Neuropsychological and Neuroanatomical Features of Patients with Behavioral/Dysexecutive Variant Alzheimer’s Disease (AD): A Comparison to Behavioral Variant Frontotemporal Dementia and Amnestic AD Groups

Article type: Research Article

Authors: Dominguez Perez, Sophia^{a; b; c} | Phillips, Jeffrey S.^{a; b} | Norise, Catherine^b | Kinney, Nikolas G.^{a; b} | Vaddi, Prerana^{a; b} | Halpin, Amy^{a; b; d} | Rascovsky, Katya^{a; b} | Irwin, David J.^{a; b; e} | McMillan, Corey T.^{a; b} | Xie, Long^{b; f} | Wisse, Laura E.M.^{b; f; g} | Yushkevich, Paul A.^{b; f} | Kallogjeri, Dorina^h | Grossman, Murray^{a; b} | Cousins, Katheryn A.Q.^{a; b; *}

Affiliations: [a] Penn Frontotemporal Degeneration Center (FTDC), University of Pennsylvania, Philadelphia, PA, USA | [b] Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA | [c] Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA | [d] Department of Psychology, University of Maine, Orono, ME, USA | [e] Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA | [f] Penn Image Computing and Science Lab & Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA | [g] Department of Diagnostic Radiology, Lund University, Lund, Sweden | [h] Department of Otolaryngology, Washington University, St. Louis, MO, USA

Correspondence: [*] Correspondence to: Katheryn Cousins, University of Pennsylvania, 3 West Gates, 3400 Spruce Street, Philadelphia, PA 19104, USA. Tel.: +1 215 349 5863; E-mail: katheryn.cousins@pennmedicine.upenn.edu.

Abstract: Background:An understudied variant of Alzheimer’s disease (AD), the behavioral/dysexecutive variant of AD (bvAD), is associated with progressive personality, behavior, and/or executive dysfunction and frontal atrophy. Objective:This study characterizes the neuropsychological and neuroanatomical features associated with bvAD by comparing it to behavioral variant frontotemporal dementia (bvFTD), amnestic AD (aAD), and subjects with normal cognition. Methods:Subjects included 16 bvAD, 67 bvFTD, 18 aAD patients, and 26 healthy controls. Neuropsychological assessment and MRI data were compared between these groups. Results:Compared to bvFTD, bvAD showed more significant visuospatial impairments (Rey Figure copy and recall), more irritability (Neuropsychological Inventory), and equivalent verbal memory (Philadelphia Verbal Learning Test). Compared to aAD, bvAD indicated more executive dysfunction (F-letter fluency) and better visuospatial performance. Neuroimaging analysis found that bvAD showed cortical thinning relative to bvFTD posteriorly in left temporal-occipital regions; bvFTD had cortical thinning relative to bvAD in left inferior frontal cortex. bvAD had cortical thinning relative to aAD in prefrontal and anterior temporal regions. All patient groups had lower volumes than controls in both anterior and posterior hippocampus. However, bvAD patients had higher average volume than aAD patients in posterior hippocampus and higher volume than bvFTD patients in anterior hippocampus after adjustment for age and intracranial volume. Conclusion:Findings demonstrated that underlying pathology mediates disease presentation in bvAD and bvFTD.

Keywords: Alzheimer’s disease, behavioral, behavioral variant frontotemporal dementia, cognitive domains, cortical thinning, frontal variant, hippocampal volumes, neuropsychiatric symptoms

DOI: 10.3233/JAD-215728

Journal: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 641-658, 2022