify individuals with these disorders and monitor treatment regimens.     

Performance variability during a multitrial list-learning task as a predictor of future cognitive decline in healthy elders

Introduction: In clinical settings, neuropsychological test performance is traditionally evaluated with total summary scores (TSS). However, recent studies demonstrated that indices of intraindividual variability (IIV) yielded unique information complementing TSS. This 18-month longitudinal study sought to determine whether IIV indices derived from a multitrial list-learning test (the Rey Auditory Verbal Learning Test) provided incremental utility in predicting cognitive decline in older adults compared to TSS. Method: Ninety-nine cognitively intact older adults (aged 65 to 89 years) underwent neuropsychological testing (including the Rey Auditory Verbal Learning Test) at baseline and 18-month follow-up. Participants were classified as cognitively stable (n = 65) or declining (n = 34) based on changes in their neuropsychological test performance. Logistic regression modeling tested the ability of baseline TSS indices (sum of Trials 1–5, immediate recall, and delayed recall) and IIV indices (lost access and gained access) to discriminate between stable and declining individuals. Results: Higher values of both lost access and gained access at baseline were associated with an increased risk for decline at 18-month follow-up. Further, the IIV indices provided predictive utility above and beyond the TSS indices. Conclusion: These results highlight the value of analyzing IIV in addition to TSS during neuropsychological evaluation in older adults. High levels of IIV may reflect impairment in anterograde memory systems and/or executive dysfunction that may serve as a prognostic indicator of cognitive decline.     

Diagnostic accuracy and practice effects in the National Alzheimer's Coordinating Center Uniform Data Set neuropsychological battery

IntroductionThe Uniform Data Set (UDS) neuropsychological battery is frequently used in clinical studies. However, practice effects, effectiveness as a measure of global cognitive functioning, and detection of mild cognitive impairment have not been examined.MethodsA normative total score for the UDS has been developed. Linear discriminant analysis determined classification accuracy in identifying cognitively normal and impaired groups. Practice effects were examined in cognitively normal and cognitively impaired groups.ResultsThe total score differentiates between cognitively normal participants and those with dementia, but does not accurately identify individuals with mild cognitive impairment (MCI). Mean total scores for test-exposed participants were significantly higher than test-naive participants in both the normal and MCI groups and were higher, but not significantly so, in the dementia group.ConclusionThe total score’s classification accuracy discriminates between cognitively normal versus participants who have dementia. The total score appears subject to practice effects.     

Cognitive function in UK community-dwelling African Caribbean and white elders: a pilot study

In recent years there has been interest in risk of cognitive impairment and dementia in populations of African origin. Little is known about this risk in older African Caribbean residents in the UK. One difficulty is lack of consensus over an adequate cognitive test battery for this community. Forty-five African Caribbean and 45 age and gender matched white community residents were recruited by household enumeration of an inner London electoral ward. These participants were administered the MMSE during a screening interview. Where possible, this was followed up by tests from the CERAD and CAMCOG neuropsychological batteries, a medical examination, and a structured interview with an informant. Based on these data, a psychiatrist blind to ethnicity independently rated 86 of these participants (41 of the African Caribbeans, all 45 of the whites) as cognitively normal, cognitively impaired, or demented. Of 41 African Caribbeans, 18 (44%) were rated as cognitively normal, 9 (22%) were rated as cognitively impaired, and 14 (34%) were rated as demented. Of the 45 whites, 39 (87%) were rated as cognitively normal, 4 (9%) were rated as cognitively impaired, and 2 (4%) were rated as demented. African Caribbeans scored significantly lower than whites in most cognitive test scores, which was not accounted for by their lower educational and occupational attainment, or their higher frequency of cardiovascular risk factors. African Caribbean elders in the UK appear to be at high risk of cognitive impairment and dementia. However, the influence of potential confounding factors such as socio-economic position and ill-health, and the effect of cultural test bias, cannot be ruled out.     

Attention and executive control predict Alzheimer disease in late life: results from the Berlin Aging Study (BASE).

OBJECTIVE: Longitudinal studies of neuropsychological changes in the preclinical phase of Alzheimer disease (AD) have yielded mixed results. Although some studies report tests of episodic memory, others report tests of attention and executive functions as reliable predictors of subsequent AD. Following theoretical models of neuropsychological processes before AD onset, the authors examined the predictive value of attention and executive function in the preclinical phase of AD in old age. METHODS: Authors studied the cognitive performance of 187 initially normal participants of the Berlin Aging Study, a community-based representative sample of Berlin citizens age 70 to 103, over a period of 4 years. Tests of attention and executive function (Digit Letter Test, Trailmaking Part B Test, Digit Symbol Substitution Test, and Identical Pictures Test) and of learning and recall functions (Activity Recall, Memory for Text, and Paired-Associate Learning) were administered at baseline. Diagnosis of AD was made according to NINCDS-ADRDA criteria (probable AD). Receiver operating characteristics curve analyses and Cox regression analyses were used to assess the diagnostic accuracy and predictive value of the neuropsychological tests at baseline for incident AD after 4 years. RESULTS: After 4 years, 15 participants had developed AD. Tests of attention and executive function discriminated best between nonconverters and incident AD cases. A similar pattern was found in survival analyses; attention and executive function tests, together with tests of learning and recall, significantly predicted incident AD over and above age, gender, and education. CONCLUSION: These results support theoretical models of attention and executive function in the preclinical phase of AD in old age.     

Do depressive symptoms in memory-impaired elders predict probable Alzheimer's disease?

Our purpose was to determine whether performance on the Geriatric Depression Scale (GDS) predicted the development of probable Alzheimer's disease (AD) in memory-impaired non-demented participants. Participants were followed for two years, after which they underwent a diagnostic assessment: 27 developed probable AD, 98 remained cognitively impaired but not demented, and 18 developed other neurological conditions.The GDS did not contribute significantly to the prediction of probable AD, it was not related to scores on selected neuropsychological tests, but it was related to complaints of memory on a self-report scale. These findings highlight the need to consider patient characteristics and the method of assessing depression when examining the role of depression in dementia.     

Predictors of self-neglect in community-dwelling elders

OBJECTIVE: The study assessed the contribution of depressive symptoms and cognitive impairment to the prediction of self-neglect in elderly persons living in the community. METHOD: Data were drawn from the New Haven Established Populations for Epidemiologic Studies of the Elderly cohort, which included 2,812 community residents age 65 years and older in 1982. The principal outcome examined was the incidence of self-neglect, corroborated by the state's investigation, during 9 years of follow-up (1982-1991). RESULTS: Among the 2,161 subjects included in the analysis, 92 corroborated cases of self-neglect occurred from 1982 to 1991. The prevalence of clinically significant depressive symptoms at baseline (score > or=16 on the Center for Epidemiologic Studies Depression Scale [CES-D]) was 15.4%, and the prevalence of clinically significant cognitive impairment (four or more errors on the Pfeiffer Short Portable Mental Status Questionnaire) was 7.5%. Subjects with clinically significant depressive symptoms and/or cognitive impairment were more likely than others to experience self-neglect. Clinically significant depressive symptoms and cognitive impairment remained significant predictors of self-neglect in a multivariate model that included age, gender, race, and income. A final model for self-neglect constructed with stepwise selection of risk factors included depressive symptoms and cognitive impairment, as well as male gender, older age, income less than $5,000 per year, living alone, history of hip fracture, and history of stroke. CONCLUSIONS: Elderly individuals living in the community who experience clinically significant depressive symptoms and/or cognitive impairment may be at risk for the development of self-neglect and may become candidates for intervention.     

Prodromal frontal/executive dysfunction predicts incident dementia in Parkinson's disease.

To identify the cognitive characteristics predictive of incident dementia in Parkinson's disease (PD), we examined the baseline neuropsychological profiles of 18 initially non-demented patients with PD who met diagnostic criteria for dementia (PDD) at one-year follow-up. PDD participants' baseline neuropsychological test scores were compared to the baseline performance of 18 patients with PD who did not meet criteria for dementia at one-year follow-up (PDND) and 18 normal controls (NC). The three groups were matched on baseline demographic and disease variables. Relative to the PDND group, the incident PDD participants demonstrated significantly poorer performance on digits backward (Wechsler Memory Scale-Revised), word list learning and recognition (California Verbal Learning Test), and perseverative errors on the Wisconsin Card Sorting Test. Each of these baseline neuropsychological variables exhibited adequate diagnostic classification accuracy in predicting PDD and PDND group membership at follow-up. These results suggest that subtle frontal/executive dysfunction is evident during the immediate PDD prodrome and may be of prognostic value in identifying PD patients at risk for dementia. Accordingly, neuropsychological evaluation may facilitate early identification of PDD and thereby inform appropriate dispositional planning.     

Accidental MCI in healthy subjects: a prospective longitudinal study.

A study was realized on 130 healthy and autonomous volunteers (60-80 years old) who met specific medical and functional inclusion criteria. A comprehensive battery of neuropsychological tests was performed at baseline (M0), 6 and 12 months (M6, M12). At M0 the results indicated that 65% were cognitively normal on each of all the neuropsychological tests, whereas 35% presented a cognitive deficit on one or more tests. At M12, 52% of the subjects who had a cognitive deficit at M0 remained impaired, whereas 48% normalized their scores: they performed as well as the subjects classified normal at M0. The results also indicated that the subjects who remained impaired at M12, had at M0 low scores on three tests or more, whereas the ones who normalized their scores had one or two failed tests. This study focuses on the risk of false positive cases and shows that low scores can be accidental. The authors propose decision rules allowing to reduce the risk of false positive cases. The observation of accidental impairment invites to be cautious and makes this 1-year follow-up study particularly relevant, since a 1-year follow-up is generally needed to diagnose very mild dementia.     

Cognitive function in early Parkinson’s disease: a population‐based study

Background and purpose: The study aims to describe the frequency, pattern and determinants of cognitive function in patients with newly diagnosed Parkinson’s disease (PD); to compare patients with impaired cognition to patients with intact cognition; and to compare to matched healthy controls. Methods: Patients were identified in a longitudinal population based study of idiopathic non‐drug induced parkinsonism. Eighty‐eight newly diagnosed patients with PD and no dementia were included during a four year period. The patients and 30 age‐ and sex‐matched healthy control subjects underwent a comprehensive neuropsychological assessment. Results: Patients performed significantly worse than healthy controls in a majority of neuropsychological tests. Test results in attention, psychomotor function, episodic memory (free recall), executive function and category fluency were significantly lower in the patient group. Comparison with normative data revealed that 30% of the patients had deficits in ≥1 cognitive domain (episodic memory, executive function and verbal function). Seventy per cent of the patients had normal performance. Unified Parkinson's Disease Rating Scale (UPDRS) III sub scores; speech, facial expression, rigidity and bradykinesia were significantly higher, and disease duration shorter amongst the cognitively impaired than amongst the cognitively intact patients. Tremor showed no difference. Education level was an independent predictor of dysfunction in patients with ≥2 cognitive domains affected. Conclusion: Cognitive dysfunction is common in untreated patients in early PD, affecting attention, psychomotor function, episodic memory, executive function and category fluency. Education level was an independent predictor of severe cognitive dysfunction.     

MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimer's disease.

BACKGROUND: Causes of cognitive impairment in subcortical ischemic vascular disease (SIVD) are less well understood than in AD, but have been thought to result from direct effects of subcortical lacunes and white matter lesions, perhaps related to disruption of important cortical-subcortical pathways. OBJECTIVE: To examine the relation between cognitive abilities and quantitative MRI measures of subcortical cerebrovascular disease and cortical and hippocampal atrophy. METHODS: Subjects were 157 participants in a multicenter study of SIVD and AD who included cognitively normal, cognitively impaired, and demented individuals with and without subcortical lacunar infarcts. Dependent variables were neuropsychological tests of global cognitive function, memory, language, and executive function. Independent variables were quantitative MRI measures of volume of lacunar infarcts in specific subcortical structures, volume of white matter lesion (WML), volume of cortical gray matter (cGM), and total hippocampal volume (HV). Multiple regression analyses were used to identify MRI predictors of cognition. RESULTS: Subcortical lacunes were not related to cognitive measures independent of effects of other MRI variables. WML was independently related to selected, timed measures. HV and cGM were strong and independent predictors of cognitive variables, with effects that did not differ in subjects with and without subcortical lacunes. CONCLUSIONS: Results suggest that cognitive impairment associated with subcortical ischemic vascular disease is primarily a result of associated hippocampal and cortical changes.     

Cognitive impairment does not cause invalid performance: analyzing performance patterns among cognitively unimpaired,impaired, and noncredible participants across six performance validity tests

Objective: Performance validity tests (PVTs) are essential in neuropsychological evaluations; however, it has been questioned how PVTs function in the context of cognitive impairment, and whether cognitive impairment alone is sufficient to cause PVT failure. Further, there is concern that some clinicians will disregard failed PVTs due to their perception that failures represent false-positive errors secondary to cognitive impairment. This study examined patterns associated with cognitively impaired versus noncredible performance across a battery of PVTs and neuropsychological tests. Additionally, the impact of VA service-connection and disability-seeking status on test validity was investigated.

Method: A mixed-clinical sample of 103 veterans were administered six PVTs and neuropsychological tests. Performance was compared across three groups: valid-cognitively unimpaired, valid-cognitively impaired, and noncredible.

Results: Significant PVT score differences and failure rates emerged across the three groups, with nonsignificant to small differences between valid-unimpaired and valid-impaired groups, and large differences between impaired and noncredible groups. In contrast, there were nonsignificant to small differences on neuropsychological tests between the valid-impaired and noncredible groups, indicating that impaired participants performed significantly better on PVTs despite comparable neurocognitive test scores. Service-connection rating itself was not associated with PVT failure, but an active disability claim to increase and/or establish service connection was associated with worse PVT performance.

Conclusion: This study supports the use of multiple PVTs during evaluations of patients with varied cognitive abilities. Results indicated increased risk of PVT failure in patients who were seeking initiation/increase in service-connected payments, and shows that cognitive impairment does not cause PVT failure.     

Cognitive remediation of working memory deficits: durability of training effects in severely impaired and less severely impaired schizophrenia

OBJECTIVE: To determine whether augmenting work therapy (WT) with neurocognitive enhancement therapy (NET) yields greater improvement in working memory performance than WT alone and whether there is an interaction with severity of impairment. METHOD: A total of 102 participants with schizophrenia or schizoaffective disorder were categorized as severely or less severely cognitively impaired and randomly assigned to receive NET + WT or WT alone. NET consisted of cognitive training exercises in attention, memory, executive function, and social information processing, and WT was a 6-month work program. RESULTS: Comparison on Digits Backwards from intake to follow-up revealed significantly greater improvement for participants receiving NET + WT, but there was no interaction with severity group. Follow-up 6 months after training showed that training effects endured. CONCLUSION: NET + WT improved working memory for most participants regardless of impairment severity. Intensity and duration of training may have contributed to duration of effects. Findings support continued exploration of cognitive remediation.     

Can a novel computerized cognitive screening test provide additional information for early detection of Alzheimer's disease?

BackgroundVirtual reality testing of everyday activities is a novel type of computerized assessment that measures cognitive, executive, and motor performance as a screening tool for early dementia. This study used a virtual reality day-out task (VR-DOT) environment to evaluate its predictive value in patients with mild cognitive impairment (MCI).MethodsOne hundred thirty-four patients with MCI were selected and compared with 75 healthy control subjects. Participants received an initial assessment that included VR-DOT, a neuropsychological evaluation, magnetic resonance imaging (MRI) scan, and event-related potentials (ERPs). After 12 months, participants were assessed again with MRI, ERP, VR-DOT, and neuropsychological tests.ResultsAt the end of the study, we differentiated two subgroups of patients with MCI according to their clinical evolution from baseline to follow-up: 56 MCI progressors and 78 MCI nonprogressors. VR-DOT performance profiles correlated strongly with existing predictive biomarkers, especially the ERP and MRI biomarkers of cortical thickness.ConclusionsCompared with ERP, MRI, or neuropsychological tests alone, the VR-DOT could provide additional predictive information in a low-cost, computerized, and noninvasive way.     

Combined effects of cognitive impairment and pre-frailty on future frailty and death in older Mexican Americans

Abstract

Objectives: Impaired cognition and pre-frailty are associated with poor health outcomes. However, research has not examined the combined impact of cognitive impairment and pre-frailty on future frailty and mortality among older Mexican Americans.

Methods: Data for this analysis came from the 2006–2007 and 2010–2011 waves of the Hispanic EPESE. The final sample included 639 Mexican Americans aged ≥77 years who were non-frail or pre-frail in 2006–2007. Frailty measure included weight loss, exhaustion, weakness, and slow walking speed. Participants were classified as non-frail (0 criteria) and pre-frail (1 criterion) at baseline. Cognitive impairment was defined as <21 points on the MMSE. At baseline, participants were grouped as: cognitively intact non-frail, cognitively intact pre-frail, cognitively impaired non-frail, and cognitively impaired pre-frail. Logistic and hazard regression models were used to evaluate the odds of being frail in 2010–2011 and risk for 10-year mortality.

Results: Cognitively impaired pre-frail participants were more likely to become frail (OR?=?4.82, 95% CI?=?2.02–11.42) and deceased (HR?=?1.99, 95% CI?=?1.42–2.78). Cognitively impaired non-frail participants had significantly higher risk for mortality (HR?=?1.55, 95% CI?=?1.12–2.19) but not frailty (OR?=?1.29, 95% CI?=?0.50–3.11). Being cognitively intact and pre-frail at baseline was not significantly associated with being frail at follow-up (OR?=?1.62, 95% CI?=?0.83–3.19) or mortality (HR?=?1.29, 95% CI?=?0.97–1.71).

Conclusions: Comorbid cognitive impairment and pre-frailty is associated with future frailty and mortality in older Mexican Americans. Screening for cognitive impairment may be effective for identifying pre-frail Mexican Americans who are at the highest risk of frailty and mortality.     

Functional magnetic resonance imaging of verbal fluency and confrontation naming using compressed image acquisition to permit overt responses

Verbal fluency and confrontation naming, two tests of word retrieval, are of great utility in the field of cognitive neuroscience. However, in the context of functional magnetic resonance imaging (fMRI), movement artefact has necessitated the use of covert paradigms, which has limited clinical application. We developed two overt fMRI paradigms that allowed for performance measurement and hence were appropriate for use with patient groups. The paradigms incorporated a blocked-design and compressed-acquisition methodology where cues were presented and responses made in a "silent" period allowing for performance measurement. The slow response pace was specifically designed for older and potentially cognitively impaired participants. Verbal fluency was associated with activation in the middle frontal gyrus (Brodmann areas 46 and 9), anterior cingulate gyrus and inferior frontal gyrus (area 44 and 45). Confrontation naming activated areas of the temporo-occipital cortices (areas 18, 19, and 37) and the inferior frontal gyrus. The two paradigms successfully activated regions involved in executive and word retrieval processes and overcame the potential artefacts resulting from overt speech during image acquisition, providing useful neuropsychological tools to investigate cognitive deficits in clinical populations.     

Similar subcortical pattern of cognitive impairment in AIDS patients with and without dementia.

The aim of this study was to develop a series of neuropsychological tests that define the cortical and subcortical features of cognitive impairment and the characteristics of memory in demented and mildly cognitively impaired AIDS patients. We attempted to establish a usable method to assess and determine the type and degree of cognitive impairment in individual AIDS patients. We examined 53 patients without central nervous system opportunistic infections. A short battery included two scales of global efficiency (the Mattis dementia rating scale and the Mini Mental State Examination), a psychomotor speed test, an executive control assessment and explicit memory evaluation. Patients were categorized into four groups based on their score on both the Mattis dementia rating scale and the DSM-IV criteria: (1) asymptomatic; (2) having AIDS without cognitive impairment; (3) having AIDS with mild cognitive impairment; and (4) having AIDS dementia. Patients with mildly impaired cognition demonstrated slowed thinking, abnormal initiation and conceptualization, and memory impairment. AIDS dementia patients had slower motor activity and memory recall was more severely affected. The short neuropsychological battery was able to characterize modified cognitive performances in both severely and mildly cognitively impaired AIDS patients. The subcortical pattern of the memory disorder was obvious, regardless of the degree of cognitive impairment.     

Cognitive decline in patients with familial Alzheimer's disease associated with E280a presenilin-1 mutation: a longitudinal study

Few longitudinal studies have been carried out to investigate the cognitive decline in early onset of familial Alzheimer's disease (FAD). In this study 12 patients with FAD (M age = 49.61 years, SD = 4.99), 10 patients with sporadic Alzheimer's disease (SAD) (M age = 71.40, SD =10.00), and 15 matched normal controls (M age = 45.01, SD = 7.24) were selected. A comprehensive neuropsychological battery was administered three times over a period of 18 months. Individuals designated as FAD met the criteria for dementia and were positive for the E280A presenilin 1 mutation. Participants with SAD met the criteria for dementia and were negative for the E280A presenilin 1 mutation. Normal control participants were the FAD patients' relatives, who were negative for the mutation. Two groups of neuropsychological instruments were administered: (1) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery, and (2) additional neuropsychological tests of abstraction and constructional abilities. Patients with FAD were significantly impaired on all measures at the first examination except for reading of words. While the performance of the normal controls remained unchanged over the 18 months for most neuropsychological tests, the patients with FAD displayed a decline in verbal memory, language, constructional and abstraction tests. The greatest decline was observed on the Mini-Mental State Exam scores. Patients with SAD demonstrated a similar pattern of cognitive decline, but the decline was faster in FAD than in SAD participants.     

A 3-year longitudinal study of cognitive impairment in patients with primary progressive multiple sclerosis: speed matters

BACKGROUND: The few controlled longitudinal studies of cognitive performance in MS patients all provide evidence of deterioration in at least a subset of the patients sampled. Only one of these studies has focused on primary progressive MS, and little attention has been paid to the specific domains of cognitive functioning that change over time. The present study examined three principal cognitive domains in samples of primary progressive MS patients and healthy controls followed over a period of 3 years. METHODS: A battery of neuropsychological tests that included measures of strategic problem solving, verbal memory, and information processing speed was administered annually to 24 MS patients and 25 controls. RESULTS: MS patients' performance on measures of processing speed showed significantly greater decline over the 3-year period than did that of controls. Similar results were not observed in the case of problem solving or verbal memory. There was no evidence of more dramatic decline occurring in patients who were initially classified as cognitively impaired relative to those who were unimpaired at baseline. However, this failure may have been influenced by differential attrition from the sample; more impaired patients were less likely to complete the study. CONCLUSION: Overall the results support the contention that information processing speed is the domain most sensitive to the impact of multiple sclerosis on cognitive functioning over time.