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      Call for Papers: Sex and Gender in Neurodegenerative Diseases

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      Increased Neurofibrillary Tangles in the Brains of Older Pedestrians Killed in Traffic Accidents

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          Abstract

          Background/Aims: Older people are over-represented in pedestrian fatalities, and it has been suggested that the presence of cognitive impairment or dementia in these individuals may contribute to their accidents. Using neuropathological methods, we aimed to compare the prevalence of dementia pathology in fatally injured older pedestrians with similarly aged ambulatory subjects who died from other causes. Methods: The brains of 52 pedestrians (65–93 years) and 52 controls (65–92 years) were assessed for neurofibrillary tangles (NFT), neuritic plaques, Lewy bodies and vascular lesions using established neuropathological criteria. Results: The examination for Alzheimer’s disease (AD) pathology showed that 43% of the pedestrians had NFT scores of III–VI using Braak and Braak staging, compared with 23% of the controls (p < 0.05, Fisher’s exact test), indicating incipient, possible or probable AD. There were no differences in the prevalence of pathology for vascular dementia or dementia with Lewy bodies. Conclusion: These results suggest that cognitive decline associated with AD, even in the earliest stages of the disease, may be a factor in fatal traffic accidents for older pedestrians. Special measures for pedestrian safety are necessary in areas with high densities of older citizens and especially for those diagnosed as having a mild cognitive impairment or AD.

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          Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment.

          Sandra Weintraub, M. Marcel Mesulam, A L Guillozet-Bongaarts … (2003)
          Large numbers of neurofibrillary tangles (NFTs) and amyloid plaques are diagnostic markers for Alzheimer disease (AD), but lesser numbers of these lesions are also seen in nondemented elderly individuals. Much of the existing literature suggests that the NFTs of AD have a closer correlation with cognitive function than do amyloid plaques. Whether a similar relationship exists in normal aging and mild cognitive impairment (MCI), a condition that frequently reflects a preclinical stage of AD, remains unknown. To determine the distribution patterns of beta-amyloid plaques and NFTs and the association of these lesions with memory performance in nondemented individuals. We investigated regional distributions and neuropsychological correlates of NFTs and amyloid plaques in cognitively normal elderly persons and subjects with MCI who received neuropsychological testing before death. Subjects Eight nondemented subjects who volunteered to receive annual neuropsychological testing and agreed to brain donation were studied. Five subjects showed no cognitive impairment, and 3 were diagnosed with MCI. Distribution of NFTs followed a rigorous and hierarchical pattern, but distribution of amyloid plaques varied among individuals. Subjects with MCI displayed higher NFT densities than did nonimpaired subjects. In addition, NFT density in the temporal lobe correlated with memory scores, whereas density of amyloid plaques did not. Neurofibrillary tangles are more numerous in medial temporal lobe regions associated with memory function and show a relationship to performance on memory tests in nondemented individuals. These results suggest that NFTs may constitute a pathological substrate for memory loss not only in AD but also in normal aging and MCI.
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            Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study.

            Kathryn P. Riley, David Snowdon, William R Markesbery (2002)
            The development of interventions designed to delay the onset of dementia highlights the need to determine the neuropathologic characteristics of individuals whose cognitive function ranges from intact to demented, including those with mild cognitive impairments. We used the Braak method of staging Alzheimer's disease pathology in 130 women ages 76-102 years who were participants in the Nun Study, a longitudinal study of aging and Alzheimer's disease. All participants had complete autopsy data and were free from neuropathologic conditions other than Alzheimer's disease lesions that could affect cognitive function. Findings showed a strong relationship between Braak stage and cognitive state. The presence of memory impairment was associated with more severe Alzheimer's disease pathology and higher incidence of conversion to dementia in the groups classified as having mild or global cognitive impairments. In addition to Braak stage, atrophy of the neocortex was significantly related to the presence of dementia. Our data indicate that Alzheimer's neurofibrillary pathology is one of the neuropathologic substrates of mild cognitive impairments. Additional studies are needed to help explain the variability in neuropathologic findings seen in individuals whose cognitive performance falls between intact function and dementia.
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              Incidence and prevalence of dementia in the Cardiovascular Health Study.

              William Jagust, G Ives, John Breitner … (2004)
              To estimate the incidence and prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in the Cardiovascular Health Study (CHS) cohort. Longitudinal cohort study using prospectively and retrospectively collected data to evaluate dementia. Four U.S. communities. There were 3,602 CHS participants, including 2,865 white and 492 African-American participants free of dementia, who completed a cranial magnetic resonance image between 1992 and 1994 and were followed for an average of 5.4 years. Dementia was classified by neurologist/psychiatrist committee review using neuropsychological tests, neurological examinations, medical records, physician questionnaires, and proxy/informant interviews. Demographics and apolipoprotein E (APOE) genotype were collected at baseline. Incidence by type of dementia was determined using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD and Alzheimer's Disease Diagnostic and Treatment Center's State of California criteria for VaD. Classification resulted in 227 persons with prevalent dementia at entry into the study and 480 incident cases during follow-up. Incidence rates of dementia scaled to age 80 were 34.7 per 1,000 person-years for white women, 35.3 for white men, 58.8 for African-American women, and 53.0 for African-American men. Sex differences were not significant within race. Adjusted for age and education, racial differences were only of borderline significance and may have been influenced by ascertainment methodology. Rates differed substantially by educational attainment but were only significant for whites. Those with the APOE epsilon4 allele had an incidence rate at age 80 of 56.4, compared with 29.6 for those without this allele (P<.001). In whites, type-specific incidence at age 80 was 19.2 for AD versus 14.6 for VaD. These rates were 34.7 and 27.2 for African Americans. At termination of observation, women had only a slightly higher prevalence of dementia (16.0%) than men (14.7%). Sex and racial differences were not found, and VaD was higher than reported in other studies. These data provide new estimates of dementia incidence in a community sample for projection of future burden.
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                Author and article information

                Journal
                Journal ID (publisher-id): DEM
                Journal ID (nlm-ta): Dement Geriatr Cogn Disord
                Journal ID (doi): 10.1159/issn.1420-8008
                Title: Dementia and Geriatric Cognitive Disorders
                Publisher: S. Karger AG
                ISSN (Print): 1420-8008
                ISSN (Electronic): 1421-9824
                Publication date Subscription-year: 2006
                Publication date (Print): June 2006
                Publication date (Electronic): 19 June 2006
                Volume: 22
                Issue: 1
                Pages: 20-26
                Affiliations
                aNeural Injury Research Unit, School of Medical Sciences, and bSchool of Psychiatry, University of New South Wales, cDepartment of Forensic Medicine, Central Sydney Laboratory Services, and dNeuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia
                Article
                Publisher ID: 93066 Other ID: Dement Geriatr Cogn Disord 2006;22:20–26
                DOI: 10.1159/000093066
                PubMed ID: 16679761
                SO-VID: b8cafdce-20aa-435d-8309-28bbec84367e
                Copyright © © 2006 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 03 December 2005
                Page count
                Figures: 1, Tables: 2, References: 39, Pages: 7
                Categories
                Subject: Original Research Article

                ScienceOpen disciplines: Geriatric medicine,Neurology,Cardiovascular Medicine,Neurosciences,Clinical Psychology & Psychiatry,Public health
                Keywords: Neuritic plaques,Alzheimer’s disease, autopsy,Neurofibrillary tangles,Pedestrian, elderly
                Data availability:
                ScienceOpen disciplines: Geriatric medicine, Neurology, Cardiovascular Medicine, Neurosciences, Clinical Psychology & Psychiatry, Public health
                Keywords: Neuritic plaques, Alzheimer’s disease, autopsy, Neurofibrillary tangles, Pedestrian, elderly

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