Comparison of Gray Matter Atrophy in Behavioral Variant Frontal Temporal Dementia and Amyotrophic Lateral Sclerosis: A Coordinate-Based Meta-Analysis

Abstract

Background: There is growing evidence supporting behavioral variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis (ALS) as extreme points of a disease spectrum. The aim of this study was to delineate the common and different patterns of gray matter atrophy associated with bvFTD and with ALS by pooling together the results of previous voxel-based morphometry (VBM) studies. Methods:We retrieved VBM studies that investigated gray matter atrophy in bvFTD patients vs. controls and in ALS patients vs. controls. Stereotactic data were extracted from those studies and subsequently tested for convergence and differences using activation likelihood estimation (ALE). A behavioral analysis using the BrainMap database was performed to assess the functional roles of the regions affected by bvFTD and/or ALS.Results: Our study demonstrated a convergence of gray matter atrophy in the frontolimbic structures that involve the bilateral anterior insula and anterior cingulate cortex. Comparing the pattern of GM atrophy in bvFTD and ALS patients revealed greater atrophy in the frontomedial cortex, bilateral caudate, left anterior insula, and right thalamus in those with bvFTD and a higher degree of atrophy in the right motor cortex of those with ALS. Behavioral analysis revealed that the pattern of the affected regions contributed to the dysfunction of emotional and cognitive processing in bvFTD patients and the dysfunction of motor execution in ALS patients. Conclusion:Our results revealed a shared neural basis between bvFTD and ALS subjects, as well as a specific and distinct neural signature that underpinned the clinical manifestations of those two diseases. Those findings outlined the role of the frontomedial-caudate circuit in the development of bvFTD-like deficits in ALS patients.

Frontal and Cerebellar Atrophy Supports FTSD-ALS Clinical Continuum

“…It is noteworthy that while areas of GM atrophy were found in all three groups of patients compared to CTR, WM atrophy was more disease specific, with extensive involvement in FTSD and some involvement in FTSD-ALS. Atrophy of frontal and temporal cortices in FTSD patients confirms previous results (Kanda et al, 2008;Luo et al, 2020), whereas spread reduced WM volumes indicates an overall network disruption that may be independent or secondary to GM atrophy. The present cross-sectional data cannot answer mechanistic questions on WM and GM alterations in FTSD patients, that need to be dealt with appropriate dedicated longitudinal studies where the interplay of GM and WM involvement can be followed over time.…”

“…In ALS patients, previous studies reported atrophy in non-motor areas involved in executive and behavioral functions, such as frontal, temporal and limbic regions (Menke et al, 2014;Luo et al, 2020). Although our ALS patients did not show atrophy in those regions, the involvement of motor and premotor regions emerging from a less stringent statistical analysis is indeed consistent with motor symptoms onset in ALS.…”

“…Family forms combining both diseases have already been described, hence FTSD and ALS may be thought as pathophysiological continuum, with up to 50% ALS patients presenting FTSD symptoms (Lattante et al, 2015). Furthermore, a recent metaanalysis has demonstrated either converging and disease-specific patterns of gray matter atrophy in bvFTSD and ALS patients, supporting the existence of a clinical continuum (Luo et al, 2020). However, it is hard to predict which patients are prone to develop both aspects of the continuum.…”

Hippocampal and insula volume in mild cognitive impairment with Lewy bodies

“…[10] A meta-analysis of voxelwise studies in grey matter in DLB found atrophy in the bilateral insula cortex [11] and some studies have also found insula atrophy in prodromal DLB. [12,13] However, insula atrophy has also been identified in AD, [14] fronto-temporal dementia, [15] and associated with cognitive impairment in HIV infected individuals. [16] Since there have been relatively few studies investigating the diagnostic utility of these two structural brain markers in mild cognitive impairment (MCI), the aim of this study was to investigate them in a cohort of probable MCI with Lewy bodies (MCI-LB) compared to MCI with no core features of Lewy body disease (MCI-AD).…”

Potential Role of Nanoparticles in Treating the Accumulation of Amyloid-Beta Peptide in Alzheimer’s Patients

“…The functional cognitive disorder may also occur well before the disease begins if Aβ is produced and cholinergic systems dislocate. Nanoparticles combine the targets, visualization, and treatment in one form to give drug molecules new hope and cross BBB [6]. Figure 1 shows the effects of different types of nanoparticles on the treatment of Alzheimer's.…”