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.

Keywords:

• Frontotemporal dementia
• Alzheimer’s disease

Additional information

Funding

Dr. Rankin is supported by the National Institute on Aging under Grant R01 AG029577. Dr. Coppola is supported by the John Douglas French Alzheimer’s Foundation and the Tau Consortium. Dr. Miller is supported by the National Institute on Aging under Grant P50 AG023501; under grant P01 AG019724. Dr. Geschwind is also supported by P01 AG019724, Miller, PI and the Tau Consortium. Dr. Lee is supported by the National Institute on Aging under grant K23 AG039414.