A M Basile

University of Florence, Florens, Tuscany, Italy

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Publications (40)128.77 Total impact

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    ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease that may lead to disability and whose phenotype modulators are still unknown. In the MIcrovascular LEukoencephalopathy Study (MILES), we assessed the influence of vascular risk factors and the effect of different cognitive domains (memory, psychomotor speed and executive functions) performances on functional abilities in CADASIL in comparison with age-related leukoencephalopathy (ARL). We evaluated 51 CADASIL patients (mean age 50.3 ± 13.8 years, 47.1% males) and 68 ARL patients (70.6 ± 7.4 years, 58.8% males). Considering vascular risk factors, after adjustment for age, CADASIL patients had higher mean BMI values than ARL patients. Stroke history frequency was similar in the two groups. After adjustment for age, more CADASIL patients were disabled (impaired on ≥2 items of the Instrumental Activities of Daily Living scale) in comparison with ARL patients, and CADASIL patients had worse functional performances evaluated with the Disability Assessment for Dementia (DAD) scale. In CADASIL patients, hypertension was related to both DAD score and disability. The cognitive profile of CADASIL and ARL patients was similar, but on a stepwise linear regression analysis functional performances were mainly associated with the memory index (β = -0.418, P < 0.003) in CADASIL patients and the executive function index (β = -0.321, P = 0.028) in ARL. This study suggests that hypertension may contribute to functional impairment in CADASIL and that memory impairment has a large influence on functional decline in contrast with that observed in a sample of subjects with ARL.
    No preview · Article · Jul 2013 · European Journal of Neurology

  • No preview · Article · Jan 2013 · Cerebrovascular Diseases

  • No preview · Article · Aug 2009 · Journal of the Neurological Sciences
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    ABSTRACT: The corpus callosum (CC) is the most important structure involved in the transmission of interhemispheric information. The aim of this study was to investigate the potential correlation between regional age-related white matter changes (ARWMC) and atrophy of CC in elderly subjects. In 578 subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the cross-sectional area of the CC was automatically segmented on the normalized midsagittal MR imaging section and subdivided into 5 regions. The ARWMC volumes were measured quantitatively by using a semiautomated technique and segmented into 6 brain regions. Significant correlation between the area of the rostrum and splenium regions of the CC and the ARWMC load in most brain regions was identified. This correlation persisted after correction for global atrophy. Increasing loads of ARWMC volume were significantly correlated with atrophy of the CC and its subregions in nondisabled elderly subjects with leukoaraiosis. However, the pattern of correlation between CC subregions and ARWMC was not specifically related to the topographic location of ARWMC. The results suggest that ARWMC may lead to a gradual loss of CC tissue.
    Full-text · Article · Jul 2008 · American Journal of Neuroradiology
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    ABSTRACT: 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.
    No preview · Article · Jul 2007 · Neurobiology of aging
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    ABSTRACT: 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. 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. 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. Our study strengthens the observation that MTA is associated with DM, independently of the amount of small vessel disease as reflected by WMH.
    Full-text · Article · Mar 2007 · Diabetic Medicine
  • Article: P2-295

    No preview · Article · Jul 2006
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    ABSTRACT: To assess the associations of medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) with cognitive function in a large group of independently functioning elderly people. Data were drawn from the multicentre, multinational leukoaraiosis and disability (LADIS) project which is studying prospectively the role of WMH as an independent predictor of the transition to disability in non-disabled elderly people. In all, 639 participants were enrolled in the LADIS study. For the present analysis, data on 581 subjects were available. Cognitive function was assessed by the mini-mental state examination (MMSE). Visual ratings of WMH and MTA were undertaken on magnetic resonance images (MRI). The presence of either severe WMH or MTA was associated with a modest but non-significant increase in frequency of mild cognitive deficits (severe WMH: odds ratio (OR) = 1.9 (95% confidence interval (CI), 1.0 to 3.7); MTA present: OR = 1.5 (95% CI, 0.8 to 2.8)). However, subjects with the combination of MTA and severe WMH had a more than fourfold increase in frequency of mild cognitive deficits (OR = 4.1 (95% CI, 2.3 to 7.4)). Analysis of variance with post hoc Bonferroni t tests showed that subjects with both MTA and severe WMH performed worse on MMSE than those with either no MRI abnormality or a single MRI abnormality (p<0.05). These results provide further evidence for the combined involvement of both Alzheimer type pathology and vascular pathology in the earliest stages of cognitive decline and suggest an additive effect of WMH and MTA.
    Full-text · Article · Dec 2005 · Journal of Neurology Neurosurgery & Psychiatry
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    ABSTRACT: 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.
    No preview · Article · Dec 2004 · European Journal of Neurology
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    ABSTRACT: The low density lipoprotein receptor-related protein 1 (LRP1 gene) is a candidate gene for Alzheimer's disease (AD), because it is a ligand for proteins involved in AD pathogenesis, such as apolipoprotein E (APOE), alpha2-macroglobulin (A2M), amyloid precursor protein (APP), and is located on chromosome 12, within a region linked with AD. An association between a silent polymorphism (C/T) in exon 3 and late onset AD has been reported, with an increased frequency of the C allele, although with conflicting results. We examined this polymorphism in a cohort of 166 sporadic AD patients and 225 sex- and age-matched nondemented controls from Southern Italy. No statistically significant differences were found in LRP1 genotype and allele frequencies between the whole AD sample and controls, nor in early- and late-onset subsets of AD patients. No statistically significant differences in frequencies between LRP1 alleles and AD among APOE allele, age, or gender strata were found. Finally, comparing our results with the findings from other European populations, the LRP1 C allele frequency showed a statistically significant decreasing trend from Northern to Southern regions of Europe, with a concomitant increase in LRP1 T allele frequency, but in AD patients only. Finally, in the AD sample, a decreasing geographical trend from North to South of Europe was found for LRP1 CC genotype, and an inverse trend for LRP1 CT genotype frequency. We suggest that these regional variations in LRP1 genotype and allele frequencies in AD could be related to the different patterns of association between this polymorphism and the disease in various European studies.
    Full-text · Article · Apr 2004 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
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    ABSTRACT: In recent years, it is becoming apparent that genes may play an important role in the development of late-onset Alzheimer's disease (LOAD), and genetic studies could unravel new clues. Based on a growing vascular hypothesis for the pathogenesis of LOAD and other dementias, there is increasing interest for environmental and genetic vascular factors. Polymorphisms in different susceptibility genes already implicated in vascular disease risk are now also being suggested as possible genetic markers for increased risk of developing LOAD; however, many of these studies have shown conflicting results. Thus far, the apolipoprotein E (APOE) gene seems to be the only vascular susceptibility factor that is agreed to play a role in the multifactorial pathogenesis of AD although emerging genetic and biological evidence is now strengthening the case for additional inclusion of angiotensin I-converting enzyme 1 (ACE1) into this category. This review will focus on the current knowledge on genetic and nongenetic vascular factors likely to be involved in LOAD, with special emphasis placed on the APOE and ACE1 genes.
    Full-text · Article · Feb 2004 · Journal of Neural Transmission
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    Full-text · Article · Feb 2004 · Journal of Neurology Neurosurgery & Psychiatry
  • D Inzitari · M Lamassa · L Pantoni · A.M. BASILE
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    ABSTRACT: Vascular dementia (VD) has not to be considered anymore as a univocal nosologic entity. Based on different types of lesions, distinct subtypes of vascular dementia may be identified, each caused by diverse pathophysiological mechanisms. Among these subtypes subcortical vascular dementia (SVD) may represent a well-defined entity in terms of pathophysiology, clinical features and neuroradiological aspects. The picture is characterized by history of arterial hypertension and other vascular risk factors, clinical symptoms and signs including, besides dementia, dysfunctions related to subcortical-frontal circuit damages, and extensive confluent or diffuse abnormalities in the subcortical brain white matter, small deep infarcts as revealed by computed tomographic (CT) or magnetic resonance imaging (MRI) scans. The homogeneity of this clinical-pathological picture is essential for the success of controlled clinical trials in the field of vascular dementia.
    No preview · Article · Feb 2004 · Archives of gerontology and geriatrics. Supplement

  • No preview · Article · Jan 2004

  • No preview · Conference Paper · Jan 2004
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    ABSTRACT: Vascular factors may play a role in the etiology of Alzheimer's disease (AD) and increased serum apolipoprotein E (APOE) levels in AD could be of interest, as APOE concentration is associated with vascular disease. Aims of this study were to evaluate the influence of APOE genotype on serum APOE levels, and, secondly, to study serum APOE concentrations in relation to age and AD. APOE genotypes, serum total cholesterol, LDL cholesterol, HDL cholesterol, total cholesterol/HDL cholesterol ratio, triglycerides, and serum APOE were performed on 52 healthy centenarians, 49 AD patients, 45 age-matched controls, and 72 young healthy adults. In all study population a significant trend in reduction of serum APOE levels from APOE epsilon2- to epsilon4 carriers was observed. The difference in serum APOE levels among age groups significantly decreased in epsilon4 carriers only, including HDL cholesterol; no significant differences between AD patients and age-matched controls were found. In these highly selected populations, APOE genotype distribution strongly influences serum APOE concentration, not suggesting, at present, a possible role as a biochemical marker for AD, but only as a putative longevity factor.
    Full-text · Article · Apr 2003 · Neuroreport
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    ABSTRACT: To explore the possible role of serum lipoprotein(a) (Lp(a)), apolipoprotein E polymorphism, and total cholesterol (TC) serum concentrations in Alzheimer's disease (AD). Lp(a) serum concentrations, apolipoprotein E genotypes, and TC serum concentrations were determined in 61 patients with a diagnosis of probable AD and in 63 healthy unrelated age matched controls. Genomic DNA was obtained and amplified by polymerase chain reaction and apolipoprotein E genotypes were defined following a previously described procedure. Lp(a) serum concentrations were significantly associated in a non-linear relation with an increased risk for AD, independently of apolipoprotein E genotypes and sex and dependent on age (truth association) and TC serum concentrations (spurious association). The effect of age adjusted for TC on the odds of having AD increased non-linearly with increasing Lp(a) serum concentrations, with a plateau between 70 and 355 mg/l (odds ratio 11.33). For Lp(a) serum concentrations > or = 360 mg/l, the effect of age (> or = 72 years) was associated with a reduction in odds of having AD (odds ratio 0.15). It is suggested that increased Lp(a) serum concentrations, by increasing the risk for cerebrovascular disease, may have a role in determining clinical AD.
    Full-text · Article · Jul 2002 · Journal of Neurology Neurosurgery & Psychiatry
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    ABSTRACT: The examination of centenarian populations for the frequency of certain alleles of pertinent genes may provide insights into the human longevity. To study the relationships between angiotensin converting enzyme (ACE) polymorphism and longevity at the lower extreme of Europe, we evaluated 63 centenarians and 204 younger middle-aged controls (19-80 years) to confirm previous data on increased prevalence of the high-risk ACE*D allele in French centenarians. No statistically significant differences were found in ACE genotype and allele frequencies between centenarians and younger controls in this Southern Italy population. We hypothesized that the variability in the strength of association between ACE polymorphism and longevity could be related to regional differences in ACE*D frequency in Europe, as recently reported for apoE ε2 and ε4 allele in centenarians.
    No preview · Article · Feb 2002 · Archives of gerontology and geriatrics. Supplement
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    ABSTRACT: We analyzed at the molecular level with presenilin-1 (PS-1) and apolipoprotein E (apoE) genotyping the affected subjects and asymptomatic relatives of an Italian family with several members affected by late-onset familial Alzheimer's disease (AD). The screen for PS-1 gene mutations revealed a novel missense substitution phenylalanine 175 to serine in 1 of the affected individuals and 2 asymptomatic sons of the patient. This change was not found in other relatives of this family, as well as in 60 individuals with sporadic late-onset AD and 40 normal controls. Furthermore, a GG/TT substitution in the 3' end of intron 6 at the boundary with exon 7 was found in all relatives of the second and third generations of this family. All the affected relatives were female homo- or heterozygotes for apoE epsilon4 allele. This study provides evidence that a PS-1 gene missense change does not necessarily associate with early-onset disease, and can occur in single cases affected by late-onset disease.
    No preview · Article · Feb 2002 · European Neurology
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    ABSTRACT: Lipoprotein(a) (= Lp(a)) concentration is generally related to vascular disease, and there are growing evidences that vascular factors play a role in the etiology of Alzheimer's disease (AD). We evaluated interactions of Lp(a) with lipid and non-lipid coronary artery disease (CAD) risk factors in free-living elderly subjects, from the randomized cohort of Casamassima (Bari, Southern Italy) of the Italian Longitudinal Study on Aging (ILSA). The results showed that in the elderly population high serum Lp(a) was not an independent predictor of CAD, but dependent on type 2 diabetes mellitus and elevated low-density lipoprotein (LDL) cholesterol levels, increasing risk of CAD by 6.65. Furthermore, we explored the possible role of serum Lp(a), apolipoprotein E (apoE) polymorphism, and total cholesterol (TC) serum levels in patients with diagnosis of probable AD, and healthy, unrelated age-matched controls. Lp(a) serum levels were significantly associated according to a nonlinear relationship with an increased risk for AD, independently of apoE genotypes and sex, and dependent on age and TC serum levels. We suggest that elevated Lp(a) serum levels, increasing the risk for cerebrovascular disease, may play a role in determining clinical AD.
    No preview · Article · Feb 2002 · Archives of gerontology and geriatrics. Supplement

Publication Stats

1k Citations
128.77 Total Impact Points

Institutions

  • 1999-2009
    • University of Florence
      • Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino
      Florens, Tuscany, Italy
    • Italian National Research Council
      • Institute of Neuroscience IN
      Oristany, Sardinia, Italy
  • 1999-2004
    • Università degli Studi di Bari Aldo Moro
      • Dipartimento di Scienze Biomediche ed Oncologia Umana (DIMO)
      Bari, Apulia, Italy
  • 2000
    • Policlinico di Bari
      • Department of Neurology
      Bari, Apulia, Italy