Evidence for Cognitive Impairment in Mastocytosis: Prevalence, Features and Correlations to Depression

Mastocytosis is a heterogeneous disease characterized by mast cells accumulation in one or more organs. We have reported that depression is frequent in mastocytosis, but although it was already described, little is known about the prevalence and features of cognitive impairment. Our objective was to describe the prevalence and features of cognitive impairment in a large cohort of patients with this rare disease (n = 57; mean age = 45) and to explore the relations between memory impairment and depression. Objective memory impairment was evaluated using the 3rd edition of the Clinical Memory scale of Wechsler. Depression symptoms were evaluated using the Hamilton Depression Rating Scale. Age and education levels were controlled for all patients. Patients with mastocytosis presented high levels of cognitive impairment (memory and/or attention) (n = 22; 38.6%). Cognitive impairment was moderate in 59% of the cases, concerned immediate auditory (41%) and working memory (73%) and was not associated to depression (p≥0.717). In conclusion, immediate auditory memory and attention impairment in mastocytosis are frequent, even in young individuals, and are not consecutive to depression. In mastocytosis, cognitive complaints call for complex neuropsychological assessment. Mild-moderate cognitive impairment and depression constitute two specific but somewhat independent syndromes in mastocytosis. These results suggest differential effects of mast-cell activity in the brain, on systems involved in emotionality and in cognition

Supplementary Material for: Neuropathology of Partial PGC-1α Deficiency Recapitulates Features of Mitochondrial Encephalopathies but Not of Neurodegenerative Diseases

<b><i>Background:</i></b> Deficient peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) function is one component of mitochondrial dysfunction in neurodegenerative diseases. Current molecular classification of such diseases is based on the predominant protein accumulating as intra- or extracellular aggregates. Experimental evidence suggests that mitochondrial dysfunction and impaired protein processing are closely interrelated. In vitro findings further indicate that PGC-1α dysfunction may contribute to protein misfolding in neurodegeneration. <b><i>Objective:</i></b> To systematically evaluate the neuropathological alterations of mice lacking the expression of the full-length PGC-1α protein (FL-PGC-1α) but expressing an N-truncated fragment. <b><i>Methods:</i></b> To assess the pattern of neurodegeneration-related proteins, we performed immunostaining for Tau, pTau, α-synuclein, amyloid-β, amyloid precursor protein, prion protein, FUS, TDP-43 and ubiquitin. Using hematoxylin and eosin, Klüver-Barrera and Bielschowsky silver stainings and anti-GFAP immunohistochemistry, we performed an anatomical mapping to provide a lesion profile. <b><i>Results:</i></b> The immunohistochemical pattern of neurodegeneration-related proteins did not differ between FL-PGC-1α knockout and wild-type animals, and there was a complete lack of protein deposits or ubiquitin-positive inclusions. The analysis of neuropathological alterations revealed widespread vacuolation predominating in the cerebral white matter, caudate-putamen, thalamus and brainstem, and reactive astrogliosis in the brainstem and cerebellar nuclei. This morphological phenotype was thus reminiscent of human mitochondrial encephalopathies, especially the Kearns-Sayre syndrome. <b><i>Conclusion:</i></b> We conclude that the lack of FL-PGC-1α per se is insufficient to recapitulate major features of neurodegenerative diseases, but evokes a pathology seen in mitochondrial encephalopathies, which makes PGC-1α-deficient mice a valuable model for this yet incurable group of diseases