The Audio Recorded Cognitive Screen (ARCS) in patients with multiple sclerosis: a practical tool for multiple sclerosis clinics.

BACKGROUND: Cognitive impairment is a common complication of multiple sclerosis, even in early stage disease, with significant impacts on life quality and social interaction. However, its detection is highly test-dependent. OBJECTIVE: To validate a recently described screening tool, the ARCS, for detecting cognitive impairment in a multiple sclerosis population. METHODS: The ARCS administers tests of executive function, memory, visual spatial construction and language via an audio device to unsupervised patients who write their responses for later scoring. Some 127 patients with a wide variety of disease course and severity were assessed by ARCS, of whom 87 also completed the Paced Auditory Serial Addition Test (PASAT) and 45 underwent formal ('gold standard') neuropsychological testing. RESULTS: Compared with PASAT, we found that the ARCS showed better sensitivity (86% versus 68%) at equivalent specificity (71%) for detection of impairment in any cognitive domain, and superiority in the detection of memory and executive impairments. Acceptance and completion rates for the ARCS were as good or better than for the PASAT. CONCLUSIONS: ARCS is sensitive, well-tolerated, easy to administer and facilitates comprehensive cognitive assessment in less than 5 min of clinician time. It has several advantages over the PASAT for detecting cognitive impairment in patients with multiple sclerosis.

Association of subjective memory complaints with subsequent cognitive decline in community-dwelling elderly individuals with baseline cognitive impairment.

OBJECTIVE: The validity of subjective memory complaints has been questioned by clinical studies that have shown little relationship between memory complaints and objective memory performance. These studies often have been cross-sectional in design, have excluded individuals with cognitive impairment, or have lacked a comparison group. The authors conducted a study that attempted to avoid these limitations. METHOD: Memory complaints of 364 nondemented, community-dwelling elderly individuals were recorded as present or absent at the baseline evaluation. After 1 year, 169 subjects were reevaluated. Standardized neurologic and neuropsychological evaluations were used at each assessment to classify subjects as normal or cognitively impaired. RESULTS: At baseline, 31% of the normal subjects and 47% of those with cognitive impairment had memory complaints. Subjects with memory complaints had higher Hamilton depression scale scores than subjects without memory complaints but equivalent scores on a measure of total recall. At follow-up, multivariate analyses showed that subjects with baseline memory complaints had significantly greater decline in memory and cognition than subjects without memory complaints. Secondary analyses showed this effect to be confined to subjects with baseline cognitive impairment. CONCLUSIONS: Memory complaints may lack validity in subjects with normal cognition, but in nondemented individuals with cognitive impairment, memory complaints may predict subsequent cognitive decline.

The age at onset of Alzheimer's disease and an intracranial area measurement. A relationship.

OBJECTIVE: To examine the possibility that premorbid brain size may influence the age at onset of symptoms of Alzheimer's disease (AD). DESIGN: Retrospective case series. SETTING: Outpatients attending a memory disorders clinic in a tertiary referral center. PATIENTS: Twenty-eight female patients with the diagnosis of probable AD, selected for the availability of informant derived estimates of age at onset of symptoms and computed tomographic scans of the head satisfying angulation criteria. MAIN OUTCOME MEASURE: An average intracranial area of two adjacent computed tomographic scan sections appropriately angled was used as a correlate of premorbid brain size. Strict intracranial volume measurement was not performed. RESULTS: Age at onset of symptoms of AD correlated positively (r = .48, P = .009) with our measure of premorbid brain size. There was no confounding by education, height, or ethnicity. CONCLUSION: Premorbid brain size may be an important determinant of the age at onset of symptoms of AD. Epidemiologic studies of AD may need to assess the relationship between brain size and putative risk factors, eg, low educational attainment, since there is evidence that brain size is not distributed uniformly across populations.

The validity of new memory complaints in the elderly.

OBJECTIVE: To determine the validity of new subjective memory complaints (MCs) from individuals who previously, when without dementia, denied having MCs. DESIGN: Prospective cohort. SETTING: Longitudinal, community-based study of aging and dementia. PATIENTS: One hundred thirty-three community-dwelling elderly individuals who were part of a registry for the study of conditions related to aging in North Manhattan, NY. Patients were selected if they were initially without dementia and had completed at least 2 successive annual clinical and neuropsychological evaluations and provided their own medical history. MAIN OUTCOME MEASURES: Performance on memory tests--the Buschke Selective Reminding Test and a visual memory task--and global performance on a neuropsychological test battery and clinical evaluation, by which questionable dementia or dementia was diagnosed according to a well-defined paradigm. RESULTS: Fifty-three subjects with MCs at the initial evaluation performed no worse on the memory test than the 80 subjects who denied MCs initially. There was a weak association between MCs and the diagnosis of questionable dementia at baseline (P = .04), but this was nonsignificant after adjusting for age and education. At 1-year follow-up, 21 of the 80 without baseline MCs now reported MCs. At the follow-up evaluation, these 21 subjects performed significantly worse on the memory tests, were 5 times more likely to have significant cognitive impairment, and had shown significantly greater decline over the preceding year on several of the cognitive measures than the 59 who continued to deny MCs. CONCLUSION: New MCs from individuals, who when without dementia recently denied MCs, may suggest the presence of significant impairment of memory or cognition.

An association between head circumference and Alzheimer's disease in a population-based study of aging and dementia.

We investigated the association between head circumference (HC) and Alzheimer's disease (AD) in a cross-sectional population-based study of aging in North Manhattan. Six hundred forty-nine subjects underwent neurologic, neuropsychological, and anthropometric evaluations; apolipoprotein E (apoE) genotype was available for a subsample of 300 individuals. Logistic regression analyses were performed with AD the outcome of interest to evaluate any association between HC and AD. In these analyses, HC evaluated as a continuous variable was associated with AD (OR 0.8, 95% CI 0.7-0.9) after adjusting for age, education, and ethnicity, gender, and height. Analyses suggested that increased risk resided mainly in those with smallest HC. Thus, women whose HC was within the lowest quintile of HC for women were 2.9 (95% CI 1.4-6.1) times more likely to have AD, after adjusting for age, education, and ethnicity; and men in the lowest quintile of HC (for men) were 2.3 times more likely to have AD (95% CI 0.6-9.8). There was no confounding by height, weight, or apoE genotype. The results are consistent with previous studies that suggest that premorbid brain size may influence the age-specific risk for AD. Future epidemiologic studies seeking environmental risk factors for AD may benefit by making HC measurements on all subjects to decrease the variance associated with other potential risk factors.

Consistency of clinical diagnosis in a community-based longitudinal study of dementia and Alzheimer's disease.

We evaluated the consistency of the diagnosis of dementia in a multicultural, longitudinal community-based study of cognitive impairment and dementia. We diagnosed dementia using a fixed neuropsychological paradigm; the diagnosis also required historical evidence of functional impairment. In a sample of 656 subjects with at least one annual follow-up examination, dementia was confirmed at 1 year in 89% of the 304 subjects initially demented, and in 90% of the 136 subjects with the initial diagnosis of probable Alzheimer's disease (AD). The 34 initially demented subjects who failed to meet criteria for dementia at follow-up included 13 with an initial diagnosis of probable AD. All 34 still had evidence of cognitive impairment; this group was more likely to have a history of pulmonary disease, multiple medication use, or chronic alcohol use than other demented patients. Consistency of dementia diagnosis did not vary according to educational attainment or ethnic background. The use of a neuropsychological paradigm such as ours in large longitudinal studies of dementia may minimize interobserver diagnostic variability or diagnostic drift over time while contributing the benefits of a comprehensive cognitive evaluation to the diagnostic process.

A preliminary study of apolipoprotein E genotype and psychiatric manifestations of Alzheimer's disease.

We evaluated the frequency of depression and psychosis in 46 patients with AD and 135 control subjects with the apolipoprotein (APO) E3/3 or E3/4 genotype. Patients with AD and the APOE3/4 genotype had a more than threefold increase in the signs of depression and psychosis when compared with either patients with the APOE3/3 genotype or to control subjects. Our preliminary study suggests that the phenotype of AD associated with the epsilon 4 allele is more likely to include psychiatric manifestations.

Validity of family history for the diagnosis of dementia among siblings of patients with late-onset Alzheimer's disease.

We examined 180 siblings of 127 probands with probable or possible Alzheimer's dementia (AD) in a family study of AD. The overall sensitivity of a simple family history questionnaire was 64% and the specificity was 84%. Sensitivity improved 90-100% with minimal decline in specificity when we considered clinic-based vs. population survey patients. Higher education among informants and the availability of a spouse or a sibling as informant significantly increased sensitivity. Awareness of such factors may improve the yield of the family history in AD using a simple questionnaire.

Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus.

BACKGROUND: Most patients with pure nonprogressive congenital cerebellar ataxia have a sporadic form of unknown heredity and etiology. Several small families have been reported with a dominantly inherited nonprogressive congenital ataxia (NPCA). METHODS: The authors ascertained and clinically characterized a four-generation pedigree segregating an autosomal dominant type of congenital nonprogressive cerebellar ataxia associated with cognitive impairment. Following the exclusion of several SCA localizations (SCA-1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 17, IOSCA, and DRPLA), a genome-wide linkage study was performed. RESULTS: Examination of the family showed that all affected members had gait ataxia and cognitive disability with variable features of dysarthria, dysmetria, dysdiadochokinesia, nystagmus, dystonic movements, and cerebellar hypoplasia on imaging. Clinical signs of pyramidal tract dysfunction and sensory changes were absent. A genome-wide search in this family detected linkage to chromosome 3p with a maximum two-point lod score of 4.26 at D3S3630. This localization to the pter is distal to D3S1304, as defined by a recombination event. This overlaps with the SCA15 locus, with the critical overlapping region between the microsatellite markers, D3S1304 and D3S1620 (approximately 8 cM). CONCLUSION: Autosomal dominant congenital nonprogressive cerebellar ataxia with or without cerebellar hypoplasia overlaps with the SCA15 locus on chromosome 3pter.

Alzheimer's disease after remote head injury: an incidence study.

OBJECTIVE: To evaluate a history of remote head injury as a risk factor for subsequent dementia due to Alzheimer's disease. METHODS: 271 participants of a community based longitudinal study of aging in north Manhattan without evidence of significant cognitive impairment were interrogated for a history of head injury on two occasions at entry into the study. The examining physician sought a history of head injury with loss of conciousness. Independently, a risk factor interviewer inquired about a history of head injury with loss of consiousness or amnesia, the duration of any loss of consiousness, and the date of the head injury. Patients were followed up with standardised annual evaluations for up to five years to determine the first occurrence of dementia. RESULTS: Over the course of the study incident dementia due to probable or possible Alzheimer's disease was diagnosed in 39 patients. Cox proportional hazards modelling showed that a history of head injury with loss of consiousness reported to the physician was associated with earlier onset of dementia due to Alzheimer's disease (relative risk (RR) = 4.1, 95% confidence interval (95% CI) 1.3-12.7). head injury with loss of consiousness or amnesia reported to the risk factor interviewer was not significantly associated with earlier onset of Alzheimer's disease overall (RR 2.0, 95% CI 0.7-6.2), but those who reported loss of consiousness exceeding five minutes were at significantly increased risk (RR 11.2, 95% CI 2.3-59.8). Incident Alzheimer's disease was significantly associated with head injury which occurred within the preceding 30 years (RR 5.4, 95% CI 1.5-19.5). CONCLUSION: The results of this cohort study are consistent with the findings of several case-control studies suggesting that head injury may be a risk factor for Alzheimer's disease.