Expanding the Neurological Phenotype of Anderson-Fabry Disease: Proof of Concept for an Extrapyramidal Neurodegenerative Pattern and Comparison with Monogenic Vascular Parkinsonism.

Anderson-Fabry disease (AFD) is a genetic sphingolipidosis involving virtually the entire body. Among its manifestation, the involvement of the central and peripheral nervous system is frequent. In recent decades, it has become evident that, besides cerebrovascular damage, a pure neuronal phenotype of AFD exists in the central nervous system, which is supported by clinical, pathological, and neuroimaging data. This neurodegenerative phenotype is often clinically characterized by an extrapyramidal component similar to the one seen in prodromal Parkinson's disease (PD). We analyzed the biological, clinical pathological, and neuroimaging data supporting this phenotype recently proposed in the literature. Moreover, we compared the neurodegenerative PD phenotype of AFD with a classical monogenic vascular disease responsible for vascular parkinsonism and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A substantial difference in the clinical and neuroimaging features of neurodegenerative and vascular parkinsonism phenotypes emerged, with AFD being potentially responsible for both forms of the extrapyramidal involvement, and CADASIL mainly associated with the vascular subtype. The available studies share some limitations regarding both patients' information and neurological and genetic investigations. Further studies are needed to clarify the potential association between AFD and extrapyramidal manifestations.

Prestroke Cognitive Impairment: Frequency and Association With Premorbid Neuropsychiatric, Functional, and Neuroimaging Features.

BACKGROUND: Some patients with stroke have prestroke cognitive impairment (pre-SCI), but its etiology is not clear. The aim of this cross-sectional study was to assess the frequency of pre-SCI and its association with premorbid neuropsychiatric, functional, and neuroimaging features. METHODS: Patients hospitalized in stroke unit with an informant who could complete IQCODE (Informant Questionnaire for Cognitive Decline in the Elderly) were included. Pre-SCI was diagnosed if the IQCODE score was >3.3. Prestroke assessment also included NPI-Q (Neuropsychiatric Inventory Questionnaire), the basic Activities of Daily Living and Instrumental Activities of Daily Living scales, and the Clinical Dementia Rating scale. A multivariate logistic regression model was used to evaluate the association of pre-SCI with age, sex, education, arterial hypertension, atrial fibrillation, white matter lesions, cerebral microbleeds, and pathological medial temporal lobe atrophy. RESULTS: IQCODE was available in 474 of 520 patients (91.2%; 45% women; mean age 75.5±13.3 years). Pre-SCI had a prevalence of 32.5% and was associated with prestroke NPI-Q (pre-SCI absent versus present, 1.7±2.3 versus 5.5±4.9; P<0.001), Activities of Daily Living scale (0.3±0.8 versus 1.8±1.9; P<0.001), Instrumental Activities of Daily Living scale (0.6±1.3 versus 3.8±4.0; P<0.001), and Clinical Dementia Rating scale score (0.7±1.7 versus 7.2±6.2; P<0.001). In the 271 patients with a magnetic resonance imaging available, the multivariate logistic regression showed that age (odds ratio [OR], 1.05 [95% CI, 1.62-9.73]), white matter lesions (OR, 1.26 [95% CI, 1.003-1.58]), and a pathological medial temporal lobe atrophy score (OR, 3.97 [95% CI, 1.62-9.73]) were independently associated with pre-SCI. In the 218 patients with ischemic stroke, white matter lesions (OR, 1.34 [95% CI, 1.04-1.72]) and medial temporal lobe atrophy (OR, 3.56 [95% CI, 1.38-9.19]), but not age, were associated with pre-SCI. CONCLUSIONS: One-third of patients admitted to a stroke unit have pre-SCI that is associated with preexisting neuropsychiatric symptoms and functional performance. White matter lesions and medial temporal lobe atrophy are associated with pre-SCI, suggesting that both small vessel disease and neurodegeneration might be involved in its etiology.

European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke.

A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We addressed acute treatment (including progressive lacunar stroke) and secondary prevention in lacunar ischaemic stroke, and prioritised the interventions of thrombolysis, antiplatelet drugs, blood pressure lowering, lipid lowering, lifestyle, and other interventions and their potential effects on the clinical outcomes recurrent stroke, dependency, major adverse cardiovascular events, death, cognitive decline, mobility, gait, or mood disorders. We systematically reviewed the literature, assessed the evidence and where feasible formulated evidence-based recommendations, and expert concensus statements. We found little direct evidence, mostly of low quality. We recommend that patients with suspected acute lacunar ischaemic stroke receive intravenous alteplase, antiplatelet drugs and avoid blood pressure lowering according to current acute ischaemic stroke guidelines. For secondary prevention, we recommend single antiplatelet treatment long-term, blood pressure control, and lipid lowering according to current guidelines. We recommend smoking cessation, regular exercise, other healthy lifestyle modifications, and avoid obesity for general health benefits. We cannot make any recommendation concerning progressive stroke or other drugs. Large randomised controlled trials with clinically important endpoints, including cognitive endpoints, are a priority for lacunar ischaemic stroke.

Brain health assessment. An exploratory review of tools related to its cognitive dimension.

Background: Brain health is an evolving concept and relates to physical and mental health, social well-being, productivity, creativity. Brain health has several dimensions (cognitive, motor, functional, social, and emotional), and should be recognized as one top global priorities of health policies. The purpose of this paper is to provide a summary of tools developed for assessing the cognitive dimension of brain health in the out-patient services. Methods: A literature search on PubMed was performed (from inception to May 31, 2023). We identified cognitive tests, functional and psychological scales, and focused on screening tools specifically proposed to characterize cognition within the construct of brain health, comparing them with common global screening tests. Results: Among 1947 records, we identified 17 cognitive screening tools used in the context of brain health assessment, of which four were ad hoc developed: Brain Health Assessment (BHA), Brain Health Test (BHT), Brain Health Test-7 (BHT-7), and The Cogniciti Brain Health Assessment. The four tests have administration time ranging from 4 to 30 min, and different administration methods (paper-and-pencil or tablet-based). All four tools assess memory and other cognitive domains. Specific cut-offs have been identified for BHT and BHT-7, while the other tools have automated scoring systems. All but one test also assess other dimensions. Compared to commonly used cognitive screening tests, the brain health tools are less widely used, translated, and validated. Conclusions: The concept of brain health is new and requires further validation of tools for its assessment, especially for the cognition dimension.

Sarcopenia and Multisensory Integration Deficit in Post-COVID Syndrome Patients: The Clinical, Ultrasound and Robotic Evaluation Protocol in a Cross-sectional Study.

INTRODUCTION: Post-COVID syndrome affects relatively young outpatients with fatigue as the mostly reported symptom. We wondered whether sarcopenia could play a role. METHODS: Seventy-four outpatients (median age: 53.8 yrs, 45 females), reporting fatigue and persistent mild neurological/motor deficits, completed the Clinical, Ultrasound and Robotic Evaluation protocol 4.8 mos after the infection. RESULTS: The incidence of sarcopenia was 41%. Sarcopenic patients were older (62.7 vs. 46.4 yrs, P < 0.001), they experienced longer infection (33 vs. 24 days, P = 0.006) and higher incidence of hospitalization (86.6 vs. 29.5%, P < 0.001), they did not report more fatigue (44.5 vs. 48, P = 0.424), but they walked slower (1.27 vs. 1.5 m/sec, P = 0.027).After multivariable adjustment using multiple logistic regression, sarcopenia was dependent on age (odds ratio = 1.09) and on the duration of the disease (odds ratio = 1.04).When expressed as z score, in 79% of patients, the sway path during elastic balance shifted significantly toward negative values with closed eye, indicating multisensory integration deficit. CONCLUSIONS: Post-COVID syndrome in relatively young outpatients complaining mild motor deficit is associated with high incidence of sarcopenia. In addition, they have multisensory integration deficit that further contributes to symptoms. The Clinical, Ultrasound and Robotic Evaluation protocol is able to objectivize symptoms that common diagnostic tool cannot reveal. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Determine the best diagnostic algorithm for the diagnosis of sarcopenia; (2) Identify and treat two additional factors that help to explain and understand the symptoms reported by relatively young post-COVID syndrome patients; and (3) Extend their diagnostic capability through the use of technology. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should only claim credit commensurate with the extent of their participation in the activity. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Fractal dimension of the cortical gray matter outweighs other brain MRI features as a predictor of transition to dementia in patients with mild cognitive impairment and leukoaraiosis.

Background: The relative contribution of changes in the cerebral white matter (WM) and cortical gray matter (GM) to the transition to dementia in patients with mild cognitive impairment (MCI) is not yet established. In this longitudinal study, we aimed to analyze MRI features that may predict the transition to dementia in patients with MCI and T2 hyperintensities in the cerebral WM, also known as leukoaraiosis. Methods: Sixty-four participants with MCI and moderate to severe leukoaraiosis underwent baseline MRI examinations and annual neuropsychological testing over a 2 year period. The diagnosis of dementia was based on established criteria. We evaluated demographic, neuropsychological, and several MRI features at baseline as predictors of the clinical transition. The MRI features included visually assessed MRI features, such as the number of lacunes, microbleeds, and dilated perivascular spaces, and quantitative MRI features, such as volumes of the cortical GM, hippocampus, T2 hyperintensities, and diffusion indices of the cerebral WM. Additionally, we examined advanced quantitative features such as the fractal dimension (FD) of cortical GM and WM, which represents an index of tissue structural complexity derived from 3D-T1 weighted images. To assess the prediction of transition to dementia, we employed an XGBoost-based machine learning system using SHapley Additive exPlanations (SHAP) values to provide explainability to the machine learning model. Results: After 2 years, 18 (28.1%) participants had transitioned from MCI to dementia. The area under the receiving operator characteristic curve was 0.69 (0.53, 0.85) [mean (90% confidence interval)]. The cortical GM-FD emerged as the top-ranking predictive feature of transition. Furthermore, aggregated quantitative neuroimaging features outperformed visually assessed MRI features in predicting conversion to dementia. Discussion: Our findings confirm the complementary roles of cortical GM and WM changes as underlying factors in the development of dementia in subjects with MCI and leukoaraiosis. FD appears to be a biomarker potentially more sensitive than other brain features.

Therapeutic strategies in vascular cognitive impairment: A systematic review of population, intervention, comparators, and outcomes.

INTRODUCTION: Vascular cognitive impairment (VCI) is a common and heterogeneous condition, clinically and pathophysiologically, that still lacks approved treatment. METHODS: We reviewed evidence from randomized and non-randomized clinical trials in VCI to explore whether any therapeutic option warrants further investigation and to assess possible flaws in previous studies. RESULTS: We identified 118 studies after searching PubMed and Embase, including 19,223 participants and 5 different VCI subtypes. We found 63 different types of intervention (51 pharmacologic, 5 employing physical agent application, 7 rehabilitation approaches) compared with either placebo, best medical treatment, or other interventions. Treatment efficacy was assessed through 125 outcome measures (with a clearly pre-specified primary outcome in 50.8% of studies). DISCUSSION: Therapeutic trials in VCI have been heterogeneous in terms of populations, types of interventions, and outcomes. Overall, a lack of clear pathophysiological rationale for tested interventions seems to emerge, together with the need to homogenize trial study design.

What do we mean by long COVID? A scoping review of the cognitive sequelae of SARS-CoV-2 infection.

BACKGROUND AND PURPOSE: Many COVID-19 patients report persistent symptoms, including cognitive disturbances. We performed a scoping review on this topic, focusing primarily on cognitive manifestations. METHODS: Abstracts and full texts of studies published on PubMed (until May 2023) addressing cognitive involvement persisting after SARS-CoV-2 infection were reviewed, focusing on terms used to name the cognitive syndrome, reported symptoms, their onset time and duration, and testing batteries employed. Reported psychiatric symptoms, their assessment tools, and more general manifestations were also extracted. RESULTS: Among the 947 records identified, 180 studies were included. Only one third of them used a label to define the syndrome. A minority of studies included patients according to stringent temporal criteria of syndrome onset (34%), whereas more studies reported a minimum required symptom duration (77%). The most frequently reported cognitive symptoms were memory and attentional-executive disturbances, and among psychiatric complaints, the most frequent were anxiety symptoms, depression, and sleep disturbances. Most studies reported fatigue among general symptoms. Thirty-six studies employed cognitive measures: screening tests alone (n = 19), full neuropsychological batteries (n = 25), or both (n = 29); 30 studies performed psychiatric testing. Cognitive deficits were demonstrated in 39% of subjects, the most frequently affected domains being attention/executive functions (90%) and memory (67%). CONCLUSIONS: Currently, no agreement exists on a label for post-COVID-19 cognitive syndrome. The time of symptom onset after acute infection and symptom duration are still discussed. Memory and attention-executive complaints and deficits, together with fatigue, anxiety, and depression symptoms, are consistently reported, but the objective evaluation of these symptoms is not standardized.

Teleneuropsychology for vascular cognitive impairment: Which tools do we have?

The halt of clinical activities imposed during the COVID-19 pandemic forced clinicians to find alternative strategies to provide continuity of care and services, and led to a renewed interest in use of teleneuropsychology (TNP) to remotely assess patients. Recent TNP guidelines recommend maximizing the reproduction of standard in-person assessment, particularly through videoconferences. However, consistency of the adaptations of usual cognitive tests to videoconference needs further elucidation. This review aims at critical reviewing which cognitive tests could be recommended for a remote evaluation of patients with vascular cognitive impairment (VCI) among those widely recognized as reference standards. Current evidence supports the use of global cognitive efficiency (MMSE and MoCA), verbal memory (Revised Hopkins Verbal Learning Test), and language tests (phonemic and semantic verbal fluencies, Boston Naming Test), while there is a lack of strong validity support for measures of visuospatial functions (Rey-Osterreith Complex Figure), and executive functioning and processing speed (Trail making Test, and Digit symbol or Symbol digit tests). This represents a major limitation in the evaluation of VCI because its cognitive profile in often characterized by attention and executive deficits. At present, a videoconference TNP visit appears useful for a brief evaluation of global cognitive efficiency, and to 'triage' patients towards a second level in person evaluation. In future, hybrid models of TNP based on data collected across multiple modalities, incorporating both adaptation of usual cognitive tools and new computerized tools in the supervised videoconference setting, are likely to become the best option for a comprehensive remote cognitive assessment.

Incidence and Long-term Functional Outcome of Neurologic Disorders in Hospitalized Patients With COVID-19 Infected With Pre-Omicron Variants.

BACKGROUND AND OBJECTIVES: A variety of neurologic disorders have been reported as presentations or complications of coronavirus disease 2019 (COVID-19) infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome. METHODS: The Neuro-COVID Italy study was a multicenter, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurologic disorders associated with COVID-19 infection (neuro-COVID), independently from respiratory severity, were systematically screened and actively recruited by neurology specialists in 38 centers in Italy and the Republic of San Marino. The primary outcomes were incidence of neuro-COVID cases during the first 70 weeks of the pandemic (March 2020-June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms, or death. RESULTS: Among 52,759 hospitalized patients with COVID-19, 1,865 patients presenting 2,881 new neurologic disorders associated with COVID-19 infection (neuro-COVID) were recruited. The incidence of neuro-COVID cases significantly declined over time, comparing the first 3 pandemic waves (8.4%, 95% CI 7.9-8.9; 5.0%, 95% CI 4.7-5.3; 3.3%, 95% CI 3.0-3.6, respectively; p = 0.027). The most frequent neurologic disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), and cognitive impairment (13.7%). The onset of neurologic disorders was more common in the prodromic phase (44.3%) or during the acute respiratory illness (40.9%), except for cognitive impairment whose onset prevailed during recovery (48.4%). A good functional outcome was achieved by most patients with neuro-COVID (64.6%) during follow-up (median 6.7 months), and the proportion of good outcome increased throughout the study period (r = 0.29, 95% CI 0.05-0.50; p = 0.019). Mild residual symptoms were frequently reported (28.1%) while disabling symptoms were common only in stroke survivors (47.6%). DISCUSSION: Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic. Long-term functional outcome was favorable in most neuro-COVID disorders, although mild symptoms commonly lasted more than 6 months after infection.

Outcome of patients older than 85 years hospitalized in a neurology unit.

BACKGROUND: Advanced age is a major determinant of mortality and poor outcome at any level. In hospitalized patients, advanced age is a major issue in terms of prognosis, resource use, and therapeutic choices. AIMS: We aimed at assessing the 1 year outcome of elderly patients admitted to a neurology unit for various acute conditions. METHODS: Consecutive patients admitted to a neurology unit were enrolled and followed-up at 3, 6, and 12 months with structured phone interviews gathering information about mortality, disability, hospital readmissions, and place of residency. Inclusion criteria were age ≥ 85 years, availability of written consent and phone contact; no exclusion criteria were applied. RESULTS: Over a period of 16 months, 131 patients (88.8 ± 3.3, 92 females, 39 males) were admitted. The pre-hospitalization modified Rankin Scale (mRS) median (IQR) score, obtainable in 125 patients, was 2 (0, 3) and > 3 in 28/125 (22.4%) patients. Fifty-eight (46.8%) patients had pre-existing dementia (this information was missing for one patient). Eleven patients died during hospitalization. Of the 120 discharged patients, 60 (50%) were alive at 12 months, 41 died during follow-up (34.2%), and 19 (15.8%) were lost. At 12 months, out of the 60 alive patients, 29 (48.3%) had a mRS > 3. We did not detect predictors of 12-month survival. Predictors of 12-month worsening of functional status were pre-hospitalization mRS, pre-existing cognitive impairment, and male sex. CONCLUSIONS: One-year mortality of elderly patients admitted to a neurology unit is extremely high. After one year, less than one fourth of elderly patients hospitalised for an acute neurological disease are left with only no-to-moderate disability.

Neuroimaging standards for research into small vessel disease-advances since 2013.

Cerebral small vessel disease (SVD) is common during ageing and can present as stroke, cognitive decline, neurobehavioural symptoms, or functional impairment. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive and other symptoms and affect activities of daily living. Standards for Reporting Vascular Changes on Neuroimaging 1 (STRIVE-1) categorised and standardised the diverse features of SVD that are visible on structural MRI. Since then, new information on these established SVD markers and novel MRI sequences and imaging features have emerged. As the effect of combined SVD imaging features becomes clearer, a key role for quantitative imaging biomarkers to determine sub-visible tissue damage, subtle abnormalities visible at high-field strength MRI, and lesion-symptom patterns, is also apparent. Together with rapidly emerging machine learning methods, these metrics can more comprehensively capture the effect of SVD on the brain than the structural MRI features alone and serve as intermediary outcomes in clinical trials and future routine practice. Using a similar approach to that adopted in STRIVE-1, we updated the guidance on neuroimaging of vascular changes in studies of ageing and neurodegeneration to create STRIVE-2.

Early predictors of dysphagia in ischaemic stroke patients.

BACKGROUND AND PURPOSE: Post-stroke dysphagia affects outcome. In acute stroke patients, the aim was to evaluate clinical, cognitive and neuroimaging features associated with dysphagia and develop a predictive score for dysphagia. METHODS: Ischaemic stroke patients underwent clinical, cognitive and pre-morbid function evaluations. Dysphagia was retrospectively scored on admission and discharge with the Functional Oral Intake Scale. RESULTS: In all, 228 patients (mean age 75.8 years; 52% males) were included. On admission, 126 (55%) were dysphagic (Functional Oral Intake Scale ≤6). Age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05), pre-event modified Rankin scale (mRS) score (OR 1.41, 95% CI 1.09-1.84), National Institutes of Health Stroke Scale (NIHSS) score (OR 1.79, 95% CI 1.49-2.14), frontal operculum lesion (OR 8.53, 95% CI 3.82-19.06) and Oxfordshire total anterior circulation infarct (TACI) (OR 1.47, 95% CI 1.05-2.04) were independently associated with dysphagia at admission. Education (OR 0.91, 95% CI 0.85-0.98) had a protective role. At discharge, 82 patients (36%) were dysphagic. Pre-event mRS (OR 1.28, 95% CI 1.04-1.56), admission NIHSS (OR 1.88, 95% CI 1.56-2.26), frontal operculum involvement (OR 15.53, 95% CI 7.44-32.43) and Oxfordshire classification TACI (OR 3.82, 95% CI 1.95-7.50) were independently associated with dysphagia at discharge. Education (OR 0.89, 95% CI 0.83-0.96) and thrombolysis (OR 0.77, 95% CI 0.23-0.95) had a protective role. The 6-point "NOTTEM" (NIHSS, opercular lesion, TACI, thrombolysis, education, mRS) score predicted dysphagia at discharge with good accuracy. Cognitive scores had no role in dysphagia risk. CONCLUSIONS: Dysphagia predictors were defined and a score was developed to evaluate dysphagia risk during stroke unit stay. In this setting, cognitive impairment is not a predictor of dysphagia. Early dysphagia assessment may help in planning future rehabilitative and nutrition strategies.

A novel CACNA1A R2201W variant in a woman with hemiplegic migraine.

INTRODUCTION: Familial hemiplegic migraine type 1 (FHM1) is a monogenic rare disease that is characterized by migraine attacks accompanied by unilateral weakness and is caused by mutations in the CACNA1A gene. We report the case of a patient with a clinical history consistent with hemiplegic migraine who underwent genetic testing that revealed a variant in the CACNA1A gene. CASE PRESENTATION: A 68-year-old woman was evaluated for progressive postural instability and subjective cognitive decline. She had suffered from recurrent migraine episodes accompanied by fully reversible unilateral weakness that had started around the age of thirty and had fully disappeared at the time of evaluation. Magnetic resonance imaging (MRI) showed an extensive leukoencephalopathy, with features suggestive of small vessel disease, significantly progressing over the years. Exome sequencing revealed the heterozygous variant c.6601C>T (p.Arg2201Trp) in the CACNA1A gene. This variant, located in a highly conserved region, causes the substitution of arginine with tryptophan at codon 2202 of exon 47, with a high likelihood of a damaging effect on protein activity and/or structure. DISCUSSION: This is the first report describing the missense mutation c.6601C>T (p.Arg2201Trp) in heterozygosity in the CACNA1A gene in a patient with clinical features of hemiplegic migraine. The presence of a diffuse leukoencephalopathy on MRI is not typical of hemiplegic migraine and may suggest a phenotypic variant related to this mutation or result from the combined effect of the patient's comorbidities.

Case Identification and Characterization of Migrants with Dementia in the Lazio Region Using Health Administrative Data.

BACKGROUND: A crucial step for planning effective public health policies for migrants with dementia is the collection of data on the local dimensions of the phenomenon and patients' characteristics. OBJECTIVE: This study aimed to identify and characterize migrants with dementia in the Lazio region using health administrative databases. METHODS: Residents with dementia aged 50 years or older, living in the Lazio region as of December 31, 2018, were identified using a validated algorithm based on hospital discharge(s), claims for antidementia drugs, and co-payment exemption for dementia. Migrants were defined as people born abroad and grouped in migrants from High Migratory Pressure Countries (HMPCs) and Highly Developed Countries (HDCs). Overall and age-specific prevalence rates were estimated in native- and foreign-born patients. RESULTS: Dementia was ascertained in 38,460 residents. Among them, 37,280 (96.9%) were born in Italy, 337 (0.9%) were migrants from HDCs, and 843 (2.2%) from HMPCs. Dementia prevalence was higher among natives (1.15%, 95% CI 1.14-1.16) relative to migrants from HDCs (0.60%, 95% CI 0.54-0.67) and HMPCs (0.29%, 95% CI 0.27-0.31). The prevalence of comorbidities did not differ between groups. Migrants with dementia had a lower likelihood of receiving antidementia treatments compared with natives (51.6% in migrants from HDCs, 49.3% in migrants from HMPCs, and 53.5% among Italians). CONCLUSION: Routinely collected data in healthcare administrative databases can support the identification of migrants with dementia. Migrants exhibited a lower age-standardized prevalence of registered dementia and lower access to dedicated treatments than Italians. These findings are suggestive of underdiagnosis and undertreatment of dementia in migrants.

Differential Diagnosis of Suspected Chronic Obstructive Pulmonary Disease Exacerbations in the Acute Care Setting: Best Practice.

Patients with chronic obstructive pulmonary disease (COPD) may suffer from acute episodes of worsening dyspnea, often associated with increased cough, sputum, and/or sputum purulence. These exacerbations of COPD (ECOPDs) impact health status, accelerate lung function decline, and increase the risk of hospitalization. Importantly, close to 20% of patients are readmitted within 30 days after hospital discharge, with great cost to the person and society. Approximately 25% and 65% of patients hospitalized for an ECOPD die within 1 and 5 years, respectively. Patients with COPD are usually older and frequently have concomitant chronic diseases, including heart failure, coronary artery disease, arrhythmias, interstitial lung diseases, bronchiectasis, asthma, anxiety, and depression, and are also at increased risk of developing pneumonia, pulmonary embolism, and pneumothorax. All of these morbidities not only increase the risk of subsequent ECOPDs but can also mimic or aggravate them. Importantly, close to 70% of readmissions after an ECOPD hospitalization result from decompensation of other morbidities. These observations suggest that in patients with COPD with worsening dyspnea but without the other classic characteristics of ECOPD, a careful search for these morbidities can help detect them and allow appropriate treatment. For most morbidities, a thorough clinical evaluation supplemented by appropriate clinical investigations can guide the healthcare provider to make a precise diagnosis. This perspective integrates the currently dispersed information available and provides a practical approach to patients with COPD complaining of worsening respiratory symptoms, particularly dyspnea. A systematic approach should help improve outcomes and the personal and societal cost of ECOPDs.

The clinical profile of cerebral small vessel disease: Toward an evidence-based identification of cognitive markers.

There is no consensus on which test is more suited to outline the cognitive deficits of cerebral small vessel disease (cSVD) patients. We explored the ability of eight cognitive tests, selected in a previous systematic review as the most commonly used in this population, to differentiate among cSVD patients, controls, and other dementing conditions performing a meta-analysis of 86 studies. We found that cSVD patients performed worse than healthy controls in all tests while data on the comparison to neurodegenerative diseases were limited. We outlined a lack of data on these tests' accuracy on the diagnosis. Cognitive tests measuring processing speed were those mostly associated with neuroimaging cSVD markers. There is currently incomplete evidence that a single test could differentiate cSVD patients with cognitive decline from other dementing diseases. We make preliminary proposals on possible strategies to gain information about the clinical definition of cSVD that currently remains a neuroimaging-based one.

The use of dual antiplatelet therapy for ischemic cerebrovascular events.

In the last 10 years, the use of dual antiplatelet therapy (DAPT) in the neurological ambit has been explored in patients with non-cardioembolic ischemic stroke, transient ischemic attack (TIA), and intracranial atherosclerotic disease. Two clinical trials (CHANCE and POINT) showed that in patients with minor non-cardioembolic ischemic stroke or high-risk TIA, the addition of clopidogrel to aspirin reduces the risk of stroke recurrence. Another trial (THALES) evaluated the association of ticagrelor and aspirin in mild-to-moderate non-cardioembolic ischemic stroke or high-risk TIA, showing a reduced risk of subsequent stroke compared to aspirin alone. Finally, the use of DAPT has been assessed in the treatment of stroke associated with atherosclerotic intracranial stenosis in the SAMMPRIS trial, showing a favorable profile compared to percutaneous angioplasty and stenting. The aim of this article is, after a review the major trials evaluating DAPT in patients with ischemic cerebrovascular events and the ways they have been implemented in Italian, European, and USA guidelines, to provide a practical algorithm to help clinicians in their everyday clinical practice and to outline possible caveats in the practical implementation of guidelines. Possible limitations and gaps in knowledge regarding specific conditions (e.g., the use of DAPT after acute phase therapies) are also underlined.