Population variation in oxidative stress and astrocyte DNA damage in relation to Alzheimer-type pathology in the ageing brain

Increasing evidence suggests a role for oxidative damage to DNA in brain ageing and in neurodegenerative disorders, including Alzheimer's disease. Most studies have focussed on the reduced capacity for DNA repair by neurones, and have not taken into account the effect of oxidative stress on astrocytes, and their contribution to pathology

Hippocampal tau pathology is related to neuroanatomical connections: an ageing population-based study

Deposits of abnormally phosphorylated tau protein are found in numerous neurodegenerative disorders; the 'tauopathies', which include Alzheimer's and Pick's diseases, but tau pathology is also found in the ageing brain. Variation in tau pathology in brain ageing and its relationship to development of tauopathies and cognitive impairment remains unclear. We aimed to determine the extent and pattern of spread of tau pathology in the hippocampus, a susceptible region important in dementia and milder states of memory impairment, using hippocampal samples from the elderly population-based Medical Research Council Cognitive Function and Ageing Study neuropathology cohort. Tau deposition was assessed in hippocampal anatomical sub-regions using the AT8 antibody to phosphorylated tau and isoform-specific antibodies to 3 and 4-repeat tau (RD3 and RD4). Abeta pathology was also assessed. In this population sample, which includes the full ageing spectrum from individuals with no cognitive impairment to those with dementia satisfying clinico-pathology criteria for Alzheimer's disease, we have demonstrated a high prevalence at death of tau pathology. AT8, Abeta, RD3 and RD4 showed similar regional distribution and increased RD3 was noted in late-stage ghost tangles. Abeta was shown to be a poor explanatory variable for tau pathology. Tau deposition progressed in a hierarchical manner. Hippocampal input regions and projection zones (such as lateral entorhinal cortex, CA1/subiculum border and outer molecular layer of dentate) were initially affected, with anterograde progression though the hippocampal circuitry. Six hippocampal tau anatomical stages were defined, each linking projectionally to their adjacent stages, suggesting spread of tau malfunction through neuroanatomical pathways in hippocampal ageing. These stages were significantly associated with dementia, and may provide a clinically useful tool in the clinico-pathological assessment of dementia and mild cognitive impairment

Neuropsychological tests for the diagnosis of Alzheimer’s disease dementia and other dementias: a generic protocol for cross-sectional and delayed-verification studies

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the cross-sectional diagnostic accuracy of [index test] at various thresholds for ADD and other dementias [target condition] in [target population].ORTo determine the accuracy of [index test] at various thresholds for diagnosing ADD and other dementias [target condition] in [target population] after a follow-up period (delayed-verification studies).To investigate the heterogeneity of test accuracy in the included studies.To highlight the quality and quantity of research evidence available on the effectiveness of the index test in the target population.To identify gaps in the evidence and determine where further research is required

Vascular Care in Patients with Alzheimer's Disease with Cerebrovascular Lesions-A Randomized Clinical Trial

OBJECTIVES: To investigate whether vascular care slows dementia progression in patients with Alzheimer's disease with cerebrovascular lesions on neuroimaging. DESIGN: Multicenter randomized controlled clinical trial with 2-year follow-up. SETTING: Neurological and geriatric outpatient clinics in 10 Dutch hospitals: three academic, five teaching, and two midsize community hospitals. PARTICIPANTS: One hundred thirty community-dwelling patients with mild dementia fulfilling clinical criteria for Alzheimer's disease with cerebrovascular lesions on neuroimaging. INTERVENTION: Patients randomized to vascular care were treated according to strict guidelines for hypercholesterolemia and hypertension. Acetylsalicylic acid, folic acid, and pyridoxine were prescribed. During visits every 3 months special attention was paid to smoking cessation, losing weight, and stimulating physical exercise. MEASUREMENTS: Primary outcome was disability, measured according to the Interview for Deterioration in Daily activities in Dementia (IDDD). Secondary outcomes were changes on the Mini-Mental State Examination (MMSE), the Revised Memory and Behavioural Problems Checklist (RMBPC), a composite measure of "poor outcome" (death, institutionalization, or severe clinical decline), and costs. RESULTS: Patients in the vascular and standard care condition declined equally on the IDDD (13.7 vs 11.0 points; difference 2.7, 95% confidence interval = -3.1-8.6). There was no treatment effect on the MMSE or RMBPC. There were no differences in institutionalization rate, "poor outcome" (41.4% vs 35.4%, P=.50), or costs. In the intervention group, there were three intracerebral hemorrhages and one gastrointestinal hemorrhage, versus none in the control group. CONCLUSION: Multicomponent vascular care, combining pharmacological and nonpharmacological interventions, does not slow decline in patients with Alzheimer's disease with cerebrovascular lesion