Luisa Sambati

Melanopsin retinal ganglion cell loss in Alzheimer disease

Melanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer disease (AD). We investigated mRGCs in AD, hypothesizing that they contribute to circadian dysfunction.

Are subjective cognitive complaints a risk factor for dementia

The objective is to evaluate the prognosis of subjective cognitive complaints (SCC) patients during 4-year follow-up. A prospective study on 92 SCC patients investigating their cognitive, affective and behavioural aspects. SCC patients were classified as having no objective cognitive impairment (NOCI), mild cognitive impairment (MCI), or subtypes of MCI. Results: 43 patients were found to have NOCI and 49 MCI. During the follow-up, 45.5% of NOCI patients remained unchanged, 13.9% were diagnosed as MCI and only one progressed to dementia. Of the MCI patients, 32.3% remained stable, 18.4% became demented and 4% reverted to NOCI. Visual attention, behavioural memory, long-term verbal memory, apathy and caregiver distress, provided independent predictors of progression to dementia.

Accelerated long-term forgetting in temporal lobe epilepsy: Evidence of improvement after left temporal pole lobectomy

Accelerated long term forgetting (ALF) is a characteristic cognitive aspect in patients affected by temporal lobe epilepsy that is probably due to an impairment of memory consolidation and retrieval caused by epileptic activity in hippocampal and parahippocampal regions. We describe a case of a patient with TLE who showed improvement in ALF and in remote memory impairment after an anterior left temporal pole lobectomy including the uncus and amygdala. Our findings confirm that impairment of hippocampal functioning leads to pathological ALF, whereas restoration of hippocampal functioning brings ALF to a level comparable to that of controls.

Orthostatic hypotension and cognitive impairment: a dangerous association?

Many studies have addressed the relation between orthostatic hypotension (OH) and cognitive impairment (CI) in the elderly, in mild cognitive impairment, vascular and neurodegenerative dementias and movement disorders, such as Parkinson’s disease. However, results concerning both the increased coexistence of the two conditions and their causal relationship remain controversial. According to the literature three hypotheses can be formulated on the relation between OH and CI. In neurodegenerative disease, OH and CI may result from a common pathological process which affects areas involved in both cognition and cardiovascular autonomic control. Alternatively, OH may lead to cerebral hypoperfusion which is supposed to play a role in the development of CI. Finally, recent data suggest that CI should probably be considered more a transient symptom of OH than a chronic effect. This study reviews the literature reports on the relationship between OH and CI, and emphasises the need for longitudinal studies designed to investigate this topic.

Cognitive and Sleep Features of Multiple System Atrophy: Review and Prospective Study

Background: The profile and degree of cognitive impairment in Multiple System Atrophy (MSA) and the impact of sleep disorders, REM sleep behavior disorder (RBD) in particular, in parkinsonism-related cognitive deficits are currently being debated. Summary: We reviewed the cognitive, affective and sleep findings in MSA and also carried out a longitudinal investigation of 10 MSA patients. At the first evaluation, 3 patients showed isolated cognitive deficits. After a mean of 16 months, these patients remained unchanged, while 1 patient worsened from a normal condition. No significant differences emerged when the cognitive, affective and video-polysomnographic findings of MSA-P and MSA-C were compared. Depression was present in half of the patients, although it did not influence their cognitive performance. Comparisons between the first and second evaluation data showed significant worsening in visual attention and in ADL/IADL and UMSARS. Key Messages: Isolated cognitive deficits are evidenced in a minority of MSA patients with the absence of a clear-cut diagnosis of dementia in the early stages of the disease. Attention and executive functions are often impaired. This study with a short follow-up period showed that RBD, although present in almost all patients affected by MSA, does not appear a clear early marker of cognitive impairment. Future longer-term studies with a larger patient sample are thus encouraged.

Accuracy of MR markers for differentiating Progressive Supranuclear Palsy from Parkinson's disease

Background Advanced brain MR techniques are useful tools for differentiating Progressive Supranuclear Palsy from Parkinsons disease, although time-consuming and unlikely to be used all together in routine clinical work. We aimed to compare the diagnostic accuracy of quantitative morphometric, volumetric and DTI metrics for differentiating Progressive Supranuclear Palsy-Richardsons Syndrome from Parkinsons disease. Methods 23 Progressive Supranuclear Palsy-Richardsons Syndrome and 42 Parkinsons disease patients underwent a standardized 1.5T brain MR protocol comprising high-resolution T1W1 and DTI sequences. Brainstem and cerebellar peduncles morphometry, automated volumetric analysis of brain deep gray matter and DTI metric analyses of specific brain structures were carried out. We determined diagnostic accuracy, sensitivity and specificity of MR-markers with respect to the clinical diagnosis by using univariate receiver operating characteristics curve analyses. Age-adjusted multivariate receiver operating characteristics analyses were then conducted including only MR-markers with a sensitivity and specificity exceeding 80%. Results Morphometric markers (midbrain area, pons to midbrain area ratio and MR Parkinsonism Index), DTI parameters (infratentorial structures) and volumetric analysis (thalamus, putamen and pallidus nuclei) presented moderate to high diagnostic accuracy in discriminating Progressive Supranuclear Palsy-Richardsons Syndrome from Parkinsons disease, with midbrain area showing the highest diagnostic accuracy (99%) (mean ± standard deviation: 75.87 ± 16.95 mm2vs 132.45 ± 20.94 mm2, respectively; p < 0.001). Conclusion Although several quantitative brain MR markers provided high diagnostic accuracy in differentiating Progressive Supranuclear Palsy-Richardsons Syndrome from Parkinsons disease, the morphometric assessment of midbrain area is the best single diagnostic marker and should be routinely included in the neuroradiological work-up of parkinsonian patients.

Cognitive function in peripheral autonomic disorders

Objective aims of the current study were 1) to evaluate global cognitive function in patients with autonomic failure (AF) of peripheral origin and 2) to investigate the effect of a documented fall in blood pressure (BP) fulfilling the criteria for orthostatic hypotension (OH) on cognitive performances. Methods we assessed 12 consecutive patients (10 males, 68±7 years old) with pure AF (PAF) or autoimmune autonomic neuropathy (AAN) and 12 age- and gender-matched controls. All patients had no clinical signs of central nervous system involvement and normal brain CT/MRI scan. Cognitive function was assessed on two consecutive days in 3 conditions: on day 1, while sitting, by means of a comprehensive battery of neuropsychological tests; on day 2, while tilted (HUT) and during supine rest (supine) in a randomized manner. BP and heart rate (HR) were continuously recorded non-invasively for the whole duration of the examination. Results patients with PAF or AAN displayed a preserved global cognitive function while sitting. However, compared to supine assessment, during HUT patients scored significantly worse during the Trail Making Test A and B, Barrage test, Analogies test, Immediate Visual Memory, Span Forward and Span Backward test. Pathological scores, with regard to Italian normative range values, were observed only during HUT in the Barrage test and in the Analogies test in 3 and 6 patients respectively. On the contrary, in healthy controls, results to neuropsychological tests were not significantly different, during HUT compared to supine rest. Conclusions these data demonstrate that patients with PAF and AAN present a normal sitting global cognitive evaluation. However, their executive functions worsen significantly during the orthostatic challenge, possibly because of transient frontal lobes hypoperfusion.

The contribution of cerebellar proton magnetic resonance spectroscopy in the differential diagnosis among parkinsonian syndromes

INTRODUCTION The in vivo differential diagnosis between idiopathic Parkinsons disease (PD) and atypical parkinsonian syndromes (PS), such as multiple system atrophy [MSA with a cerebellar (C) and parkinsonian (P) subtype] and progressive supranuclear palsy - Richardsons Syndrome (PSP-RS) is often challenging. Previous brain MR proton spectroscopy ((1)H-MRS) studies showed biochemical alterations in PS, despite results are conflicting. Cerebellum plays a central role in motor control and its alterations has been already demonstrated in atypical PS. The main aim of this study was to evaluate diagnostic accuracy of cerebellar (1)H-MRS in the differential diagnosis between PD and atypical PS. METHODS We obtained (1)H-MRS spectra from the left cerebellar hemisphere of 57 PS (21 PD, and 36 atypical PS) and 14 unaffected controls by using a 1.5 T GE scanner. N-acetyl-aspartate (NAA)/Creatine (Cr), choline-containing compounds (Cho)/Cr, myoinositol (mI)/Cr, and NAA/mI ratios were calculated. RESULTS NAA/Cr and NAA/mI ratios were significantly lower (p < 0.01) in atypical PS compared to PD and controls, and in MSA-C compared to PD, MSA-P, PSP-RS and controls. PSP-RS group showed reduced NAA/Cr ratios compared to PD (p < 0.05) and controls (p < 0.05), and reduced NAA/mI compared to controls (p < 0.01). NAA/Cr ratio values higher than 1.016 showed 100% sensitivity and negative predictive value, 62% positive predictive value and 64% specificity in discriminating PD. CONCLUSION Cerebellar biochemical alterations detected by using (1)H-MRS could represent an adjunctive diagnostic tool to improve the differential diagnosis of PS.

Migraine: risk factor and comorbidity

The burden of migraine strongly increases considering its linkage with other psychiatric, neurological, cardiovascular and cerebrovascular diseases. Migraine is positively associated with many disorders: some are confirmed by several studies whereas others remain uncertain or controversial. The association with some disorders is not simply due to concomitance but it implies a linkage in terms of causality. Highlighting these relationships is important to improve treatment strategies, broaden our knowledge of the pathophysiology and understand if migraine is per se a modifiable risk factor for some disorders.

REM sleep behavior disorder, autonomic dysfunction and synuclein-related neurodegeneration: where do we stand?

IntroductionFrom newfound parasomnia to a marker of future synucleinopathy, since its first description in 1986, REM sleep behavior disorder (RBD) has been systematically tackled from virtually many viewpoints in basic, translational, and clinical studies. The time delay between RBD and synucleinopathy onset offers an exceptional window for observation and design of neuroprotective trials. In the last few years, research has focused on characterizing possible differences within RBD patients in order to draw potential profiles more or less susceptible to further neurodegeneration. Attention has been drawn towards autonomic dysfunction in RBD as one of such variables.OverviewIn this review, REM sleep physiology and relevant brain anatomy is briefly mentioned and integrated with neuroanatomical and physiological concepts regarding the central autonomic network. A detailed summary of works showing the presence of autonomic dysfunction in RBD is provided, and clinical and electrophysiological features of RBD in synucleinopathies are discussed. A short overview of RBD in other neurodegenerative diseases is also provided.