Polyneuropathy is a disabling condition of the peripheral nerves, characterized by symmetrical distal numbness and paresthesia, often accompanied with pain and weakness. Although the disease is often ...encountered in neurological clinics and is well known by physicians, incidence and prevalence rates are not well known. We searched EMBASE, Medline, Web-of-science, Cochrane, PubMed Publisher, and Google Scholar, for populationbased studies investigating the prevalence of polyneuropathy and its risk factors. Out of 5119 papers, we identified 29 eligible studies, consisting of 11 door-to-door survey studies, 7 case-control studies and 11 cohort/database studies. Prevalence of polyneuropathy across these studies varies substantially. This can partly be explained by differences in assessment protocols and study populations. The overall prevalence of polyneuropathy in the general population seems around 1 % and rises to up to 7 % in the elderly. Polyneuropathy seemed more common in Western countries than in developing countries and there are indications that females are more often affected than males. Risk factor profiles differ across countries. In developing countries communicable diseases, like leprosy, are more common causes of neuropathy, whereas in Western countries especially diabetes, alcohol overconsumption, cytostatic drugs and cardiovascular disease are more commonly associated with polyneuropathy. In all studies a substantial proportion of polyneuropathy cases (20-30 %) remains idiopathic. Most of these studies have been performed over 15 years ago. More recent evidence suggests that the prevalence of polyneuropathy in the general population has increased over the years. Future research is necessary to confirm this increase in prevalence and to identify new and potentially modifiable risk factors.
Objective
To investigate the association between diet quality and chronic axonal polyneuropathy.
Methods
Between June 2013 and January 2017, among 1650 participants of the Rotterdam Study (median age ...69.1 years, 54.2% women), diet quality was quantified based on food frequency questionnaires as a sum score of adherence (yes/no) to 14 components of the Dutch dietary guidelines. Presence of polyneuropathy was determined based on a questionnaire, neurological examination of the legs, and nerve conduction studies. We used logistic regression to associate diet quality with the presence of chronic axonal polyneuropathy and linear regression to associate with sural sensory nerve action potential (SNAP) amplitude in participants without polyneuropathy. Results were adjusted for age, sex, time between measurements, body mass index, blood pressure, diabetes mellitus, smoking, kidney function, and education.
Results
Overall diet quality was not associated with chronic axonal polyneuropathy (odds ratio OR = 0.99, 95% confidence interval CI 0.88; 1.12, P = 0.842), nor with sural SNAP amplitude in participants without polyneuropathy (difference = 0.01, 95% CI −0.14; 0.15, P = 0.993). Although not surviving multiple testing, a nominally significant association was found between salt intake ≤6 g/day and presence of chronic axonal polyneuropathy (OR = 0.55, 95% CI 0.35; 0.86, P = 0.008).
Interpretation
We did not find an association between diet quality and chronic axonal polyneuropathy.
OBJECTIVE:To determine the prevalence of chronic polyneuropathy in an unselected community-dwelling population of middle-aged and elderly people.
METHODS:The current study was embedded in the ...prospective, population-based Rotterdam Study. Between June 2013 and October 2015, 1,310 participants (mean age 70 years, 55% female) were screened for the presence of polyneuropathy. This screening consisted of a questionnaire, neurologic examination, and nerve conduction studies. Polyneuropathy was diagnosed by a consensus panel that categorized participants into no, possible, probable, or definite polyneuropathy, depending on the level of abnormality of the screening. Medical records were scrutinized to evaluate whether the disorder was diagnosed before and laboratory investigations were performed to determine the presence of associated risk factors.
RESULTS:Prevalence of definite polyneuropathy was 5.5% (95% confidence interval 4.4–6.9), age-standardized to the population of the Netherlands 4.0% (3.1–5.3). Prevalence was higher in male participants (6.7% compared to 4.5%) and increased with age. When combining probable and definite polyneuropathy, age-standardized prevalence was 9.4% (7.9–11.1). Almost half of the polyneuropathies (49%) were newly diagnosed. The majority of polyneuropathies were idiopathic (46%). Diabetes, present in 31% of participants with polyneuropathy, was the most commonly found risk factor.
CONCLUSIONS:Prevalence of polyneuropathy in the general middle-aged and elderly population is at least 4%, and increases with age. Almost half of the cases were newly diagnosed, indicating that the presence of polyneuropathy is underreported or underdiagnosed. Currently, almost half of the polyneuropathies are idiopathic. Future prospective cohort studies should focus on identifying new determinants of polyneuropathy.
Chronic axonal polyneuropathy is a common disease of the peripheral nervous system with increasing prevalence with age. Typical neurological signs are present in patients with polyneuropathy, but may ...also occur in individuals without disease. Due to limited knowledge on normal aging of the peripheral nervous system, it can be difficult to distinguish peripheral nerve dysfunction due to disease from variations in normal aging. Therefore, we described the changes in neurological examination and nerve conduction studies that accompany aging in the general population.
In this cross-sectional population-based study, we screened participants for chronic polyneuropathy in a controlled environment using standardized methods including a symptom questionnaire, neurological examination and nerve conduction studies (NCS). Inclusion criteria were age ≥40 years old and living in a suburb of Rotterdam, the Netherlands. Participants not diagnosed with chronic polyneuropathy, based on the discussion of findings in the screening by an expert team, were included to determine the effect of age (range 41-96years) on features of neurological examination and NCS using frequency calculations and quantile regression analysis.
In total, 4179 participants (mean age 64.5±12.7 years, 54.9% female) were included of whom 3780 (90.5%) did not fulfil the criteria for polyneuropathy. In the population without polyneuropathy, the frequency of normal features at neurological examination declined with age, most pronounced for vibration sense at the hallux (from 6.6 sd±1.5 in 40-49 years old to 3.6 sd±3.1 in ≥80 years old) and Achilles tendon reflexes (absent in 9% in 40-49 years old up to 33% in ≥80 years old). Superficial pain sensation and patellar tendon reflexes remained stable over time. Sural sensory nerve action potential (SNAP) amplitude declined with age from 11.2µV in 40-49years old to 3.3µV in ≥80 years old. Non-recordable SNAP amplitudes were found in 25.1% of the participants over 80 years old, more often in men (30.3%) than in women (21.0%).
This study showed the effect of age on features of neurological examination and sural nerve amplitude in the general population. These findings are helpful to distinguish features suggesting polyneuropathy from variations of normal aging of the peripheral nervous system.
Chronic axonal polyneuropathy is a common disease with increasing prevalence with age. It majorly affects quality of life and leads to difficulties with various activities. Persons with ...polyneuropathy often not seek medical care and thus the societal burden of disease is likely underreported. Given the aging populations, contemporary data on the prevalence and risk factor profiles of polyneuropathy in the general population are required. Therefore, we estimated the current and expected prevalence and investigated the (co-)occurrence of risk factors in participants with chronic axonal polyneuropathy.
Between June 2013 and January 2020, participants of the population-based Rotterdam Study underwent extensive in-person examination to diagnose polyneuropathy. Age-standardized prevalence's were calculated for populations age 40 years or older of the Netherlands, Europe, the United States, and the world population. Putative risk factors were identified using laboratory findings, interviews, questionnaire data, and a review of medical records.
In total, 4,114 participants were included (mean age 64.3 years, 55.2% females), of whom 167 had chronic axonal polyneuropathy. More than half (54.5%) had yet not received the diagnosis through regular care. Age-standardized prevalence's were 3.3% (95% CI 2.8-4.0) for the European, 3.0% (95% CI 2.5-3.5) for the United States, and 2.3% (95% CI 1.9-2.8) for the world population. Based on the expected age distributions, the prevalence of chronic axonal polyneuropathy will increase with ±25% in the next 20 years. Known risk factors were present in 62.9% (N = 105) of the cases with polyneuropathy and most often included diabetes (34.1%) and vitamin deficiencies (15.1%). Importantly, combinations of various risk factors were found in 20.4% (N = 34) of cases with polyneuropathy.
Prevalence of chronic axonal polyneuropathy increases with age and is expected to further rise over time. Combinations of multiple known risk factors are often present, indicating the need for a full diagnostic workup, even when a single risk factor for polyneuropathy is known. These findings suggest that cumulative effects of multiple risk factors are important in the development and course of disease.
Diabetes mellitus is a known risk factor for polyneuropathy, but the role of pre-diabetes and metabolic syndrome remains unclear. We aimed to investigate the role of these factors in a ...community-dwelling middle-aged and elderly population.
1256 participants of the population-based Rotterdam Study (mean age 70.0, 54.5% females) were screened for polyneuropathy with a questionnaire, neurological examination and nerve conduction studies. Data on type 2 diabetes and components of metabolic syndrome were also collected. Logistic regression was used to investigate associations of diabetes, pre-diabetes and metabolic syndrome and its separate components with polyneuropathy. Linear regression was used to investigate associations with nerve conduction parameters in participants without polyneuropathy.
Diabetes was associated with polyneuropathy (OR 3.01, 95% CI 1.60 to 5.65), while impaired fasting glucose was not (OR 1.55, 95% CI 0.70 to 3.44). Metabolic syndrome was associated with polyneuropathy (OR 1.92, 95% CI 1.09 to 3.38), with a stronger association when more components of the syndrome were present. Analysing separate components of metabolic syndrome revealed associations for elevated waist circumference (OR 2.84, 95% CI 1.35 to 5.99) and elevated triglycerides (OR 2.01, 95% CI 1.11 to 3.62). Similar associations were found after excluding participants with diabetes. In participants without polyneuropathy, metabolic syndrome associated with lower sural sensory nerve action potential amplitudes.
Metabolic syndrome, abdominal obesity and dyslipidaemia, are strongly associated with polyneuropathy, irrespective of the presence of diabetes. Metabolic syndrome also associates with impaired nerve function in people without polyneuropathy. Our study therefore suggests that cardiometabolic disturbances have an impact on peripheral nerve function that extends beyond clinically manifest disease.
Introduction Disease susceptibility of chronic axonal polyneuropathy is not fully explained by clinical risk factors. Therefore, we determined the contribution of common genetic variants in chronic ...axonal polyneuropathy in the general population. Methods This study was performed in two population-based studies. Polyneuropathy diagnosis was based on screening in the Rotterdam Study and on ICD-10 codes in the UK Biobank. We determined the heritability of the sural nerve amplitude and performed genome-wide association studies of chronic axonal polyneuropathy and sural sensory nerve amplitude. Furthermore, we zoomed in on variants in and surrounding 100 autosomal genes known to cause polyneuropathy based on literature and expert knowledge (candidate genes), and we performed a gene-based analysis. Analyses were adjusted for age, sex and population stratification. Results Chronic axonal polyneuropathy was present in 2,357 of the 458,567 participants and 54.3% of the total population was female. Heritability of sural nerve amplitude was 0.49 ( p = 0.067) ( N = 1,153). No variants ( p < 5.0×10 −8 ) or genes ( p < 2.7×10 −6 ) reached genome-wide significance for its association with polyneuropathy. Focusing on variants in and surrounding the candidate genes in the GWAS ( p < 3.9×10 −6 ) and on these genes in the gene-based analysis ( p < 5.0×10 −4 ) neither yielded significant results. Discussion We did not find common variants associated with chronic axonal polyneuropathy in the general population. Larger studies are needed to determine if genetic susceptibility based on both common and rare genetic variants affect the risk for chronic axonal polyneuropathy in the general population.
Background and purpose
Chronic axonal polyneuropathy is a common disease, but the etiology remains only partially understood. Previous etiologic studies have identified clinical risk factors, but ...genetic evidence supporting causality between these factors and polyneuropathy are largely lacking. In this study, we investigate whether there is a genetic association of clinically established important risk factors (diabetes, body mass index BMI, vitamin B12 levels, and alcohol intake) with chronic axonal polyneuropathy.
Methods
This study was performed within the population‐based Rotterdam Study and included 1565 participants (median age = 73.6 years, interquartile range = 64.6–78.8, 53.5% female), of whom 215 participants (13.7%) had polyneuropathy. Polygenic scores (PGSs) for diabetes, BMI, vitamin B12 levels, and alcohol intake were calculated at multiple significance thresholds based on published genome‐wide association studies.
Results
Higher PGSs of diabetes, BMI, and alcohol intake were associated with higher prevalence of chronic axonal polyneuropathy, whereas higher PGS of vitamin B12 levels was associated with lower prevalence of polyneuropathy. These effects were most pronounced for PGSs with lenient significance thresholds for diabetes and BMI (odds ratio ORdiabetes, p < 1.0 = 1.21, 95% confidence interval CI = 1.05–1.39 and ORBMI, p < 1.0 = 1.21, 95% CI = 1.04–1.41) and for the strictest significance thresholds for vitamin B12 level and alcohol intake (OR vitamin B12, p < 5e‐6 = 0.79, 95% CI = 0.68–0.92 and ORalcohol, p < 5e‐8 = 1.17, 95% CI = 1.02–1.35). We did not find an association between different PGSs and sural sensory nerve action potential amplitude, nor between individual lead variants of PGSp < 5e‐8 and polyneuropathy.
Conclusions
This study provides evidence for polygenic associations of diabetes, BMI, vitamin B12 level, and alcohol intake with chronic axonal polyneuropathy. This supports the hypothesis of causal associations between well‐known clinical risk factors and polyneuropathy.
Chronic axonal polyneuropathy is a common disease, but the etiology remains only partially understood. In this study, we investigate whether there is a genetic association of clinically established important risk factors (diabetes, body mass index BMI, vitamin B12 levels, and alcohol intake) with chronic axonal polyneuropathy. Higher polygenic scores (PGSs) of diabetes, BMI, and alcohol intake were associated with higher prevalence of chronic axonal polyneuropathy, whereas higher PGS of vitamin B12 levels was associated with lower prevalence of polyneuropathy. This supports the hypothesis of causal associations between well‐known clinical risk factors and chronic axonal polyneuropathy.
Background and purpose
Chronic axonal polyneuropathy is a common, usually multifactorial, disease for which there is no treatment yet available. We investigated the association between cardiovascular ...health, defined by the health score of the American Heart Association, and chronic axonal polyneuropathy.
Methods
Between June 2013 and January 2017, we investigated participants of the Rotterdam Study, a population‐based cohort study. Participants were screened for polyneuropathy and categorized as having no, possible, probable or definite polyneuropathy. The cardiovascular health score (range 0–14; higher score reflecting better health) consisted of four health behaviours (diet, physical activity, smoking and body mass index) and three health factors (blood pressure, serum cholesterol and fasting glucose level).
Results
We included 1919 participants, of whom 120 (6.3%) had definite polyneuropathy. The median (interquartile range IQR) age was 69.0 (58.6–73.7) years and 53.4% were women. A higher cardiovascular health score was associated with a lower prevalence of definite polyneuropathy (per point increase: odds ratio OR 0.90, 95% confidence interval CI 0.84–0.96). Optimal cardiovascular health (score≥10) was strongly associated with a lower prevalence of definite polyneuropathy (OR 0.55, 95% CI 0.32–0.90). An increase in health factors and health behaviour scores separately was associated with a lower prevalence of polyneuropathy (per point increase: OR 0.82, 95% CI 0.71–0.95 and OR 0.86, 95% CI 0.78–0.96, respectively). The association between a lower cardiovascular health score and lower sural nerve amplitude was not significant after correction for covariates (difference 0.07µV, 95% CI −0.02–0.17).
Conclusions
Better cardiovascular health, consisting of both modifiable health behaviours and health factors, is associated with a lower prevalence of chronic axonal polyneuropathy.
Chronic axonal polyneuropathy is a common, disabling disease for which there is no treatment yet available. This highlights the need to identify modifiable risk factors. In this population‐based study, we investigated the association between cardiovascular health, defined by the seven‐item American Heart Association score, and chronic axonal polyneuropathy. Better cardiovascular health, consisting of both modifiable health behaviour and health factors, is associated with lower prevalence of chronic axonal polyneuropathy in the general population. This is of interest because individuals can potentially modify their health behaviour.
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