Rapidly Progressing Neurocognitive Disorder in a Male with FXTAS and Alzheimer’s Disease

Elber Yuksel Aydin, ^{1, 2} Andrea Schneider, ^{1, 3} Dragana Protic, ^{1, 4} Jun Yi Wang, ^{1, 5} Veronica Martínez-Cerdeño, ^{1, 6} Flora Tassone, ^{1, 7} Hiu-Tung Tang, ⁷ Susan Perlman, ⁸ Randi J Hagerman <sup>1, 3

1</sup>Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, Sacramento, CA, USA; ²Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; ³Department of Pediatrics, University of California Davis School of Medicine, Sacramento, CA, USA; ⁴Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia; ⁵Center for Mind and Brain, University of California Davis School of Medicine, Sacramento, CA, USA; ⁶Department of Pathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine, University of California Davis School of Medicine and Shriners Hospital, Sacramento, CA, USA; ⁷Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA, USA; ⁸Department of Neurology, University of California Los Angeles School of Medicine, Los Angeles, CA, USA

Correspondence: Randi J Hagerman
MIND Institute UCDMC, 2825 50th Street, Sacramento, CA 95817, USA
Email rjhagerman@ucdavis.edu

Abstract: Fragile X–associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that usually begins in the early 60s and affects carriers of premutation expansion (55– 200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. Additional disorders can co-occur with FXTAS including Alzheimer’s disease (AD). Here we discuss a case report of a male with 67 CGG repeats in FMR1 who had mild late-onset FXTAS symptoms followed by neurocognitive disorder symptoms consistent with AD. The patient has developed tremor and ataxia that are the two characteristic symptoms of FXTAS. In addition, he shows rapid cognitive decline, brain atrophy most substantial in the medial temporal lobe, and decreased metabolism in the brain regions that are the characteristic findings of AD. The purpose of this study is to describe a patient profile with both diseases and review the details of an overlap between these two diseases.

Keywords: FXTAS, Alzheimer’s disease, cognitive decline, neurocognitive disorder, premutation, neurogenetics