Simon D. Israeli-Korn

Aspirin Responsiveness in Acute Brain Ischaemia: Association with Stroke Severity and Clinical Outcome

Purpose: Platelets play a critical role in the pathogenesis of acute brain ischaemia. We studied the association between the degree of inhibition of platelet function by aspirin (ASA) and the severity and outcome of acute brain ischaemia. Methods: Platelet responsiveness to ASA was assessed in patients with acute brain ischaemia, treated with ASA since hospital admission. The degree of ASA responsiveness was assessed by optical aggregometry and categorized into patients with good response, partial response and complete unresponsiveness to ASA (good responders, partial responders and non-responders, respectively). An additional evaluation of responsiveness to ASA was performed by Impact-R (cone and platelet analyzer). Patients underwent serial clinical assessment during hospitalization, at discharge and during follow-up. Results: Among 105 patients (mean age 63 ± 12 years; 66% men), impaired ASA responsiveness at baseline as assessed by aggregometry was associated with increased stroke severity at baseline, unfavourable clinical course, and poor functional outcome during follow-up (p < 0.05 for all). Age-adjusted odds ratios in non-responders compared to good responders were 9.8 for severe stroke on admission (95% CI 2.8–34.9), 3.1 for lack of early clinical improvement (95% CI 1.1–8.8) and 8.6 for poor functional outcome during follow-up (95% CI 2.4–30.4). Less robust trends were observed with the Impact-R. Conclusions: Impaired responsiveness to ASA in acute brain ischaemia is common and is associated with worse neurological deficits at stroke onset, early clinical deterioration and poorer functional outcome. The clinical significance of these findings requires further evaluation in larger longitudinal studies.

Hypertension Increases the Probability of Alzheimer's Disease and of Mild Cognitive Impairment in an Arab Community in Northern Israel

Background: We aimed to determine whether vascular risk factors are associated with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) in an elderly Arab population. Methods: An Arabic-speaking team performed a door-to-door survey of consecutive residents aged ≧65 years. We estimated the odds of AD or MCI versus normal controls as a function of age, gender, education and presence of vascular factors by multinomial logistic regression with interactions. Results: Out of 767 subjects (54% men), 444 were cognitively normal, 234 had MCI and 89 had AD. AD was significantly associated with hypertension (p = 0.01; OR = 2.08; 95% CI: 1.18–3.65), age (p < 0.0001; OR = 1.19; 95% CI: 1.14–1.24), female gender (p = 0.0016; OR = 3.06; 95% CI: 1.53–6.15) and education (p = 0.0002; OR = 0.75; 95% CI: 0.65–0.88). MCI was significantly associated with hypertension (p = 0.0042; OR = 1.69; 95% CI: 1.25–2.44), age (p < 0.0001; OR = 1.06; 95% CI: 1.03–1.09) and education (p < 0.0001; OR = 0.76; 95% CI: 0.71–0.83), but not with gender. Conclusions: Hypertension, older age and low education significantly increase the probability of AD and MCI. The effect of hypertension on the odds of AD versus controls is over and above the effects of age, gender and education. For MCI versus controls there is no gender effect, and the effect of hypertension is over and above the effects of age and education.

The particular relationship between Parkinson’s disease and malignancy: a focus on skin cancers

Although the risk for most cancers appears to be relatively low in patients with Parkinson’s disease (PD), skin cancers and melanomas occur more frequently in the PD population as compared to controls. This article summarizes the findings of cohort studies on skin cancer in Parkinson’s disease. Given that melanoma may precede use of l-dopa, the increased risk of melanoma for PD patients cannot be attributed to l-dopa. On the basis of these observations it may be reasonable to recommend that all patients with PD, whether treated with l-dopa or not, should undergo regular dermatological screening for neoplastic or pre-neoplastic skin lesions, especially melanoma.

High Prevalence of Mild Cognitive Impairment and Alzheimer's Disease in Arabic Villages in Northern Israel: Impact of Gender and Education

The prevalence of mild cognitive impairment (MCI) and Alzheimers disease (AD) have not been well been studied in Arab populations. In a door-to-door study of all residents aged ≥ 65 years in Wadi-Ara, an Arab community in northern Israel, we estimated the prevalence of AD, MCI, and the risk of conversion to AD. Subjects were classified as cognitively normal, MCI, AD, or other based on neurological and cognitive examination (in Arabic). MCI subjects were re-examined (interval ≥ 1 year) to determine conversion to AD and contributions of age, gender, and education to the probability of conversion. Of the 944 participants (96.6% of those approached; 49.4% men), 92 (9.8%) had AD. An unusually high prevalence of MCI (n = 303, 32.1%) was observed. Since the majority of women (77.2%) had no schooling, we estimated the effect of gender on the risk of AD and MCI among subjects without schooling and of school years among men. Among subjects with no schooling (n = 452), age (p = 0.02) and female gender (p < 0.0001) were significant predictors of AD, whereas risk of MCI increased only with age (p = 0.0001). Among men (n = 318), age increased the risk (p < 0.0001), school years reduced the risk of AD (p = 0.039) and similarly for MCI [age (p = 0.0001); school years (p = 0.0007)]. Age (p = 0.013), but not gender or school years, was a significant predictor of conversion from MCI to AD (annual rate 5.7%). The prevalence of MCI and AD are unusually high in Wadi Ara, while the rate of conversion from MCI to AD is low. Yet unidentified genetic factors might underlie this observation.

Prayer at Midlife is Associated with Reduced Risk of Cognitive Decline in Arabic Women

Midlife habits may be important for the later development of Alzheimers disease (AD). We estimated the contribution of midlife prayer to the development of cognitive decline. In a door-to-door survey, residents aged ≥65 years were systematically evaluated in Arabic including medical history, neurological, cognitive examination, and a midlife leisure-activities questionnaire. Praying was assessed by the number of monthly praying hours at midlife. Stepwise logistic regression models were used to evaluate the effect of prayer on the odds of mild cognitive impairment (MCI) and AD versus cognitively normal individuals. Of 935 individuals that were approached, 778 [normal controls (n=448), AD (n=92) and MCI (n=238)] were evaluated. A higher proportion of cognitively normal individuals engaged in prayer at midlife [(87%) versus MCI (71%) or AD (69%) (p<0.0001)]. Since 94% of males engaged in prayer, the effect on cognitive decline could not be assessed in men. Among women, stepwise logistic regression adjusted for age and education, showed that prayer was significantly associated with reduced risk of MCI (p=0.027, OR=0.55, 95% CI 0.33-0.94), but not AD. Among individuals endorsing prayer activity, the amount of prayer was not associated with MCI or AD in either gender. Praying at midlife is associated with lower risk of mild cognitive impairment in women.

Mild Cognitive Impairment is Associated with Mild Parkinsonian Signs in a Door-to-Door Study

Mild cognitive impairment (MCI) and healthy aging have been shown to be associated with mild parkinsonian signs (MPS). We performed a door-to-door observational and follow-up study amongst consenting residents of Wadi Ara Arab villages in northern Israel aged ≥65 years (n=687) to examine whether MPS represent a risk factor for MCI and/or conversion from MCI to Alzheimers disease (AD). In Phase 1, 223 cognitively normal (CN) and 173 MCI subjects were assessed by interview for medical history, neurological examination, motor part of the Unified Parkinson Disease Rating Scale (mUPDRS) (divided into item-clusters: axial, limb bradykinesia, tremor and rigidity) and cognitive tests. MCI subjects (n=111) were re-evaluated in Phase 2 for conversion to AD at least one year after initial assessment. MCI subjects had a higher frequency of axial dysfunction (8.7% vs. 1.3%) and limb bradykinesia (10.4% vs. 1.3%) than CN subjects (p<0.001, both). Stepwise logistic regression analysis estimating the probability of MCI vs. CN revealed higher mUPDRS (OR =1.19, 95% CI, 1.05 to 1.35, p=0.006) and higher limb bradykinesia scores (OR=1.75, 95% CI, 1.2 to 2.56, p=0.003) and not age as explanatory variables. Presence of MPS did not predict conversion to AD after adjustment for age and time-interval. These results suggest that axial and bradykinetic parkinsonian signs represent risk factors for MCI but MPS may not predict conversion from MCI to AD.

The LRRK2 G2019S mutation status does not affect the outcome of subthalamic stimulation in patients with Parkinson's disease

BACKGROUND Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established therapy for advanced Parkinsons disease (PD). The most common genetic mutation associated with PD identified to date is the G2019S mutation of the LRRK2 gene, which is highly prevalent in the Ashkenazi Jewish population. The effect of STN-DBS surgery in patients carrying this mutation has not been systematically studied. We therefore performed a case-control study to evaluate the impact of the G2019S mutation status on the outcomes of bilateral STN-DBS. METHODS The study sample included 39 Jewish PD patients with bilateral STN-DBS. Thirteen patients (5 females) were G2019S mutation heterozygous. The control group consisted of 26 PD patients with bilateral STN-DBS, negative for the mutation, matched (2:1) for gender, age at PD onset, and disease duration at surgery. Clinical data including the Unified PD Rating Scale scores (UPDRS), levodopa equivalent daily dose (LEDD), and clinical global impression of change (CGIC) concerning both motor and neuropsychiatric outcome- were available at 3 time points (preoperative baseline, 6-12 months and 3 years postoperatively). RESULTS Implementing a linear mixed model, a significant improvement (p < 0.05) was found for the whole group concerning reduction in motor UPRDS (off state) and LEDD pre- vs. postoperatively, as expected. No difference in clinical outcome was found between carriers and matched non-carriers at baseline or at postoperative follow-up (up to 3 years). CONCLUSIONS In our study, STN-DBS outcomes were not influenced by the LRRK2 G2019S mutation, and thus knowledge of carrier status may not be relevant to the considerations of patient selection for surgery.

Subthalamic Nucleus Deep Brain Stimulation Does Not Improve Visuo-Motor Impairment in Parkinson’s Disease

Objective To evaluate how bilateral subthalamic nucleus deep brain stimulation (STN-DBS) affects visuo-motor coordination (VMC) in patients with Parkinson’s disease (PD). Background VMC involves multi-sensory integration, motor planning, executive function and attention. VMC deficits are well-described in PD. STN-DBS conveys marked motor benefit in PD, but pyscho-cognitive complications are recognized and the effect on VMC is not known. Methods Thirteen PD patients with bilateral STN-DBS underwent neurological, cognitive, and mood assessment before VMC testing with optimal DBS stimulation parameters (‘on-stimulation’) and then, on the same day without any medication changes, after DBS silencing and establishing motor function deterioration (‘off-stimulation’). Twelve age-matched healthy controls performed 2 successive VMC testing sessions, with a break of similar duration to that of the PD group. The computer cursor was controlled with a dome-shaped ‘mouse’ hidden from view that minimized tremor effects. Movement duration, hand velocity, tracking continuity, directional control variables, and feedback utilization variables were measured. MANOVA was performed on (1) clinically measured motor function, (2) VMC performance and (3) mood and attention, looking for main and interaction effects of: (1) group (controls/PD), (2) test-order (controls: first/second, PD: on-stimulation/off-stimulation), (3) path (sine/square/circle) and (4) hand (dominant/non-dominant). Results Unified PD Rating Scale (UPDRS) Part III worsened off-stimulation versus on-stimulation (mean: 42.3 versus 21.6, p = 0.02), as did finger tapping (p = 0.02), posture-gait (p = 0.01), upper limb function (p<0.001) and backwards digit span (p = 0.02). Stimulation state did not affect mood. PD patients performed worse in non-velocity related VMC variables than controls (F(5,18) = 8.5, p<0.001). In the control group there were significant main effects of hand (dominant/non-dominant), path (sine/square/circle) and test-order (Test_1/Test_2). In the PD group, hand and path effects, but no test-order (on-stimulation/off-stimulation), were found. Conclusions ‘Low-level’ clinically-measured motor function responds to STN-DBS but ‘high-level’ motor and cognitive functions relating to VMC may be unresponsive to STN-DBS.

Phenotype of the 202 Adenine Deletion in the parkin Gene: 40 Years of Follow-Up

We describe the four decades follow‐up of 14 parkin patients belonging to two large eight‐generation‐long in‐bred Muslim‐Arab kindreds.

Acquired premature ejaculation in Parkinson’s disease and possible mechanisms

Premature ejaculation (PE) has been reported in 40.6–51.5% of men affected by Parkinson’s disease (PD), however, this non-motor sexual complaint has not been studied in detail. We describe eight PD patients who asked for a sexological consultation between 2008 and 2014 because of a new-onset of PE. They were diagnosed with acquired PE (APE) according to the DSM-V criteria and the International Society for Sexual Medicine (ISSM) committee. Patients’ demographic, medical and sexual related data were retrieved and studied. The average age of onset of PD was 53.3 ± 12.7 years (range 38–77 years) and the sexual problem appeared 4.0 ± 3.1 years later. The mean intravaginal ejaculation latency (IELT) before APE onset was 7.3 (range 2–20) min. Interestingly, the ejaculatory disorder appeared abruptly, characterized by a dramatically shortened IELT in all patients, while in three of the cases ejaculation occurred before vaginal penetration, hampering sexual intercourse. Some patients had 2 additional sexual problems, (four with erectile dysfunctions, five with libido changes: increased desire in four and reduced in one). In this case series of PD patients with APE, the ejaculatory dysfunction developed when patients were on antiparkinsonian medications, suggesting a possible medication effect.