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Gregory A. Jicha, MD, PhD; Joseph E. Parisi, MD; Dennis W. Dickson, MD; Kris Johnson, RN; Ruth Cha, MS; Robert J. Ivnik, PhD; Eric G. Tangalos, MD; Bradley F. Boeve, MD; David S. Knopman, MD; Heiko Braak, MD; Ronald C. Petersen, PhD, MD

Arch Neurol. 2006;63:674-681.

Background  The pathologic outcome of patients diagnosed with mild cognitive impairment (MCI) following progression to dementia is poorly understood.

Objective  To determine the pathologic substrates of dementia in cases with prior diagnosis of amnestic MCI.

Design and Setting  Community-based cohort.

Patients  Thirty-four subjects followed up prospectively as part of a community-based study who were diagnosed with amnestic MCI, progressed to clinical dementia, and underwent subsequent postmortem brain analysis.

Main Outcome Measures  Neuropathologic analyses resulted in assignment of a primary pathologic diagnosis and included staging of Alzheimer pathologic abnormalities and identification of contributing vascular disease, Lewy bodies, and argyrophilic grains.

Results  Although the majority of subjects progressed both clinically and pathologically to Alzheimer disease (AD), 10 (29%) of them developed non-AD primary pathologic abnormalities. All of the cases were found to have sufficient pathologic abnormalities in mesial temporal lobe structures to account for their amnestic symptoms regardless of the cause. Most subjects were found to have secondary contributing pathologic abnormalities in addition to primary pathologic diagnoses. No significant differences between subjects with and without neuropathologically proven AD were detected in demographic variables, apolipoprotein E genotype, or cognitive test measures at onset of MCI, onset of dementia, or last clinical evaluation.

Conclusions  The neuropathologic outcome of amnestic MCI following progression to dementia is heterogeneous, and it includes AD at a high frequency. Complex neuropathologic findings including 2 or more distinct pathologic entities contributing to dementia may be common in community-based cohorts. Neither demographic variables nor cognitive measures had predictive value in determining which patients diagnosed with MCI will develop the neuropathologic features of AD.

Author Affiliations: Alzheimer's Disease Research Center (Drs Jicha, Parisi, Ivnik, Tangalos, Boeve, Knopman, and Petersen and Ms Johnson), Departments of Neurology (Drs Jicha, Boeve, Knopman, and Petersen), Laboratory Medicine and Pathology (Dr Parisi), Psychiatry and Psychology (Dr Ivnik), and Internal Medicine (Dr Tangalos), and Health Sciences Research (Ms Cha), Mayo Clinic, Rochester, Minn; Alzheimer's Disease Research Center and Department of Neurosciences, Mayo Clinic, Jacksonville, Fla (Dr Dickson); and Institute for Clinical Neuroanatomy, J. W. Goethe University, Frankfurt/Main, Germany (Dr Braak).

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