APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson's disease

The relationship between APOE polymorphisms and Parkinson's disease (PD) in black Africans has not been previously investigated. We evaluated the association between APOE polymorphic variability and self-declared cognition in 1100 Nigerians with PD and 1097 age-matched healthy controls. Cognition in PD was assessed using the single item cognition question (item 1.1) of the MDS-UPDRS. APOE genotype and allele frequencies did not differ between PD and controls (p > 0.05). No allelic or genotypic association was observed between APOE and age at onset of PD. In PD, APOE ε4/ε4 conferred a two-fold risk of cognitive impairment compared to one or no ε4 (HR: 2.09 (95% CI: 1.13-3.89; p = 0.02)), while APOE ε2 was associated with modest protection against cognitive impairment (HR: 0.41 (95% CI 0.19-0.99, p = 0.02)). Of 773 PD with motor phenotype and APOE characterized, tremor-dominant (TD) phenotype predominated significantly in ε2 carriers (87/135, 64.4%) compared to 22.2% in persons with postural instability/gait difficulty (PIGD) (30/135) and 13.3% in indeterminate (ID) (18/135, 13.3%) (p = 0.037). Although the frequency of the TD phenotype was highest in homozygous ε2 carriers (85.7%), the distribution of motor phenotypes across the six genotypes did not differ significantly (p = 0.18). Altogether, our findings support previous studies in other ethnicities, implying a role for APOE ε4 and ε2 as risk and protective factors, respectively, for cognitive impairment in PD

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Frequency & factors associated with recurrent stroke in Ghana and Nigeria

Background Data on the burden and outcomes of recurrent strokes in sub-Saharan Africa are limited, impeding efforts at optimal recurrent stroke prevention. Objective To assess the prevalence, risk factor profile, stroke types and mortality from recurrent strokes in Ghana and Nigeria. Methods We analyzed data from 3553 stroke cases involved in the Stroke Investigative Research and Educational Networks (SIREN) study for proportion with recurrent strokes. Conditional logistic regression models were constructed to interrogate for risk factors of recurrent stroke compared with stroke-free controls. Generalized Linear models were used to assess correlates of recurrent strokes relative to index strokes. Results Among stroke cases, 335 (9.4%) were recurrent strokes, of which 79.9% were ischemic and 20.1% hemorrhagic. Those with recurrent stroke were significantly older than index stroke cases 62.2 ± 12.9 years vs 58.9 ± 14.0 years, p \u3c 0.01 respectively. Topmost risk factors associated with recurrent stroke were hypertension adjusted odds ratio 50.7 (95%CI: 6.6–392.7), dyslipidemia 2.8 (1.3–6.2), diabetes mellitus 4.0 (2.1–7.7) and family history of cardiovascular disease (CVD) 2.1 (1.1–4.2). The relative risk (95%CI) of factors associated with recurrent stroke vs index stroke were age \u3e 50 years (1.5: 1.1–2.0); Hausa ethnicity (1.5:1.1–2.1), Yoruba ethnicity with Akan as referent; table added salt (0.4:0.2–0.8) and current alcohol intake (0.6:0.4–0.9). In-patient mortality among those with recurrent stroke vs. primary stroke was 20.5% vs. 21.4%. Conclusion Several modifiable lifestyle related factors may warrant additional emphasis as targets for reducing the burden of recurrent stroke in sub-Saharan Africa

Guillain barre syndrome as initial presentation of systemic lupus erythematosus

Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement including the peripheral nervous system. Guillan- Barrè syndrome (GBS) has an established association with SLE as one of its neurologic manifestations. However, GBS as an initial manifestation of SLE is only sparingly reported in the literature.Methods: We present a case of a 26 year old woman who was initially managed by neurology unit for GBS but subsequently developed body swelling, hypertension and polyarthritis. She was evaluated and managed by both rheumatology and nephrology units.Results: Renal biopsy showed histological features of membranous nephropathy suggestive of stage V lupus nephritis. The patient responded well to high dose corticosteroid, intravenous cyclophosphamide and azathioprine.Conclusion: This case highlights that GBS can be an initial presentation of SLE and the usefulness of immunosuppressants in the management of such cases.Keywords: Guillan-Barrè syndrome, Systemic Lupus Erythematosus, Lupus Nephritis, Immunosuppressant

Clinical and neuroimaging factors associated with 30-day fatality among indigenous West Africans with spontaneous intracerebral hemorrhage

Background Spontaneous intracerebral hemorrhage (ICH) is associated with a high case fatality rate in resource-limited settings. The independent predictors of poor outcome after ICH in sub-Saharan Africa remains to be characterized in large epidemiological studies. We aimed to determine factors associated with 30-day fatality among West African patients with ICH. Methods The Stroke Investigative Research and Educational Network (SIREN) study is a multicentre, case-control study conducted at 15 sites in Nigeria and Ghana. Adults aged ≥18 years with spontaneous ICH confirmed with neuroimaging. Demographic, cardiovascular risk factors, clinical features and neuroimaging markers of severity were assessed. The independent risk factors for 30-day mortality were determined using a multivariate logistic regression analysis with an adjusted odds ratio (OR) and 95% confidence interval (CI). Results Among 964 patients with ICH, 590 (61.2%) were males with a mean age (SD) of 54.3(13.6) years and a case fatality of 34.3%. Factors associated with 30-day mortality among ICH patients include: Elevated mean National Institute of Health Stroke Scale(mNIHSS);(OR 1.06; 95% CI 1.02–1.11), aspiration pneumonitis; (OR 7.17; 95% CI 2.82–18.24), ICH volume \u3e 30mls; OR 2.68; 95% CI 1.02–7.00)) low consumption of leafy vegetables (OR 0.36; 95% CI 0.15–0.85). Conclusion This study identified risk and protective factors associated with 30-day mortality among West Africans with spontaneous ICH. These factors should be further investigated in other populations in Africa to enable the development of ICH mortality predictions models among indigenous Africans

Determinants of metabolic syndrome and its prognostic implications among stroke patients in Africa: Findings from the Stroke Investigative Research and Educational Network (SIREN) study

Background The prognostic implications of metabolic syndrome (METS) among African stroke patients are poorly understood. This study aimed to investigate the determinants of METS and its prognostic implications among Africans with newly diagnosed stroke in the SIREN study. Methods We included stroke cases (adults aged \u3e18 years with CT/MRI confirmed stroke). The validated tools comprehensively evaluated vascular, lifestyle, and psychosocial factors. We used logistic regression to estimate adjusted odds ratios (OR) with 95% CIs for the association between METS and risk factors. We also computed the prediction power of the domain of covariates in a sequential manner using the area under the receiver operating curve (ROC) curve. Results Among 3998 stroke subjects enrolled in the study, 76.8% had METS by at least one of the clinical definitions. Factors associated with METS were age \u3e 50 years (OR- 1.46, CI-1.19-1.80), male gender (OR 4.06, CI- 3.28-5.03), income \u3e100USD (OR1.42, CI-1.17-1.71), stress (OR1.46, CI-1.14-1.87), family history of diabetes mellitus (OR1.38, CI-1.06-1.78), and cardiac disease (OR1.42, CI-1.18-1.65). Stroke severity was higher among those with METS (SLS = 5.8 ± 4.3) compared with those without METS (6.2 ± 4.5) at p = 0.037. METS was associated with higher odds (aOR 1.31, CI-1.08-1.58) of one-month fatality after adjusting for stroke severity, age \u3e 50 years, and average monthly income \u3e100USD. Conclusion METS is very common among African stroke patients and is associated with stroke severity and worse one-month fatality. Lifestyle interventions may prevent METS and attenuate its impact on stroke occurrence and outcomes

Determinants of First‐Ever Stroke Severity in West Africans: Evidence From the SIREN Study

Background Baseline stroke severity is probably partly responsible for poor stroke outcomes in sub‐Saharan Africa. However, there is a paucity of information on determinants of stroke severity among indigenous Africans. We sought to identify the factors associated with stroke severity among West Africans in the SIREN (Stroke Investigative Research and Educational Networks) study. Methods and Results Stroke was diagnosed clinically and confirmed with brain neuroimaging. Severe stroke was defined as a Stroke Levity Scale score of ≤5. A multivariate logistic regression model was constructed to identify factors associated with stroke severity at 95% CI and a nominal cutoff of 5% type 1 error. A total of 3660 stroke cases were included. Overall, 50.7%% had severe stroke, including 47.6% of all ischemic strokes and 56.1% of intracerebral hemorrhage. Factors independently associated with severe stroke were meat consumption (adjusted odds ratio [aOR], 1.97 [95% CI, 1.43–2.73]), low vegetable consumption (aOR, 2.45 [95% CI, 1.93–3.12]), and lesion volume, with an aOR of 1.67 (95% CI, 1.03–2.72) for lesion volume of 10 to 30 cm3 and aOR of 3.88 (95% CI, 1.93–7.81) for lesion volume >30 cm3. Severe ischemic stroke was independently associated with total anterior circulation infarction (aOR, 3.1 [95% CI, 1.5–6.9]), posterior circulation infarction (aOR, 2.2 [95% CI, 1.1–4.2]), and partial anterior circulation infarction (aOR, 2.0 [95% CI, 1.2–3.3]) compared with lacunar stroke. Increasing age (aOR, 2.6 [95% CI, 1.3–5.2]) and lesion volume >30 cm3 (aOR, 6.2 [95% CI, 2.0–19.3]) were independently associated with severe intracerebral hemorrhage. Conclusions Severe stroke is common among indigenous West Africans, where modifiable dietary factors are independently associated with it. These factors could be targeted to reduce the burden of severe stroke

MAPT allele and haplotype frequencies in Nigerian Africans: Population distribution and association with Parkinson's disease risk and age at onset

INTRODUCTION: The association between MAPT and PD risk may be subject to ethnic variability even within populations of similar geographical origin. Data on MAPT haplotype frequencies, and its association with PD risk in black Africans are lacking. We aimed to determine the frequencies of MAPT haplotypes and their role as risk factors for PD and age at onset in Nigerians. METHODS: The haplotype and genotype frequencies of MAPT rs1052553 were analysed in 907 individuals with PD and 1022 age-matched healthy controls from the Nigeria Parkinson's Disease Research network cohort. Clinical data related to PD included age at study, age at onset (AAO), and disease duration. RESULTS: The frequency of the H1 haplotype was 98.7% in PD, and 99.1% in controls (p = 0.19). The H2 haplotype was present in - 1.3% of PD and 0.9% of controls (p = 0.24). The most frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype was not associated with PD risk after accounting for gender and AAO (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p = 0.23). CONCLUSIONS: Our findings support previous studies that report a low frequency of the MAPT H2 haplotype in black ancestry Africans but document its occurrence in Nigerians. The MAPT H1 haplotype was not associated with an increased risk or age at onset of PD in this cohort

Dominant modifiable risk factors for stroke in Ghana and Nigeria (SIREN): a case-control study

Summary: Background: Sub-Saharan Africa has the highest incidence, prevalence, and fatality from stroke globally. Yet, only little information about context-specific risk factors for prioritising interventions to reduce the stroke burden in sub-Saharan Africa is available. We aimed to identify and characterise the effect of the top modifiable risk factors for stroke in sub-Saharan Africa. Methods: The Stroke Investigative Research and Educational Network (SIREN) study is a multicentre, case-control study done at 15 sites in Nigeria and Ghana. Cases were adults (aged ≥18 years) with stroke confirmed by CT or MRI. Controls were age-matched and gender-matched stroke-free adults (aged ≥18 years) recruited from the communities in catchment areas of cases. Comprehensive assessment for vascular, lifestyle, and psychosocial factors was done using standard instruments. We used conditional logistic regression to estimate odds ratios (ORs) and population-attributable risks (PARs) with 95% CIs. Findings: Between Aug 28, 2014, and June 15, 2017, we enrolled 2118 case-control pairs (1192 [56%] men) with mean ages of 59·0 years (SD 13·8) for cases and 57·8 years (13·7) for controls. 1430 (68%) had ischaemic stoke, 682 (32%) had haemorrhagic stroke, and six (<1%) had discrete ischaemic and haemorrhagic lesions. 98·2% (95% CI 97·2–99·0) of adjusted PAR of stroke was associated with 11 potentially modifiable risk factors with ORs and PARs in descending order of PAR of 19·36 (95% CI 12·11–30·93) and 90·8% (95% CI 87·9–93·7) for hypertension, 1·85 (1·44–2·38) and 35·8% (25·3–46·2) for dyslipidaemia, 1·59 (1·19–2·13) and 31·1% (13·3–48·9) for regular meat consumption, 1·48 (1·13–1·94) and 26·5% (12·9–40·2) for elevated waist-to-hip ratio, 2·58 (1·98–3·37) and 22·1% (17·8–26·4) for diabetes, 2·43 (1·81–3·26) and 18·2% (14·1–22·3) for low green leafy vegetable consumption, 1·89 (1·40–2·54) and 11·6% (6·6–16·7) for stress, 2·14 (1·34–3·43) and 5·3% (3·3–7·3) for added salt at the table, 1·65 (1·09–2·49) and 4·3% (0·6–7·9) for cardiac disease, 2·13 (1·12–4·05) and 2·4% (0·7–4·1) for physical inactivity, and 4·42 (1·75–11·16) and 2·3% (1·5–3·1) for current cigarette smoking. Ten of these factors were associated with ischaemic stroke and six with haemorrhagic stroke occurrence. Interpretation: Implementation of interventions targeting these leading risk factors at the population level should substantially curtail the burden of stroke among Africans. Funding: National Institutes of Health