A graph theoretic approach to neurodegeneration: five data-driven neuropsychological subtypes in mild cognitive impairment.

Mild cognitive Impairment (MCI) is notoriously heterogenous in terms of clinical presentation, neuroimaging correlates, and subsequent progression. Predicting who will progress to dementia, which type of dementia, and over what timeframe is challenging. Previous work has attempted to identify MCI subtypes using neuropsychological measures in an effort to address this challenge; however, there is no consensus on approach, which may account for some of the variability. Using a hierarchical community detection approach, we examined cognitive subtypes within an MCI sample (from the Alzheimer's Disease Neuroimaging Initiative [ADNI] study). We then examined whether these subtypes were related to biomarkers (e.g., cortical volumes, fluorodeoxyglucose (FDG)-positron emission tomography (PET) hypometabolism) or clinical progression. We identified five communities (i.e., cognitive subtypes) within the MCI sample: 1) predominantly memory impairment, 2) predominantly language impairment, 3) cognitively normal, 4) multidomain, with notable executive dysfunction, 5) multidomain, with notable processing speed impairment. Community membership was significantly associated with 1) cortical volume in the hippocampus, entorhinal cortex, and fusiform cortex; 2) FDG PET hypometabolism in the posterior cingulate, angular gyrus, and inferior/middle temporal gyrus; and 3) conversion to dementia at follow up. Overall, community detection as an approach appears a viable method for identifying unique cognitive subtypes in a neurodegenerative sample that were linked to several meaningful biomarkers and modestly with progression at one year follow up.

Relationship between cognitive reserve, brain volume, and neuropsychological performance in amnestic and nonamnestic MCI.

Cognitive Reserve (CR) is a theoretical construct that influences the onset and course of cognitive and structural changes that occur with aging and mild cognitive impairment (MCI). There is a paucity of research that examines the relationship of CR and brain volumes in amnestic (aMCI) and nonamnestic (naMCI) separately. This study is a retrospective chart review of MCI patients who underwent neuropsychological evaluation and brain MRI with NeuroReader™ (NR). NR is an FDA-cleared software that standardizes MRI volumes to a control sample. Classifications of aMCI and naMCI were based on Petersen criteria. CR was measured as education, occupation, and word reading. Data analysis included bivariate correlations between CR, neuropsychological test scores, and NR-brain volumes by MCI subtype. The Benjamini-Hochberg method corrected for multiple comparisons. The sample included 91 participants with aMCI and 41 with naMCI. Within naMCI, positive correlations were observed between CR and whole brain volume, total gray matter, bifrontal, left parietal, left occipital, and bilateral cerebellum. Within aMCI, no significant correlations were observed between CR and brain volumes. Positive correlations with CR were observed in language, attention, and visual learning in both aMCI and naMCI groups. The current study adds to the minimal literature on CR and naMCI. Results revealed that CR is associated with volumetrics in naMCI only, though cognitive findings were similar in both MCI groups. Possible explanations include heterogeneous disease pathologies, disease stage, or a differential influence of CR on volumetrics in MCI. Additional longitudinal and biomarker studies will better elucidate this relationship.