X-Message-Number: 30809 Date: Tue, 10 Jun 2008 09:31:53 -0700 (PDT) From: Subject: No disease in the brain of a 115-year-old woman [So much for inevitability of dementia.] Neurobiol Aging. 2008 Jun 3. [Epub ahead of print] Links Clinicopathologic correlates in the oldest-old Commentary on "No disease in the brain of a 115-year-old woman" Giannakopoulos P, Bouras C, Hof PR. Department of Psychiatry, University Hospitals of Geneva, 1225 Geneva, Switzerland; Service of Old Age Psychiatry, University of Lausanne School of Medicine, 1008 Prilly, Lausanne, Switzerland. den Dunnen et al. [den Dunnen, W.F.A., Brouwer, W.H., Bijlard, E., Kamphuis, J., van Linschoten, K., Eggens-Meijer, E., Holstege, G., 2008. No disease in the brain of a 115-year-old woman. Neurobiol. Aging] had the opportunity to follow up the cognitive functioning of one of the world's oldest woman during the last 3 years of her life. They performed two neuropsychological evaluations at age 112 and 115 that revealed a striking preservation of immediate recall abilities and orientation. In contrast, working memory, retrieval from semantic memory and mental arithmetic performances declined after age 112. Overall, only a one-point decrease of MMSE score occurred (from 27 to 26) reflecting the remarkable preservation of cognitive abilities. The neuropathological assessment showed few neurofibrillary tangles (NFT) in the hippocampal formation compatible with Braak staging II, absence of amyloid deposits and other types of neurodegenerative lesions as well as preservation of neuron numbers in locus coeruleus. This finding was related to a striking paucity of Alzheimer disease (AD)-related lesions in the hippocampal formation. The present report parallels the early descriptions of rare "supernormal" centenarians supporting the dissociation between brain aging and AD processes. In conjunction with recent stereological analyses in cases aged from 90 to 102 years, it also points to the marked resistance of the hippocampal formation to the degenerative process in this age group and possible dissociation between the occurrence of slight cognitive deficits and development of AD-related pathologic changes in neocortical areas. This work is discussed in the context of current efforts to identify the biological and genetic parameters of human longevity. PMID: 18534719 Neurobiol Aging. 2008 Jun 3. [Epub ahead of print] No disease in the brain of a 115-year-old woman. den Dunnen WF, Brouwer WH, Bijlard E, Kamphuis J, van Linschoten K, Eggens-Meijer E, Holstege G. Department of Pathology and Medical Biology, University Medical Centre Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Are there limits to the duration of high quality of life? Are there limits to healthy life for a human brain? We have had the opportunity to evaluate the performance of a 112-113-year-old woman and perform full pathological examination of her body immediately after death at the age of 115. The psychological tests revealed that her general performance was above average of healthy adults of 60-75 years. The pathological observations revealed almost no atherosclerotic changes throughout the body. In the brain almost no beta-amyloid plaques or vascular changes were found and only slight accumulation of hyperphosphorylated tau protein with a Braak-stage 2. Counts of the number of locus coeruleus neurons corresponded with the number of neurons found in the brains of healthy people of 60-80 years old. Our observations indicate that the limits of human cognitive function extends far beyond the range that is currently enjoyed by most individuals and that brain disease, even in supercentanarians, is not inevitable. PMID: 18534718 Neurobiol Aging. 2008 Jun 2. [Epub ahead of print] Links What does it take to stay healthy past 100? Commentary on "No disease in the brain of a 115-year-old woman" Price JL. Department of Anatomy & Neurobiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, United States. The description of an 115-year-old woman without dementia or Alzheimer's disease (AD) is remarkable, but fits well with previous accounts of aging and AD. Several similar non-demented cases aged 85-105 years have been reported previously, who had neurofibrillary tangles in the medial temporal lobe, but no deposition of amyloid plaques. Together with observations on other aging and very mild AD cases, these can be related to a model of aging and AD. In this model, tangles develop independently but relatively slowly during aging; these represent neurodegeneration, but by themselves may not represent AD. In contrast, amyloid may be the driving factor in AD, exacerbating neurofibrillary changes and other neurodegeneration. There is a pre-clinical period when the process has begun but has not produced sufficient degeneration to produce clinical symptoms. Critical questions raised by the present report include what genetic or other factors allowed healthy survival to age 115 year, and whether anti-amyloid therapies will allow more general survival in good mental health beyond age 100? PMID: 18524418 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=30809