Robust evidence suggests that the glymphatic system plays a key role in preserving brain health. Indeed, its activity in maintaining homeostasis by clearing neurotoxic proteins such as beta-amyloid ...from the human brain is essential. Sleep represents the factor that mainly influences this system, since it is selectively active during the night, in particular during non-rapid eye movement (NREM) sleep. This is true, since the sleep head position, in particular the supine position for its relationship to the status of opening/closing of the jugular veins, appears to be determinant for the development of future neurodegeneration. Growing evidence from human and animal models highlights the neurobiological link between sleep, glymphatic dysfunction and neurodegeneration. On the other hand, several modifiable factors have been recently identified modulating (improve/reduce) glymphatic system activity, such as Omega-3 polyunsaturated fatty acids, stress, hypertension, physical activity, alcohol, gender and genetic predisposition, in particular variants of aquaporin-4 (AQP4). From this viewpoint, our ambition is to discuss how the glymphatic system works in the brain, what factors mainly impact on this activity and its strict relation with the neurodegeneration. Future directions might include the analysis of factors modulating glymphatic system activity and a personalized glymphatic profile, “glymphatom”, as a natural target for preventive neurodegenerative treatment.
Differentiating clinically progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) may be challenging, especially in the absence of vertical supranuclear gaze palsy (VSGP). ...The Magnetic Resonance Parkinsonism Index (MRPI) has been reported to accurately distinguish between PSP and PD, yet few data exist on the usefulness of this biomarker for the differentiation of PSP-P from PD.
Thirty-four patients with PSP-P, 46 with PSP-Richardson's syndrome (PSP-RS), 53 with PD, and 53 controls were enrolled. New consensus criteria for the clinical diagnosis of PSP were used as the reference standard. The MRPI, and a new index termed MRPI 2.0 including the measurement of the third ventricle width (MRPI multiplied by third ventricle width/frontal horns width ratio), were calculated on T1-weighted MR images.
The MRPI differentiated patients with PSP-P from those with PD with sensitivity and specificity of 73.5% and 98.1%, respectively, while the MRPI 2.0 showed higher sensitivity (100%) and similar specificity (94.3%) in differentiating between these two groups. Both biomarkers showed excellent performance in differentiating PSP-P patients with VSGP from those with PD, but the MRPI 2.0 was much more accurate (95.8%) than MRPI in differentiating PSP-P patients with slowness of vertical saccades from PD patients.
The MRPI 2.0 accurately differentiated PSP-P patients from those with PD. This new index was more powerful than MRPI in differentiating PSP patients in the early stage of the disease with slowness of vertical saccades from patients with PD, thus helping clinicians to consolidate the diagnosis based on clinical features, in vivo.
•Distinguishing PSP-P from PD is challenging in the early stages of the disease.•Few data exist on the usefulness of MRPI for diagnosing PSP-P patients.•MRPI 2.0 is a new version of MRPI which includes the 3rd ventricular width.•MRPI 2.0 accurately differentiated patients with PSP-P from those with PD.•MRPI 2.0 accurately diagnosed PSP-P in the absence of vertical ocular palsy.
Dementia with Lewy bodies (DLB) is one of the most common causes of dementia and belongs to the group of α-synucleinopathies. Due to its clinical overlap with other neurodegenerative disorders and ...its high clinical heterogeneity, the clinical differential diagnosis of DLB from other similar disorders is often difficult and it is frequently underdiagnosed. Moreover, its genetic etiology has been studied only recently due to the unavailability of large cohorts with a certain diagnosis and shows genetic heterogeneity with a rare contribution of pathogenic mutations and relatively common risk factors. The rapid increase in the reported cases of DLB highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods proposed by the International DLB consortium rely on a list of criteria that comprises both clinical observations and the use of biomarkers. Herein, we summarize the up-to-now reported knowledge on the genetic architecture of DLB and discuss the use of prodromal biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.
•We investigated how hippocampal changes relate to memory cued recall in AD and PDD.•We performed a multimodal hippocampal MRI study and a memory evaluation trough FCSRT.•Hippocampal subfields showed ...different vulnerability to damage related to AD and PDD.•CA1, CA4-DG and subiculum were the subfields differently involved in AD and PDD.•CA1, CA4-DG and subiculum were related to total recall items of FCSRT in AD group.
Alzheimer’s disease (AD) and Parkinson’s disease with dementia (PDD) are characterized by a different mnesic failure, particularly in memory cued recall. Although hippocampal involvement has been shown in both these diseases, it remains unknown whether a selective damage of specific subfields within the hippocampus may be responsible for the peculiar mnesic profile observed in AD and PDD. To explore this topic, we combined a multimodal 3 T-MRI hippocampal evaluation (whole-brain T1-weighted and diffusion tensor imaging) with a hippocampal-targeted neuropsychological assessment (Free and Cued Selective Reminding Test FCSRT) in 22 AD subjects, 18 PDD and 17 healthy controls. Macro- and microstructural features (volume; shape; mean diffusivity MD; fractional anisotropy FA) of bilateral hippocampi (whole and subfields) were obtained. Correlations between MRI-derived parameters and neuropsychological evaluations were performed.
In the comparison between AD and PDD, the multimodal analysis allowed us to identify that subiculum, CA1 and CA4-DG were differently involved in these diseases and correlated with immediate and delayed total recall items of FCSRT. Moreover, compared to controls, AD showed a reduction in almost all subfields, with a MD increase in the same regions, whereas PDD displayed a volume loss, less severe than AD, more evident in the CA2-3 and presubiculum subfields.
Our study provides new evidence that hippocampal subregions had different vulnerability to damage related to AD and PDD. The combination of the in vivo analysis of hippocampal subfields with the FCSRT paradigm provided important insights into whether changes within specific hippocampal subfields are related to the different mnesic profile in AD and PDD patients.
We investigated the disease progression rate in patients with progressive supranuclear palsy-Richardson syndrome (PSP-RS) and PSP-parkinsonism (PSP-P) in comparison with Parkinson disease (PD) ...patients, using MRPI (Magnetic Resonance Parkinsonism Index), and MRPI 2.0.
Fifteen PSP-RS patients (disease duration, y, mean ± SD: 2.5 ± 1.1), 16 PSP-P patients (disease duration, y, mean ± SD: 6.5 ± 3.2) and 19 PD patients (disease duration, y, mean ± SD: 3.2 ± 2.3) were enrolled. All patients underwent clinical assessment and MRI at baseline, 1-year, and 2-year follow-up. MRPI, MRPI 2.0 and clinical scores over 1 and 2-years were used to evaluate disease progression rate, and to calculate sample sizes required to power placebo-controlled trials.
All groups showed increased clinical motor scores over time whereas only PSP groups had increased MRPI and MRPI 2.0 values over T1 and T2 intervals. The percentage increase over 1 and 2-years of MRPI and MRPI 2.0 values was significantly higher in PSP groups than in PD group, and in PSP-RS than in PSP-P patients while no difference between patient groups was observed when clinical motor scores were considered. Sample size estimates showed that MRPI 2.0 performed better than MRPI and clinical scales. Treatment trials with MRPI 2.0 could be performed over 2-years both in PSP-RS and PSP-P with a sample size per treatment arm of 89 and 170 patients, respectively.
Our results demonstrate that MRPI 2.0 was more powerful than MRPI and clinical motor scales in evaluating PSP progression, and in providing the best sample size estimates for clinical trials.
•MRPI and MRPI 2.0 detected disease progression in PSP patients.•MRPI 2.0 was more powerful than MRPI and motor scales in detecting PSP progression.•MRPI 2.0 was the best measure for assessing sample size for clinical trials.
To evaluate circadian fluctuations and night/day ratio of Heart Rate Variability (HRV) spectral components in patients with obstructive sleep apnea (OSA) in comparison with controls.
This is a ...simultaneous HRV-polysomnographic (PSG) study including 29 patients with OSA and 18 age-sex-matched controls. Four patients with OSA dropped out. All participants underwent PSG and HRV analysis. We measured the 24-hour fluctuations and the night/day ratio of low frequency (LF) and high frequency (HF) spectral components of HRV in all subjects and controls. The LF night/day ratio was termed the cardiac sympathetic index while the HF night/day ratio was termed the cardiac parasympathetic index.
All twenty-five OSA patients were PSG positive (presence of OSA) while 18 controls were PSG negative (absence of OSA). There was no significant difference in LF and HF 24-hour fluctuation values between OSA patients and controls. In OSA patients, LF and HF values were significantly higher during night-time than day time recordings (p<0.001). HF night/day ratio (cardiac parasympathetic index) accurately (100%) differentiated OSA patients from controls without an overlap of individual values. The LF night/day ratio (cardiac sympathetic index) had sensitivity of 84%, specificity of 72.2% and accuracy of 79.1% in distinguishing between groups.
The cardiac parasympathetic index accurately differentiated patients with OSA from controls, on an individual basis.
Abstract Background and purpose Quantitative analysis of brain atrophy may be useful in differentiating Parkinson’s Disease (PD) from Progressive Supranuclear Palsy (PSP) and parkinsonian variant of ...Multiple System Atrophy (MSA-P); the aim of this study was to identify the volumetric differences of subcortical structures in patients with PD, PSP and MSA-P using a novel and validated fully-automated whole brain segmentation method. Methods Volumetric MRIs were obtained in 72 patients with PD, 32 patients with PSP, 15 patients with MSA-P, and in 46 control subjects. Subcortical volume was measured automatically by FreeSurfer. Multivariate analysis of covariance, adjusted for intracranial volume (ICV), sex and age, was used to explore group differences. Results No volumetric differences were found between PD and controls group; otherwise the volumes of the cerebellum, the thalamus, the putamen, the pallidum, the hippocampus, and the brainstem were significantly reduced in PSP and MSA-P compared to patients with PD and control subjects. PSP and MSA-P patients only differed in thalamus volume which was smaller in PSP group ( p < 0.001). Moreover, patients with PSP and MSA-P showed a ventricular system (including lateral, third and fourth ventricles) larger than that detected in PD and controls ( p < 0.001). Conclusions Volumetric data obtained with automated segmentation of cerebral regions show a significant atrophy of different brain structures in parkinsonisms rather than in PD. Our study also demonstrates that the atrophy of the thalamus only occurs in PSP while the enlargement of the whole ventricular system characterizes both PSP and MSA-P.
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