The effects of CNS atrophy and ICVD on tests of executive function and functional status are mediated by intelligence

Background: Impairments in executive function (EF) are often attributed to ischemic cerebrovascular disease (ICVD) and frontal circuit pathology. However, EF can be distinguished from general intelligence and the latter is likely to manifest in “executive” measures. We aimed to distinguish the effects of imaging biomarkers on these constructs. Methods: We tested neuroimaging biomarkers as independent predictors of observed 12 month-prospective cognitive performance by a Multiple Indicators Multiple Causes (MIMIC) model in the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N ≅ 1750). Results: ICVD was associated with ‘’Organization” (ORG) and “Planning” (PLAN) domain scores from the test of Every Day Cognition. Left anterior cingulate (LAC) atrophy was independently associated with Trail-Making part B and Animal Naming. The MIMIC model had excellent fit and tests additional latent variables i.e., EF and dEF (a latent δ homolog derived from Spearman's general intelligence factor, g). Only dEF was associated with instrumental activities of daily living (IADL). ICVD and LAC were both associated with observed executive measures through dEF. ICVD was independently associated with those same measures through EF. Conclusions: Observed EF is independently determined by multiple factors. The effects of EF-associated MRI biomarkers can be related to disability and dementia only via their effects on g. Because g /δ are unlikely to be located within the frontal lobes, the dementia-specific variance in executive measures may have little to do with either frontal structure or function. Conversely, domain-specific variance in EF may have little to do with either IADL-impairment or dementia.