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: 68.0-98.6 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).
References
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