Giuseppe Bellelli

Diffusion tensor imaging and voxel based morphometry study in early progressive supranuclear palsy

Background: A comprehensive characterisation of grey and white matter changes in progressive supranuclear palsy (PSP), the second most common extrapyramidal syndrome after Parkinson disease, is still not available. Objective: To evaluate grey and white matter changes in mild PSP patients by voxel based morphometry (VBM) and diffusion tensor imaging (DTI), respectively. Methods: 14 mild PSP patients and 14 healthy controls entered the study and underwent a clinical and neuropsychological evaluation according with a standardised assessment. Each subject had a structural magnetic resonance imaging (MRI) study. Processing analysis of MRI data was carried out according to optimised VBM and fractional anisotropy was determined. Results: Compared with the controls, in PSP patients VBM analysis showed a significant clusters of reduced grey matter in premotor cortex, frontal operculum, anterior insula, hippocampus, and parahippocampal gyrus, bilaterally. With regard to subcortical brain regions, the pulvinar, dorsomedial and anterior nuclei of the thalamus, and superior and inferior culliculum were affected bilaterally. A bilateral decrease in fractional anisotropy in superior longitudinal fasciculus, anterior part of corpus callosum, arcuate fascicolus, posterior thalamic radiations, and internal capsule, probably involving the cortico-bulbar tracts, was present in PSP patients. Conclusions: These data provide evidence for both grey and white matter degeneration in PSP from the early disease stage. These structural changes suggest that atrophy of cortical and subcortical structures and neurodegeneration of specific fibre tracts contribute to neurological deficits in PSP.

Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people

Objective: to evaluate the performance of the 4 ‘A’s Test (4AT) in screening for delirium in older patients. The 4AT is a new test for rapid screening of delirium in routine clinical practice. Design: prospective study of consecutively admitted elderly patients with independent 4AT and reference standard assessments. Setting: an acute geriatrics ward and a department of rehabilitation. Participants: two hundred and thirty-six patients (aged ≥70 years) consecutively admitted over a period of 4 months. Measurements: in each centre, the 4AT was administered by a geriatrician to eligible patients within 24 h of admission. Reference standard delirium diagnosis (DSM-IV-TR criteria) was obtained within 30 min by a different geriatrician who was blind to the 4AT score. The presence of dementia was assessed using the Alzheimers Questionnaire and the informant section of the Clinical Dementia Rating scale. The main outcome measure was the accuracy of the 4AT in diagnosing delirium. Results: patients were 83.9 ± 6.1 years old, and the majority were women (64%). Delirium was detected in 12.3% (n = 29), dementia in 31.2% (n = 74) and a combination of both in 7.2% (n = 17). The 4AT had a sensitivity of 89.7% and specificity 84.1% for delirium. The areas under the receiver operating characteristic curves for delirium diagnosis were 0.93 in the whole population, 0.92 in patients without dementia and 0.89 in patients with dementia. Conclusions: the 4AT is a sensitive and specific method of screening for delirium in hospitalised older people. Its brevity and simplicity support its use in routine clinical practice.

Tools to Detect Delirium Superimposed on Dementia: A Systematic Review

To identify valid tools to diagnose delirium superimposed on dementia.

Efficacy of music therapy treatment based on cycles of sessions: A randomised controlled trial

We undertook a randomised controlled trial to assess whether a music therapy (MT) scheme of administration, including three working cycles of one month spaced out by one month of no treatment, is effective to reduce behavioural disturbances in severely demented patients. Sixty persons with severe dementia (30 in the experimental and 30 in the control group) were enrolled. Baseline multidimensional assessment included demographics, Mini Mental State Examination (MMSE), Barthel Index and Neuropsychiatry Inventory (NPI) for all patients. All the patients of the experimental and control groups received standard care (educational and entertainment activities). In addition, the experimental group received three cycles of 12 active MT sessions each, three times a week. Each 30-min session included a group of three patients. Every cycle of treatment was followed by one month of wash-out. At the end of this study, MT treatment resulted to be more effective than standard care to reduce behavioural disorders. We observed a significant reduction over time in the NPI global scores in both groups (F 7,357 = 9.06, p < 0.001) and a significant difference between groups (F 1,51 = 4.84, p < 0.05) due to a higher reduction of behavioural disturbances in the experimental group at the end of the treatment (Cohens d = 0.63). The analysis of single NPI items shows that delusions, agitation and apathy significantly improved in the experimental, but not in the control group. This study suggests the effectiveness of MT approach with working cycles in reducing behavioural disorders of severely demented patients.

Duration of Postoperative Delirium Is an Independent Predictor of 6‐Month Mortality in Older Adults After Hip Fracture

To evaluate the association between number of days with delirium and 6‐month mortality in elderly adults after hip fracture surgery.

Outcomes at 12 Months in a Population of Elderly Patients Discharged From a Rehabilitation Unit

OBJECTIVES This study investigates the cognitive, functional, and clinical variables associated with the risk of institutionalization, rehospitalization, and death at 12 months among a population of elderly discharged from a Rehabilitation and Aged Care Unit (RACU) within a 1-year period (May 1, 2004 to April 30, 2005). The RACU is a relatively new setting of care providing intensive rehabilitation and clinical support to elderly with highly heterogeneous reasons for admission. METHODS There were 1303 patients (> or =65 years old) contacted 12 months after discharge from the RACU. We obtained information about institutionalization, rehospitalization, and death. Predictors were all the demographic and clinical variables potentially related to these outcomes. The relationship among predictors and outcomes was tested with multiple stepwise logistic regression models. RESULTS Among the 1072 patients alive at the 12-month follow-up, 90 (8.4%) were institutionalized (3.4% early at discharge and 4.9% within the next period). The logistic regression analysis showed that 2 ranges of age (78 to 83 years and 84 years or more), living alone, occurrence of delirium, cognitive impairment (Mini Mental State Examination lower or equal to 20/30), and poor functional status at discharge (Barthel Index scores ranging from 69 to 85 and Barthel Index scores lower than 68/100) were independently and significantly associated with the risk of institutionalization during the 12 months following discharge from the RACU. Three hundred and twenty-three (30.1%) patients had been rehospitalized once and 86 (8.0%) patients twice at the 12-month follow-up. In the multivariate analysis, comorbidity (Charlson Index scores ranging from 2 to 3 and Charlson Index scores higher than 4) and delirium were significantly and independently associated with this outcome. One hundred and thirty-six (11.3%) patients had died by the 12-month follow-up. The stepwise logistic regression analysis showed that age greater than 83 years, poor functional status (Barthel Index lower than 60/100 at discharge), high comorbidity (Charlson Index scores ranging from 3 to 4 and Charlson Index scores higher than 4, respectively), and albumin serum levels ranging from 3.2 to 2.9 mg/dL and lower than 2.9 mg/dL independently and significantly predicted the 12-month risk of death. Absence of depressive symptoms (Geriatric Depression Scale <2/15) had instead a protective effect. CONCLUSION Variables related to the sociodemographic, cognitive, functional, and health status predicted, with different degree of association, the 12-month risk of institutionalization, rehospitalization, and death among a population of elderly patients discharged from a RACU. Accordingly, various clinical and organizational approaches may be planned for prevention.

Atrial fibrillation and cognitive disorders in older people

OBJECTIVES: To find a correlation between chronic non‐rheumatic atrial fibrillation (CNRAF) and cognitive impairment in a group of older, nondemented patients.

Delirium Superimposed on Dementia Strongly Predicts Worse Outcomes in Older Rehabilitation Inpatients

Objective Delirium superimposed on dementia (DSD) is common in many settings. Nonetheless, little is known about the association between DSD and clinical outcomes. The study aim was to evaluate the association between DSD and related adverse outcomes at discharge from rehabilitation and at 1-year follow-up in older inpatients undergoing rehabilitation. Design Prospective cohort study. Setting Hospital rehabilitation unit. Participants A total of 2642 patients aged 65 years or older admitted between January 2002 and December 2006. Measurements Dementia predating rehabilitation admission was detected by DSM-III-R criteria. Delirium was diagnosed with the DSM-IV-TR. The primary outcome was that of walking dependence (Barthel Index mobility subitem score of <15) captured as a trajectory from discharge to 1-year follow-up. A mixed-effects multivariate logistic regression model was used to analyze the association between DSD and outcome, after adjusting for relevant covariates. Secondary outcomes were institutionalization and mortality at 1-year follow-up, and logistic regression models were used to analyze these associations. Results The median age was 77 years (interquartile range: 71–83). The prevalence of DSD was 8%, and the prevalence of delirium and dementia alone were 4% and 22%, respectively. DSD at admission was found to be significantly associated with almost a 15-fold increase in the odds of walking dependence (odds ratio [OR] 15.5; 95% Confidence Interval [CI] 5.6–42.7; P < .01). DSD was also significantly associated with a fivefold increase in the risk of institutionalization (OR 5.0; 95% CI 2.8–8.9; P < .01) and an almost twofold increase in the risk of mortality (OR 1.8; 95% CI 1.1–2.8; P = .01). Conclusions DSD is a strong predictor of functional dependence, institutionalization, and mortality in older patients admitted to a rehabilitation setting, suggesting that strategies to detect DSD routinely in practice should be developed and DSD should be included in prognostic models of health care.

Rehabilitation of older adults with hip fracture: cognitive function and walking abilities.

OBJECTIVES: To investigate the association between baseline cognitive function and the achievement of walking independence and its maintenance at 1 year in a population of older adults who underwent post‐hip fracture (HF) surgery rehabilitation.

Randomized, Double-Blind, Parallel-Group, 48-Week Study for Efficacy and Safety of a Higher-Dose Rivastigmine Patch (15 vs. 10 cm2) in Alzheimer’s Disease

Aim: Determine whether patients with Alzheimer’s disease demonstrating functional and cognitive decline, following 24–48 weeks of open-label treatment with 9.5 mg/24 h (10 cm2) rivastigmine patch, benefit from a dose increase in a double-blind (DB) comparative trial of two patch doses. Methods: Patients meeting prespecified decline criteria were randomized to receive 9.5 or 13.3 mg/24 h (15 cm2) patch during a 48-week, DB phase. Coprimary outcomes were change from baseline to week 48 on the Instrumental Activities of Daily Living domain of the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-IADL) scale and the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog). Safety and tolerability were assessed. Results: Of 1,584 patients enrolled, 567 met decline criteria and were randomized. At all timepoints, ADCS-IADL and ADAS-cog scores favoured the 13.3 mg/24 h patch. The 13.3 mg/24 h patch was statistically superior to the 9.5 mg/24 h patch on the ADCS-IADL scale from week 16 (p = 0.025) onwards including week 48 (p = 0.002), and ADAS-cog at week 24 (p = 0.027), but not at week 48 (p = 0.227). No unexpected safety concerns were observed. Conclusions: The 13.3 mg/24 h rivastigmine patch significantly reduced deterioration in IADL, compared with the 9.5 mg/24 h patch, and was well tolerated.