Isolated, Subtle Neurological Abnormalities in Mild Cognitive Impairment Types.

BACKGROUND: Isolated, subtle neurological abnormalities (ISNA) are commonly seen in aging and have been related to cerebral small vessel disease (SVD) and subcortical atrophy in neurologically and cognitively healthy aging subjects. OBJECTIVE: To investigate the frequency of ISNA in different mild cognitive impairment (MCI) types and to evaluate for each MCI type, the cross-sectional relation between ISNA and white matter hyperintensities (WMH), lacunes, caudate atrophy, and ventricular enlargement. METHODS: One thousand two hundred fifty subjects with different MCI types were included in the analysis and underwent brain magnetic resonance imaging. WMHs were assessed through two visual rating scales. Lacunes were also rated. Atrophy of the caudate nuclei and ventricular enlargement were assessed through the bicaudate ratio (BCr) and the lateral ventricles to brain ratio (LVBr), respectively. Apolipoprotein E (APOE) genotypes were also assessed. The routine neurological examination was used to evaluate ISNAs that were clustered as central-based signs, cerebellar-based signs, and primitive reflexes. The items of Part-III of the Unified Parkinson's Disease Rating Scale were used to evaluate ISNAs that were clustered as mild parkinsonian signs. Associations of ISNAs with imaging findings were determined through logistic regression analysis. RESULTS: The ISNAs increase with the age and are present in all MCI types, particularly in those multiple domains, and carrying the APOE ϵ4 allele, and are associated with WMH, lacunes, BCr, and LVBr. CONCLUSION: This study demonstrates that cortical and subcortical vascular and atrophic processes contribute to ISNAs. Long prospective population-based studies are needed to disentangle the role of ISNAs in the conversion from MCI to dementia.

Des anomalies neurologiques subtiles et isolées associées à différents types de déficience cognitive légère. Contexte: Des anomalies neurologiques à la fois subtiles et isolées sont fréquemment observées chez les personnes vieillissantes. Elles ont été associées à la maladie des petits vaisseaux du cerveau (cerebral small vessel disease) et à une atrophie des structures sous-corticales chez des sujets âgés en santé sur les plans neurologique et cognitif. Objectif: Étudier la fréquence de ces anomalies dans le cas de différents types de déficience cognitive légère ; évaluer, pour chaque type de déficience, la relation transversale entre ces anomalies et des hyper-signaux de la substance blanche, des lacunes cérébrales, l'atrophie du noyau caudé et l'élargissement des ventricules. Méthodes: Au total, 1250 sujets atteints de différents types de déficience cognitive légère ont été inclus dans notre analyse et ont passé un examen d'IRM du cerveau. On a évalué les hyper-signaux de la substance blanche à l'aide de deux échelles d'évaluation visuelle. À noter que les lacunes cérébrales ont également été évaluées. Du côté de l'atrophie du noyau caudé et de l'élargissement des ventricules, ces anomalies ont été mesurées respectivement au moyen de l'index bicaudé (bicaudate ratio) et du ratio volumique ventricule-cerveau (lateral ventricles to brain ratio). Enfin, les génotypes associés à l'apolipoprotéine E (ApoE) ont été examinés. Fait à souligner, des examens neurologiques de routine portant sur les signes du système nerveux central, sur les signes du cervelet et sur les réflexes archaïques ont été utilisés pour tenter de cerner les anomalies évoquées ci-dessus. Des éléments de la partie III de l'échelle UPDRS (Unified Parkinson's Disease Rating Scale) ont été par ailleurs mis à profit pour évaluer les anomalies regroupées au sein de la catégorie des signes bénins de la maladie de Parkinson. Les liens entre ces anomalies et les résultats aux examens d'IRM ont été déterminés à l'aide d'une analyse de régression logistique. Résultats: Ces anomalies neurologiques à la fois subtiles et isolées augmentent en fonction de l'âge et sont présentes parmi tous les types de déficience cognitive légère, en particulier dans ces domaines multiples et chez les sujets porteurs de l'allèle ϵ4 du gène de l'ApoE. On a vu également qu'elles sont associées à des hyper-signaux de la substance blanche, à des lacunes cérébrales, à l'atrophie du noyau caudé et à l'élargissement des ventricules. Conclusion: Cette étude démontre que les processus vasculaires et atrophiques des structures corticales et sous-corticales contribuent à l'apparition d'anomalies neurologiques à la fois subtiles et isolées. Des études prospectives de longue haleine basées sur la population sont toutefois nécessaires pour mieux comprendre le rôle de ces anomalies dans l'évolution des cas de déficience cognitive légère vers la démence.

Nociceptive Primitive Reflexes in Neurologically and Cognitively Healthy Aging Subjects.

BACKGROUND: To assess the prevalence of three nociceptive primitive reflexes (nPR), i.e., glabellar tap, snout reflex, and palmomental reflex, in neurologically and cognitively healthy (NCH) aging subjects. OBJECTIVE: To investigate whether nPR are cross-sectionally associated with white matter hyperintensities (WMH), lacunes, atrophy of the caudate nuclei, and global brain atrophy. METHODS: A total of 1246 NCH subjects aged 45-91 years were included in the study and underwent standard brain MRI. Atrophy of the caudate nuclei and global brain atrophy were assessed through the bicaudate ratio (BCr) and lateral ventricles to brain ratio (LVBr), respectively. WMH were assessed through visual rating scales. Lacunes were also rated. Association of nPR with vascular risk factors/diseases and imaging findings was evaluated using logistic regression analysis. RESULTS: nPR were exhibited by 33.1% of subjects and increased with age. Subjects with nPR performed less than subjects without nPR in tests evaluating global cognition, executive functions, attention, and language. Snout reflex was the most common nPR, followed by glabellar tap and palmomental reflex. Glabellar tap was associated with parieto-temporal WMH, BCr, and LVBr; snout reflex was associated with frontal lacunes, temporal WMH, BCr, and LVBr; palmomental reflex was associated with parieto-occipital WMH, basal ganglia lacunes, BCr, and LVBr. CONCLUSIONS: This study demonstrates that in NCH aging individuals, nPR are associated with WMH, lacunes, BCr, and LVBr and are probably a warning sign of incipient cognitive decline. Therefore, NCH subjects presenting nPR should manage their vascular risk factors/vascular diseases rigorously in order to prevent or delay progression of small vessel disease, and future neurological and cognitive disabilities.

The neuropsychiatric profile of Parkinson's disease subjects with and without mild cognitive impairment.

Neuropsychiatric symptoms (NPS) are common clinical features of Parkinson's disease (PD). However, NPS profiles in PD subjects with mild cognitive impairment (MCI) have scarcely been investigated. We aimed to describe the NPS profiles of non-demented PD subjects with and without MCI. A total of 410 non-demented PD subjects were included. Of these, 164 were cognitively normal PD subjects (PD-cn), 142 PD had amnestic MCI (PD-aMCI), and 104 had PD with non-amnestic MCI (PD-naMCI). NPS were evaluated in accordance with the Neuropsychiatric Inventory (NPI). PD-aMCI subjects revealed the highest NPS burden, followed by PD-naMCI and then PD-cn. Overall, the most common NPS in PD-MCI were in order: depression, sleep disturbance, anxiety and apathy. Irritability was significantly associated with PD-aMCI and PD-naMCI. Prospective studies are required to evaluate the significance, clinical correlates and prognostic role of NPS in subject with PD-MCI.

Prevalence and profile of mild cognitive impairment in Parkinson's disease.

BACKGROUND/AIMS: The frequency of mild cognitive impairment (MCI) in Parkinson's disease (PD) ranges from 19 to 40%, and this is probably due to methodological differences between the studies. The aim of this study was to evaluate the frequency and profile of MCI in a large sample of nondemented PD subjects and neurologically healthy subjects (NHS). METHODS: A total of 872 subjects (582 controls and 290 PD) were included. The association between MCI and PD was tested, using logistic regression models; odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Fifty-three percent of PD subjects and 45% NHS met the criteria for MCI (p = 0.001). The PD subjects showed a higher frequency of nonamnestic MCI (naMCI), compared to NHS (23.8 vs. 14.4%, p ≤ 0.0001). In comparison to NHS, PD was associated with a univariate OR of 1.9 (95% CI = 1.3-2.8) for naMCI, and this association was marginally significant after multiple comparisons (multivariate OR = 1.5, 95% CI = 0.96-2.3, p = 0.077). CONCLUSION: The association between PD and the impairment of nonmemory domains is probably due to frontal-subcortical involvement, which characterizes the disease.

Activation-Induced Rigidity in Neurologically and Cognitively Healthy Individuals Aged 18-90 Years: A Cross-Sectional Study.

BACKGROUND: Rigidity is a key clinical feature of Parkinson's disease (PD), but in a very early phase of the disease it may be absent and can be enhanced through active movements of the arm contralateral to the one being tested. OBJECTIVE: To evaluate in a large cohort of neurologically and cognitively healthy (NCH) subjects aged 18-90 years if activation-induced rigidity (AR) is present in all age classes, and if there are biological differences between subjects showing AR (AR+) and not showing AR (AR-). METHODS: 2,228 NCH subjects categorized as young adult (18-44 years), adult (45-64 years), elderly (65-74 years), and old/oldest-old (75-90 years) were included in the analysis, and underwent brain MRI. White matter hyperintensities were assessed through two visual rating scales. Lacunes were also rated. Atrophy of the caudate nuclei and ventricular enlargement were assessed through the bicaudate ratio and the lateral ventricles to brain ratio. To elicit AR, the Froment's maneuver (FM) and the instructions of the UPDRS-ME were used. RESULTS: Among the sample, 1,689 (75.81%) subjects showed AR, of which 1,270 (57.00%) subjects showed AR by using FM, and 419 (18.81%) showed AR by using UPDRS-ME instructions. The latter subjects also showed AR by using FM. The number of AR+ subjects significantly increased with increasing age, regardless of the activation maneuver used. In each age class, the number of AR+ subjects was significantly higher by using the FM than the UPDRS-ME instructions. CONCLUSION: Our findings suggest that AR is likely to be one of the signs of the prodromal phase of PD.

APOE Genotypes and Brain Imaging Classes in Normal Cognition, Mild Cognitive Impairment, and Alzheimer's Disease: A Longitudinal Study.

OBJECTIVE: To evaluate in 419 stroke-free cognitively normal subjects (CN) aged 45-82 years covering during a long prospective study (11.54 ± 1.47 years) the preclinical to dementia spectrum: 1) the distribution of small vessel disease (V) and brain atrophy (A) aggregated as following: V-/A-, V-/A+, V+/A-, V+/A+; 2) the relationship of these imaging classes with individual apolipoprotein E (APOE) genotypes; 3) the risk of progression to Alzheimer Disease (AD) of the individual APOE genotypes. METHODS: Participants underwent one baseline (t0), and 4 clinical and neuropsychological assessments (t1,t2,t3, and t4). Brain MRI was performed in all subjects at t0, t2, t3 and t4.. White matter hyperintensities were assessed through two visual rating scales. Lacunes were also rated. Subcortical and global brain atrophy were determined through the bicaudate ratio and the lateral ventricle to brain ratio, respectively. APOE genotypes were determined at t0 in all subjects. Cox proportional hazard model was used to evaluate the risk of progression to AD. RESULTS: The imaging class of mixed type was very common in AD, and in non amnestic mild cognitive impaired APOE ε4 non carriers. In these subjects, frontal and parieto-occipital regions were most affected by small vessel disease. CONCLUSION: Our findings suggest that the APOE ε3 allele is probably linked to the brain vascular pathology.

Mild Parkinsonian Signs in a Hospital-based Cohort of Mild Cognitive Impairment Types: A Cross-sectional Study.

BACKGROUND: Mild Parkinsonian Signs (MPS) have been associated with Mild Cognitive Impairment (MCI) types with conflicting results. OBJECTIVE: To investigate the association of individual MPS with different MCI types using logistic ridge regression analysis, and to evaluate for each MCI type, the association of MPS with caudate atrophy, global cerebral atrophy, and the topographical location of White Matter Hyperintensities (WMH), and lacunes. METHODS: A cross-sectional study was performed among 1,168 subjects with different types of MCI aged 45-97 (70,52 ± 9,41) years, who underwent brain MRI. WMH were assessed through two visual rating scales. The number and location of lacunes were also rated. Atrophy of the caudate nuclei and global cerebral atrophy were assessed through the bicaudate ratio, and the lateral ventricles to brain ratio, respectively. Apolipoprotein E (APOE) genotypes were also assessed. Using the items of the motor section of the Unified Parkinson's Disease Rating Scale, tremor, rigidity, bradykinesia, and gait/balance/axial dysfunction were evaluated. RESULTS: Bradykinesia, and gait/balance/axial dysfunction were the MPS more frequently encountered followed by rigidity, and tremor. MPS were present in both amnestic and non-amnestic MCI types, and were associated with WMH, lacunes, bicaudate ratio, and lateral ventricles to brain ratio. CONCLUSION: MPS are present in both amnestic and non-amnestic MCI types, particularly in those multiple domain, and carrying the APOE ε4 allele. Cortical and subcortical vascular and atrophic processes contribute to MPS. Long prospective studies are needed to disentangle the contribution of MPS to the conversion from MCI to dementia.

Chronic paroxysmal hemicrania and hemicrania continua responding to topiramate: two case reports.

Chronic paroxysmal hemicrania (CPH) is a rare primary headache syndrome, which is classified along with cluster headache and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing as a trigeminal autonomic cephalalgia (TACs). Hemicrania continua (HC) was previously classified as one of the TACs, but in the recent second classification of the International Headache Society this disorder was moved to the group of other primary headaches. Both CPH and HC are characterised by moderate to excruciating pain requiring pharmacological treatment; furthermore, both conditions are characterised by an absolute response to indomethacin, which represents one of the current diagnostic criteria for these two syndromes. Unfortunately, in about one-fourth of cases treatment with indomethacin may cause adverse events, mostly gastrointestinal. We report one subject with CPH and another with HC intolerant to indomethacin, who responded remarkably well to topiramate.

Vascular Risk Factors, Vascular Diseases, and Imaging Findings in a Hospital-based Cohort of Mild Cognitive Impairment Types.

BACKGROUND: Mild Cognitive Impairment (MCI) is a transitional state between normal cognition and dementia. OBJECTIVE: The aim of this study is to investigate the role of vascular risk factors, vascular diseases, cerebrovascular disease and brain atrophy in a large hospital-based cohort of MCI types including 471 amnestic MCI (a-MCI), 693 amnestic MCI multiple domain (a-MCImd), 322 single non-memory MCI (snm-MCI), and 202 non amnestic MCI multiple domain (na-MCImd). For comparison, 1,005 neurologically and cognitively healthy subjects were also evaluated. METHOD: Several vascular risk factors and vascular diseases were assessed. All participants underwent neurological, neuropsychological and behavioural assessments as well as carotid ultrasonography and standard brain MRI. Multinomial logistic regression models on the MCI cohort with the NCH group and a-MCI type as reference categories were used to assess the effects of the variables evaluated on the estimated probability of one of the four MCI types. RESULTS: This study demonstrates that cerebrovascular disease contributes substantially to the risk of non-memory MCI types and a-MCImd type, and that brain atrophy is present in all MCI types and is greater in multiple domain types particularly in the na-MCI type. CONCLUSION: Improving detection and control of cerebrovascular disease in aging individuals should be mandatory. Since the incidence of MCI and dementia will be expected to rise because of the progressive life expectancy, a better management of cerebrovascular disease could indeed prevent or delay the onset of MCI, or could delay progression of MCI to dementia.

Association Between Atrophy of the Caudate Nuclei, Global Brain Atrophy, Cerebral Small Vessel Disease and Mild Parkinsonian Signs in Neurologically and Cognitively Healthy Subjects Aged 45-84 Years: A Crosssectional Study.

BACKGROUND: Mild Parkinsonian signs (MPS) are commonly seen in aging, and have been related to cerebral Small Vessel Diseases (SVD) with no univocal results. OBJECTIVE: The aim of this study was to investigate the cross-sectional relation between MPS and White Matter Hyperintensities (WMH), lacunes, caudate atrophy, and global cerebral atrophy in a large cohort of Neurologically and Cognitively Healthy (NCH) aging individuals. METHOD: 1,219 NCH individuals were included in the analysis, and underwent standard brain MRI. The items of the motor section of the Unified Parkinson's Disease Rating Scale were used to evaluate tremor, rigidity, bradykinesia, and gait/balance/axial dysfunction. Caudate atrophy and global cerebral atrophy were assessed through the bicaudate ratio and the lateral ventricles to brain ratio, respectively. WMH were assessed through two visual rating scales. Lacunes were also rated. Associations of MPS with vascular risk factors/diseases and imaging findings were determined through the logistic regression analysis. RESULTS: Frontal and basal ganglia lacunes, frontal WMH, caudate atrophy, and global cerebral atrophy were associated with bradykinesia. Basal ganglia lacunes, caudate atrophy, and global cerebral atrophy were associated with gait/balance/axial dysfunction. Rigidity was associated with frontal WMH, and tremor with caudate atrophy and global cerebral atrophy. NCH subjects with MPS, performed less than subjects without MPS in tests evaluating global cognition and language. CONCLUSION: This study demonstrates that in NCH aging individuals, MPS are associated with cortical and subcortical vascular and atrophic changes, and are probably, a warning sign of incipient cognitive decline. Subjects with MPS should manage rigorously cerebral SVD to prevent future physical and cognitive disabilities.

Migraine mediates the influence of C677T MTHFR genotypes on ischemic stroke risk with a stroke-subtype effect.

BACKGROUND AND PURPOSE: The objective was to investigate the role of C677T MTHFR polymorphism in migraine pathogenesis and in the migraine-ischemic stroke pathway. METHODS: A first genotype-migraine association study was conducted on 100 patients with migraine with aura (MA), 106 with migraine without aura (MO), and 105 subjects without migraine, which provided evidence in favor of association of the TT677 MTHFR genotype with increased risk of MA compared with both control subjects (OR, 2.48; 95% CI, 1.11 to 5.58) and patients with MO (OR, 2.21; 95% CI, 1.01 to 4.82). Based on these findings, mediational models of the genotype-migraine-stroke pathway were fitted on a group of 106 patients with spontaneous cervical artery dissection, 227 young patients whose ischemic stroke was unrelated to a spontaneous cervical artery dissection (noncervical artery dissection), and 187 control subjects, and a genotype-migraine partial mediation model was selected. RESULTS: Both migraine and the TT genotype were more strongly associated to the subgroup of patients with spontaneous cervical artery dissection (OR, 4.06; 95% CI, 1.63 to 10.02 for MA; OR, 5.45; 95% CI, 3.03 to 9.79 for MO; OR, 2.87; 95% CI, 1.45 to 5.68 for TT genotype) than to the subgroup of patients with noncervical artery dissection ischemic stroke (OR, 2.22; 95% CI, 1.00 to 4.96 for MA; OR, 1.81; 95% CI, 1.02 to 3.22 for TT genotype) as compared with controls. CONCLUSIONS: Migraine may act as mediator in the methylenetetrahydrofolate reductase-ischemic stroke pathway with a more prominent effect in the subgroup of patients with spontaneous artery dissection.

Potential drug-drug interaction between duloxetine and acenocoumarol in a patient with Alzheimer's disease.

BACKGROUND: Recent evidence suggests that duloxetine may increase the effect of warfarin, thereby increasing the possibility of bleeding. However, a MEDLINE search for articles published between 1980 and May 2007 (terms: duloxetine, anticoagulants, acenocoumarol, and interaction; no language restriction) did not yield any reports of an interaction between concomitant use of duloxetine and acenocoumarol. OBJECTIVE: The aim of this study was to describe a potential drug-drug interaction between duloxetine and acenocoumarol in a patient with Alzheimer's disease. The possible mechanism of this potential interaction is examined. CASE SUMMARY: This report presents the case of a 63-year-old white female patient weighing 64 kg receiving oral treatment with the synthetic coumarin anticoagulant acenocoumarol (mean dosage, 9 mg/wk) for 8 years who experienced a persistent (3-week) decrease in international normalized ratio (INR) to 1.49 after taking a single 60-mg dose of duloxetine. Three weeks after discontinuation of duloxetine, the INR returned to the previous baseline level (2.58). CONCLUSIONS: This case report suggests a possible drug-drug interaction between duloxetine and acenocoumarol. Duloxetine should be administered with caution in patients receiving acenocoumarol therapy.

Movements execution in amnestic mild cognitive impairment and Alzheimer's disease.

We evaluated the relationship between motor and neuropsychological deficits in subjects affected by amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer's Disease (AD). Kinematics of goal-directed movement of aMCI and AD subjects were compared to those of age-matched control subjects. AD showed a slowing down of motor performance compared to aMCI and controls. No relationships were found between motor and cognitive performances in both AD and aMCI. Our results suggest that the different motor behaviour between AD and aMCI cannot be related to memory deficits, probably reflecting the initial degeneration of parietal-frontal circuits for movement planning. The onset of motor dysfunction in early AD could represent the transition from aMCI to AD.

Association of estrogen receptor alpha gene with Alzheimer's disease: a case-control study.

Recent experimental data have offered the biological background to study the estrogen receptor (ER) alpha gene as a candidate gene for AD. Genetic association studies proposed ERalpha PvuII and XbaI gene polymorphisms as susceptibility factors for AD, although subsequent studies did not replicate this finding. To verify this association in a Caucasian Italian sample, we conducted a case-control study in a dataset of 172 clinic-based probable AD cases and 172 age- and sex-matched controls. Possible interaction between ERalpha polymorphisms and sex, age at onset of AD or apolipoprotein E (APOE) was examined. The xx-genotype of the XbaI polymorphism was associated with the risk of developing AD in the total sample (OR 1.9, 95% CI [1.2-3.1]). The risk increased in women (OR 2.3, 95% CI [1.3-4.2]), and in subjects with late-onset AD (OR 2.1, 95% CI [1.2-3.5]). PvuII polymorphism did not contribute to the risk of AD. There was no evidence for a statistical interaction between the APOE and either the PvuII and XbaI polymorphisms. This result shows that ERalpha XbaI polymorphism is an additional risk factor for women with late-onset AD.

No association between the cystatin C gene polymorphism and Alzheimer's disease: a case-control study in an Italian population.

Cystatin C is an amyloidogenic protein found together with beta-amyloid in cerebral arteriolar walls of both patients with Alzheimer's Disease (AD) and conghopilic amyloid angiopathy. Several findings implicate cystatin C in the pathogenesis of vascular diseases. Recent genetic association studies proposed cystatin C gene (CST3) as a susceptibility factor for AD, although other reports did not replicate this finding. We conducted a case-control study including 192 probable AD cases and 192 age- and sex-matched controls to test the association between CST3 and AD. Possible interaction between CST3 and age at onset of AD or apolipoprotein E (APOE) was also examined. No significant differences in CST3 genotype or allele frequencies between cases and controls was observed, while the risk of AD increased in subjects carrying the APOE epsilon4 allele (OR 3.5, 95% CI [2.1-5.9]). There was no interaction between CST3 with age or APOE. Our findings do not support a role of CST3 gene in Italian sporadic AD.

Isolated, subtle, neurological abnormalities in neurologically and cognitively healthy aging subjects.

The aim of this study is to describe the frequency of isolated, subtle, neurological abnormalities (ISNAs) in a large population of neurologically and cognitively healthy subjects and to compare ISNAs to various types of MRI-detected cerebrovascular lesions and subcortical brain atrophy in different age classes. 907 subjects were selected from a large, prospective hospital-based study. At baseline neurological examination, 17 ISNAs were selected. Primitive reflexes were the most common ISNAs (35.8%), while dysphagia was the most rarely encountered (0.3%). Measures of small vessel disease, i.e., deep and subcortical white matter hyperintensity and lacunar infarcts as well as subcortical atrophy, were variously associated with ISNAs. In the adult group, the ISNAs were associated with hypertriglyceridemia, TIA, and subcortical lacunar infarcts, while in the elderly-old group they were associated with arterial hypertension, subcortical white matter hyperintensity, and subcortical atrophy. An increased risk of ISNAs was associated with lacunae and white matter hyperintensity in the parietal region. This study shows that white matter hyperintensity, lacunae, and subcortical atrophy are associated with an increased risk of ISNAs in cognitively and neurologically healthy aging subjects. ISNAs are not benign signs. Therefore, adults and elderly people presenting with ISNAs should have access to accurate history and diagnosis to prevent progression of small vessel disease and future neurological and cognitive disabilities.

Lack of association between angiotensin converting enzyme polymorphism and sporadic Alzheimer's disease.

Epidemiological and pathogenetic evidences suggest a strong association between vascular risk factors and sporadic Alzheimer's disease (sAD). In agreement with the vascular hypothesis of AD, the role of various candidate genes for atherosclerosis has been investigated, leading to conflicting results. In order to clarify the significance of angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism in a group of patients with sAD, we conducted a case-control study including 149 cases and 149 age and sex matched controls. All subjects were genotyped for ACE and Apolipoprotein E (APOE). There were no significant differences in ACE genotype or allele frequencies between cases and controls, even after stratification for APOE4 carrier status. Our data suggest that the ACE I/D polymorphism is not associated to genetic susceptibility in sAD patients.

No association between Glu298Asp endothelial nitric oxide synthase polymorphism and Italian sporadic Alzheimer's disease.

A great amount of evidence suggests that neuroinflammation may be a major pathogenetic mechanism in the pathophysiology of sporadic Alzheimer's Disease (sAD). Recently, polymorphisms in the endothelial nitric oxide synthase (NOS3) gene have been associated to late onset Alzheimer's Disease in a British population. However, other groups failed to replicate this finding in Asiatic and Caucasian populations. We conducted a case-control study including a clinically well-defined group of 149 sAD patients and 149 age and sex matched controls to test the association between NOS3 Glu298Asp polymorphism and sAD in an ethnically homogenous Italian population. All subjects were genotyped at NOS3 and apolipoprotein E. No significant difference was found in either allele or genotype frequencies between cases and controls, even after stratification for Apolipoprotein E4 carrier status. The NOS3 Glu298Asp polymorphism does not appear to influence the risk of developing sAD in an Italian population.

Cognitive impairment in Behçet's disease patients without overt neurological involvement.

We investigated the prevalence of cognitive impairment in patients with Behçet's disease (BD) without overt neurological involvement. The influence of disease duration, disease activity, prednisone dosage, and anxiety and depression levels was evaluated. Twenty-six consecutive BD outpatients and 26 healthy controls matched for age, education and sex completed a comprehensive neuropsychological battery including tests of memory, visuospatial and constructional abilities, language, attention and psychomotor speed, non-verbal reasoning and executive functioning. The Hamilton scales for anxiety and depression were administered. Disease activity was assessed using the Behçet's Disease Current Activity Form (BDCAF). Compared to controls, BD patients were significantly impaired on tasks evaluating long-term verbal and non-verbal memory, and visuospatial skills. In addition, BD patients were significantly more anxious and depressed than controls. Cognitive impairment was evident in 46.1% of BD patients compared with none of control subjects (p<0.0001), with memory representing the cognitive domain most affected. Both high disease activity (OR 1.3, 95% CI 1.0-1.5, p<0.04) and high prednisone dosage (OR 1.3, 95% CI 1.0-1.7, p<0.03) were independently associated with cognitive impairment in BD after adjustment for demographic variables. Cognitive impairment, involving mainly memory functions, occurs frequently in BD patients. It may occur independently of clinically overt neurological involvement, and is more common in patients with an active disease and in those receiving prednisone.