The phase coherence of the neurovascular unit is reduced in Huntington's disease.

Huntington's disease is a neurodegenerative disorder in which neuronal death leads to chorea and cognitive decline. Individuals with ≥40 cytosine-adenine-guanine repeats on the interesting transcript 15 gene develop Huntington's disease due to a mutated huntingtin protein. While the associated structural and molecular changes are well characterized, the alterations in neurovascular function that lead to the symptoms are not yet fully understood. Recently, the neurovascular unit has gained attention as a key player in neurodegenerative diseases. The mutant huntingtin protein is known to be present in the major parts of the neurovascular unit in individuals with Huntington's disease. However, a non-invasive assessment of neurovascular unit function in Huntington's disease has not yet been performed. Here, we investigate neurovascular interactions in presymptomatic (N = 13) and symptomatic (N = 15) Huntington's disease participants compared to healthy controls (N = 36). To assess the dynamics of oxygen transport to the brain, functional near-infrared spectroscopy, ECG and respiration effort were recorded. Simultaneously, neuronal activity was assessed using EEG. The resultant time series were analysed using methods for discerning time-resolved multiscale dynamics, such as wavelet transform power and wavelet phase coherence. Neurovascular phase coherence in the interval around 0.1 Hz is significantly reduced in both Huntington's disease groups. The presymptomatic Huntington's disease group has a lower power of oxygenation oscillations compared to controls. The spatial coherence of the oxygenation oscillations is lower in the symptomatic Huntington's disease group compared to the controls. The EEG phase coherence, especially in the α band, is reduced in both Huntington's disease groups and, to a significantly greater extent, in the symptomatic group. Our results show a reduced efficiency of the neurovascular unit in Huntington's disease both in the presymptomatic and symptomatic stages of the disease. The vasculature is already significantly impaired in the presymptomatic stage of the disease, resulting in reduced cerebral blood flow control. The results indicate vascular remodelling, which is most likely a compensatory mechanism. In contrast, the declines in α and γ coherence indicate a gradual deterioration of neuronal activity. The results raise the question of whether functional changes in the vasculature precede the functional changes in neuronal activity, which requires further investigation. The observation of altered dynamics paves the way for a simple method to monitor the progression of Huntington's disease non-invasively and evaluate the efficacy of treatments.

Cognitive function in early clinical phase huntington disease after rivastigmine treatment.

BACKGROUND: In Huntington disease (HD) patients receiving rivastigmine treatment improvement of behavioral symptoms and of cognitive function (assessed with screening diagnostic instruments) has been reported. The aim of the present study was to verify such improvement in cognitive function by cognitive function assessment with a detailed neuropsychological battery covering all relevant cognitive systems expected to be impaired in early phase HD. SUBJECTS AND METHODS: Eighteen (18) HD patients entered the study and were randomly allocated to the rivastigmine and placebo group. All subjects underwent neuropsychological assessment at baseline. Follow-up neuropsychological assessment was applied after 6 months of rivastigmine or placebo treatment. Eighteen (18) healthy controls entered the study to control for practice effect and underwent neuropsychological assessment at baseline and after 6 months, without treatment. The neuropsychological battery consisted of assessment tools that are sensitive to cognitive impairment seen in early phase HD: CTMT, SDMT, Stroop (attention and information control), RFFT, TOL, Verbal fluency (executive functioning), CVLT-II, RCFT (learning and memory). Effect of rivastigmine and possible effect of practice was assessed using the mixed ANOVA model. RESULTS: No statistically significant effect of rivastigmine treatment on cognitive function in HD patients was detected. There was no evidence for practice or placebo effect. CONCLUSIONS: Detailed neuropsychological assessment did not confirm previously reported effect of rivastigmine treatment on cognitive function in HD patients. The limitations of our study are, in particular, small sample size and the lack of a single measure of relevant cognitive functioning in HD patients. Instead of focusing solely on statistical significance, a clinical relevance study is proposed to clarify the issue of rivastigmine effects in HD.

Long-term cognitive deficits in patients with good outcomes after aneurysmal subarachnoid hemorrhage from anterior communicating artery.

AIM: To evaluate long-term cognitive consequences of subarachnoid hemorrhage with good outcome and the opinion of patients and their relatives about these consequences. METHODS: The study included 10 patients surgically treated for subarachnoid hemorrhage due to the rupture of aneurysm of the anterior communicating artery 2 or more years earlier, and 10 age- and sex-matched healthy controls. The preoperative and postoperative course in the patients was uneventful. Clinical and psychosocial factors and cognitive status of the patients were assessed by use of checklists and neuropsychological tests for executive functions, attention, and memory, and event-related potential recordings (waves P3a and P3b) with tree-stimulus auditory oddball paradigm, which was also performed in healthy controls. RESULTS: The number of reported cognitive problems negatively correlated with the patients' level of community integration (rho range, -0.22 to -0.75). The average neuropsychological results ranged between the 12th and 46th percentile. Impaired results were found in 7 patients across different tests and were most frequent for visual memory, followed by verbal memory and executive functions. A clear decline in cognitive functioning was observed in 3 patients. Neither P3a nor P3b wave could be found in 3 patients. In comparison with controls, patients had significantly longer P3b wave latencies (364 vs 334 ms; Mann-Whitney U test, P = 0.025). We found statistically non-significant, but still prominent negative correlations between the sustained attention results and latencies of P3a (rho = -0.58; P = 0.172) and P3b (rho = -0.58; P = 0.172) waves. CONCLUSION: Despite good outcome after subarachnoid hemorrhage, persistent cognitive consequences were still manifest, limiting the patients' psychosocial functioning. The correlation between neuropsychological and neurophysiological measures indicated frontal lobe damage, which in some patients persisted for years after the hemorrhage.