Acta Neuropathologica

, Volume 123, Issue 1, pp 13–30 | Cite as

Mild cognitive impairment: pathology and mechanisms

  • Elliott J. Mufson
  • Lester Binder
  • Scott E. Counts
  • Steven T. DeKosky
  • Leyla deToledo-Morrell
  • Stephen D. Ginsberg
  • Milos D. Ikonomovic
  • Sylvia E. Perez
  • Stephen W. Scheff


Mild cognitive impairment (MCI) is rapidly becoming one of the most common clinical manifestations affecting the elderly. The pathologic and molecular substrate of people diagnosed with MCI is not well established. Since MCI is a human specific disorder and neither the clinical nor the neuropathological course appears to follow a direct linear path, it is imperative to characterize neuropathology changes in the brains of people who came to autopsy with a well-characterized clinical diagnosis of MCI. Herein, we discuss findings derived from clinical pathologic studies of autopsy cases who died with a clinical diagnosis of MCI. The heterogeneity of clinical MCI imparts significant challenges to any review of this subject. The pathologic substrate of MCI is equally complex and must take into account not only conventional plaque and tangle pathology but also a wide range of cellular, biochemical and molecular deficits, many of which relate to cognitive decline as well as compensatory responses to the progressive disease process. The multifaceted nature of the neuronal disconnection syndrome associated with MCI suggests that there is no single event which precipitates this prodromal stage of AD. In fact, it can be argued that neuronal degeneration initiated at different levels of the central nervous system drives cognitive decline as a final common pathway at this stage of the dementing disease process.


Alzheimer’s disease Amyloid Cholinergic Dementia MCI Neurofibrillary tangles Neuropathology Molecular Neurotrophins Synapses 



This study was supported by NIA grants PO1 AG14999, PO1 AG09466, AG10688 and AG025204. We thank all our collaborators and the participants in each Alzheimer’s Disease Center, institute and organization without whom the information reviewed would not have been possible.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Elliott J. Mufson
    • 1
  • Lester Binder
    • 2
  • Scott E. Counts
    • 1
  • Steven T. DeKosky
    • 3
  • Leyla deToledo-Morrell
    • 1
  • Stephen D. Ginsberg
    • 4
  • Milos D. Ikonomovic
    • 5
  • Sylvia E. Perez
    • 1
  • Stephen W. Scheff
    • 6
  1. 1.Department of Neurological SciencesRush University Medical CenterChicagoUSA
  2. 2.Department of Cell and Molecular BiologyFeinberg School of Medicine, Northwestern UniversityChicagoUSA
  3. 3.University of Virginia School of MedicineCharlottesvilleUSA
  4. 4.Departments of Psychiatry, Physiology and NeuroscienceCenter for Dementia Research, Nathan Kline Institute, New York University Langone Medical CenterOrangeburgUSA
  5. 5.Departments of Neurology, Psychiatry, and Geriatric Research Educational and Clinical CenterUniversity of Pittsburgh and VA Pittsburgh Healthcare SystemPittsburghUSA
  6. 6.Sanders Brown Center on AgingUniversity of KentuckyLexingtonUSA

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