Clinical profile of parkinsonism and Parkinson's disease in Lagos, Southwestern Nigeria

<p>Abstract</p> <p>Background</p> <p>Current data on the pattern of parkinsonism and Parkinson's disease in Nigerians are sparse.</p> <p>This database was designed to document the clinical profile of PD in Nigerians, and compare this to prior observations.</p> <p>Methods</p> <p>A database of patients presenting to the Neurology out-patients clinic of the Lagos University Teaching Hospital was established in October 1996. Demographic and clinical data at presentation (disease stage using Hoehn and Yahr scale; 'off' state severity on the Unified Parkinson's disease Rating Scale) were documented for patients diagnosed with parkinsonism between October 1996 and December 2006. Cases were classified as Parkinson's disease or secondary parkinsonism (in the presence of criteria suggestive of a secondary aetiology).</p> <p>Results</p> <p>The hospital frequency of parkinsonism (over a 2-year period, and relative to other neurologic disorders) was 1.47% (i.e. 20/1360). Of the 124 patients with parkinsonism, 98 (79.0%) had PD, while 26 (21.0%) had secondary parkinsonism. Mean age (SD) at onset of PD (61.5 (10.0) years) was slightly higher than for secondary parkinsonism (57.5 (14.0) years) (P = 0.10). There was a male preponderance in PD (3.3 to 1) and secondary parkinsonism (2.7 to 1), while a positive family history of parkinsonism was present in only 1.02% (1/98) of PD. There was a modestly significant difference in age at onset (SD) of PD in men (60.3 (10.4)) compared to women (65.2 (7.9)) (T = 2.08; P = 0.04). The frequency of young onset PD (≤ 50 years) was 16.3% (16/98). The mean time interval from onset of motor symptoms to diagnosis of PD was 24.6 ± 26.1 months with majority presenting at a median 12 months from onset. On the H&Y scale, severity of PD at presentation was a median 2.0 (range 1 to 4). PD disease subtype was tremor-dominant in 31 (31.6%), mixed 54 (55.1%) and akinetic-rigid 14 (14.3%). Hypertension was present as a co-morbidity in 20 (20.4%), and diabetes in 6 (6.12%).</p> <p>Conclusions</p> <p>The clinical profile of PD in Nigerians is similar to that in other populations, but is characterized by delayed presentation as has been reported in other developing countries. Young-onset disease occurs but may be less commonly encountered, and frequency of a positive family history is lower than in western populations.</p

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

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Frequency of cognitive impairment and depression in Parkinson’s disease: A preliminary case-control study

Background: This study aimed to determine the frequency of cognitive impairment and depression in our Parkinson's Disease (PD) and their relationship with disease severity and disability. Patients and Methods: A total of 40 PD patients and 40 age-, sex-, and educationally matched controls were studied. The Unified Parkinson Disease Rating Scale (UPDRS) Motor and Activities of Daily Living (ADL) scores and the Hoehn and Yahr (HY) stage were documented. Depression was assessed using the Zung Self-Rating Depression Scale (ZSDS), while cognition was evaluated using a composite score of the mini-mental state examination (MMSE) score and category fluency score. Results: A total of 55% (22/40) of PD and 10% (4 of 40) of controls had depression (P &lt; 0.001). A total of 60% of PD (24/40) and 5% of controls (2/40) had cognitive impairment (P &lt; 0.001). Both NMS coexisted in 16 of 40 PD (40%) compared with none of the controls (P 0.001). UPDRS (motor and ADL) scores and HY stage were significantly worse with impaired ZSDS scores – P &lt; 0.001. UPDRS ADL was significantly impaired by the presence of cognitive impairment. Coexisting depression and cognitive impairment were associated with significant worsening of all scores of severity and disability. Conclusion: Cognitive impairment and depression accompany our PD and are related to disability and worsening disease severity.Keywords: Cognitive impairment, depression, disability, Parkinson’s disease, severityNigerian Medical Journal | Vol. 53 | Issue 2 | April-June | 201

Frequency of neuropathic pain in type 2 diabetes mellitus at the Lagos University Teaching Hospital: A questionnaire-based outpatient survey

Background: Neuropathic pain (NP) is one of the most common complications of type 2 diabetes mellitus (DM). The frequency of NP in population living with type 2 DM is unclear. Objective: To determine the frequency of NP symptoms in patients with type 2 DM. Materials and Methods: This cross-sectional study recruited 250 type 2 DM patients attending the outpatient diabetes clinic of the Lagos University Teaching Hospital (LUTH) over a period of 4 weeks. Demographic data and data regarding current DM treatment, prior diagnosis of NP, and current treatment of NP were obtained using a structured questionnaire. Glycaemic status of the patients was assessed measuring fasting blood glucose and glycosylated hemoglobin level. Presence of NP was documented using the painDETECT questionnaire (PDQ). Results: NP was present in 54 out of the 250 type 2 DM patients studied giving a frequency of  21.6%. Out of 54 patients 36 (66.7%) were females and 18 (33.3%) were males giving a male: female ratio of 1:2 (P < 0.05). The mean age of type 2 DM patients with NP was significantly higher than the mean age of type 2 DM patients without NP (62.4 ± 10.9 years vs 58.9 ± 11.7 years; P = 0.05). Glycaemic status and disease duration did not differ among DM patients with or without NP. Only 10 out of 54 (18.5%) patients were treatment naοve at the time of study; however, out of the 44 patients receiving treatment only 9 (20.5%) were on appropriate treatment compared to international guidelines on treatment of diabetic NP. Conclusion: NP was present in 21.6% of type 2 DM patients attending the LUTH

Comparison of the Minimental State Examination Scale and the International HIV Dementia Scale in Assessing Cognitive Function in Nigerian HIV Patients on Antiretroviral Therapy

Introduction. HIV-associated neurocognitive disorder (HAND) remains common despite the availability of antiretroviral therapy. Routine screening will improve early detections. Objective. To compare the performance of the minimental state examination (MMSE) and international HIV dementia scale (IHDS) in assessing neurocognitive function in HIV/AIDS patients on antiretroviral therapy. Methods. A case-control study of 208 HIV-positive and 121 HIV-negative individuals. Baseline demographic data were documented and cognitive function assessed using the two instruments. CD4 cell counts were recorded. Results. Cases comprised 137 females and 71 males. Controls were 86 females and 35 males. Mean MMSE score of cases was 27.7±1.8 compared to 27.8±1.3 in controls (P=0.54). Mean IHDS score in cases was 8.36±3.1 compared to 10.7±0.9 in controls (P 200 had HAND compared with 92.5% with CD4 count < 200 (P<0.001). Conclusion. These findings indicate that the IHDS detects higher rates of HAND and may identify HIV/AIDS patients who require further cognitive assessment using more robust assessment batteries