Frontal variant of Alzheimer's disease with asymmetric presentation mimicking frontotemporal dementia: Case report and literature review

Abstract

Introduction Frontal variant of Alzheimer's disease (fvAD) is a rare nonamnestic syndrome of Alzheimer's disease (AD). Differentiating it from behavior variant of frontotemporal dementia (bvFTD), which has implications for treatment responses and prognosis, remains a clinical challenge. Methods Molecular neuroimaging and biofluid markers were performed for the index patient for accurate premortem diagnosis of fvAD. The clinical, neuroimaging, and biofluid characteristics of the patient were compared to those reported in previous studies of fvAD from 1999 to 2019. Results A 66‐year‐old man presented with progressive executive dysfunction, personality and behavioral changes, and memory decline since age 59. He had no family history of neurodegenerative disorders. A stimulus‐sensitive myoclonus was noted over his left upper extremity. Neuropsychological assessment revealed moderate dementia with a Mini‐Mental State Exam score of 10/30 and compromised executive and memory performance. Brain imaging showed asymmetrical atrophy and hypometabolism over the right frontal and temporal areas, mimicking bvFTD. However, we observed increased tau depositions based on 18F‐labeled T807 Tau PET in these areas and diffusely increased amyloid deposition based on 11C‐labeled Pittsburgh compound B positron emission tomography (PET). Plasma biomarker measures indicated an AD profile with increased Aβ1‐42 (18.66 pg/ml; cutoff: 16.42 pg/ml), Aβ1‐42/Aβ1‐40 ratio (0.45; cutoff: 0.30), total tau (29.78 pg/ml; cutoff: 23.89 pg/ml), and phosphorylated tau (4.11 pg/ml; cutoff: 3.08 pg/ml). These results supported a diagnosis of fvAD. Conclusions Our results with asymmetrical presentations extend current knowledge about this rare AD variant. Application of biofluid and molecular imaging markers could assist in early, accurate diagnosis.

<p>Incidence of and Mortality Due to Human Prion Diseases in Taiwan: A Prospective 20-Year Nationwide Surveillance Study from 1998 to 2017</p>

“…Globally, most countries reported increasing trends in incidence as CJD surveillance mechanisms have been optimized, the diagnostic testing capabilities have improved, and physicians have developed a greater awareness of this rare disease. 8 Since the Taiwan CJDSU has been operating for more than 20 years, whether the incidence of and mortality due to CJD have temporal trends should be assessed. Besides, a very long disease duration was noted in some of our cases.…”

Heterogeneous distribution of tau pathology in the behavioral variant of Alzheimer’s disease

“…However, given the demonstrated right hemispheric dominance in bvFTD 45 and suggested dominance in bvAD 3,5,13 as well as established relationships between right frontal areas and behavioral deficits like apathy, disinhibition and aberrant motor behavior 46 , it is unlikely that this affected our results. Fourth, the comparison of the frontal pole in the postmortem study against the medial and lateral prefrontal cortices in the tau PET study may introduce a bias, as these regions have been differentially implicated in behavioral disturbances 47 .…”

“…However, the only in-vivo investigations of tau PET in cases with bvAD to date have shown somewhat contradictory results. While one study suggested frontal involvement in addition to a temporoparietal pattern in a bvAD case with advanced dementia (MMSE: 10/30) 13 , another bvAD case with mild dementia (MMSE: 21/30) showed a predominant temporoparietal pattern of tracer retention with sparing of frontal regions 9 . Our extended case series shows that patients with bvAD are primarily characterized by a classical temporoparietal pattern of tau, with, in some cases, pronounced involvement of (mostly lateral) frontal areas, which did not strongly depend on disease severity or age of onset.…”

“…Our results corroborate the remarkable heterogeneity of tau distributions described in the scarce neuropathological and PET literature on bvAD. While some neuropathological studies indicate more pronounced tau pathology in frontal regions than in other brain regions 6,27,28 , others describe a widespread distribution of tau across different lobes in bvAD participants 13,29,30 or no differences in the burden of frontal tau pathology in bvAD compared to typical AD 4 . However, neuropathological studies typically lack the ability to make inferences on the distributions of tau in early stages of the disease, which is a major advantage of neuroimaging techniques like PET.…”

“…This apparent clinico-anatomical dissociation indicates the need for a better understanding of the neurobiological factors underlying the bvAD phenotype. To that end, it is crucial to study the distribution of tau deposition in bvAD, as this central neuropathological hallmark of AD is closely related to type and severity of cognitive symptoms 9, 10 and precedes and predicts patterns of neurodegeneration detected by MRI and [ 18 F]FDG PET 11, 12 To date, only two bvAD case studies with tau PET have been reported, one showing a posterior pattern of tau pathology 9 and the other one a more diffuse uptake pattern including both temporoparietal and frontal regions 13 . In this study, we had three objectives: to investigate the regional distribution of tau pathology in bvAD i) in-vivo using tau PET and ii) ex-vivo using postmortem examination, and iii) to assess the relationship between tau PET patterns and behavioral symptoms in typical AD.…”