Operationalizing mild cognitive impairment criteria in small vessel disease: The VMCI-Tuscany Study

Introduction Mild cognitive impairment (MCI) prodromic of vascular dementia is expected to have a multidomain profile. Methods In a sample of cerebral small vessel disease (SVD) patients, we assessed MCI subtypes distributions according to different operationalization of Winblad criteria and compared the neuroimaging features of single versus multidomain MCI. We applied three MCI diagnostic scenarios in which the cutoffs for objective impairment and the number of considered neuropsychological tests varied. Results Passing from a liberal to more conservative diagnostic scenarios, of 153 patients, 5% were no longer classified as MCI, amnestic multidomain frequency decreased, and nonamnestic single domain increased. Considering neuroimaging features, severe medial temporal lobe atrophy was more frequent in multidomain compared with single domain. Discussion Operationalizing MCI criteria changes the relative frequency of MCI subtypes. Nonamnestic single domain MCI may be a previously nonrecognized type of MCI associated with SVD

Therapy of episodic ataxias: case report and review of the literature

Episodic ataxias (EAs) are characterized by recurrent, discrete episodes of vertigo and ataxia. EA1 and EA2 are the two most common forms. In the interictal interval, myokymia is typically present in EA1, whereas EA2 patients present with interictal nystagmus. Specific pharmacological therapies are available for EA1 and especially EA2. We briefly discuss the case of an Italian young man with EA2, with a novel de novo CACNA1A mutation, who in our opinion is particularly illustrative for introducing the therapeutic approach. Acetazolamide could fully suppress EA episodes in our patient. We also provide a perspective review of the topic. 4-Aminopyridine is another valid treatment option. For EA1 (and for rarer EAs), the therapeutic possibilities are more limited. Carbamazepine is probably the treatment of choice for EA1, but the optimal treatment plan is unknown. A better understanding of the molecular processes involved in the mediation of EAs will lead to more specific and efficacious therapies for this still elusive group of disorders

The Impact of Anxiety, Depression, and Suicidality on Quality of Life and Functional Status of Patients With Congestive Heart Failure and Hypertension: An Observational Cross-Sectional Study

OBJECTIVE: Congestive heart failure (CHF) and hypertension are prevalent diseases with high mortality and morbidity rates. Depression and anxiety are frequently associated with cardiovascular diseases. This observational cross-sectional study assessed depression, anxiety, suicidality, and quality of life in 240 patients with CHF (with or without hypertension) or hypertension (without CHF). METHOD: Subjects were evaluated between June 2005 and June 2007 using the Hamilton Anxiety Rating Scale (HARS), Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale, Medical Outcomes Study 36-item Short-Form Health Survey (both physical component score and mental component score), and Satisfaction With Life Scale (SWLS). Patients with CHF were assigned a New York Heart Association functional classification. RESULTS: The CHF patients had higher scores on the depressive factor and the HARS and higher suicidality. Furthermore, they had lower scores on the physical component score, higher scores on the mental component score, and lower scores on the SWLS. Depressive symptom level was a significant predictor of lower physical health (P = .012), whereas anxiety was a significant predictor of satisfaction with life (P = .002). CHF compared to hypertension was a predictor of higher mental health as measured with the mental component score and lower satisfaction with life. Higher anxiety predicted lower satisfaction with life both in patients with CHF and with hypertension. CONCLUSIONS: Anxiety and depressive symptoms and cardiovascular disease were frequently associated. Screening for anxiety and depression in cardiovascular patients may be crucia

Clinical Perception and Treatment Options for Behavioral and Psychological Symptoms of Dementia (BPSD) in Italy

Background: Behavioral and psychological symptoms of dementia (BPSD) have a high prevalence, and their presence is associated with a severe impact in terms of social costs. However, dedicated clinical tools or biomarkers to detect these symptoms are lacking. Thus, BPSD management in clinical settings is challenging. The aim of this study was to investigate the perception and the treatment strategies for BPSD in Italian centers working in the dementia field. Methods: A multicenter, national survey was developed by BPSD Study Group of the Italian Neurological Society for Dementia (SINDEM). The survey consisted of a semi-structured questionnaire that was e-mailed to SINDEM members, dementia centers part of the national network of memory clinics (Centers for Cognitive Deterioration and Dementia [CDCD]), and clinicians working in dementia care settings. The questions were focused on (1) perceived global frequency and relevance of BPSD; (2) tools used to assess BPSD; (3) pharmacological treatment for psychosis, apathy, agitation, aggression, depression, anxiety, sleep, and nutrition disturbances; (4) non-pharmacological treatments; (5) drugs side effects. Results: One-hundred and thirty-six clinicians participated in this study. Seventy-nine participants worked in a CDCD and 57 in other settings. The perceived frequency of BPSD was 74%. BPSD are detected by means of a clinical assessment for 96.3% or a caregiver interview for 97%. For psychosis treatment the first choice was atypical antipsychotics (83.3%), followed by typical antipsychotic (8.9%) and antidepressants (4.8%). For agitation, atypical antipsychotics were the first-choice treatment in 64% of cases and antidepressants in 16.1%. For aggression, the most used drugs were atypical antipsychotics (82.9%). For anxiety, 55.2% use antidepressants, 17.9% use atypical antipsychotics, and 16.9% use benzodiazepines. Interestingly, most of the centers apply non-pharmacological treatments for BPSD. Some differences emerged comparing the responses from CDCD and other care settings. Conclusion: The survey results revealed many differences in BPSD perception, treatment options, and observed side effect according to the clinical setting. This variability can be explained by the absence of clear guidelines, by differences in patients' characteristics, and by clinical practice based on subjective experience. These results suggest that producing guidelines for the pharmacological treatment of BPSD is a major need

The burden of microstructural damage modulates cortical activation in elderly subjects with MCI and leuko-araiosis. A DTI and fMRI study

The term leuko-araiosis (LA) describes a common chronic affection of the cerebral white matter (WM) in the elderly due to small vessel disease with variable clinical correlates. To explore whether severity of LA entails some adaptive reorganization in the cerebral cortex we evaluated with functional MRI (fMRI) the cortical activation pattern during a simple motor task in 60 subjects with mild cognitive impairment and moderate or severe (moderate-to-severe LA group, n = 46) and mild (mild LA group, n = 14) LA extension on visual rating. The microstructural damage associated with LA was measured on diffusion tensor data by computation of the mean diffusivity (MD) of the cerebral WM and by applying tract based spatial statistics (TBSS). Subjects were examined with fMRI during continuous tapping of the right dominant hand with task performance measurement. Moderate-to-severe LA group showed hyperactivation of left primary sensorimotor cortex (SM1) and right cerebellum. Regression analyses using the individual median of WM MD as explanatory variable revealed a posterior shift of activation within the left SM1 and hyperactivation of the left SMA and paracentral lobule and of the bilateral cerebellar crus. These data indicate that brain activation is modulated by increasing severity of LA with a local remapping within the SM1 and increased activity in ipsilateral nonprimary sensorimotor cortex and bilateral cerebellum. These potentially adaptive changes as well lack of contralateral cerebral hemisphere hyperactivation are in line with sparing of the U fibers and brainstem and cerebellar WM tracts and the emerging microstructual damage of the corpus callosum revealed by TBSS with increasing severity of LA. © 2012 Wiley Periodicals, Inc

Development and psychometric properties of a neuropsychological battery for mild cognitive impairment with small vessel disease: The VMCI-tuscany study

BACKGROUND AND OBJECTIVE: Vascular cognitive impairment may have a selective neuropsychological profile. We developed a battery for assessing mild cognitive impairment (MCI) in patients with small vessel disease (SVD), its applicability, and psychometric properties. METHODS: Among those proposed by the 2006 NINDS-CSN Consensus Conference, we selected tests for which norms based on healthy Italians and equivalent scores methodology were available. Confirmatory factor analysis was applied to ascertain the fit of the theoretically assumed dimensions to empirical data and to derive each cognitive dimension compound measures. RESULTS: The entire battery was applied to 146 out of a cohort of 201 patients with MCI and SVD. Most tests showed good applicability. Fifty-five patients, who were older and cognitively more impaired, proved unable to complete the Trail Making Test part B, the Rey-Osterrieth Complex Figure, and the Stroop test, and were excluded from the analysis. Among the remaining patients, Mini-Mental State Examination proved largely normal, while Rey-Osterrieth Complex Figure, Symbol digit modalities test, and Trail Making Test part B were most frequently abnormal. Confirmatory factor analysis showed a good fit of the 4-factor theoretical model to empirical data. Praxis domain resulted in the highest percentage of abnormal performance (65%), followed by Memory and Attention/EF domains (19% and 15%), and Language (8%). CONCLUSIONS: Our battery proved to be comprehensive, robust, and applicable. Attention-executive dysfunction and impaired memory and visuo-constructional abilities, were the prominent features. The assessment of the Consensus Conference, that included Trial Making Test, looks poorly applicable to older and cognitively impaired patients

Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry

Background: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). Methods: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. Results: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. Conclusion: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening

The instruments used by the Italian centres for cognitive disorders and dementia to diagnose mild cognitive impairment (MCI)

Aims: The purpose of this study was to examine the tools used in Italy to diagnose mild cognitive impairment (MCI). Methods: In collaboration with the Luigi Amaducci Research Consortium, the Italian Network of Alzheimer Evaluation Units prepared a questionnaire to describe how MCI is diagnosed in the Italian Centres for cognitive disorders and dementia (CCDD). Results: Most of the ninety-two CCDDs participating in the survey were located in hospitals (54.7%); large percentages were coordinated by neurologists (50.8%) and geriatricians (44.6%). Almost all (98.5%) used the Mini Mental State Examination to diagnose MCI; the Clock Drawing Test was also frequently used (83.9%). Other neuropsychological, imaging and biomarker tests were utilized less frequently and a wide diversity in the instruments used was noted. Conclusions: According to the results, diagnoses of MCI are based on a multitude of instruments, with major differences in the clinical assessment of geriatricians and neurologists. Standardized testing protocols, validated instruments and cut-off points need to be identified and adopted by the CCDDs for assessing MCI

Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study

© 2020 Elsevier Ltd. All rights reserved.Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.info:eu-repo/semantics/publishedVersio