Jicha GA, Parisi JE, Dickson DW, Johnson K, Cha R, Ivnik RJ, Tangalos EG, Boeve BF, Knopman DS, Braak H, Petersen RC. Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia. Arch Neurol. 2006 May;63(5):674-81. PubMed.

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  1. The number of patients with mild cognitive impairment (MCI) is increasing and many of them are referred to memory clinics. The cognitive decline in MCI is greater than in normal aging, but the clinical characteristics are heterogeneous and some people may return to normal. It is, therefore, a challenge to detect subgroups that represent a prodromal stage of Alzheimer disease (AD). In two recent papers, Petersen et al. present the histopathology of some MCI cases that remain as MCI subjects or progress to clinical dementia. The advantage of this study is that the interval between the last clinical investigation (including cognitive tests) and death is fairly short (0.72 years), but the drawback is that the subjects are very old (88.9 years). The neuropathological investigations showed that, with respect to various types of plaques, the amnestic MCI subjects (aMCI) more resembled healthy individuals than AD patients. This contrasts recent in vivo amyloid imaging findings using Pittsburgh compound B (PIB) in MCI patients, where high PIB retentions, similar to AD patients, were measured in MCI patients (1,2,3). These observations might represent differences in plaque properties in different courses of the disease as well as age and/or ApoE genotype properties.

    In the second paper from Petersen’s group, Jicha et al. studied the pathological outcome of progression of MCI to dementia in 34 subjects. The majority of aMCI patients progressed to both clinical and pathological AD (19 out of 24 subjects). If in vivo imaging will reveal high amyloid load in aMCI patients, amyloid imaging might be a promising diagnostic technique. The papers by Petersen et al. stress the importance of postmortem follow-up studies of patients undergoing amyloid imaging. By combining data from in vivo and autopsy studies, as well as CSF analysis, we will obtain a deeper insight into the pathophysiological mechanism of AD.

    See also:

    DeKosky ST, Mathis CA, Price JC et al. Human amyloid imaging studies with Pittsburgh compound-B in mild cognitive impairment (MC): Is MCI the critical period of amyloid plaque deposition? AAN San Diego 2006: S01.004

    References:

    Lopresti BJ, Klunk WE, Mathis CA, Hoge JA, Ziolko SK, Lu X, Meltzer CC, Schimmel K, Tsopelas ND, Dekosky ST, Price JC. Simplified quantification of Pittsburgh Compound B amyloid imaging PET studies: a comparative analysis. J Nucl Med. 2005 Dec;46(12):1959-72. PubMed.

    Nordberg A, Forsberg A, Engler H. Amyloid imaging in MCI patients. Neurobiol Aging 2006; 27(Suppl 1):S6.

    View all comments by Agneta Nordberg

  2. These studies confirm the confusion that developed over the years that AD and AD with dementia are the same issue. Progression to AD with dementia is a separate issue from Braak stage. A growing number of autopsy studies confirm the findings of the Nun Study that brain atrophy, i.e. brain cell death, is the key issue in AD with dementia. Forty-four percent of the nondemented group of the 33 religious sisters studied by Grosch et al. met the AD neuropathological criteria upon autopsy at ages ranging from 88 to 93. Hippocampal volume was the primary variable in determining whether a person had just AD with near normal cognition or AD with dementia. Much is known about the environmental, nutritional, social and medical factors that effectively kill brain cells: e.g. folic acid deficiency, aluminum overload, strokes, etc. The research community needs to throw a much wider net beyond Braak stage, to integrate epidemiology, nutrition, toxicology, etc., so that prevention and therapy programs can be developed to assist the patients. We have recently proposed software for this purpose.

    References:

    Gosche KM, Mortimer JA, Smith CD, Markesbery WR, Snowdon DA. Hippocampal volume as an index of Alzheimer neuropathology: findings from the Nun Study. Neurology. 2002 May 28;58(10):1476-82. PubMed.

    Jansson ET. Alzheimer disease is substantially preventable in the United States -- review of risk factors, therapy, and the prospects for an expert software system. Med Hypotheses. 2005;64(5):960-7. PubMed.

    View all comments by Erik Jansson

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