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

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