Abstract
Apathy is recognized as the most common behavioral change in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), a multisystem neurodegenerative disorder. Particularly, apathy has been reported to be associated with poor ALS prognosis. However, the brain microstructural correlates of this behavioral symptom, reported as the most common in ALS, have not been completely elucidated. Using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS), here we aimed to quantify the correlation between brain microstructural damage and apathy scores in the early stages of ALS. Twenty-one consecutive ALS patients, in King's clinical stage 1 or 2, and 19 age- and sex-matched healthy controls (HCs) underwent magnetic resonance imaging and neuropsychological examination. Between-group comparisons did not show any significant difference on cognitive and behavioral variables. When compared to HCs, ALS patients exhibited a decreased fractional anisotropy (FA) [p < .05, threshold-free cluster enhancement (TFCE) corrected] in the corpus callosum and in bilateral anterior cingulate cortices. Self-rated Apathy Evaluation Scale (AES) scores and self-rated apathy T-scores of the Frontal Systems Behavior (FrSBe) scale were found inversely correlated to FA measures (p < .05, TFCE corrected) in widespread white matter (WM) areas, including several associative fiber tracts in the frontal, temporal, and parietal lobes. These results point towards an early microstructural degeneration of brain areas biologically involved in cognition and behavior regulation in ALS. Moreover, the significant correlations between apathy and DTI measures in several brain areas may suggest that subtle WM changes may be associated with mild behavioral symptoms in ALS even in the absence of overt cognitive and behavioral impairment.
Highlights
Apathy is defined as decreased motivation towards goaldirected behaviors [1] and may occur as a symptom of a variety of different psychiatric and neurodegenerative diseases [2, 3]
Our findings revealed that amyotrophic lateral sclerosis (ALS) patients, in early stages of disease and without cognitive or behavioral impairment, may exhibit microstructural changes in both motor and extra-motor white matter (WM) tracts
We performed a tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) data, a hypothesis-free technique which is capable of detecting structural changes over the whole brain and highlights the structural process of disease spreading across WM fibers known to connect motor areas [59, 60, 63]
Summary
Apathy is defined as decreased motivation towards goaldirected behaviors [1] and may occur as a symptom of a variety of different psychiatric and neurodegenerative diseases [2, 3]. While FrSBe is not designed for testing patients with physical disability [18, 19], AES is a well-established method for assessing apathy in several neurodegenerative diseases [3, 22] Both FrSBe and AES allow performing a monodimensional evaluation of apathy. This symptom is composed of multiple factors related to the cognitive, behavioral, and emotional domains [23], and recent studies employed a factorial analysis of AES scores revealing a triadic or four-factor substructure of the scale in Parkinson’s disease [24, 25]
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