Graham Ratcliff

Cognitive tests that best discriminate between presymptomatic AD and those who remain nondemented

Objective: To identify the most accurate cognitive measures in discriminating between individuals with presymptomatic AD and individuals who remained nondemented. Methods: During a 10-year prospective community study, 120 nondemented subjects completed a battery of standard cognitive tests and clinically manifested AD 1.5 years later. Performance on each of 16 cognitive tests was compared between these 120 presymptomatic cases and 483 controls who remained nondemented over the 10-year follow-up period. The area under the receiver operating characteristic (AUC) curve for each test was used to measure its accuracy of discrimination between cases and controls. Results: Among the 16 neuropsychological tests, Word List Delayed Recall discriminated best between cases and controls (AUC = 0.806), followed by the Word List 3rd Learning Trial (0.787), Word List 1st Learning Trial (0.774), and Trail-making Test B (0.773), compared to the Mini-Mental State Examination (MMSE) (0.726). Both Word List Delayed Recall and Word List 3rd Learning Trial were significantly more accurate than the MMSE. The combination of Word List Delayed Recall and Trail-making Test B comprised the optimal set of cognitive measures, with the highest AUC (0.852). Conclusion: Measures of delayed recall and executive functions were the best discriminators between those who would manifest AD 1.5 years later and those who would remain nondemented. These findings are relevant for the early detection of AD and, therefore, for prevention and early intervention trials. Executive dysfunction may be a subtle manifestation of incipient AD, along with memory dysfunction.

Factors associated with perceived quality of life many years after traumatic brain injury.

Objectives:To explore factors associated with perceived quality of life (QOL) 8 to 24 years after traumatic brain injury (TBI). Design:Retrospective cohort study. Participants:Two hundred seventy-five individuals who sustained moderate to severe TBI who were discharged from a rehabilitation hospital participated in this study. We interviewed consenting participants up to 24 years after injury. Outcome Measures:Self-rated Quality of Life Scale. Results:Multivariate linear regression analyses revealed that perceived mental health, self-rated health, gender (women rating QOL higher), participation in work and leisure, and the availability of emotional support were significantly associated with QOL (P < .05). Conclusion:The importance of designing ongoing support programs to further reintegrate TBI survivors several years after injury is discussed.

Relation of education to brain size in normal aging: implications for the reserve hypothesis.

Objective: To examine the relations between education and age-related changes in brain structure in a nonclinical sample of elderly adults. Background: Education may protect against cognitive decline in late life—an observation that has led to the “reserve” hypothesis of brain aging. Little is known, however, about the effect of education on age-related changes in brain structure. Methods: Quantitative MRI of the brain was performed in 320 elderly volunteers (age range, 66 to 90 years) living independently in the community (Mini-Mental State Examination scores ≥ 24), all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images using computer-assisted edge detection and trace methodology. High measurement reliabilities were obtained. Results: Regression analyses (adjusting for the effects of intracranial size, sex, age, age-by-sex interactions, and potential confounders) revealed significant main effects of education on peripheral (sulcal) CSF volume—a marker of cortical atrophy. Each year of education was associated with an increase in peripheral CSF volume of 1.77 mL (p < 0.03). As reported previously, main effects of age (but not education) were observed for all of the remaining brain regions examined, including cerebral hemisphere volume, frontal region area, temporoparietal region area, parieto-occipital region area, lateral (Sylvian) fissure volume, lateral ventricular volume, and third ventricle volume. Conclusions: The authors’ findings demonstrate a relation between education and age-related cortical atrophy in a nonclinical sample of elderly persons, and are consistent with the reserve hypothesis as well as with a small number of brain imaging studies in patients with dementia. The neurobiological basis and functional correlates of this education effect require additional investigation.

Effects of Age, Gender, and Education on Cognitive Tests in a Rural Elderly Community Sample: Norms from the Monongahela Valley Independent Elders Survey

A random sample of 1,350 persons aged 65 years and older in a rural community underwent cognitive screening as part of a survey to establish a population-based registry of dementing disorders. The screening battery included the neuropsychological tests of the assessment protocol used in the National Institute on Aging multicenter Consortium to Establish a Registry for Alzheimers Disease (CERAD). This paper reports a large body of normative neuropsychological data from this sample with members of relatively low socioeconomic status. Age, sex, and educational level were found to have statistically significant effects on test scores. The implications of these findings for the establishment of screening cutoff scores are discussed.

Long term outcomes after moderate to severe traumatic brain injury

Objective: This research examined the long-term outcomes of rehabilitation patients with moderate to severe traumatic brain injury (TBI). Design: Retrospective cohort study. Setting and subjects: We examined consecutive records of persons with moderate to severe traumatic brain injury who were discharged from a large rehabilitation hospital in Pennsylvania from 1973 to 1989. We interviewed consenting participants (n = 306) up to 24 years post-injury. Main outcome measures: Self-rated health, activity limitations, employment, living arrangements, marital status, Community Integration Questionnaire, and use of rehabilitation services. Results: Participants were most limited in activities such as managing money and shopping. Twenty-nine per cent of our participants were working full time. There were significant relationships between activity limitations and residual cognitive impairment at follow-up. Self-rated health was correlated with most instrumental activities of daily living. Conclusion: Our findings document health and function in a large post acute TBI population and implications for rehabilitation are discussed.

Preclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset.

Objective: To determine if individuals ultimately diagnosed with Alzheimer disease (AD) exhibited evidence of cognitive impairment on neuropsychological tests administered between 1.5 years and 8.1 years before dementia onset. Methods: A total of 693 community-dwelling individuals, part of the Cardiovascular Health Study, completed a neuropsychological test battery in 1991/92. Subjects were followed annually over the next 8 years (median follow-up = 7.4 years). Seventy-two individuals were ultimately diagnosed with AD (median follow-up = 4.5 years): 24 with AD onset 1.5 to 3.4 years after baseline neuropsychological testing, 20 with AD onset 3.5 to 5.0 years after testing, and 28 with onset 5.1 to 8.1 years after testing. A total of 621 individuals remained nondemented throughout the 8 years of follow-up (median follow-up = 7.5 years). Results: Subjects ultimately diagnosed with AD had poorer scores on baseline neuropsychological measures than subjects who remained nondemented. Although individuals closest to AD onset (i.e., 1.5 to 3.4 years) performed the most poorly, cognitive impairment was detected in individuals who did not develop AD until 5 to 8 years later. Conclusions: Cognitive changes can be detected well before onset of Alzheimer disease.

Category-specificity and modality-specificity in semantic memory

Studies of agnosia have revealed two apparently orthogonal dimensions along which knowledge may break down. In some cases, knowledge of specific categories (such as living things) seems lost, regardless of the modality being tested. In other cases, knowledge in specific modalities (such as vision) seems lost, regardless of the category of stimuli being tested. These different sets of phenomena suggest different organizations for knowledge in the brain, the first by category and the second by modality. Unfortunately, possible confoundings between category, modality, and difficulty level in the previous studies prevent us from drawing strong conclusions from these data. The present study was aimed at assessing the nature of the breakdown in the semantic memory of a prosopagnosic patient, by orthogonally varying category and modality, while assessing difficulty level. The findings do not implicate a simple categorical or modality-dependent organization of his knowledge, but rather an organization in which both category and modality play a role.

Cognitive Test Performance in a Community-Based Nondemented Elderly Sample in Rural India: The Indo-U.S. Cross-National Dementia Epidemiology Study

Interpretation of cognitive test performance among individuals from a given population requires an understanding of cognitive norms in that population. Little is known about normative test performance among elderly illiterate non-English-speaking individuals. An age-stratified random sample of men and women, aged 55 years and older, was drawn from a community-based population in the rural area of Ballabgarh in northern India. These Hindi-speaking individuals had little or no education and were largely illiterate. A battery of neuropsychological tests, specially adapted from the CERAD neuropsychological battery, which was administered to this sample, is described. Subjects also underwent a protocol diagnostic examination for dementia. Norms for test performance of 374 nondemented subjects on these tests are reported across the sample and also by age, gender, and literacy.

Effects of Literacy and Education on Measures of Word Fluency

As part of a cross-national study of dementia epidemiology, two types of verbal fluency tasks were administered to three groups of subjects, varying in level of literacy and education, recruited from the rural district of Ballabgarh in northern India. Subjects were asked to list items in a given semantic category (animals; fruits) or words beginning with a given sound (the phonemes /p/ and /s/) the latter being a minor modification of the more familiar initial letter fluency task in view of the high prevalence of illiteracy in Ballabgarh. Analysis of variance revealed main effects of education and task with a task by education interaction such that education had a greater effect on initial sound fluency than on category fluency. The results are discussed in terms of their implication for the design of cross-cultural studies and the evidence that the ability to segment speech into phonemic units is dependent on literacy.

Prediction of long-term occupational performance outcomes for adults after moderate to severe traumatic brain injury

Purpose. To examine predictors of long-term occupational performance outcomes for adults after moderate to severe traumatic brain injury (TBI). Method. This study involved analysis of data from a retrospective cohort of adults (N = 306) with moderate to severe TBI discharged from a Pennsylvania rehabilitation treatment facility. Extensive pre-injury sociodemographic, injury-severity, post-injury personal (cognitive, physical, affective), post-injury environmental (social, institutional, physical), and post-injury occupational performance (participation in self-care, productivity, leisure activities) data were gathered from hospital records and using in-person interviews. Interviews occurred at a mean time of 14 (range, 7–24) years post-injury. Hierarchical multiple regression analysis was used to investigate determinants of long-term occupational performance outcomes. Results. Pre-injury behavioural problems, male gender, post-injury cognitive and physical deficits, and lack of access to transportation were significant independent predictors of worse occupational performance outcomes. Conclusions. The study supports the use of a comprehensive model for long-term outcomes after TBI where pre-injury characteristics and post-injury cognitive and physical characteristics account for the greatest proportion of explained variance.