Striatal Atrophy in the Behavioural Variant of Frontotemporal Dementia: Correlation with Diagnosis, Negative Symptoms and Disease Severity

Abstract

IntroductionBehavioural variant frontotemporal dementia (bvFTD) is associated with changes in dorsal striatal parts of the basal ganglia (caudate nucleus and putamen), related to dysfunction in the cortico-striato-thalamic circuits which help mediate executive and motor functions. We aimed to determine whether the size and shape of striatal structures correlated with diagnosis of bvFTD, and measures of clinical severity, behaviour and cognition.Materials and MethodsMagnetic resonance imaging scans from 28 patients with bvFTD and 26 healthy controls were manually traced using image analysis software (ITK-SNAP). The resulting 3-D objects underwent volumetric analysis and shape analysis, through spherical harmonic description with point distribution models (SPHARM-PDM). Correlations with size and shape were sought with clinical measures in the bvTFD group, including Frontal Behavioural Inventory, Clinical Dementia Rating for bvFTD, Color Word Interference, Hayling part B and Brixton tests, and Trail-Making Test.ResultsCaudate nuclei and putamina were significantly smaller in the bvFTD group compared to controls (left caudate 16% smaller, partial eta squared 0.173, p=0.003; right caudate 11% smaller, partial eta squared 0.103, p=0.023; left putamen 18% smaller, partial eta squared 0.179, p=0.002; right putamen 12% smaller, partial eta squared 0.081, p=0.045), with global shape deflation in the caudate bilaterally but no localised shape change in putamen. In the bvFTD group, shape deflations on the left, corresponding to afferent connections from dorsolateral prefrontal mediofrontal/anterior cingulate and orbitofrontal cortex, correlated with worsening disease severity. Global shape deflation in the putamen correlated with Frontal Behavioural Inventory scores—higher scoring on negative symptoms was associated with the left putamen, while positive symptoms were associated with the right. Other cognitive tests had poor completion rates.ConclusionBehavioural symptoms and severity of bvFTD are correlated with abnormalities in striatal size and shape. This adds to the promise of imaging the striatum as a biomarker in this disease.

GRN mutation in a patient with a behavioral variant of frontotemporal lobar degeneration (bvFTD)

“…The 2010 brain MRI examination of our proband revealed not only asymmetric involvement with pronounced brain atrophy of the left temporal and frontal lobes and asymmetric caudate nucleus atrophy, which is in agreement with the literature [3,14], but also revealed greatly pronounced caudate nucleus and gyrus rectus atrophy on the left side, with virtually normal findings for the right caudate nucleus, and it would have been very interesting to follow the changes in asymmetry over time. Such a finding appears to be, according to some authors, a typical finding in bvFTD [8].…”

“…However, the asymmetric atrophy of the left hemisphere with predominance in temporal and frontal lobes, hippocampi and insula including subcortical atrophy with basal ganglia and the large atrophy of the left caudate nucleus indicate the diagnosis of bvFTD in our case. The shape deflation of the left caudate nucleus, which corresponded to afferent connections from the dorsolateral prefrontal mediofrontal/anterior cingulate and orbitofrontal cortex, correlated with worsening disease severity [14]. Our proband with dementia and pathogenic mutation in the GRN gene and a clinical manifestation of the disease fulfilled the diagnostic criteria for bvFTD.…”

“…The redefined clinical criteria recognize different phenotypes based on the clinical symptoms at presentation, including a possible behavioral variant of FTLD (bvFTD), two language variants, primary progressive nonfluent aphasia (PNFA), and a semantic variant. Notably, all variants can overlap with atypical Parkinsonian disorders such as progressive supranuclear palsy and corticobasal degeneration [5,12,14].…”

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

“…An overlap of gray matter atrophy in frontolimbic regions involving the bilateral anterior insula and anterior cingulate cortex was revealed. early in bvFTD (Garibotto et al, 2011;O'Callaghan et al, 2014;Macfarlane et al, 2015). There is increasing evidence from functional neuroimaging studies of the healthy that striatal regions modulate behavior and cognition (O'Callaghan et al, 2014), impairments of which are the manifestations of bvFTD.…”

Assessment of Iron Deposition in the Brain in Frontotemporal Dementia and Its Correlation with Behavioral Traits

“…44,45 The role of PUT in disinhibition may be due to its afferent connections to the medial, orbital and dorsolateral prefrontal regions as well as its link with prefrontal and motor circuits. 46 Therefore the regional iron deposition, as measured by SWI, may be used as a novel biomarker in the diagnosis of FTD subtypes.…”