Cognitive Deficits in Machado–Joseph Disease Correlate with Hypoperfusion of Visual System Areas

Abstract

Cognitive and olfactory impairments have previously been demonstrated in patients with spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD)-SCA3/MJD. We investigated changes in regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) imaging in a cohort of Brazilian patients with SCA3/MJD. The aim of the present study was to evaluate the correlation among rCBF, cognitive deficits, and olfactory dysfunction in SCA3/MJD. Twenty-nine genetically confirmed SCA3/MJD patients and 25 control subjects were enrolled in the study. The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. Psychiatric symptoms were evaluated by the Hamilton Anxiety Scale and Beck Depression Inventory. The neuropsychological assessment consisted of Spatial Span, Symbol Search, Picture Completion, the Stroop Color Word Test, Trail Making Test (TMT), and Phonemic Verbal Fluency. Subjects were also submitted to odor identification evaluation using the 16-item Sniffin' Sticks. SPECT was performed using ethyl cysteine dimer labeled with technetium-99m. SCA3/MJD patients showed reduced brain perfusion in the cerebellum, temporal, limbic, and occipital lobes compared to control subjects (pFDR <0.001). A significant positive correlation was found between the Picture Completion test and perfusion of the left parahippocampal gyrus and basal ganglia in the patient group as well as a negative correlation between the TMT part A and bilateral thalamus perfusion. The visuospatial system is affected in patients with SCA3/MJD and may be responsible for the cognitive deficits seen in this disease.

Bidirectional Connections between Depression and Ataxia Severity in Spinocerebellar Ataxia Type 3 Patients

“…First, BDI was the only tool available for the evaluation of the subjects’ depression. The degree of depression would be accurate when assessed by a series of tools related to patients’ psychiatric symptoms, although BDI had also been used solely in several studies on the depression in SCA3 patients [15, 16, 18-21]. Second, although in our cohort, the frequency of depression was extremely high, we lacked an age- and sex-matched control group to compare between the 2 groups.…”

“…The severity of the subjects’ depression in SCA3 patients was evaluated by Beck depression inventory (BDI), which was solely and widely used for evaluating the depression of SCA3 patients [15, 16, 18-21]. Since the participating subjects were Chinese, the adopted BDI in Chinese version was found to exhibit optimal sensitivity and specificity in recognizing the depression among the ­Chinese-speaking population [22].…”

Diffusion Tensor Magnetic Resonance Imaging for Differentiating Multiple System Atrophy Cerebellar Type and Spinocerebellar Ataxia Type 3

“…The cognitive impairments in patients with SCA3, including verbal and visual memory deficits, visuospatial dysfunction, and executive dysfunction, have been described previously [22,45]. These neuropsychological abnormalities in SCA3 may be associated with cerebellar cognitive affective syndrome (CCAS) [46][47][48]. CCAS potentially involves the dysfunction of circuits connecting the cerebellum to the prefrontal lobe.…”

Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

“…Regional perfusion was correlated with clinical features in spinocerebellar ataxia type 3(SCA3) [9], SCA6 and ataxia telangectasia [1]. More importantly, SPECT perfusion data were recently utilized as surrogate biomarkers of the efficacy of thyrotropin releasing hormone or immunoglobulin therapy in pilot studies of degenerative and autoimmune ataxias and documented increased cerebellar blood flow in line with clinical improvement in patients with ILOCA, SCA6, or autoantibody-positive cerebellar ataxia, but not in those with MSA [10–12].…”