title: Early-onset Alzheimer's disease versus frontotemporal dementia: resolution with genetic diagnoses?
abstract: We report a diagnostically challenging case of a 64-year-old man with a history of remote head trauma who developed mild behavioral changes and dyscalculia. He was diagnosed with clinical Alzheimer's disease (AD), with additional features consistent with behavioral variant frontotemporal dementia. Structural magnetic resonance imaging revealed atrophy in bilateral frontal and parietal cortices and hippocampi on visual inspection and left frontal pole and bilateral anterior temporal encephalomalacia, suspected to be due to head trauma. Consistent with the diagnosis of Alzheimer's pathology, positron emission tomography (PET) with Pittsburgh compound B suggested the presence of beta-amyloid. Fluorodeoxyglucose PET demonstrated hypometabolism in bilateral frontal and temporoparietal cortices. Voxel-based morphometry showed atrophy predominant in ventral frontal regions (bilateral orbitofrontal cortex, pregenual anterior cingulate/medial superior frontal gyrus), bilateral mid cingulate, bilateral lateral temporal cortex, and posterior insula. Bilateral caudate, thalamus, hippocampi, and cerebellum were prominently atrophied. Unexpectedly, a pathologic hexanucleotide repeat expansion in C9ORF72 was identified in this patient. This report underscores the clinical variability in C9ORF72 expansion carriers and the need to consider mixed pathologies, particularly when imaging studies are inconsistent with a single syndrome or pathology.
authors: a Department of Neurology and Neurological Sciences , Stanford University , Stanford , CA , USA.
authors: Sharon J
authors: SJ
authors: Sha
authors: b Department of Neurology, Memory and Aging Center , University of California , San Francisco , CA , USA.
authors: Anna M
authors: AM
authors: Khazenzon
authors: b Department of Neurology, Memory and Aging Center , University of California , San Francisco , CA , USA.|c Helen Wills Neuroscience Institute, University of California , Berkeley , CA , USA.
authors: Pia M
authors: PM
authors: Ghosh
authors: b Department of Neurology, Memory and Aging Center , University of California , San Francisco , CA , USA.
authors: Katherine P
authors: KP
authors: Rankin
authors: d Departments of Psychiatry and Neurology , Semel Institute for Neuroscience and Human Behavior, University of California , Los Angeles , CA , USA.
authors: Mochtar
authors: M
authors: Pribadi
authors: d Departments of Psychiatry and Neurology , Semel Institute for Neuroscience and Human Behavior, University of California , Los Angeles , CA , USA.
authors: Giovanni
authors: G
authors: Coppola
authors: d Departments of Psychiatry and Neurology , Semel Institute for Neuroscience and Human Behavior, University of California , Los Angeles , CA , USA.
authors: Daniel H
authors: DH
authors: Geschwind
authors: b Department of Neurology, Memory and Aging Center , University of California , San Francisco , CA , USA.|c Helen Wills Neuroscience Institute, University of California , Berkeley , CA , USA.|e Department of Radiology, Lawrence Berkeley National Laboratory , University of California , Berkeley , CA , USA.
authors: Gil D
authors: GD
authors: Rabinovici
authors: b Department of Neurology, Memory and Aging Center , University of California , San Francisco , CA , USA.
authors: Bruce L
authors: BL
authors: Miller
authors: b Department of Neurology, Memory and Aging Center , University of California , San Francisco , CA , USA.
authors: Suzee E
authors: SE
authors: Lee
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D000814:Aniline Compounds / Q000493:pharmacokinetics; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D000073885:C9orf72 Protein; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D004644:Emotions; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D057180:Frontotemporal Dementia / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011506:Proteins / Q000235:genetics*; D012919:Social Behavior; D013844:Thiazoles / Q000493:pharmacokinetics; D014706:Verbal Learning
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D001057:Apolipoproteins E; D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D002247:Carbon Isotopes; D011506:Proteins; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18
keywords: Alzheimer’s disease; Frontotemporal dementia