Outcomes after diagnosis of mild cognitive impairment in a large autopsy series

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Mild cognitive impairment (MCI) is a clinical term referring to a portion of the cognitive continuum between intact (or “normal”) cognition and dementia. By definition, individuals with MCI are not demented, have cognitive deficits that may or may not include memory impairment, and are functionally intact in terms of activities of daily living.1 Most estimates of MCI prevalence among adults aged >60 years range between 16% and 20% of the population.2
MCI often precedes dementia due to Alzheimer disease (AD), but persons diagnosed with MCI may later be diagnosed as cognitively normal, remain diagnosed with MCI until death, or in many cases progress to clinical dementia due to non‐AD brain diseases.3 Studies of MCI suggest an annual progression rate to dementia of about 10% when conducted in specialist settings and about 5% when conducted in community settings.3 Such rates imply that after 10 years of follow‐up, many MCI cases will not progress to dementia; however, in this meta‐analysis of MCI transition,3 studies with <3 years of follow‐up were excluded. Progression rates and survival time in MCI depend on many factors, including severity at diagnosis and diagnostic criteria,4 but the role of specific neuropathologies in progression rates is not clear.
Prior MCI studies underscore disease heterogeneity underlying this clinical condition.6 For example, up to 30% of community‐based MCI subjects have biomarker profiles that are consistent with neurodegeneration but inconsistent with AD (ie, suspected non‐Alzheimer pathophysiology [SNAP]).9 Prior clinical–pathologic studies have reported that MCI is often associated with mixed pathologies,10 and there have been recent advances in the study of non‐AD pathologies. For example, there is new understanding of the frequency of hippocampal sclerosis of aging (HS‐Aging),11 primary age‐related tauopathy (PART),12 and arteriolosclerosis,13 which may contribute to a clinical MCI diagnosis. These associations have not, to our knowledge, yet been evaluated in large autopsy cohorts focusing on MCI. In the current study, we examined part of the Statistical Modeling of Aging and Risk of Transition (SMART) project database,14 analyzing longitudinal clinical data and neuropathologic outcomes of individuals from 4 AD Centers (ADCs). The inclusion of multiple large autopsy cohorts with longitudinal follow‐up provides the basis for a study of neuropathologic correlates of MCI among adults who died in old age.
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