Polymorphism in the sorbin and SH3-domain-containing-1 (SORBS1) gene and the risk of brain infarction in the Japanese population: the Fukuoka Stroke Registry and the Hisayama study

Background and purpose:  Sorbin and SH3-domain-containing-1 (SORBS1) is an important adaptor protein in insulin-signalling pathway, and its genetic polymorphism may regulate the activity of insulin resistance. We investigated the association between the SORBS1 T228A polymorphism and ischaemic stroke.
Methods:  Genotyping was achieved by a rapid-cycle PCR and melting curve analysis using fluorescent probes in 1049 incident cases of ischaemic stroke and 1049 age- and sex-matched control subjects recruited from the Hisayama study.
Results:  The allele distributions of the SORBS1 T228A polymorphism were similar amongst cases and controls. The multivariate-adjusted odds ratio (OR) of the AA genotype for ischaemic stroke was 2.897 (95% CI, 0.907–8.018) compared with the TT genotype. In terms of stroke subtype, there was a trend toward a difference in the AA genotypes for lacunar infarction, compared with the TT genotype (OR = 8.740, P  = 0.0510), and combined TT and TA genotypes (OR = 8.768, P  = 0.0505). The other polymorphisms genotyped were not associated with any subtypes of ischaemic stroke. T228A polymorphism of SORBS1 was not associated with the prevalence of diabetes.
Conclusions:  The AA genotype of SORBS1 T228A polymorphism may play a role in lacunar infarction in the Japanese population.     

DCUN1D1 is a risk factor for frontotemporal lobar degeneration

Background and purpose:  Frontotemporal lobar degeneration (FTLD) is considered as a proteinopathy; therefore, it is conceivable that genes encoding for factors involved in protein misfolding and/or degradation could play a role in its pathogenesis.
Methods:  An association study of defective in cullin neddylation 1 ( DCN-1 )-domain containing 1 ( DCUN1D1 ), which is involved in protein degradation, was carried out in a population of 220 patients with FTLD as compared with 229 age-matched controls.
Results:  A statistically significant increased frequency of the GG genotype of the DCUN1D1 rs4859146 single nucleotide polymorphism (SNP) was observed in patients compared with controls (6.9 vs. 1.7%, P  =   0.011, adjusted OR: 4.39, 95% CI: 1.40–13.78). Stratifying according to the clinical syndrome, significant differences were observed between the behavioral variant of frontotemporal dementia and controls ( GG frequency: 6.3 vs. 1.7%, P  =   0.02, OR:4.0, 95%, CI = 1.24–12.92), as well as between patients with progressive aphasia compared with controls (15.4 vs. 1.7%, P  =   0.014, OR = 11.30, 95%, CI = 1.63–78.45), but not in patients with SD versus controls (8.3 vs. 1.7%, P  =   0.18, OR = 5.24, 95% C.I. = 0.45–60.63). No significant differences in allelic and genotypic frequencies of the DCUN1D1 rs4859147 SNP were found.
Conclusions:  The GG genotype of the DCUN1D1 rs4859147 SNP represents a risk factor for the development of FTLD, increasing the risk of about fourfold.     

Association between seropositivity to Chlamydia pneumoniae and acute ischaemic stroke

Recent studies suggest an association between Chlamydia pneumoniae infection with atherosclerosis, including cerebrovascular disease. We investigated the prevalence of Chlamydial seropositivity in patients with acute ischaemic stroke syndrome compared with age- and sex-matched control subjects. Specific antibodies (IgA) to C. pneumoniae were measured by microimmunofluorescence in both the clinical group (n=91) and the control group (n=112). Forty patients (43.9%) and 34 controls (30.3%) had positive IgA titres (P < 0.05). The pooled data from this and previous series yielded 45% of seropositivity in cerebrovascular patients vs. 19% in control subjects (P < 0.001). In conclusion, we suggest an association between chronic infection by C. pneumoniae and acute ischaemic stroke.     

Bipolar-panic disorder comorbidity within bipolar disorder families: a study of siblings

Objectives:  Although anxiety disorders often co-occur with bipolar disorder in clinical settings, relatively few studies of bipolar disorder have looked specifically at panic comorbidity. This report examines lifetime panic comorbidity within a sample of families with a history of bipolar disorder.
Methods:  One hundred and nine probands with bipolar disorder and their 226 siblings were interviewed as part of a family-genetic study. Logistic regression was used to model bipolar disorder as a predictor of comorbid panic in those with affective disorder, with age at interview and gender included as covariates.
Results:  The percentage with panic attacks was low in those without affective disorder (3%) compared with those with unipolar depression (22%) or bipolar disorder (32%). Panic disorder was found only in those with affective disorder (6% for unipolar, 16% for bipolar). When bipolar disorder and unipolar disorder were compared, controlling for age and sex, having bipolar disorder was associated with panic disorder (OR = 3.0, 95% CI = 1.1, 7.8) and any panic symptoms (OR = 2.0, CI = 1.0,3.8) and more weakly with the combination of panic disorder and recurrent attacks (OR = 1.8, CI = 0.9, 3.5).
Conclusions:  The absence of panic disorder and the low prevalence of any panic symptoms in those without bipolar or unipolar disorder suggest that panic is associated primarily with affective disorder within families with a history of bipolar disorder. Furthermore, panic disorder and symptoms are more common in bipolar disorder than in unipolar disorder in these families.     

Pilot sample of very early onset bipolar disorder in a military population moderates the association of negative life events and non-fatal suicide attempt

Objective:  To examine the moderating effects of very early onset diagnostic status (≤ 13 years) upon the association between life events and non-fatal suicide attempt.
Methods:  Measures of negative life events, suicidal ideation and current suicide attempt were administered to 298 military-based young adults at entry to treatment for suicidality. Current and lifetime diagnoses were assigned using the Diagnostic Interview Schedule. The predictive ability of negative life events for non-fatal suicide attempt was examined separately for the total sample and for those with retrospectively determined histories of very early onset bipolar disorder (VEOBPD; n = 16), very early onset major depressive disorder (VEOMDD; n = 21) and very early onset anxiety disorder (VEOANX; n = 53).
Results:  Negative life events and suicide attempt were significantly and positively associated among those with no history of VEOBPD (OR = 1.30, 95% CI = 1.02–1.65, p < 0.05), including those with VEOMDD and VEOANX. Consistent with expectation, VEOBPD moderated the association between negative life events and suicide attempt (OR = 0.88, 95% CI = 0.78–0.99, p < 0.05), such that negative life events were non-significantly and negatively associated with the presence of a suicide attempt (OR = 0.21, 95% CI = 0.04–1.02, p = 0.09) among patients with a history of VEOBPD.
Conclusions:  Despite similar rates of suicide attempt among all diagnostic groups, life stress did not contribute to attempt among those with VEOBPD. These findings are consistent with the severity and chronicity of VEOBPD. Potential explanations of these findings include a scarring effect on coping skills and increased sensitization to life stress.     

Body mass index does not change before Parkinson's disease onset

Background and purpose:  Previous studies on the association between Parkinson's disease (PD) and body mass index (BMI) have reported conflicting results. We investigated the relationship between PD and BMI by a case–control study.
Methods:  PD patients were randomly matched to healthy individuals by sex and age. BMI distribution in cases has been compared with BMI of controls and odd ratios (ORs) with 95% CI were calculated.
Results:  We included 318 PD patients and 318 controls. We observed no association between PD and BMI. BMI distribution in cases and controls was similar also when we adjusted for diabetes, hypercholesterolemia and the time elapsed between PD onset and the interview (OR = 0.99; CI = 0.94–1.03; P  = 0.51).
Conclusions:  These results did not confirm the previously reported association between PD and BMI. Population characteristics and methodological issues may partially account for the differences observed between the present study and the others.     

Novel associations with dyspepsia: a community-based study of familial aggregation, sleep dysfunction and somatization

Abstract  Dyspepsia is a common phenomenon and the majority of patients have functional dyspepsia; however, potential risk factors are unclear, with conflicting results in the literature. Although several risk factors have been evaluated previously, this knowledge has not led to more effective management of the disease. The aim of this study was to assess potential novel risk factors for dyspepsia in both a cross-sectional and a nested case–control study among a randomly selected community-based cohort. A valid questionnaire was mailed to a random sample of Olmsted County, MN residents ( n  = 659 responders; 133 had dyspepsia). In a nested case–control study, dyspeptic patients ( n  = 52) and healthy controls ( n  = 40) identified among community respondents completed further questionnaires on diet. Independent risk factors for dyspepsia adjusted for age, sex, body mass index and anti-secretory therapy were a positive family history of abdominal pain [odds ratio (OR) = 4.7, 95% confidence interval (CI) = 1.5–14.9, P  = 0.008] and indigestion (OR = 3.4, 95% CI = 1.0–11.5, P  = 0.048), difficulty falling asleep (OR = 8.2, 95% CI = 2.2–31.5, P  = 0.002), poor sleep associated with worsening symptoms (OR = 15.9, 95% CI = 2.0–124.9, P  = 0.009) and a high somatic symptom checklist score (OR = 5.6, 95% CI = 1.5–20.7, P  = 0.01). Diet, including total calories (kcal day⁻¹) and total protein, carbohydrate and fat intake (g day⁻¹), was not significantly associated with dyspepsia. Familial aggregation raises the possibility of a genetic component, although environmental factors also need to be considered. Sleep dysfunction and somatization suggest a primary psychological component.     

Polymorphism of the MDR1/ABCB1 C3435T drug-transporter and resistance to anticonvulsant drugs: A meta-analysis

Background:   Approximately one-third of patients with epilepsy patients have recurrent seizures despite therapy. It has been suggested that therapeutic failure is associated with high expression of the multidrug efflux ABCB1 (MDR1) drug-transporter; specifically, that patients with the 3435CC genotype have higher efflux of anticonvulsants out of brain tissue, with correspondingly lower concentrations in the central nervous system.
Methods:   We conducted a meta-analysis to examine the association between MDR1 polymorphisms and the response to anticonvulsants. We included all published studies until September 2007, in which patients with responsive and unresponsive seizure disorders underwent genotyping for ABCB1 C3435T. Individual and summary odds ratios were calculated using a random effects model. A secondary analysis was also performed, stratifying the studies by their ethnic distribution to account for genetic heterogeneity. We also performed a cumulative analysis by date of publication for the included studies using a random effects model.
Results:   We identified 11 case-control studies involving 3,371 patients (1,646 patients with drug-resistant epilepsy and 1,725 controls). We identified no significant association between anticonvulsant drug resistance and MDR1 polymorphism [odds ratio 1.15; 95% confidence interval (CI) 0.78–1.70; p = 0.48). Subanalysis of studies according to ethnicity yielded similar findings [European cohort: OR = 1.31; 95% CI 0.89–1.94, p = 0.18; Asian cohort: OR = 0.99; 95% CI 0.51–1.89, p = 0.96).
Conclusions:   We found no association between ABCB1 genotype and response to anticonvulsant drugs. At the present time, genetic typing for MDR1 polymorphism is not warranted for patients with drug-resistant epilepsy.     

Elevated levels of anti-Chlamydia pneumoniae IgA and IgG antibodies in young adults with ischemic stroke

INTRODUCTION: Data on the role of Chlamydia pneumoniae in patients with ischemic stroke are inconsistent. We investigated the presence of anti-C. pneumoniae antibodies in young adults with ischemic stroke. METHODS: 94 patients (<55 years) with ischemic stroke and 103 controls were enrolled. Indices of anti-C. pneumoniae IgA and IgG were assessed with an ELISA. We determined OR and 95% CI for the IgA and IgG seropositivity in stroke cases. RESULTS: Mean IgA and IgG indices were higher in stroke patients vs controls (IgA: 1.40 vs 0.56; P < 0.001; IgG: 0.85 vs. 0.78; P < 0.003). The IgA seropositivity was associated with stroke risk (11.92; 5.94-23.92; P < 0.001) as well as IgG seropositivity was (2.31; 1.15-4.61; P < 0.016). Seropositivity assessed with combined IgA and IgG indices was associated with increased stroke risk (OR 9.35; 95% CI 4.78-18.29; P < 0.0001). After controlling for age and sex, the IgA seropositivity yielded a significantly adjusted OR for stroke (8.95; 4.44-18.07; P < 0.002), while IgG seropositivity did not (0.85; 0.53-1.63). CONCLUSIONS: We find an increased risk of stroke in young patients seropositive to C. pneumoniae in the IgA antibody class. Further studies to explore this finding are warranted.     

Gene–gene interaction between 14-3-3 zeta and butyrylcholinesterase modulates Alzheimer's disease risk

A loss in the regulatory mechanism that controls tau phosphorylation in normal brain is suggested to cause tau hyperphosphorylation in Alzheimer's disease (AD) brain and the development of neurofibrillary tangles (NFT). 14-3-3 zeta protein and butyrylcholinesterase (BCHE) are associated with NFT in AD brain and stimulate tau phosphorylation. In a case–control study in 231 AD patients and 221 healthy controls, we examined whether the combined effects between 14-3-3 zeta (rs964917 and rs983583) and BCHE (K variant) polymorphisms might be responsible for susceptibility to AD. Subjects carrying both the BCHE K allele and the 14-3-3 zeta rs964917 G/G genotype (OR = 0.44, 95% CI = 0.20–0.95, P  = 0.03), or 14-3-3 zeta rs983583 G/G genotype (OR = 0.46, 95% CI = 0.21–1.00, P  = 0.05) had a lower risk of developing AD than subjects without these risk genotypes. Considering synergistic effects between polymorphisms in tau phosphorylation relate-genes may help in determining the risk profile for AD.     

Associations between meteorological variables and acute stroke hospital admissions in the west of Scotland

Background –  We combined a large clinical stroke registry with the UK Met Office database to assess the association between meteorological variables and specific clinical subtypes of acute stroke.
Methods –  We used negative binomial regression and Poisson regression techniques to explore the effect of meteorological values to hospital with acute stroke. Differential effects of atmospheric conditions upon stroke subtypes were also investigated.
Results –  Data from 6389 patients with acute stroke were examined. The mean age (SD) was 71.2 (13.0) years. About 5723 (90%) patients suffered ischaemic stroke of which 1943 (34%) were lacunar. Six hundred and sixty-six patients (10%) had haemorrhagic stroke. Every 1°C increase in mean temperature during the preceding 24 h was associated with a 2.1% increase in ischaemic stroke admissions ( P  = 0.004). A fall in atmospheric pressure over the preceding 48 h was associated with increased rate of haemorrhagic stroke admissions ( P  = 0.045). Higher maximum daily temperature gave a greater increase in lacunar stroke admissions than in other ischaemic strokes ( P  = 0.035).
Conclusion –  We report a measurable effect of atmospheric conditions upon stroke incidence in a temperate climate.     

Risk factors for stroke-related pain 1 year after first-ever stroke

Objective:  To estimate the prevalence of stroke-related pain and to explore its relation to spasticity.
Design:  Cross-sectional survey.
Patients and methods:  One hundred and forty patients were examined at 1 year after first-ever stroke. Pain was assessed by a structured interview and categorized as stroke-related or not, pain intensity by use of the visual analogue scale (VAS), spasticity by use of the modified Ashworth scale, stroke severity and the presence of specific neurological impairments by use of the National Institute of Health Stroke Scale (NIHSS), and depression by use of the Montgomery–Åsberg Depression Scale.
Results:  Pain was reported by 68 patients (49%) with a mean VAS of 42 (95% CI 36–47). In 29 patients (21%), pain was categorized as stroke-related pain. Univariate analyses demonstrated correlations between stroke-related pain and total NIHSS score, paresis, sensory disturbance, depression and spasticity respectively. A multiple regression analysis demonstrated an independent association of stroke-related pain with paresis (OR = 3.1, 95% CI 1.2–7.7), sensory disturbance (OR = 3.1, 95% CI 1.1–8.9) and depression (OR = 4.1, 95% CI 1.4–13).
Conclusions:  The estimated prevalence of stroke-related pain was 21%. Stroke-related pain was associated with sensorimotor impairments and depression, but not with spasticity as an independent variable.     

Brain-derived neurotrophic factor (BDNF) genetic polymorphism greatly increases risk of leucine-rich repeat kinase 2 (LRRK2) for Parkinson's disease

Parkinson's disease (PD) is a complex neurodegenerative disorder. Although the p.G2385R allele of leucine-rich repeat kinase 2 (LRRK2) has been recently reported as a common genetic variant that increases the risk for typical PD exclusively among Asian population, its genetic modifiers is yet to be studied. Brain-derived neurotrophic factor (BDNF) has been shown to play an important role in the survival of dopaminergic neurons and its genetic polymorphism was associated with an increased risk for PD at an older age onset. The current case–control study was performed to investigate the interaction between LRRK2 p.G2385R and BDNF p.V66M in a Chinese PD cohort. A total of 464 PD patients and 549 controls were involved in this study. LRRK2 p.G2385R variant (odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.96–5.15, p < 0.0001), not BDNF p.V66M alone significantly increased the risk of PD. However, the simultaneous presence of both LRRK2 and BDNF variants significantly enhanced the risk for PD (OR = 4.033; 95% CI = 2.188–7.435, p < 0.0001), particularly in patients with an onset age of older than 60 (OR = 6.439; 95% CI = 3.096–13.389, p < 0.0001). Our results further support that LRRK2 variants are an independent genetic risk factor for typical PD, but BDNF variants can greatly increase LRRK2-induced risk for patients with an onset age of older than 60 indicating an additive effect between the 2 genes, which might aid in studying the mechanism underlying LRRK2 parkinsonism and developing potential therapeutic strategies.     

Acute ischemic stroke and transient ischemic attack in the very old – risk factor profile and stroke subtype between patients older than 80 years and patients aged less than 80 years

Old age groups have different risk profile and stroke features compared to younger groups. Our aim was to examine the risk factor profile and stroke subtype in patients older than 80 years with ischemic stroke. Data of 535 patients with ischemic stroke or transient ischemic attack (TIA) were prospectively recorded. Cardiovascular risk factors and stroke subtype in individuals aged 80 years or older were compared with patients under 80. Of 535 patients a total of 179 were over 80 years (33.5%). The mean age was 84.4 ± 4.4 years (61.8%; 111 women). The most common risk factors included hypertension (82.7%) and hyperlipidemia (40.2%). Lacunar stroke was the most frequent subtype of stroke (41.7%). When the groups were compared, we observed the following risk factors more frequently in the group older than 80: female patients ( P  = <0.001), hypertension (OR = 1.62), atrial fibrillation (OR = 2.64); whereas diabetes (OR = 0.54), hyperlipidemia (OR = 0.57), smoking (OR = 0.17) and obesity (OR = 0.58) were more frequent in the group younger than 80. In the old group we found a high incidence of ischemic stroke in women. We also found a higher frequency of hypertension and atrial fibrillation. The available and future epidemiological data will provide a better knowledge about the effect of typical risk factors in old people.     

Ultrasound, atherosclerosis and stroke at a young age: a cross-sectional long-term follow-up in western Norway

Background and purpose:  Previous studies have shown significantly higher mortality and vascular morbidity amongst patients with ischaemic stroke onset at a young age compared with controls after a mean observation time of more than 11 years.
Methods:  In the present cross-sectional study, we measured the carotid intima-media thickness (IMT) in 140 (75%) of 187 survivors of ischaemic stroke after a mean observation time of 11.9 years. Their mean age when included was 41.1 years. IMT was measured by B-mode ultrasonography.
Results:  Total maximum IMT <1.0 mm was found in 34 (24%) patients, [1.0–1.2 mm) in 29 (21%) patients, [1.2–1.5 mm) in 29 (21%) patients and ≥1.5 mm in 48 (34%) patients. Increasing total maximum IMT was related to increasing age, male gender, recurrent ischaemic stroke, coronary atherosclerosis, peripheral atherosclerosis, smoking, hypertension and diabetes mellitus.
Discussion:  IMT changes confirm increased vascular morbidity in patients who suffered ischaemic stroke at a young age.     

Emergency perception and other variables associated with extra-hospital delay in stroke patients in the Maresme region (Spain)

Delay in arrival to the emergency room (ER) may negatively influence outcome of stroke patients. We aim to analyze factors that influence extra-hospital delay in stroke patients. Two hundred and ninety-two consecutive stroke patients admitted in the ER were prospectively studied. Analysis was made to identify variables associated with <1- and <3 h delays from onset. About 18.8% of patients arrived before 1 h and 57.5% before 3 h. Factors independently associated with <3 h delay were decision to go immediately to ER (OR = 8.17; 95% IC = 4.47–18.8), ambulance transportation (OR = 2.35; 1.36–4.05) and total anterior circulation syndrome (TACS) (OR = 3.74; 1.51–9.24). History of >1 vascular risk factor was associated with a greater delay (OR = 0.47; 0.26–0.86). Factors associated with a <1 h delay were: (i) immediate decision to attend the ER (OR = 3.55; 1.85–6.81), (ii) stroke on Sunday (OR = 3.46; 1.56–7.66), (iii) aphasia (OR = 2.41; 1.23–4.74), (iv) absence of stairs at home (OR = 0.37; 0.17–0.81) and (v) absence of diabetes mellitus (OR = 0.42; 0.20–0.88). In our area, nearly 60% of stroke patients arrive to ER before 3 h from onset. Immediate decision to attend the ER has the strongest association with a short delay. Patients with TACS arrived mainly before 3 h and those with isolated aphasia arrived before 1 h. Patients with vascular risk factors attended the hospital later. Ambulance transportation is associated with <3 h delay, but not with <1 h.     

Arterial stiffness, metabolic syndrome and inflammation amongst Asian ischaemic stroke patients

Background and purpose:  Arterial stiffness and metabolic syndrome (MetS) are risk factors for ischaemic stroke. We studied the association of arterial stiffness, measured by carotid–femoral pulse wave velocity (PWV) and MetS amongst ischaemic stroke patients. We also investigated the role of inflammation measured by serum erythrocyte sedimentation rate (ESR) in the metabolic syndrome–arterial stiffness relationship.
Methods:  Amongst the 229 prospectively recruited acute ischaemic stroke patients, we measured carotid–femoral PWV using applanation tonometry and the inflammatory marker serum ESR.
Results:  Carotid–femoral PWV was significantly higher amongst patients with MetS ( P  = 0.002), increased waist circumference ( P  = 0.010), raised blood pressure ( P  < 0.001) and abnormal glycemia ( P  = 0.002); and increased with the number of MetS components ( P  = 0.002). In a sub-group of 199 patients, carotid–femoral PWV was significantly correlated with serum ESR ( P  < 0.001). In multivariate regression analysis including serum ESR and MetS as variables, carotid–femoral PWV was independently associated with higher ESR ( P  = 0.002) but not with MetS ( P  = 0.139).
Conclusions:  Arterial stiffness is significantly associated with MetS amongst ischaemic stroke patients, and inflammation appears to be involved in this relationship.     

High prevalence of unrecognized cerebral infarcts in first-ever stroke patients with cardioembolic sources

Background:  With magnetic resonance imaging (MRI) analysis, we investigated the prevalence, clinical significance, and factors related to the presence of unrecognized cerebral infarcts in patients with first-ever ischaemic stroke.
Methods:  We consecutively included patients who were admitted with first-ever stroke. Unrecognized cerebral infarct was defined as an ischaemic infarction or primary intracerebral hemorrhage on MRI irrelevant to the index stroke, without acute lesions on diffusion-weighted image.
Results:  Of the total 203 patients, 78 (39.4%) patients were observed as having unrecognized cerebral infarct. Patients with high-risk cardioembolic sources (e.g., atrial fibrillation) more frequently had unrecognized stroke than those without ( P  = 0.008, 21/36 [58.3%] vs. 57/167 [34.1%]). On univariate analysis, male sex ( P  = 0.027) and cardioembolic source ( P  = 0.008) were associated with the presence of unrecognized cerebral infarcts. After adjustment for gender, age and risk factors, the presence of cardioembolic sources independently increased the risk of unrecognized cerebral infarct ( P  = 0.002, odds ratio 3.56, 95% confidence interval 1.58–8.02). Regarding clinical outcome at 3 months, the presence of unrecognized cerebral infarct was not associated with the poor clinical outcome.
Conclusion:  In our study, the presence of cardioembolic sources was an independent risk factor for the unrecognized cerebral infarct in patients with first-ever stroke.     

The CST3 B haplotype is associated with frontotemporal lobar degeneration

Background and purpose:  Frontotemporal lobar degeneration (FTLD) is a common cause of early-onset dementia. Given the role of cystatin C in brain neurodegeneration and neuroregeneration, the aim of this study was to determine whether the cystatin C gene ( CST3 ) was genetically associated with FTLD.
Methods:  Hundred and eighty-six FTLD patients and 457 controls underwent CST3 analysis by PCR and KspI enzyme digestion.
Results:  In FTLD patients negative for the presence of PGRN mutations, we found an over-representation of the CST3 haplotype B [odds ratio (OR = 1.619, P  = 0.002)] and of AB/BB genotypes (OR = 1.704, P  =   0.008) in FTLD patients.
Conclusions:  The present study indicated the CST3 B haplotype as a putative risk factor for FTLD in PGRN mutations negative patients. The reduced level of cystatin C, previously associated with the B haplotype, might represent the molecular factor responsible for the increased risk. Long-term depletion of neurotrophic factors, such as cystatin C and progranulin proteins, seem to be a common theme in FTLD: boosting the expression of such proteins might be a promising therapeutic strategy for FTLD.     

Chlamydia pneumoniae in elderly patients with stroke (C-PEPS): a case-control study on the seroprevalence of Chlamydia pneumoniae in elderly patients with acute cerebrovascular disease

BACKGROUND AND PURPOSE: Multiple studies have suggested an association between Chlamydia pneumoniae infection and atherosclerotic vascular disease. We investigated whether serological markers of C. pneumoniae infection were associated with acute stroke or transient ischaemic attack (TIA), exclusively in elderly patients. METHODS: One-hundred white patients aged over 65 years admitted with acute stroke or TIA, and 87 control patients admitted with acute non-cardiopulmonary, non-infective disorders were recruited prospectively. Using an enzyme-linked immunosorbent assay kit, the presence of C. pneumoniae immunoglobulins IgA, IgG, IgM in patients' sera was determined. RESULTS: The seroprevalence of C. pneumoniae-specific IgA, IgG, IgM were 63, 71, and 14% in the stroke/TIA group (median age = 80), and 62, 65, and 17% in the control group (median age = 80), respectively. Using a logistic regression statistical model, adjusting for age and sex, history of hypertension, smoking, diabetes, ischaemic heart disease (IHD), ischaemic electrocardiogram (ECG), the odds ratios (ORs) of having a stroke/TIA in relation to C. pneumoniae-specific IgA, IgG, IgM were 1.04, 1.24, 0.79 (p = NS). Further analysis identified 43 acute stroke/TIA cases and 44 controls without history of IHD or ischaemic ECG or both. After adjusting for history of hypertension, smoking, diabetes, age and sex, the ORs in this subgroup were 1.40 for IgA [95% confidence interval (CI) 0.53-3.65; p = 0.49], 2.41 for IgG (95% CI 0.90-6.46; p = 0.08) and 1.55 for IgM (95% CI 0.45-5.40; p = 0.49). CONCLUSIONS: Although a high seroprevalence of C. pneumoniae in elderly patients was confirmed, no significant association between serological markers of C. pneumoniae infection and acute cerebrovascular events was found. There was, however, a weak trend towards increased ORs for acute cerebrovascular disease in a subgroup of C. pneumoniae seropositive elderly patients without any history of IHD or ischaemic ECG.