SUPPLEMENTARY APPENDIX 1: SYSTEMATIC REVIEW METHODS
Search Strategy Papers were identified by searches of EMBASE and Medline (1966 to 26
August 2010) with the search terms (("mild cognitive impairment" OR MCI OR preclinical
OR prodrom* OR "early stage") AND (pathology OR neuropath* OR clinicopath*)). Articles
published online ahead of print, secondary references and review articles were also retrieved.
There were no limits on the study population (clinic vs. population-based) or the case
definition of MCI, if clearly described and representing an intermediate cognitive state.
Exclusion Criteria As the aim was to include all published papers that had investigated the
neuropathological profile of MCI, papers where MCI and NCI or MCI and dementia groups
had been combined for analysis or where MCI had progressed to dementia at time of death
were excluded. Further, papers where case selection criteria combined neuropsychological
and neuropathological thresholds were also excluded as the aim of the review was to assess
whether there are neuropathological differences across different cognitive profiles, including
NCI, MCI and dementia (1-22). Full details of these studies are outlined in Supplementary
Table 3. Where MCI occurred within the framework of other diseases, for example
psychiatric disorders (depression, and schizophrenia) or Parkinson’s disease (PD), these
papers were excluded. Other restrictions included studies on humans and in English language.
Search Outcome The initial search yielded 2,808 articles. Titles and abstracts were then
assessed for inclusion by two authors (BS and DH). From the electronic search 46 articles
meet inclusion criteria and 116 were identified from other sources including reference lists of
included articles and reviews. Therefore, a total of 162 articles were identified for inclusion.
RESULTS
Description of Studies One hundred and sixty two articles were identified. Of these, 46 came
from the Religious Orders Study and 5 from the Nun Study. Seventy-six came from university
affiliated dementia research centres including: 4 from universities in California, 20 from the
University of Geneva, 30 from the University of Kentucky, 18 from Washington University, 3
from the University of Miami and 1 from the University of Leipzig. Thirteen were from
cohort studies, 2 were from hospital based samples, 18 from academic affiliates of the Mount
Sinai School of Medicine (New York, NY) and 2 from other sources (not specified). A
description of the included papers is outlined in Supplementary Table 1. Diversity of sample
source across studies raises questions of comparability. Indeed, where clinical and community
cohorts have been compared the spectrum of pathologies in NCI, MCI and dementia groups
are found to differ across the two samples (23).
Sample Demographics The demographic profile of MCI samples varies considerably across
studies. Samples range from young-old to oldest-old (range of means for MCI samples: 68.098.6 years). On average, educational attainment was high (range of means for MCI samples:
13.0 years-college graduate), however, there were a considerable number of studies (n=99)
where education attainment was not reported. Generally, samples were similar in general
cognitive ability as indicated by mean Mini Mental State Examination (MMSE) score (Mean
Range: 22.1-28.5).
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