Neurological Consequences, Mental Health, Physical Care, and Appropriate Nutrition in Long-COVID-19.

SARS-CoV-2 pandemic has caused a collapse of the world health systems. Now, vaccines and more effective therapies have reversed this crisis but the scenario is further aggravated by the appearance of a new pathology, occurring as SARS-CoV-2 infection consequence: the long-COVID-19. This term is commonly used to describe signs and symptoms that continue or develop after acute infection of COVID-19 up to several months. In this review, the consequences of the disease on mental health and the neurological implications due to the long-COVID are described. Furthermore, the appropriate nutritional approach and some recommendations to relieve the symptoms of the pathology are presented. Data collected indicated that in the next future the disease will affect an increasing number of individuals and that interdisciplinary action is needed to counteract it.

Internal carotid artery dissection in a patient with hemophilia A: a case report and literature review.

Spontaneous cervical artery dissection (sCeAD) is the most common cause of ischemic stroke at a young age, but its pathogenetic mechanism and risk factors are not fully elucidated. It is reasonable to think that bleeding propensity, vascular risk factors such as hypertension and head or neck trauma, and constitutional weakness of the arterial wall together play a role in the pathogenesis of sCeAD. Hemophilia A is known to be an X-linked condition that leads to spontaneous bleeding in various tissues and organs. To date, a few cases of acute arterial dissection in patients with hemophilia have been reported, but the relationship between these two diseases has not been studied so far. In addition, there are no guidelines indicating the best antithrombotic treatment option in these patients. We report the case of a man with hemophilia A who developed sCeAD and transient oculo-pyramidal syndrome and was treated with acetylsalicylic acid. We also review previous published cases of arterial dissection in patients with hemophilia, discussing the potential pathogenetic mechanism underlying this rare association and potential antithrombotic therapeutic options.

Executive functioning and serum lipid fractions in Parkinson's disease-a possible sex-effect: the PACOS study.

The association between dyslipidemia and cognitive performance in Parkinson's disease (PD) patients still needs to be clarified. Aim of the study was to evaluate the presence of possible associations between serum lipids fractions and executive dysfunction also exploring the sex-specific contribute of lipids level on cognition. Patients from the PACOS cohort, who underwent a complete serum lipid profile measures (total cholesterol-TC, low-density lipoprotein cholesterol-LDL, high-density lipoprotein cholesterol-HDL and triglycerides-TG) were selected. Adult Treatment Panel III guidelines of the National Cholesterol Education Program were used to classify normal/abnormal lipid fractions. Executive functioning was assessed with the Frontal Assessment Battery (FAB). Logistic regression was performed to assess associations between lipids fractions and FAB score. Correlations between lipids fractions and FAB score were explored. Sex-stratified analysis was performed. Three hundred and forty-eight PD patients (148 women; age 66.5 ± 9.5 years; disease duration 3.9 ± 4.9 years) were enrolled. Women presented significantly higher TC, LDL and HDL than men. In the whole sample, any association between lipid profile measures and FAB score was found. Among women, a positive association between hypertriglyceridemia and FAB score under cutoff was found (OR 3.4; 95%CI 1.29-9.03; p value 0.013). A statistically significant negative correlation was found between the FAB score and triglyceride serum levels (r = - 0.226; p value 0.005). Differently, among men, a statistically significant negative association between hypercholesterolemia and FAB score under cutoff (OR 0.4; 95%CI 0.17-0.84; p value 0.018) and between high LDL levels and FAB score under cutoff (OR 0.4; 95%CI 0.18-0.90; p value 0.027) were found. Our data suggest a sex-specific different role of lipids in executive functioning.

Morphometric magnetic resonance imaging cortico-subcortical features in Parkinson's disease with mild cognitive impairment.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) patients with cognitive impairment undergo progressive atrophy of several cortical and subcortical areas. The aim was to study the magnetic resonance imaging (MRI) morphometric features of PD patients with mild cognitive impairment (MCI). METHODS: Patients from the Parkinson's Disease Cognitive Impairment Study (PACOS) cohort with an available structural volumetric brain MRI and morphometric measurements of the midbrain and pons areas, middle cerebellar peduncle, superior cerebellar peduncle width and midbrain anteroposterior diameter (A-Pdiam) were included. MCI was diagnosed according to the Movement Disorder Society level II criteria. Additionally, cortical thickness analysis was performed and correlated with morphometric brainstem measurements. RESULTS: Morphometric measurements were available for 168 subjects, of whom 67 (39.9%) were diagnosed with PD-MCI. The mean age (± standard deviation) of the sample was 64.2 ± 9.8. Amongst patients, 84 (50%) were men with a disease duration of 5.2 ± 5.4 years and a Unified Parkinson's Disease Rating Scale-Motor Examination score of 32.1 ± 12.9. In the univariate and multivariate analysis, after adjusting for age, sex, years of schooling and disease duration, MCI was associated with midbrain area (odds ratio 0.98; 95% confidence interval 0.96-0.99; p = 0.048) and A-Pdiam (odds ratio 0.63; 95% confidence interval 0.46-0.86; p = 0.005). Furthermore, 121 PD patients underwent cortical thickness analysis, which showed the presence of cortical thinning in lateral orbitofrontal regions of patients with PD-MCI. No correlation was found between cortical thickness and brainstem morphometric measurements. CONCLUSIONS: A mild midbrain atrophy and the presence of frontal cortical thickness reduction might be considered a structural MRI feature of PD patients with MCI.

Neuroanatomical changes in early Parkinson's disease with mild cognitive impairment: a VBM study; the Parkinson's Disease Cognitive Impairment Study (PaCoS).

INTRODUCTION: Mild cognitive impairment (MCI) is common in Parkinson's disease (PD), but the underlying pathological mechanism has not been fully understood. Voxel-based morphometry could be used to evaluate regional atrophy and its relationship with cognitive performances in early PD-MCI. PATIENTS AND METHODS: One hundred and six patients with PD were recruited from a larger cohort of patients, the Parkinson's Disease Cognitive Impairment Study (PaCoS). Subject underwent a T1-3D MRI and a complete clinical and neuropsychological evaluation. Patients were divided into PD with normal cognition (PD-NC) and PD-MCI according to the MDS level II criteria-modified for PD-MCI. A subgroup of early patients with short disease duration (≤ 2 years) was also identified. VBM analysis between PD-NC and PD-MCI and between early PD-NC and PD-MCI was performed using two-sample t tests with whole-brain statistical threshold of p < 0.001 uncorrected in the entire PD group and p < 0.05 FWE inside ROIs, in the early PD. RESULTS: Forty patients were diagnosed with MCI and 66 were PD-NC. PD-MCI patients showed significant gray matter (GM) reduction in several brain regions, including frontal gyrus, precuneus, angular gyrus, temporal lobe, and cerebellum. Early PD-MCI showed reduction in GM density in superior frontal gyrus and cerebellum. Moreover, correlation analysis between neuropsychological performances and GM volume of early PD-MCI patients showed associations between performances of Raven and superior frontal gyrus volume, Stroop time and inferior frontal gyrus volume, accuracy of Barrage and volume of precuneus. CONCLUSION: The detection of frontal and cerebellar atrophy, even at an early stage, could be used as an early marker of PD-related cognitive impairment.

Transcranial random noise stimulation over the primary motor cortex in PD-MCI patients: a crossover, randomized, sham-controlled study.

Mild cognitive impairment (MCI) is a very common non-motor feature of Parkinson's disease (PD) and the non-amnestic single-domain is the most frequent subtype. Transcranial random noise stimulation (tRNS) is a non-invasive technique, which is capable of enhancing cortical excitability. As the main contributor to voluntary movement control, the primary motor cortex (M1) has been recently reported to be involved in higher cognitive functioning. The aim of this study is to evaluate the effects of tRNS applied over M1 in PD-MCI patients in cognitive and motor tasks. Ten PD-MCI patients, diagnosed according to the Movement Disorder Society, Level II criteria for MCI, underwent active (real) and placebo (sham) tRNS single sessions, at least 1 week apart. Patients underwent cognitive (Digit Span Forward and Backward, Digit Symbol, Visual Search, Letter Fluency, Stroop Test) and motor assessments (Unified Parkinson's Disease Rating Scale [UPDRS-ME], specific timed trials for bradykinesia, 10-m walk and Timed up and go tests) before and after each session. A significant improvement in motor ability (UPDRS-ME and lateralized scores, ps from 0.049 to 0.003) was observed after real versus sham tRNS. On the contrary, no significant differences were found in other motor tasks and cognitive assessment both after real and sham stimulations. These results confirm that tRNS is a safe and effective tool for improving motor functioning in PD-MCI. Future studies using a multisession tRNS applied over multitargeted brain areas (i.e., dorsolateral prefrontal cortex and M1) are required to clarify the role of tRNS regarding rehabilitative intervention in PD.

Visuospatial learning is fostered in migraine: evidence by a neuropsychological study.

BACKGROUND: Cognitive profile in migraine patients still remains undefined. Contradictory evidence has been provided, with impairments in different cognitive domains, normal cognition, or even better performance compared to healthy controls (HC). The latter is of particular interest considering the evidence of glutamatergic upregulation in migraine, particularly in the visual cortex, and the role of the glutamatergic system in synaptic plasticity and learning. The aim of our study is to compare cognitive performance for visuospatial memory and learning (supraspan modality) between migraineurs without aura (MwoA) and HC. METHODS: Twenty-one subjects suffering from MwoA and 21 HC were enrolled. Migraineurs during the interictal phase and HC underwent visuospatial memory test (Corsi test) and verbal memory test (Buschke Selective Reminding Test) in supraspan modality, Trial Making Test A (TMTA) and B (TMTB) as test exploring attention, and TMTB-TMTA as test of executive functioning. Depression was assessed with the Beck Depression Inventory Short Form (BDI-SF). Migraine characteristics (i.e., disease duration and frequency expressed as attacks per month) were collected. RESULTS: Subjects with MwoA showed better performance than HC in test exploring both short (p = 0.002) and long-term (p = 0.001) visuospatial memory. No significant difference between groups was found in verbal memory, attention, executive functioning, and depression (BDI-SF). No significant association emerged between cognitive performance and migraine characteristics. DISCUSSION: Subjects with MwoA had significant better performance in visuospatial memory and learning than HC. Occipito-parietal hyperexcitability (in particular in the visual cortex), which is a hallmark of the migraine brain, would probably explain these results. These data need to be confirmed in larger samples of migraineurs.

Motor cortex tRNS improves pain, affective and cognitive impairment in patients with fibromyalgia: preliminary results of a randomised sham-controlled trial.

OBJECTIVES: Fibromyalgia (FM) is a clinical syndrome characterised by widespread musculoskeletal pain, chronic fatigue, cognitive deficits, and sleep and mood disorders. The effectiveness of most pharmacological treatments is limited, and there is a need for new, effective and well-tolerated therapies. It has recently been shown that transcranial direct-current stimulation (tDCS) of the motor cortex reduces pain, and that tDCS of the dorso-lateral prefrontal cortex (DLPFC) improves anxiety, depression and cognitive impairment in FM patients. The new technique of transcranial random noise stimulation (tRNS) using randomly changing alternating currents has very recently been shown to improve working memory and pain in limited series of patients with FM or neuropathic pain. The aim of this study was to investigate the clinical effects of primary motor cortex (M1) tRNS in FM patients. METHODS: Twenty female FM patients aged 26-67 years were randomised to undergo active (real) or placebo (sham) tRNS sessions on five days a week (Monday-Friday) for two weeks. Each patient was evaluated before and after treatment using a visual analogue scale (VAS), the Fibromyalgia Impact Questionnaire (FIQ), the Hospital Anxiety and Depression Scale (HADS), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test (RAVLT), the Forward and Backward Digit Span test, and the FAS verbal fluency test. RESULTS: In comparison with sham treatment, active tRNS of M1 induced a general improvement in the clinical picture of FM, with a significant reduction in pain, depression, anxiety and FIQ scores and a significant improvement in TMT (A), RAVLT and FAS scores. CONCLUSIONS: These findings suggest that tRNS of M1 can be very effective in relieving FM symptoms. Unlike motor cortex tDCS, it seems to counteract both pain and cognitive disturbances, possibly because the invoked mechanism of stochastic resonance synchronises neural firing and thus leads to more widespread and lasting effects.

Reduced threshold for inhibitory homeostatic responses in migraine motor cortex? A tDCS/TMS study.

BACKGROUND AND OBJECTIVE: Neurophysiological studies in migraine have reported conflicting findings of either cortical hyper- or hypoexcitability. In migraine with aura (MwA) patients, we recently documented an inhibitory response to suprathreshold, high-frequency repetitive transcranial magnetic stimulation (hf-rTMS) trains applied to the primary motor cortex, which is in contrast with the facilitatory response observed in the healthy subjects. The aim of the present study was to support the hypothesis that in migraine, because of a condition of basal increased cortical responsivity, inhibitory homeostatic like mechanisms of cortical excitability could be induced by high magnitude stimulation. For this purpose, the hf-rTMS trains were preconditioned by transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique able to modulate the cortical excitability state. METHODS: Twenty-two MwA patients and 20 patients with migraine without aura (MwoA) underwent trains of 5-Hz repetitive transcranial magnetic stimulation at an intensity of 130% of the resting motor threshold, both at baseline and after conditioning by 15 minutes of cathodal or anodal tDCS. Motor cortical responses to the hf-rTMS trains were compared with those of 14 healthy subjects. RESULTS: We observed abnormal inhibitory responses to the hf-rTMS trains given at baseline in both MwA and MwoA patients as compared with the healthy subjects (P < .00001).The main result of the study was that cathodal tDCS, which reduces the cortical excitability level, but not anodal tDCS, which increases it, restored the normal facilitatory response to the hf-rTMS trains in both MwA and MwoA. CONCLUSIONS: The present findings strengthen the notion that, in migraine with and without aura, the threshold for inducing inhibitory mechanisms of cortical excitability might be lower in the interictal period. This could represent a protective mechanism counteracting cortical hyperresponsivity. Our results could be helpful to explain some conflicting neurophysiological findings in migraine and to get insight into the mechanisms underlying recurrence of the migraine attacks.

Safety and patients' satisfaction of transcutaneous supraorbital neurostimulation (tSNS) with the Cefaly® device in headache treatment: a survey of 2,313 headache sufferers in the general population.

BACKGROUND: Transcutaneous supraorbital nerve stimulation (tSNS) with the Cefaly® device was recently found superior to sham stimulation for episodic migraine prevention in a randomized trial. Its safety and efficiency in larger cohorts of headache sufferers in the general population remain to be determined.The objective of this study was to assess the satisfaction with the Cefaly® device in 2,313 headache sufferers who rented the device for a 40-day trial period via Internet. METHODS: Only subjects using specific anti-migraine drugs, and thus most likely suffering from migraine, were included in the survey. Adverse events (AEs) and willingness to continue tSNS were monitored via phone interviews after the trial period. A built-in software allowed monitoring the total duration of use and hence compliance in subjects who returned the device to the manufacturer after the trial period. RESULTS: After a testing period of 58.2 days on average, 46.6% of the 2,313 renters were not satisfied and returned the device, but the compliance check showed that they used it only for 48.6% of the recommended time. The remaining 54.4% of subjects were satisfied with the tSNS treatment and willing to purchase the device. Ninety-nine subjects out of the 2,313 (4.3%) reported one or more AEs, but none of them was serious. The most frequent AEs were local pain/intolerance to paresthesia (47 subjects, i.e. 2.03%), arousal changes (mostly sleepiness/fatigue, sometimes insomnia, 19 subjects, i.e. 0.82%), headache after the stimulation (12 subjects, i.e. 0.52%). A transient local skin allergy was seen in 2 subjects, i.e. 0.09%. CONCLUSIONS: This survey of 2,313 headache sufferers in the general population confirms that tSNS with is a safe and well-tolerated treatment for migraine headaches that provides satisfaction to a majority of patients who tested it for 40 days. Only 4.3% of subjects reported AEs, all of them were minor and fully reversible.

Persistent Cognitive Dysfunction in a Non-Hospitalized COVID-19 Long-Hauler Patient Responding to Cognitive Rehabilitation and Citicoline Treatment.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is characterized by severe flu-like symptoms, which can progress to life-threatening systemic inflammation and multiorgan dysfunction. The nervous system is involved in over one-third of patients, and the most common neurological manifestations concern the central nervous system, such as headache, fatigue, and brain fog. The activation of innate, humoral, and cellular immune responses, resulting in a cytokine storm and endothelial and mitochondrial dysfunctions, are the main pathophysiological mechanisms of SARS-CoV-2 infection. Citicoline is an exogenous source of choline and cytidine involved in intracellular phospholipid synthesis, which improves blood flow, brain activity, and mitochondrial dysfunction. This report will present the case of a non-hospitalized, 59-year-old female. After a mild form of SARS-CoV-2 infection, the patient developed cognitive disturbances such as forgetfulness and anomia. The multidimensional neuropsychological assessment revealed an impairment in episodic memory with borderline performance in executive and visuospatial functioning. Cognitive rehabilitation and treatment with citicoline 1000 mg/daily led to a marked improvement in symptoms after six months. Early identification of the neurological sequelae of the Coronavirus Disease 2019 (COVID-19) and timely rehabilitation interventions are required in non-hospitalized long-hauler patients with COVID-19. Long-term treatment with citicoline should be considered as potentially effective in improving cognitive functioning in subjects with Post COVID-19 Neurological Syndrome.

Sex and gender differences in Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis: A narrative review.

Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), exhibit high phenotypic variability and they are very common in the general population. These diseases are associated with poor prognosis and a significant burden on patients and their caregivers. Although increasing evidence suggests that biological sex is an important factor for the development and phenotypical expression of some NDs, the role of sex and gender in the diagnosis and prognosis of NDs has been poorly explored. Current knowledge relating to sex- and gender-related differences in the epidemiology, clinical features, biomarkers, and treatment of AD, PD, and ALS will be summarized in this narrative review. The cumulative evidence hitherto collected suggests that sex and gender are factors to be considered in explaining the heterogeneity of these NDs. Clarifying the role of sex and gender in AD, PD, and ALS is a key topic in precision medicine, which will facilitate sex-specific prevention and treatment strategies to be implemented in the near future.

New-onset headache following COVID-19: An Italian multicentre case series.

OBJECTIVE: To describe the characteristics of patients with new-onset headache following SARS-CoV-2 infection. BACKGROUND: SARS-CoV-2 infection leads to several neurological manifestations, and headache is a frequent and disabling symptom, both exacerbating pre-existing headache syndromes and causing new-onset ones. METHODS: Patients with new-onset headache after SARS-CoV-2 infection with consent to participate were included, while those ones with previous headaches were excluded. The temporal latency of headache after infection, pain characteristics, and concomitant symptoms were analysed. Moreover, the efficacy of acute and preventive medications was explored. RESULTS: Eleven females (median age 37.0 [10.0-60.0] years old) were included. In most cases, headache onset occurred with the infection, the location of pain varied, and the quality was either pulsating or tightening. Headache was persistent and daily in 8 patients (72.7%), while it occurred in episodes in the remaining subjects. Baseline diagnoses were new daily persistent headache (36.4%), probable new daily persistent headache (36.4%), probable migraine (9.1%), and migraine-like headache secondary to COVID-19 (18.2%). Ten patients received one or more preventive treatments and six of them showed an improvement. CONCLUSION: New-onset headache following COVID-19 is a heterogenous condition with uncertain pathogenesis. This type of headache can become persistent and severe, with a wide spectrum of manifestations (new daily persistent headache being the most represented one) and variable response to treatment.

Oral Health Status in Subjects with Amnestic Mild Cognitive Impairment and Alzheimer's Disease: Data from the Zabút Aging Project.

BACKGROUND: The relationship between Alzheimer's disease (AD) and periodontitis has been recently investigated with heterogenous results. OBJECTIVE: This study aims to evaluate the oral health status and its relationship with cognitive impairment of participants, enrolled in the Zabút Aging Project, a community-based cohort study performed in a rural community in Sicily, Italy. METHODS: A case-control study (20 subjects with AD, 20 with amnestic mild cognitive impairment [aMCI], and 20 controls) was conducted. The protocol included a comprehensive medical and cognitive-behavioral examination. Full-mouth evaluation, microbial analysis of subgingival plaque samples (by RT-PCR analysis), and oral health-related quality of life (OHR-QoL) were evaluated. RESULTS: The decayed, missing, and filled teeth (DMFT) total score of AD subjects was significantly higher than aMCI (p = 0.009) and controls (p = 0.001). Furthermore, the "M" component of DMFT (i.e., the number of missing teeth) was significantly higher in AD than in aMCI (p < 0.001) and controls (p < 0.001). A Poisson regression model revealed that age (p < 0.001), male gender (p = 0.001), and AD (p = 0.001) were positively correlated with DMFT. Concerning oral microbial load, the presence of Fusobacterium nucleatum was significantly higher in AD than in controls (p = 0.02), and a higher load of Treponema denticola was found in aMCI than with AD (p = 0.004). OHR-QoL scores did not differ among the groups. CONCLUSION: The current research suggests that AD is associated with chronic periodontitis, which is capable of determining tooth loss due to the pathogenicity of Fusobacterium nucleatum. These data remain to be confirmed in larger population-based cohorts.

Influence of Drugs on Mild Cognitive Impairment in Parkinson's Disease: Evidence from the PACOS Study.

BACKGROUND: polytherapy and the anticholinergic activity of several drugs negatively influence cognition in the elderly. However, little is known on the effect on Mild Cognitive Impairment (MCI) in Parkinson's Disease (PD). METHODS: patients with PD belonging to the baseline PACOS cohort with full pharmacological data have been included in this study. MCI diagnosis was made according to the MDS level II criteria. Polytherapy was defined as patients assuming ≥6 drugs. The anticholinergic burden has been calculated using the Anticholinergic Drug Scale (ADS). Molecules have been classified according to the ATC classification. Association with MCI has been assessed with a multivariate logistic regression analysis with MCI as the dependent variable. RESULTS: pharmacological data were available for 238 patients (mean age 64.7±9.7). One hundred (42.0%) were diagnosed with MCI. No association was found in the full multivariate model (correcting for age, sex, disease duration, education, UPDRS-ME, LEDD-DAs) with either polytherapy or the ADS. Concerning drug classes, anti-hypertensive medications were positively associated with PD-MCI (OR 2.02;95%CI 1.04-3.89; p=0.035) while gastroprotective agents were negatively associated (OR 0.51; 95%CI 0.27-0.99; p=0.047). CONCLUSION: the magnitude of polytherapy and anticholinergic drugs burden does not appear to modulate MCI risk in PD, probably due to cautious prescription patterns. The effect of antihypertensive and gastroprotective agents on PD-MCI risk, while needing further confirmations, could be relevant for clinical practice.

Circulating Molecular Chaperones in Subjects with Amnestic Mild Cognitive Impairment and Alzheimer's Disease: Data from the Zabùt Aging Project.

Molecular chaperones play essential roles in many processes such as cell differentiation, tissue homeostasis, and organ remodeling. Recent data indicate that chaperones can act as cytoprotectants for brain cells during the progression of neurodegenerative diseases, including Alzheimer's disease (AD). However, very few data on the levels of chaperones in dementia, including its prodromal phases, have been reported. In this study, we used biological samples and epidemiological data collected during the Zabùt Aging Project (a prospective, community-based, cohort study of normal/pathological aging conducted in Sicily, Italy, with a follow-up of ten years) to determine if there is an association between plasma levels of the chaperones Hsp60, Hsp70, and Hsp90 with amnestic mild cognitive impairment (aMCI) and AD. Twenty-six aMCI individuals, 26 AD and 26 controls, matched for age and sex, were enrolled. After adjustment for education, subjects with AD showed significantly higher levels of Hsp60 than aMCI (OR = 1.16, 95% CI 1.04-1.30) and controls (OR = 1.12, 95% CI 1.03-1.22), while Hsp70 was significantly higher only in AD (OR = 1.84, 95% CI 1.09-3.10) than controls. In contrast, circulating levels of Hsp90 were significantly diminished in aMCI (OR = 0.69, 95% CI 0.52-0.91) and AD (OR = 0.51, 95% CI 0.35-0.75) compared to controls. However, these results were no longer significant after adjustment for multiple comparisons. Although the results lost significance after adjustment for multiple comparisons, they are encouraging despite the smallness of the sample and new studies should be carried out with larger populations to determine to what extent sequential measurement of serum chaperones in aMCI and AD can be trusted as indicators of disease status and progression.

Cognitive impairment and levodopa induced dyskinesia in Parkinson's disease: a longitudinal study from the PACOS cohort.

Aim of the study was to evaluate possible associations between cognitive dysfunctions and development of Levodopa Induced Dyskinesia (LID). PD patients from the Parkinson's disease Cognitive impairment Study cohort who underwent a baseline and follow-up neuropsychological evaluations were enrolled. Mild Cognitive Impairment (PD-MCI) was diagnosed according to MDS level II criteria. The following cognitive domains were evaluated: episodic memory, attention, executive function, visuo-spatial function and language. A domain was considered as impaired when the subject scored 2 standard deviation below normality cut-off values in at least one test for each domain. Levodopa equivalent dose, UPDRS-ME and LID were recorded at baseline and follow-up. To identify possible neuropsychological predictors associated with the probability of LID development at follow-up, Cox proportional-hazards regression model was used. Out of 139 PD patients enrolled (87 men, mean age 65.7 ± 9.4), 18 (12.9%) were dyskinetic at baseline. Out of 121 patients non-dyskinetic at baseline, 22 (18.1%) developed LID at follow-up. The impairment of the attention and executive domains strongly predicted the development of LID (HR 4.45;95%CI 1.49-13.23 and HR 3.46; 95%CI 1.26-9.48 respectively). Impairment of the attention and executive domains increased the risk of dyskinesia reflecting the alteration of common cortical network.

Vascular risk factors, white matter lesions and cognitive impairment in Parkinson's disease: the PACOS longitudinal study.

BACKGROUND: Vascular risk factors (VRFs) may be associated with cognitive decline in early Parkinson's disease (PD) but results are inconclusive. The identification of modifiable risk factors is relevant for prevention and treatment. METHODS: Parkinson's disease (PD) patients of the PACOS cohort who underwent a baseline and follow-up neuropsychological evaluation were enrolled in the study. PD with Mild Cognitive Impairment (MCI) and dementia (PDD) were diagnosed according to the MDS criteria. A Baseline 1.5 T brain MRI was used to calculate the white matter lesions (WMLs) burden using the Wahlund visual scale. Laboratory data, presence of hypertension, diabetes and use of anti-hypertensive drugs were collected and the Framingham Risk (FR) score was calculated. VRFs predicting PD-MCI and PDD were evaluated using Cox proportional hazard regression model. RESULTS: Out of 139 enrolled patients, 84 (60.4%) were classified as normal cognition (NC) and 55 (39.6%) as MCI at baseline. At follow-up 28 (33.3%) PD-NC developed MCI and 4 (4.8%) PDD (follow-up time 23.5 ± 10.3 months). Out of 55 PD-MCI patients at baseline, 14 (25.4%) converted to PDD. At multivariate analysis among PD-NC a systolic blood pressure (SBP) > 140 mmHg was the stronger predictor of MCI (adjHR 4.04; 95% CI 1.41-11.3) while the presence of MCI at baseline (adj HR 7.55; 95% CI 1.76-32.3) and a severe WMLs burden (adj HR 2.80; 95% CI 0.86-9.04) were the strongest predictors of PDD, even if this latter association has a trend towards significance. CONCLUSION: Hypertension represents the most important modifiable risk factor for PD-MCI in the PACOS cohort, increasing the risk of about four times.

Imaging of Substantia Nigra in Parkinson's Disease: A Narrative Review.

Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by motor and non-motor symptoms due to the degeneration of the pars compacta of the substantia nigra (SNc) with dopaminergic denervation of the striatum. Although the diagnosis of PD is principally based on a clinical assessment, great efforts have been expended over the past two decades to evaluate reliable biomarkers for PD. Among these biomarkers, magnetic resonance imaging (MRI)-based biomarkers may play a key role. Conventional MRI sequences are considered by many in the field to have low sensitivity, while advanced pulse sequences and ultra-high-field MRI techniques have brought many advantages, particularly regarding the study of brainstem and subcortical structures. Nowadays, nigrosome imaging, neuromelanine-sensitive sequences, iron-sensitive sequences, and advanced diffusion weighted imaging techniques afford new insights to the non-invasive study of the SNc. The use of these imaging methods, alone or in combination, may also help to discriminate PD patients from control patients, in addition to discriminating atypical parkinsonian syndromes (PS). A total of 92 articles were identified from an extensive review of the literature on PubMed in order to ascertain the-state-of-the-art of MRI techniques, as applied to the study of SNc in PD patients, as well as their potential future applications as imaging biomarkers of disease. Whilst none of these MRI-imaging biomarkers could be successfully validated for routine clinical practice, in achieving high levels of accuracy and reproducibility in the diagnosis of PD, a multimodal MRI-PD protocol may assist neuroradiologists and clinicians in the early and differential diagnosis of a wide spectrum of neurodegenerative disorders.