Memory, executive, and multidomain subtle cognitive impairment

Abstract

Objective: We studied the biomarker signatures and prognoses of 3 different subtle cognitive impairment (SCI) groups (executive, memory, and multidomain) as well as the subjective memory complaints (SMC) group. Methods:We studied 522 healthy controls in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cutoffs for executive, memory, and multidomain SCI were defined using participants who remained cognitively normal (CN) for 7 years. CSF Alzheimer disease (AD) biomarkers, composite and region-of-interest (ROI) MRI, and fluorodeoxyglucose-PET measures were compared in these participants.Results: Using a stringent cutoff (fifth percentile), 27.6% of the ADNI participants were classified as SCI. Most single ROI or global-based measures were not sensitive to detect differences between groups. Only MRI-SPARE-AD (Spatial Pattern of Abnormalities for Recognition of Early AD), a quantitative MRI pattern-based global index, showed differences between all groups, excluding the executive SCI group. Atrophy patterns differed in memory SCI and SMC. The CN and the SMC groups presented a similar distribution of preclinical dementia stages. Fifty percent of the participants with executive, memory, and multidomain SCI progressed to mild cognitive impairment or dementia at 7, 5, and 2 years, respectively. Conclusions:Our results indicate that (1) the different SCI categories have different clinical prognoses and biomarker signatures, (2) longitudinally followed CN subjects are needed to establish clinical cutoffs, (3) subjects with SMC show a frontal pattern of brain atrophy, and (4) patternbased analyses outperform commonly used single ROI-based neuroimaging biomarkers and are needed to detect initial stages of cognitive impairment. Neurology ® 2015;85:144-153 GLOSSARY Ab 5 b-amyloid; AD 5 Alzheimer disease; ADNI 5 Alzheimer's Disease Neuroimaging Initiative; aHV 5 adjusted hippocampal volume; CN 5 cognitively normal; FDG 5 fluorodeoxyglucose; HC 5 healthy control; MCI 5 mild cognitive impairment; MRI-SPARE-AD 5 MRI Spatial Pattern of Abnormalities for Recognition of Early Alzheimer Disease; PET-HCI 5 PET hypometabolic convergence index; p-tau181 5 tau phosphorylated at threonine 181; ROI 5 region of interest; SCI 5 subtle cognitive impairment; SCINIB 5 subtle cognitive impairment with normal neuronal injury biomarkers; SMC 5 subjective memory complaints; SNAP 5 suspected nonamyloid pathology; t-tau 5 total tau; WMI 5 white matter hyperintensity.The development of different neuropsychological batteries and biomarkers and their use in different cohorts have led to the study of earlier stages of dementia. Therefore, mild cognitive impairment (MCI) was defined as a stage that may precede Alzheimer disease (AD) or other dementias. MCI is characterized by moderate cognitive impairment without impairment of daily living activities, 1 that can be further categorized based on the cognitive profile into amnestic and nonamnestic MCI subtypes. Biomarkers correlate with neuropathologic hallmarks of AD 2-4 and a model of biomark...

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