Examining Cerebrovascular Disease as the Underlying Pathophysiology of
Dysexecutive Alzheimer's disease 
   Lead Investigator:    Michael Alosco
   Institution      :    Boston University School of Medicine
   E-Mail           :    malosco@bu.edu
   Proposal ID      :    1240



   Proposal Description:
   The traditional initial presentation of clinical Alzheimer?s disease (AD) includes impairments in episodic memory and language functions (e.g., confrontation naming). However, about 15-40 of AD dementia cases that have underlying AD pathology actually present with dysexecutive phenotypes.     Dysexecutive AD include deficits in planning, judgement, reasoning, problem solving, organization, attention, abstraction, and mental flexibility (Stuss Alexander, 2007). Previous research has found predictors for dysexecutive AD include disproportionate amyloid plaque and neurofibrillary tangle burden in the frontal lobes as compared to typical AD pathology (Johnson et al., 2004). It has also been suggested this cohort of AD patients have greater frontoparietal cortical thinning and hypometabolism compared to traditional AD and healthy controls (Brickman et al., 2015). This subtype also has a faster rate of clinical progression compared to the amnestic subgroup. An additional predictor of dysexecutive AD include APOEe4 allele, which has been found to be less frequent in dysexecutive AD compared to amnestic AD (Mez et al., 2014). Advanced age, diabetes, hypertension, and fewer years of education have been independently associated with lower scores on executive functioning assessments in healthy older adults. Currently, there is limited research on the risk factors for dysexecutive AD.    Cerebrovascular disease (CVD) may be one contributor to the dysexecutive phenotypes of AD. White matter hyperintensities (WMH) on FLAIR MRI have been linked to increased risk for and diagnosis of AD, as well as rate of cognitive decline in those who have AD, specifically in the parietal lobe region (Brickman et al., 2015). Other research has found that increases in frontal WMH in AD has been shown to cause executive dysfunction, which is highly dependent on frontal lobe functioning. When analyzing WMH in relation to MCI subgroup with predominant executive/processing speed impairments, this sub