Frontal variant of Alzheimer’s disease masquerading as behavioural-variant frontotemporal dementia: a case study comparison

Wong, Stephanie; Strudwick, Jessica; Devenney, Emma; Hodges, John R.; Piguet, Olivier; Kumfor, Fiona

doi:10.1080/13554794.2019.1609523

Cited by 12 publications

(11 citation statements)

References 72 publications

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“…Individuals with the behavioral variant of Alzheimer's disease (bvAD) present with early and prominent behavioral and personality changes, with AD as the primary etiology [1]. Case reports and small sample studies have suggested prominent frontal atrophy and pathology in bvAD patients [2][3][4][5]. The largest neuroimaging study to date in clinically defined bvAD patients revealed a prominent temporoparietal atrophy pattern with a relative lack of frontal atrophy [1], questioning the neurobiological basis of the prominent behavioral deficits.…”

Section: Introductionmentioning

confidence: 99%

“…Exploring these neuroimaging features will enhance our neurobiological understanding of the prominently behavioral phenotype in bvAD. In addition, it may aid the often challenging differential diagnosis of bvAD versus "typical" AD or the behavioral variant of frontotemporal dementia (bvFTD) [5,10], and potentially lead to more accurate diagnoses and patient management. We had two objectives: (i) to increase our understanding of the relative lack of frontal atrophy in patients with the behavioral variant of AD through the assessment of multiple neuroimaging markers and (ii) to identify the diagnostic accuracy of several neuroimaging measures in the differential diagnosis of bvAD vs. typical AD and bvFTD.…”

Section: Introductionmentioning

confidence: 99%

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Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease

et al. 2020

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Background We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer’s disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers. Methods We retrospectively included 150 participants, including 29 bvAD, 28 “typical” amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [18F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy. Results bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvAD<bvFTD), MRI posterior-DMN-ratios (bvAD<bvFTD), MRI salience-network-ratios (bvAD>bvFTD, area under the curve [AUC] range 0.85–0.91, all p < 0.001). The top-3 for bvAD vs. tAD were amygdalar volume (bvAD>tAD), MRI anterior-DMN-ratios (bvAD<tAD), FDG anterior-DMN-ratios (bvAD<tAD, AUC range 0.71–0.84, all p < 0.05). Conclusions Subtle frontoinsular hypometabolism and anterior DMN involvement may underlie the prominent behavioral phenotype in bvAD.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease

et al. 2020

View full text Add to dashboard Cite

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“…Individuals with the behavioral variant of Alzheimer’s disease (bvAD) present early and prominent behavioral and personality changes, with AD as the primary etiology 1 . Case reports and small sample studies have suggested prominent frontal atrophy and pathology in bvAD patients 2-5 . The largest neuroimaging study to date in clinically defined bvAD patients revealed a prominent temporoparietal atrophy pattern with a relative lack of frontal atrophy 1 , questioning the neurobiological basis of the prominent behavioral deficits.…”

Section: Introductionmentioning

confidence: 99%

“…Exploring these neuroimaging features will enhance our neurobiological understanding of the prominently behavioral phenotype in bvAD. In addition, it may aid the often challenging differential diagnosis of bvAD versus ‘typical’ AD or the behavioral variant of frontotemporal dementia (bvFTD) 5, 10 , and potentially lead to more accurate diagnoses and patient management. We had two study objectives: (i) to increase our understanding of the relative lack of frontal atrophy in patients with the behavioral variant of AD through the assessment of multiple neuroimaging markers, and (ii) to identify the diagnostic accuracy of several neuroimaging, neuropsychological and neuropsychiatric measures in the differential diagnosis of bvAD vs .…”

Section: Introductionmentioning

confidence: 99%

Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer’s disease

Singleton

Pijnenburg

Sudre

et al. 2019

Preprint

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Objective: We previously found temporoparietal “Alzheimer-typical” atrophy in patients with the behavioral variant of Alzheimer's disease (bvAD) with relative sparing of frontal regions. Here, we aimed to understand the pathophysiological mechanisms of bvAD based on alternative neuroimaging markers. Methods: We retrospectively included 150 participants at the University of California San Francisco and University of Berkeley, including 29 bvAD, 28 “typical” amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other groups on glucose metabolism and metabolic connectivity on [18F]FDG-PET, and subcortical gray matter volumes and white matter hyperintensity volumes (WMHV) on MRI. A receiver-operating-characteristic-analysis was performed to determine the measures yielding the highest contrast between groups. Results: bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD compared to tAD, partially overlapping with bvFTD. Metabolic connectivity analyses indicated greater anterior default mode network (DMN) involvement in bvAD compared to tAD, mimicking bvFTD. Analyses of subcortical volume and WMHV showed no relevant group differences. The top-3 discriminative measures for bvAD vs. bvFTD were: metabolism in posterior (bvAD<bvFTD), anterior DMN (bvAD>bvFTD) and parietal cortex (bvAD<bvFTD; AUC: 0.80-0.91, p<0.01), while the top-3 discriminators for bvAD vs. tAD were amygdalar volume (bvAD>tAD), anterior DMN (bvAD<tAD) and salience network metabolism (bvAD<tAD; AUC: 0.66-0.75, p<0.05). Conclusion: Subtle frontoinsular hypometabolism and anterior DMN involvement may underlie the prominent behavioral phenotype in bvAD.

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“…Patients with AD may mimic the behavioural variant of frontotemporal dementia (bvFTD). [52][53][54] These AD patients are said to have suffered from the behavioural/dysexecutive variant (bvAD) or frontal variant AD. 52 These patients usually present as young onset of AD (i.e.…”

Section: Clinical Manifestationsmentioning

confidence: 99%

A systematic review of atypical Alzheimer's disease including behavioural and psychological symptoms

et al. 2021

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Alzheimer's disease (AD) is the commonest cause of dementia, characterized by the clinical presentation of progressive anterograde episodic memory impairment. However, atypical presentation of patients is increasingly recognized. These atypical AD include logopenic aphasia, behavioural variant AD, posterior cortical atrophy, and corticobasal syndrome. These atypical AD are more common in patients with young onset AD before the age of 65 years old. Since medical needs (including the behavioural and psychological symptoms of dementia) of atypical AD patients could be different from typical AD patients, it is important for clinicians to be aware of these atypical forms of AD. In addition, disease modifying treatment may be available in the future. This review aims at providing an update on various important subtypes of atypical AD including behavioural and psychological symptoms.

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Frontal variant of Alzheimer’s disease masquerading as behavioural-variant frontotemporal dementia: a case study comparison

Cited by 12 publications

References 72 publications

Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease

Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease

Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer’s disease

A systematic review of atypical Alzheimer's disease including behavioural and psychological symptoms

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