Renal dysfunction and 30-day mortality risk in patients with acute stroke

Background: Chronic kidney disease (CKD) and stroke constitute worldwide public health problems with rising incidence, prevalence and poor outcomes. While the link between renal dysfunction and myocardial infarction is well established, the link with stroke has been less well investigated. In this study, the prevalence and prognostic implication of renal dysfunction in patients admitted with acute stroke was assessed.Methods: This was a prospective observational study of 130 patients with first-ever stroke admitted within 7 days of stroke onset and followed up for 30 days. The study outcome measure was 30-day mortality. Stroke subtype was verified by a computerized tomography (CT) scan of the brain. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the 4-variable Modification of Diet in Renal Disease (MDRD) equation. Renal dysfunction was defined as eGFR < 60 mL/min/1.73 m2 and significant proteinuria was defined as urinary protein excretion ≥ 0.5 g in 24 hours. The Cox proportional hazards regression model was used to determine the relationship between GFR, proteinuria and 30-day mortality.Results: The majority of the patients studied (56%) were male and their mean age was 61.3 ± 13.9 years. Ischaemic stroke was the most common stroke subtype, accounting for 74% of all cases. Overall, 38% of patients had reduced eGFR < 60 mL/min/1.72 m2 while 35% had significant proteinuria. eGFR < 60 mL/min/1.73 m2 (hazard ratio, HR 3.59, 95% CI 1.03–13.26, p < 0.001) and proteinuria (HR 1.86, CI 1.00–8.14, p = 0.035) were independent predictors of mortality. Other independent predictors were age > 70 years, haemorrhagic stroke subtype, CNS score < 6.5 and random blood glucose > 7.8 mmol/L.Conclusions:Renal dysfunction is common among adult Nigerian patients with acute stroke. Both reduced eGFR and proteinuria were independent predictors of 30-day mortality in these patients

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

Poststroke anxiety disorders in a Nigerian hospital: Prevalence, associated factors, and impacts on quality of life

Background and Purpose: Anxiety disorders impact negatively on morbidity and mortality poststroke. Few studies have, however, been done on poststroke anxiety disorders (PSAD), particularly in Africa. The study aims to determine the prevalence, associated clinicodemographic factors, and impact of PSAD on quality of life (QoL) among outpatients at a tertiary hospital in Nigeria. Methods: Seventy stroke survivors attending Outpatient Clinics at Lagos University Teaching Hospital, Nigeria, were recruited into the study. Participants were assessed using sociodemographic/clinical questionnaire, the modified Mini–Mental State Examination, the Modified Rankin Scale, the Schedule for Clinical Assessment in Neuropsychiatry, and the World Health Organization-QoL-Bref. Data collection took 5 months and analyzed using the Statistical Package for the Social Sciences (SPSS®) software version 17.0. Results: The mean age of respondents was 57.43 (±9.67) years and 38 respondents (54%) were male. Majority of the stroke survivors had infarctive stroke 55 (78.6%), right hemispheric lesions 37 (52.9%), and significant poststroke disabilities 57 (81.4%). The prevalence of PSAD was 10% and agoraphobia with panic attacks was elicited in 42.8% of those diagnosed with PSAD. Participants with PSAD were significantly more likely to be unemployed (P = 0.01) and pay more than ₦10,000 ($62.50 at December 2013) monthly for health care. The mean QoL scores were lower in participants with PSAD across all QoL spheres, and significantly so for overall health (P = 0.04), health satisfaction (P = 0.02), and physical health (P = 0.01) domains. Conclusion: PSAD, especially agoraphobia in association with unemployment and high health-care costs correlated with poor well-being among stroke survivors. Proactive measures to ensure prompt identification and management may potentially improve outcome and QoL after stroke

Post-stroke depression: Prevalence, associated factors and impact on quality of life among outpatients in a Nigerian hospital

Objectives: To investigate the prevalence of post-stroke depression (PSD), its associated factors and impact on quality of life (QoL) among outpatients in a Nigerian hospital. Methods: This cross-sectional study was carried out among 140 adults made up of 70 stroke survivors and matched controls with stable hypertension. Participants were administered questionnaires to profile their socio-demographic and clinical characteristics. Subsequently, they were assessed with the modified mini-mental state examination (MMSE), modified Rankin Scale (mRS), schedule for clinical assessment in neuropsychiatry (SCAN) and World Health Organization Quality of Life-BREF (WHOQoL-BREF). Results: The mean ages (± s.d.) of stroke survivors and controls were 57.43 (± 9.67) years and 57.33 (± 9.33) years, respectively. Majority of stroke survivors (n = 55 [78.6%]) had infarctive stroke, and 37 (52.9%) had right hemispheric lesion. Sixteen (22.9%) stroke survivors had PSD, with moderate to severe depression (F32.1) being the most prevalent, while none of the controls was clinically depressed. PSD correlated positively with monthly health bill above 10 000 naira ($61), significant post-stroke disability and poorer scores on all QoL domains (p < 0.05). Conclusion: Depression was 20-fold prevalent in stroke survivors compared to controls with stable hypertension, and sevenfold the life-time prevalence reported among adult general population in Nigeria. Furthermore, increased health care bills per month, significant post-stroke disability and poorer QoL indicated survivors more likely to have depression. Findings in this study support the need to pay closer attention to psychosocial needs of stroke survivors to improve well-being. Future longitudinal study on psychosocial burden of stroke is warranted

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

Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study

BACKGROUND: An understanding of the genetic mechanisms underlying diseases in ancestrally diverse populations is an important step towards development of targeted treatments. Research in African and African admixed populations can enable mapping of complex traits, because of their genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. We aimed to do a comprehensive genome-wide assessment in African and African admixed individuals to better understand the genetic architecture of Parkinson's disease in these underserved populations. METHODS: We performed a genome-wide association study (GWAS) in people of African and African admixed ancestry with and without Parkinson's disease. Individuals were included from several cohorts that were available as a part of the Global Parkinson's Genetics Program, the International Parkinson's Disease Genomics Consortium Africa, and 23andMe. A diagnosis of Parkinson's disease was confirmed clinically by a movement disorder specialist for every individual in each cohort, except for 23andMe, in which it was self-reported based on clinical diagnosis. We characterised ancestry-specific risk, differential haplotype structure and admixture, coding and structural genetic variation, and enzymatic activity. FINDINGS: We included 197 918 individuals (1488 cases and 196 430 controls) in our genome-wide analysis. We identified a novel common risk factor for Parkinson's disease (overall meta-analysis odds ratio for risk of Parkinson's disease 1·58 [95% CI 1·37-1·80], p=2·397 × 10-14) and age at onset at the GBA1 locus, rs3115534-G (age at onset β=-2·00 [SE=0·57], p=0·0005, for African ancestry; and β=-4·15 [0·58], p=0·015, for African admixed ancestry), which was rare in non-African or non-African admixed populations. Downstream short-read and long-read whole-genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. The identified signal seems to be associated with decreased glucocerebrosidase activity. INTERPRETATION: Our study identified a novel genetic risk factor in GBA1 in people of African ancestry, which has not been seen in European populations, and it could be a major mechanistic basis of Parkinson's disease in African populations. This population-specific variant exerts substantial risk on Parkinson's disease as compared with common variation identified through GWAS and it was found to be present in 39% of the cases assessed in this study. This finding highlights the importance of understanding ancestry-specific genetic risk in complex diseases, a particularly crucial point as the Parkinson's disease field moves towards targeted treatments in clinical trials. The distinctive genetics of African populations highlights the need for equitable inclusion of ancestrally diverse groups in future trials, which will be a valuable step towards gaining insights into novel genetic determinants underlying the causes of Parkinson's disease. This finding opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk of Parkinson's disease. FUNDING: The Global Parkinson's Genetics Program, which is funded by the Aligning Science Across Parkinson's initiative, and The Michael J Fox Foundation for Parkinson's Research