Hayley P. Bennett

Gait slowing as a predictor of incident dementia: 6-year longitudinal data from the Sydney Older Persons Study

Current definitions for the preclinical phase of dementia focus predominantly on cognitive measures, with particular emphasis on memory and the prediction of Alzheimers disease. Incorporation of non-cognitive, clinical markers into preclinical definitions may improve their predictive power. The Sydney Older Persons Study examined 6-year outcomes of 630 community-dwelling participants aged 75 or over at recruitment. At baseline, participants were defined as demented, cognitively intact or having a syndrome possibly representing the preclinical phase of Alzheimers disease, vascular dementia, an extrapyramidal dementia or various combinations of the three. Those with cognitive impairment in combination with gait and motor slowing were the most likely to dement over the 6-year period (OR 5.6; 95% CI 2.5-12.6). This group was also the most likely to die (OR 3.3; 95% CI 1.6-6.9). White matter indices on MRI scanning were not consistently correlated with gait abnormalities. Simple measures of gait may provide useful clinical tools, assisting in the prediction of dementia. However, the underlying nature of these deficits is not yet known.

Health habits and risk of cognitive impairment and dementia in old age: a prospective study on the effects of exercise, smoking and alcohol consumption.

Previous research has yielded inconsistent results on the effects of exercise, smoking and alcohol use on cognitive impairment and dementia in old age. We analysed data from the Sydney Older Persons Study to see if these health habits were associated with cognitive functioning, dementia or Alzheimers disease. Health habits were assessed in Wave 1 of the study, when the subjects were aged 75 years or over. Three years later, the subjects were tested for cognitive functioning and clinically examined for dementia and Alzheimers disease. The analysis was restricted to the 327 subjects examined in Wave 2 who were non‐demented in Wave 1. There were few significant associations between health habits and cognitive performance and these were not found consistently across cognitive measures. No associations were found with dementia or Alzheimers disease. While these health habits do not affect risk for dementia and cognitive impairment in the very elderly, who are at highest risk for these disorders, we cannot discount a role at younger ages.

Vascular risk factors, cognition and dementia incidence over 6 years in the Sydney Older Persons Study.

The specific contributions of factors associated with an increased risk of stroke to cognitive decline and vascular dementia in elderly people remain somewhat unclear. We investigated the prevalence of vascular risk factors (RFs) and their role on the incidence of dementia, cognitive decline and death over a 6-year period in a sample of 377 non-demented community dwellers aged 75 years and over at the time of study entry. Presence and history of vascular RFs and cognitive decline over 6 years were ascertained using direct interviews, medical and cognitive examinations. Hypertension and history of heart disease were very common affecting about 50% of the participants. At 6 years, 114 (30%) participants had died, and 63 (16.7%) met diagnostic criteria for dementia. Hypertension was significantly associated with a greater cognitive decline but not with dementia. Smoking and stroke diagnosis showed a significant positive association with death. Reported hypercholesterolaemia was found to be associated with a protective effect for the development of dementia, for cognitive decline and for death over the 6-year period. All other associations were non-significant. Figures of dementia incidence are similar to previous studies in contrast to the lack of anticipated effects of the vascular RFs. The results indicate that in very old participants, the impact of vascular RFs changes with time and may no longer contribute to the development of dementia and cognitive decline.

Informant-based staging of dementia using the clinical dementia rating.

The staging of dementia is ideally based on both an examination of the patient and a history taken from an informant. However, in some circumstances, only an informant history is possible. The aim of this study was to assess the validity of the Clinical Dementia Rating (CDR) when the rating is based solely on informant data. The CDR was used in a study of 360 persons aged 78 or older who were participants in a community survey, the Sydney Older Persons Study. The CDR was completed in two ways: (1) a social scientist made the ratings based on an informant interview; and (2) a physician made the ratings after an examination of the subject. All CDRs were scored in the conventional way, as well as by the revised method proposed by Gelb and St. Laurent (Alzheimer Dis Assoc Disord 1993;4:202-11). The informant CDR showed moderate agreement with the clinician CDR, showing that it would be a valid substitute in situations in which the subject could not be examined. The revised scoring method was slightly easier to implement than the conventional method.

Subcortical Vascular Disease and Functional Decline: A 6‐Year Predictor Study

OBJECTIVES: To identify predictors of activity of daily living (ADL) and instrumental activity of daily living (IADL) decline in a population with subcortical vascular dementia (SVD) and to evaluate potential mechanism of decline.

Impact of chronic systemic and neurological disorders on disability, depression and life satisfaction

Objective. To assess the effects of a range of chronic systemic and neurological disorders on three life quality indicators: disability, depressive symptoms and life satisfaction.

Cortical degeneration associated with phonologic and semantic language impairments in AD.

Objective: To compare the pattern of cortical degeneration associated with different language deficits in cases of AD. Methods: Cases for detailed neuropathologic analysis (Patients 1 and 2) were selected because of their detailed clinical and neuropsychological assessments of language dysfunction in AD. Patient 1 had severe phonologic impairment with relatively preserved semantic aspects of language. Patient 2 had severe semantic language impairment with relatively preserved phonologic skills. The tissue volume of cortical regions associated with speech and language function was measured using standardized three-dimensional techniques. Neuronal areal fraction was also measured from histologic tissue samples. The degree of volume atrophy and neuronal loss was calculated in comparison to control measures (n = 10 men and 11 women). Measurements more than 2 SD from controls were considered abnormal. Results: Both AD cases had significant degeneration of the superior temporal gyrus and area 37. Cortical language regions affected only in Patient 1 included the anterior and posterior insula and part of Broca’s area. In contrast, Patient 2 had a greater degree of degeneration in the temporal gyri and their white matter connections with the hippocampal/entorhinal complex. Conclusions: Variable patterns of neurodegeneration underlie the clinical differences observed in patients with AD. Disconnection within the temporal lobe appears associated with semantic language difficulties, whereas disconnection of the anterior and posterior language areas appears associated with phonologic and grammatical impairment.

Cognitive, Extrapyramidal, and Magnetic Resonance Imaging Predictors of Functional Impairment in Nondemented Older Community Dwellers: The Sydney Older Person Study

Objectives: To identify the clinical correlates of functional incapacity in the community living “old‐old.”

Are MRI White Matter Lesions Clinically Significant in the ‘Old-Old’? Evidence from the Sydney Older Persons Study

Background: The number of individuals aged over 80 years is the fastest increasing group in developed countries. White matter lesions (WML) observed on magnetic resonance imaging (MRI) have uncertain clinical significance, particularly in the old. Objectives: To determine the prevalence of periventricular and deep WML in survivors of an original cohort of randomly selected elderly community dwellers, and to examine their associations with clinical markers of vascular and extrapyramidal disorders of ageing, as well as quantitative cognitive measures. Methods: Brain MRI, lifestyle interview, cognitive testing and medical examination were administered to 122 participants from the Sydney Older Persons Study 6-year review (mean age: 85.5 years). Apolipoprotein E (ApoE) genotype was also established. Presence and severity of periventricular and deep WML were ascertained using semi-quantitative rating methods and their relations to the cognitive and clinical variables investigated. Results: Periventricular WML were present in all participants in similar severity for all three regions sampled. In contrast, a gradient of severity was observed for the deep WML: most severe in the parietal region, followed by the frontal and occipital regions, and least severe in the temporal region. Associations with gender or with the ApoE Ε4 allele were non-significant. WML were inconsistently associated with age and cognitive functioning or with the clinical markers of dementia. No frontal specificity emerged. Examination of individual lesion types did not change the general pattern of associations. Supporting evidence for a threshold effect was observed on some measures. Conclusions: WML are extremely common in elderly, non-demented individuals. Unlike in younger individuals, MRI abnormalities may not be evidence of a current pathological process and their importance may change with advancing age.

Association of alleles carried at TNFA -850 and BAT1 -22 with Alzheimer's disease

BackgroundInflammatory changes are a prominent feature of brains affected by Alzheimers disease (AD). Activated glial cells release inflammatory cytokines which modulate the neurodegenerative process. These cytokines are encoded by genes representing several interleukins and TNFA, which are associated with AD. The gene coding for HLA-B associated transcript 1 (BAT1) lies adjacent to TNFA in the central major histocompatibility complex (MHC). BAT1, a member of the DEAD-box family of RNA helicases, appears to regulate the production of inflammatory cytokines associated with AD pathology. In the current study TNFA and BAT1 promoter polymorphisms were analysed in AD and control cases and BAT1 mRNA levels were investigated in brain tissue from AD and control cases.MethodsGenotyping was performed for polymorphisms at positions -850 and -308 in the proximal promoter of TNFA and position -22 in the promoter of BAT1. These were investigated singly or in haplotypic association in a cohort of Australian AD patients with AD stratified on the basis of their APOE ε4 genotype. Semi-quantitative RT-PCR was also performed for BAT1 from RNA isolated from brain tissue from AD and control cases.ResultsAPOE ε4 was associated with an independent increase in risk for AD in individuals with TNFA -850*2, while carriage of BAT1 -22*2 reduced the risk for AD, independent of APOE ε4 genotype. Semi-quantitative mRNA analysis in human brain tissue showed elevated levels of BAT1 mRNA in frontal cortex of AD cases.ConclusionThese findings lend support to the application of TNFA and BAT1 polymorphisms in early diagnosis or risk assessment strategies for AD and suggest a potential role for BAT1 in the regulation of inflammatory reactions in AD pathology.