George Dooneief

Neuropsychological detection and characterization of preclinical Alzheimer's disease

Article abstract—We attempted to characterize the changes in cognition associated with the earliest, or preclinical, stages of Alzheimers disease (AD) by administering a comprehensive neuropsychological test battery to a group of initially nondemented older adults participating in a prospective epidemiologic study of dementia. Using Cox regression analyses, we examined the associations between baseline neuropsychological test scores and subsequent development of AD. Results confirmed preliminary findings that baseline scores on the Boston Naming Test, Immediate Recall on the Selective Reminding Test, and the Similarities subtest of the Wechsler Adult Intelligence Scale-Revised were significantly and independently associated with later diagnosis of AD. Analyses controlled for the effects of age, education, sex, and language of test administration. These results lend support to the notion of a preclinical phase of AD and indicate that this very early stage of AD is characterized by poor word-finding ability, abstract reasoning, and memory.

Cognitive function in nondemented older women who took estrogen after menopause

Investigations of the effects of estrogen replacement on cognitive function in healthy older women have yielded disparate results. We evaluated the relationship between a history of estrogen use and cognitive test performance in 727 women participating in a large community-based study. Participants were followed longitudinally for an average of 2.5 years. Estrogen use history was obtained at baseline. Standardized tests of memory, language, and abstract reasoning were administered at baseline and at follow-up. Results indicate that women who had used estrogen replacement scored significantly higher on cognitive testing at baseline than nonusers, and their performance on verbal memory improved slightly over time. The effect of estrogen on cognition was independent of age, education, ethnicity, and APOE genotype. Results suggest that estrogen replacement therapy may help to maintain cognitive function in nondemented postmenopausal women.

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 Alzheimers 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 Alzheimers 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 Alzheimers 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 Alzheimers 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 Alzheimers 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 Alzheimers disease.

An estimate of the incidence of dementia in idiopathic Parkinson's disease

The proportion of patients with idiopathic Parkinsons disease (PD) who are considered demented ranges from 10% to 15%. Because dementia may affect survival in PD, the incidence rate of dementia, rather than proportion, would be a more accurate measure of disease frequency. We previously estimated the proportion of patients with PD and dementia to be 10.9% from the records of a cohort with the idiopathic form of PD in a major medical center. We reviewed the clinical records of this cohort after 4 years and 9 months to estimate the incidence rate of dementia. We identified 65 new cases of dementia from the 249 patient-records available. Using the number of person-years of follow-up for each case as the denominator, we estimated the overall incidence rate to be 69 per 1,000 person-years of observation. The mean age of this cohort was 71.4 years. The cumulative incidence of dementia increased with age. By 85 years of age, over 65% of the surviving members of the cohort were demented. The age-specific incidence rates for dementia in this cohort of PD were significantly greater than for a similarly aged cohort of healthy elderly people. The age-specific standard morbidity ratios indicated that, compared with people of similar ages, patients with PD have the highest increase in risk for dementia between ages 65 and 75.

Cross-cultural neuropsychological assessment: a comparison of randomly selected, demographically matched cohorts of English- and Spanish-speaking older adults.

As the US population of elderly Hispanics continues to grow, there is an increasingly greater need for neuropsychological measures that are appropriate for assessing Spanish-speaking elders. The current study compared the performance of randomly selected, community-based samples of English- and Spanish-speaking elders on a brief neuropsychological test battery. Subject groups were matched for age and education. Multivariate analysis indicated significant group differences on the test battery. English and Spanish speakers scored comparably on many language-based tasks, but Spanish speakers scored significantly lower on almost all of the nonverbal measures. Significant group differences were observed on multiple-choice matching and recognition memory for stimuli from the Benton Visual Retention Test, as well as on Identities and Oddities from the Mattis Dementia Rating Scale, category fluency, and Complex Ideational Material from the Boston Diagnostic Aphasia Examination (BDAE). Results suggest that caution is warranted when using nonverbal as well as verbal measures to assess non-English-speaking individuals.

Are demented patients with Parkinson's disease accurately reflected in prevalence surveys ? a survival analysis

We re-reviewed 257 patient records previously reviewed for an incidence study of dementia in Parkinsons disease (PD) to determine the frequency, date of death, and cause of death. We posited that if disease duration is shortened when dementia occurs, then dementia may be far more common than reflected in prevalence studies. There were 17 deaths among 65 demented patients and 28 deaths among 168 nondemented patients. When we matched a subset of the nondemented patients to the demented patients by age and disease duration distributions, the demented subjects had significantly more deaths (p < 0.02), and survival among demented subjects was decreased (p < 0.05). Dementia was a significant predictor of death in this sample. We conclude that dementia reduces survival in patients with PD. Incidence is a much better measure of dementia in PD than prevalence because shortened duration makes it less likely to detect dementia in prevalence surveys.

Neurologic Signs and Symptoms in a Cohort of Homosexual Men Followed for 4.5 Years

Article abstract—We traced the development of neurologic impairment in 207 homosexual men (123 human immunodeficiency virus [HIV]-positive and 84 HIV-negative controls) over 4.5 years of follow-up. We applied generalized estimating equations to logistic regression analyses with repeated measures to examine the differences between HIV-positive and HIV-negative subjects with respect to the likelihood of developing six neurologic outcomes derived from a factor analysis, significant neurologic impairment (modified Kurtzke disability score of ≥3), or significant neuropsycholog-ical impairment. We found that, over time, HIV-positive subjects were more likely to develop clinically significant ex-trapyramidal signs and frontal release signs than HIV-negative subjects. Controlling for age or education, as CD4 count declined, the odds of developing significant extrapyramidal signs, abnormalities in alternating movements, frontal release signs, and a Kurtzke score ≥3 increased. HIV-positive subjects were almost five times as likely (odds ratio [OR], 4.6; 95% CI, 1.6 to 13.4) as HIV-negative subjects to stay the same or worsen neurologically on the next visit, and those with CD4 ≥200 were 4.8 times as likely (OR, 4.8; 95% CI, 2.2 to 10.7) to maintain or worsen neurologically relative to those with higher CD4 counts. We conclude that neurologic impairment becomes increasingly apparent over time in HIV-infected men, especially in those with low CD4 counts.

Neurologic consequences of HTLV-II infection in injection-drug users

Several case reports have suggested an association between human T-cell lymphotropic virus type II (HTLV-II) infection and chronic neurologic disease. We performed serial neurologic examinations in injection-drug users (IDU), a group known to be at increased risk for HTLV-II infection. At baseline, those infected with HTLV-II alone, human immunodeficiency virus (HIV) alone, or both were significantly more likely to have neurologic disability than uninfected subjects. Longitudinally, HTLV-II infection was independently associated with the development of global neurologic disability and neuropathy, suggesting that HTLV-II causes neurologic disease. NEUROLOGY 1996;46: 1556-1560

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 Alzheimers 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. NEUROLOGY 1995;45: 2159-2164

Patterns of neuropsychological performance in Alzheimer's disease patients with and without extrapyramidal signs

We investigated the relationship between extrapyramidal signs (EPS) and the cognitive function in 90 patients meeting NINCDS-ADRDA criteria for probable Alzheimers disease (AD) by dividing them into those showing no evidence of EPS and those showing at least one EPS on the Unified Parkinsons Disease Rating Scale. Cognitive function was assessed by neuropsychological tests of verbal memory, orientation, abstract reasoning, language, and construction. Patients with EPS were significantly more impaired than patients without EPS on tests of short-term learning and memory, orientation, naming, verbal fluency, and construction, but not on tests of long-term memory, abstract reasoning, or verbal comprehension. These results could not be explained by any differences in age, education, or disease duration between the groups. Since this pattern of neuropsychological impairment resembles that of patients with Parkinsons disease and other EPS syndromes, we hypothesize that EPS are associated with neuropathologic and neuropsychological changes that are superimposed over the classic features of AD.