Diagnosing the frontal variant of Alzheimer's disease: a clinician's yellow brick road

Abstract

Background: Disruption of the frontal lobes and its associated networks are a common consequence of neurodegenerative disorders. Given the wide range of cognitive, behavioral and motor processes in which the frontal lobes are involved, there can be a great variety of manifestations depending on the pathology distribution. The most common are the behavioral variant of frontotemporal dementia (bvFTD) and the frontal variant of Alzheimer's disease (fvAD), which are particularly challenging to disentangle. Recognizing fvAD from bvFTD-related pathologies is a diagnostic challenge and a critical need in the management and counseling of these patients.

Case presentation: Here we present three pathology-proven cases of Alzheimer's disease initially misdiagnosed as bvFTD and discuss the distinctive or less overlapping historical, examination, and laboratory findings of fvAD and bvFTD, deriving analogies for mnemonic endurance from the Wizard of Oz worldview.

Conclusion: The Yellow Brick Road to diagnosing these disorders may be served by the metaphor of fvAD as the irritable, paranoid, and tremulous Scarecrow and bvFTD the heartless, ritualistic, and rigid Tin Man. An Oz-inspired creative license may help the clinician recognize the differential disease progression, caregiver burden, and treatment response of fvAD compared with bvFTD.

Keywords: Behavioral disorder; Frontal variant of Alzheimer’s disease; Frontotemporal Dementia; Movement disorders; Parkinsonism.

Fig. 1

Brain MRI of Case #1–3. Sagittal T2-weighted (upper row) and axial FLAIR (lower row) brain MRIs. Patient 1 (a and d) showed mild to moderate atrophy in the frontotemporal regions, minimally asymmetric, with right frontal encephalomalacia. Patient 2 (b and e) showed similar findings with somewhat lower burden of associated periventricular and spotty subcortical white matter increased signal. Patient 3 (c and f) showed mild diffuse atrophy with minimal periventricular and subcortical white matter disease

Fig. 2

fvAD and bvFTD in the Wizard of Oz. a fvAD Scarecrow was searching for a brain because he had none, and without a brain he had no memory or object knowledge. While his phonemic fluency was preserved, fvAD Scarecrow had difficulty with semantics and was irritable and paranoid, believing the crows were gearing to bothering and stealing from him. Furthermore, fvAD Scarecrow was very tremulous (myoclonus). The wind could suddenly jolt him (stimulus-sensitive myoclonus). b bvFTD Tin Man had no heart, so his behavior and emotions were affected from the outset. The “heartless” bvFTD Tin Man lacked empathy and was very ritualistic, only going out to chop wood. His rituals included hyperphagia, making him heavier than the straw-filled fvAD Scarecrow. Furthermore, bvFTD Tin Man was insufficiently lubricated, making him appear parkinsonian. This particular bvFTD Tin Man was missing progranulin, rendering his frontotemporal region asymmetric, as judged by a crooked hat. Both images are from 1900; US Copyright law on public domain

Fig. 3

Chronology of symptoms. The diagram illustrates the severity and timing of cognitive impairments, motor manifestations, and behavioral changes as they may appear across disease stages in bvFTD

Fig. 4

Chronology of symptoms. The diagram illustrates the severity and timing onset of cognitive impairments, motor manifestations, and behavioral changes as they may appear across disease stages in fvAD