Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study.

HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white matter hyperintensities. METHODS: In the Leukoaraiosis And DISability in the elderly (LADIS) study, we investigated the relationships between DM, hypertension, blood pressure and MTA in 582 subjects, stratified by white matter hyperintensity severity, using multinomial logistic regression. MTA was visually scored for the left and right medial temporal lobe (score 0-4), and meaned. RESULTS: Mean age was 73.5 years (sd 5.1), 54% was female. Of the subjects, 15% had DM, and 70% had a history of hypertension. The likelihood of having MTA score 3 was significantly higher in subjects with DM (OR 2.9; 95% CI: 1.1-7.8) compared with an MTA score of 0 (no atrophy). The odds ratio for MTA score 2 was not significantly increased (OR 1.8; CI: 0.9-4). Systolic and diastolic blood pressure and a history of hypertension were not associated with MTA. There was no interaction between DM and hypertension. Stratification on white matter hyperintensities (WMH) did not alter the associations. CONCLUSION: Our study strengthens the observation that MTA is associated with DM, independently of the amount of small vessel disease as reflected by WMH.     

Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted cerebrovascular disease. Typically, the first clinical manifestation is migraine and the full clinical spectrum of the disease with recurrent strokes of the subcortical type, cognitive, and mood disorders is seen during the fourth and fifth decades of life. Vascular risk factors are usually absent in CADASIL patients and the diagnosis of the disease is particularly suspected in young adults with cerebrovascular events of unknown cause, diffuse leukoencephalopathy on computed tomography or magnetic resonance imaging, and a history of cerebrovascular diseases or dementia in many family members. We describe three Italian CADASIL patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. Symptoms possibly related to cortical involvement, such as dysphasia and visual field deficits, were reported by two of these patients. We conclude that a diagnosis of CADASIL should not be disregarded in patients with vascular risk factors and presenting with symptoms not immediately referable to subcortical damage at ages more advanced than commonly reported.     

Visual and Hearing Impairment Are Associated With Delirium in Hospitalized Patients: Results of a Multisite Prevalence Study

ObjectiveSensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium.DesignCross-sectional study nested in the 2017 “Delirium Day” project.Setting and ParticipantsPatients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy.MethodsDelirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters).ResultsA total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2–2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1–1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6–1.2, P = .36; OR 1.1; CI 0.8–1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6–1.2, P = .27; OR 1.1, CI 0.8–1.4, P = .63).Conclusions and implicationsOur findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.     

Dementia is a major predictor of death among the Italian elderly. ILSA Working Group. Italian Longitudinal Study on Aging

BACKGROUND: Neurologic diseases are rarely listed on death certificates because death is more often attributed to cardiovascular and pneumonic events occurring during terminal stages. OBJECTIVE: To evaluate the effect of major age-associated neurologic and non-neurologic diseases on survival in a cohort of Italian elderly. METHODS: A population-based multicenter survey, carried out in eight Italian municipalities, with a sample of 5,632 individuals aged 65 to 84 years. The entire sample was screened for all the diseases under study, and all individuals were interviewed about risk factors. Those who screened positive underwent clinical assessments by specialists. Two years after the baseline survey, the study population was followed up to determine the vital status either directly from the individuals or from proxy respondents. A copy of the death certificate was obtained for each individual who had died. The risk of dying (mortality risk ratio [MRR]) was calculated using the Cox proportional hazards model in which we included all the diseases under study, age, gender, and years of education. RESULTS: At follow-up (mean duration 26.7 +/- 5.4 months) 444 individuals had died. The Cox proportional hazards model selected the following as significant predictors of death: age (for year of age MRR = 1.12; 95% confidence interval [CI], 1.08 to 1.15), male gender (MRR = 1.72; 95% CI, 1.27 to 2.34), institutionalization (MRR = 4.17; 95% CI, 2.20 to 7.94), dementia (MRR = 3.61; 95% CI, 2.55 to 5.11), neoplasm (MRR = 2.01; 95% CI, 1.20 to 3.38), heart failure (MRR = 1.87; 95% CI, 1.27 to 2.76), and diabetes (MRR = 1.62; 95% CI, 1.12 to 2.34). CONCLUSIONS: These data provide further evidence on the malignancy of dementia, which proved the major predictor of death in the elderly, with an MRR higher than neoplastic diseases and other severe age-associated conditions.     

Role of white matter lesions in cognitive impairment of vascular origin

White matter changes are detected with high frequency by neuroimaging techniques in aged subjects with cerebrovascular risk factors or diseases and in cognitively impaired patients. Their direct role in causing cognitive deterioration has not been established, although their frequency is higher in demented subjects than in normal controls, and they are associated with specific cognitive deficits, particularly those related to impairment of frontal lobe functions. The aim of this paper is to critically review the existing knowledge about the role of white matter lesions in cognitive impairment of vascular origin. After reviewing the scarce evidence and the numerous clues suggesting a possible role of white matter lesions in causing mental decline, proposals are advanced about elements that could be a basis for revised criteria for vascular dementia for clinical trials. Finally, some items requiring future joint investigations in the fields of age-related white matter lesions are identified.     

The Scandinavian Multi-Infarct Dementia Trial: a double-blind, placebo-controlled trial on nimodipine in multi-infarct dementia

Vascular dementia is a major cause of mental and physical disability in Western countries. Treatment of vascular dementia is currently based on the recognition and control of vascular risk factors, while specific drugs have not been approved yet. The aim of the present multinational, double-blind, placebo-controlled study was to evaluate the safety and efficacy of nimodipine administered for as long as 26 weeks in improving cognition or slowing cognitive deterioration in patients defined as having multi-infarct dementia (DSM-III-R criteria). Two hundred and fifty-nine patients were included (128 nimodipine, 131 placebo), and 251 were available for the intention-to-treat analysis. No significant difference between drug-treated and placebo patients was noted on the Gottfries-Brane-Steen scale score (primary efficacy criterion), the remaining neuropsychological tests (Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency Test, Digit Span, Mini-Mental State Examination), and the functional scales (index of Activity of Daily Living, Instrumental Activity of Daily Living, Rapid Disability Scale, Clinical Dementia Rating), although the majority of changes were in favor of the active drug group. A lower incidence of cerebrovascular and cardiac events was observed in the nimodipine-treated patients in comparison with the placebo group. This study failed to show a significant effect of nimodipine on cognitive, social or global assessments in patients defined as affected by multi-infarct dementia according to the DSM-III-R criteria. A post-hoc analysis (presented in an accompanying paper) suggests that nimodipine may have a favorable effect in the subgroup of patients defined as affected by subcortical (small vessel) vascular dementia.     

Factors predicting the Montreal cognitive assessment (MoCA) applicability and performances in a stroke unit

The evaluation of cognitive status is not routine in the acute stroke setting. We aimed to investigate feasibility, applicability, and performances of the Montreal cognitive assessment (MoCA) in acute stroke patients. Consecutive stroke patients (ischemic or hemorrhagic) admitted to one stroke unit were evaluated 5–9 days after stroke with MoCA (score range: 0–30; higher scores indicate better cognitive performance). Pre-morbid functional and cognitive status was assessed by a structured interview to caregivers. Neuroimaging data regarding index stroke and pre-existing lesions were collected. From December 2009 to December 2010, out of 207 patients with stroke, 137 (66 %) were enrolled [mean age 69.2 ± 14.8 years; males 62 %; mean National Institute of Health and Stroke Scale (NIHSS) score 5.9 ± 7.9]. The most common reason for non-enrolment was unfitting the time window inclusion criteria. MoCA was entirely applicable to 113/137 (82.5 %) patients and the mean score was 17.8 ± 7.1. Multivariate analyses showed that non-applicability was associated with higher NIHSS scores [OR (95 % CI) = 1.4 (1.2–1.7) for each point], left sided lesions [OR (95 % CI) = 18.8 (2.3–155.2)], and worse pre-morbid functional status [OR (95 % CI) = 0.7 (0.6–0.9) for each point of the instrumental activity of daily living scale]. Factors influencing MoCA performance were low education (β = 0.264, p < 0.01), higher NIHSS scores (β = ?0.277, p < 0.01) and worse pre-morbid functional status (β = 0.504, p < 0.001). MoCA administration is feasible in acute patients with mild-to-moderate stroke, with lesion location, stroke severity, and pre-morbid functional status as major determinants of its applicability and performance. MoCA seems to reveal some degree of cognitive deficit even in patients with mild stroke.     

Carotid revascularization and cognitive impairment: the neglected role of cerebral small vessel disease

Neurological Sciences - Carotid atherosclerosis is a pathological process that leads to narrowing of the vessel lumen and a consequent risk of stroke. Revascularization procedures such as carotid...     

Clinical significance of corpus callosum atrophy in a mixed elderly population

Corpus callosum (CC) is the main tract connecting the hemispheres, but the clinical significance of CC atrophy is poorly understood. The aim of this work was to investigate clinical and functional correlates of CC atrophy in subjects with age-related white matter changes (ARWMC). In 569 elderly subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented on the normalised mid-sagittal magnetic resonance imaging (MRI) slice and subdivided into five regions. Correlations between the CC areas and subjective memory complaints, mini mental state examination (MMSE) score, history of depression, geriatric depression scale (GDS) score, subjective gait difficulty, history of falls, walking speed, and total score on the short physical performance battery (SPPB) were analyzed. Significant correlations between CC atrophy and MMSE, SPPB, and walking speed were identified, and the CC areas were smaller in subjects with subjective gait difficulty. The correlations remained significant after correction for ARWMC grade. In conclusion, CC atrophy was independently associated with impaired global cognitive and motor function in subjects with ARWMC.