Showing papers by "Giuliano Binetti published in 2002"

Association between the BDNF 196 A/G polymorphism and sporadic Alzheimer's disease.

Abstract: SIR – Alzheimer's disease (AD) is a chronic brain disorder associated with specific pathological changes resulting in neurodegeneration and in progressive development of dementia. This disease is clinically characterized by memory, reasoning and speech disorders and pathologically by the presence of senile plaques (SP), neurofibrillary tangles, and loss of syn-apses. 1 There are various hypotheses regarding an involvement of genetic factors in the development of AD. Mutations of genes encoding amyloid precursor protein, presenilin-1 and presenilin-2 cause familial AD, 2,3 and the ⑀4 allele of apolipoprotein E (APOE) gene gives susceptibility to familial and sporadic AD. 4 However, this genetic marker cannot explain the overall genetic susceptibility and additional/other genes may be involved in the development of AD. Genes involved in the neurodevelopmental process may be considered good candidates to confer susceptibility to AD. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors which promotes survival, differentiation and maintenance of neurons in peripheral and central nervous system during normal development, 5 influences axonal growth and connectivity 6 and participates in the local responses to various types of neuronal stress or insults. 7 Table 1 Allele and genotype frequencies of the BDNF gene polymorphism at position 196 in Alzheimer patients and controls Alzheimer patients (n = 130) Healthy volunteers (n = 111) BDNF allele frequency Several lines of evidence have suggested altered functions of this gene in the pathogenesis of neurodeg-enerative diseases including Alzheimer's disease: reduced levels of BDNF mRNA in the hippocampus, in the temporal cortex, in brain homogenates and in frontal cortex neurons have been found in individuals with AD. 8 In order to verify a potential role of the BDNF gene in the neuropathogenesis of Alzheimer's disease, we analyzed allelic distribution of a polymorphism in the coding region of the BDNF gene in a diagnosed AD sample and in a control group. The polymorphism studied is a A/G (Met/Val) substitution located in the propeptide region, a highly unstable region constituted by 110 aa, in the BDNF gene at position 196 (codon 66) (SWISS.PROT: P23560.VAR 004626). Genomic DNA was extracted from blood samples obtained, after informed consent, from 130 Alzheimer's patients (mean age 72 ± 3 years; 90 women and 40 men) recruited at the Alzheimer Unit of IRCCS-Fatebenefrat-elli (Brescia, Italy) and 111 healthy ethnically and age-matched volunteers. Patients and controls were Cauca-sians living in Northern Italy. Genotyping for this polymorphism has been done …

Radial width of the temporal horn: a sensitive measure in Alzheimer disease.

Abstract: BACKGROUND AND PURPOSE: Atrophy in the medial temporal lobe (MTL) structures depicted with brain imaging is one of the most accurate markers of Alzheimer disease (AD), but practical considerations have thus far limited their routine clinical use. The aim of this study was to explore the validity of a CT- and MR-based measure of MTL atrophy that would be feasible for routine clinical use. METHODS: We acquired brain CT scans in the temporal lobe plane with thin sections in 42 patients with AD and in 29 control patients without dementia. We also acquired MR images (according to a 3D magnetization-prepared rapid gradient-echo protocol) in 28 patients with AD and in 28 control subjects without dementia. The radial width of the temporal horn (rWTH) of the lateral ventricle was measured with a precision caliper at the tip of the horn on CT scans or high-quality MR images. The validity of the rWTH variable was assessed by test-retest and interrater reliability, convergent and discriminant validity compared with progressively distant brain regions, and known-group validity (accuracy of the separation of patients with AD from control subjects). Convergent and discriminant validity compared with volumetric measures was tested in the patients who underwent MR imaging. RESULTS: Intraclass correlation coefficients for inter- and intrarater reliability were between 0.94 and 0.98. On CT scans, Pearson’s correlation of the rWTH with the transverse width of the temporal horn was between 0.60 and 0.79; with Jobst’s minimum thickness of the MTL, between 0.63 and 0.78 (interuncal distance ∼0.50); and with an index of frontal atrophy, between 0.35 and 0.42. On MR images, the correlation with volumetric MR measures was 0.80 in the temporal horn, 0.74 in the hippocampus, 0.68 in the temporal lobe, 0.58 in the entorhinal cortex, and 0.49 in the frontal lobe. On CT scans (cutoff value for AD, >5.3 mm; age range of subjects, 50–90 y), the rWTH measure was a sensitive marker for AD in 39 of 42 patients with AD (sensitivity, 93%) and was a specific marker in 28 of the 29 control patients (specificity, 97%). On MR images (cutoff 3.6–6.7 mm; age range of subject, 50–90 y), the rWTH was a sensitive marker for AD in 21 of 28 patients with AD (sensitivity, 75%) and was a specific marker in 26 of 28 control subjects (specificity, 93%). The accuracy of other linear CT-based measures of MTL atrophy and linear and volumetric MR-based measures was lower. With specificity set to 95%, sensitivity ranged from 57% to 74% for CT-based measures and from 52% to 74% for MR-based measures. CONCLUSION: The rWTH is an accurate marker of AD that could be used in routine clinical settings.

Predictors of cognitive improvement after reality orientation in Alzheimer's disease

Abstract: Background: there is increasing evidence to support the efficacy of reality orientation in cognitive deficits in patients with Alzheimer’s disease. The clinical characteristics of patients who respond to reality orientation are poorly understood; this knowledge could be important, given that the provision of reality orientation therapy is labour-intensive and may provoke emotional distress. Aim: to evaluate retrospectively which demographic and clinical characteristics of Alzheimer’s patients predict cognitive outcomes. Method: we analysed 38 mild-to-moderately demented outpatients who regularly attended a one-month formal reality orientation programme. The mini mental state examination score changes from baseline—and immediately after—reality orientation were correlated with demographic and pre-treatment clinical characteristics by a linear regression analysis. Results: short-term responsiveness to reality orientation was significantly predicted by a lower level of cognitive functioning (as measured by the mini mental state examination) at baseline and by the absence of euphoria, accounting together for 57.6% of variance. Conclusion: a lower mini mental state examination and the absence of euphoric behaviour in patients with mild-to-moderate Alzheimer’s disease may predict a good cognitive outcome of reality orientation therapy.

No association between DCP1 genotype and late-onset Alzheimer disease.

Abstract: In a study of 261 patients with Alzheimer disease (AD) and 306 cognitively normal control subjects from Germany, Switzerland, and Italy, we found no association between genotype counts or allelic frequencies of DCP1, the gene encoding angiotensin-converting enzyme. In accordance with several other studies, our data could not confirm previous association findings. Critical review about all studies available on DCP1 genotyping and AD, age-associated cognitive decline, longevity, and other conditions revealed remarkable inconsistencies. Several studies showed significant deviations of genotype counts from Hardy Weinberg equilibrium (HWE). Deviations from HWE may limit the comparability of study results and require clarification before drawing conclusions with respect to disease risk, health conditions, or longevity in association with DCP1 genotype.

A Transcultural Study of Agitation in Dementia

Abstract: Agitation is one of the most troublesome behaviors in demented patients. It is etiologically heterogeneous and has varied associated behaviors. To explore the transcultural differences in the manifestation of agitation, we evaluated 50 consecutive Alzheimer's disease (AD) patients in three countries (Taiwan, Italy, and the United States) using the Neuropsychiatric Inventory (NPI) and the Mini-Mental State Examination (MMSE). In a focused analysis, only patients with composite NPI scores > 2 for agitation were selected, with similar levels of disease severity as measured by the MMSE, from the three groups (n = 15 per group) to evaluate culturally specific correlates of agitation. Agitated Taiwanese had significantly more hallucinations than either Italian or American patients. Agitated Italian patients had significantly more apathy than both Taiwanese and American patients. Cultural factors may influence the manifestation of agitation more than a common underlying neuropathology. Management strategies targeting unique behavioral instigators of agitation may be specific for different ethnic groups.