Introduction: Peripheral neuropathy (PN) becomes more common with increasing life expectancy, but general population prevalence estimates are lacking. We investigated an epidemiological distribution of signs of PN among 2,996 community-dwelling participants in Good Aging in Skåne Study, age 60–97, and their impact on physical and autonomic function. Methods: Signs of PN were measured with Utah Early Neuropathy Scale (UENS). Associations between UENS and physical tests, pain, and dysautonomic phenomena were calculated for each sex, adjusted for age, with estimated marginal means (EMM) and odds ratios (ORs) in four UENS quantiles (Q1–Q4). Results: Participants in Q4 had worse EMM for: time to complete Timed Up and Go test (Q4–Q1: male 10.8–9.6 s; female 11.7–10.2 s), 15 m Walk test (Q4–Q1: male 11.1–9.9 s; female 11.2–10.4 s), and fewer repetitions in Step test (Q4–Q1: male 15.2–17.0 steps; female 14.5–15.8 steps). Higher OR of failing one-leg balance 60 s test {male 2.5 (confidence interval [CI] 95%: 1.7–3.8); female 2.1 (1.1–3.2)}, Foam Pad Balance test (male 4.6 [CI 95%: 3.2–6.7]; female 1.8 [1.3–2.6]), and lower physical quality of life were seen in Q4 compared to Q1. Participants in Q4 had higher OR for walking aid usage, falls, fear of falling, pain, and urinary incontinence, while in males, higher OR for orthostatic intolerance, fecal incontinence, and constipation. Conclusions: In a general population, 20–25% of older adults who have highest UENS scores, a sensitive measure of early PN, express slower gait, worse balance, lower quality of life, pain, falls and fear of falling, and autonomic symptoms.

Peripheral neuropathy (PN) results in neurogenic muscle atrophy, with loss of muscle strength, power, and endurance, contributing to altered gait and impaired balance, falls, bone fractures, and leading to chronic infections and amputations. The current prevalence and incidence of PN in the general population is not certain. Previous reports vary wildly, with estimates ranging up to 30%, depending on study setting, the diagnostic method and when the study was conducted. Current prevalence estimates are 1–3% in the general population and 7% in older adults [1]; however, new studies in unselected population of older adults are lacking. There are different phenotypes of chronic peripheral neuropathies, with the most common distal symmetric polyneuropathy (DSP), often as a chronic idiopathic axonal polyneuropathy, and frequently affecting small fibers, where patients can present with or without pain, and with or without motor involvement [2, 3]. The three commonest etiologies of DSP are current diabetes mellitus or impaired glucose tolerance, chronic alcohol use, and idiopathic origin [4]. Symptoms and associated signs vary slightly in reported frequencies between subjects with DSP, depending on different etiologies and heterogeneous definitions of polyneuropathy across time, making inter- and intragroup comparisons difficult [1]. Many older adults with pain-free neuropathy, who have an insidious progress and risk developing advanced disease with motor problems, become incorrectly diagnosed or receive erroneous explanations. Studying the epidemiology of PN, it is feasible to define cases as probable polyneuropathy based on neurological examination findings, past medical history, and symptoms [5, 6]. Electrodiagnostic tests and diagnostic imaging could be of interest to ensure if PN is of mononeuropathy or radiculopathy type, but they rarely change management in older adults with chronic DSP [5].

Persons with definite polyneuropathy, based on a symptom questionnaire, neurologic examination of the legs and nerve conduction studies, had higher odds of falling, resulting in injury and of being dependent on their basic and instrumental activities of daily living [7]. Thus, the early identification of PN as a contributing factor to falls and other “geriatric syndromes” may be of particular importance to facilitate early interventions and new rehabilitation methods [8, 9].

The development of autonomic neuropathy is often parallel to sensory neuropathy [10], with multiple symptoms from different organs. The mechanisms affecting peristaltic function, continence, and orthostasis are complex; hence, there is a need to study in a general population the covariation between autonomic dysfunction and PN.

The Utah Early Neuropathy Scale (UENS) (online suppl. Fig. S1; for all online suppl. material, see https://doi.org/10.1159/000535620) was designed to detect and quantify early small-fiber sensory neuropathy and to recognize modest changes in sensory severity and distribution in the foot and legs [11]. UENS is suggested to be a simple, rapid, reproducible sensitive and valid measure of early neuropathy and its progression. However, the association between early neuropathy, in terms of UENS scores, and physical function in general older population is unclear. This could be of particular interest because of many older adults with pain-free neuropathy who develop advanced disease with motor problems. Moreover, the UENS due to its sensitivity to early sensory loss and being able to record moderate anatomic changes in sensory function, is recommended to seek and enroll patients in clinical trials, and to treat patients with milder neuropathy. Thus, the aim of our study was to estimate an epidemiological distribution and the extent of signs of early PN, assessed by the UENS in a general population of older adults, and analyze the impact on their physical function, as measured by five tests spanning different motor domains, on autonomic function, symptoms, falls, fear of falling (FOF), and on quality-of-life estimates.

Population

This study used data from 3,611 participants in the ongoing, longitudinal study “Good Aging in Skåne” [12, 13], a part of the Swedish National study on Aging and Care [14]. The subjects were randomized from the municipality registers and included men and women in nine age cohorts: 60, 66, 72, 78, 81, 84, 87, 90, and 93 years and above, from five urban and rural areas. Participation rate was between 60 and 66%. Re-examinations were offered every third year for subjects above 78 years old and every sixth year for those between 60 and 78 years old. All examinations include the same protocol with a medical examination, self-assessment questionnaires, and cognitive and physical functioning tests, and were examined in the research clinic, or in a minority: at home and in an institution. The analyzed data were collected between 2012 and 2017 and included 2,261 re-examined participants (ages 65–102 years) and 1,350 new recruited (ages 60–82 years) (shown in Fig. 1). No exclusion criteria were applied in this study, however in those subjects who were examined at home some physical tests were not performed at all (15 m-walk) or were restricted by patients’ physical or cognitive status, why those subjects were not included in analysis of those outcome measures. The baseline characteristics were derived from self-questionnaire data obtained during the surveys, medical records and during a comprehensive medical examination made by a physician. All tests of physical function were performed by a trained registered nurse.

Fig. 1.

Flowchart of study participation.

Fig. 1.

Flowchart of study participation.

Close modal

Peripheral Neuropathy

2,996 participants had been neurologically examined according to the UENS (0–42 points), developed to measure peripheral nerve function of the lower limb weighted toward signs typical in early polyneuropathy, characteristic of small fiber dysfunction (shown in online suppl. Fig. S1). All modalities were assessed with the participant supine, except the subscale for deep tendon reflexes which were assessed with the participant seated [11]. The examinations were conducted both at research clinic and at home (shown in online suppl. Table S1) by a physician at the respective research teams and the charted results were reviewed in the event of irregularities in UENS scores.

UENS is highly correlated with several ancillary measures of neuropathy severity: with electrophysiological – sural sensory amplitude and peroneal motor response proximal conduction velocity; with QSART in the foot (quantitative sudomotor axon reflex testing); and with intreaepidermal nerve fiber density. Changes in the last one correlated with UENS score increase over a 1-year follow-up. The ROC curves demonstrated high sensitivity and specificity for UENS throughout its score with AUC 0.88 (SE 0.029, 95% confidence interval [CI] 0.81–0.94) [11].

Physical Function

Participants were subjects to five tests of physical function: Timed Up and Go (TUG) [15, 16], Walking 15 m (15), Step test [17, 18], one-leg standing (OLS) [15‒18], and Foam pad balance test [19]. Their measurement and reliability are described in online supplementary Table S2.

Autonomic Dysfunction

Participants answered questionnaire items, both during the medical examination and solitarily, regarding phenomena related to the functions of the autonomic nervous system. Urinary incontinence, constipation, and fecal incontinence were self-reported in the context of questions on the participant’s activities of daily living. Autonomic control of the circulatory system was tested during the medical examination with a standard orthostatic blood pressure testing protocol. After participants rested in the supine position for 10 min before starting the test, blood pressure and pulse were assessed immediately after the rise from the supine to a standing position and after 1, 3, 5, and 10 min of standing without external help. Orthostatic hypotension was defined as a fall in SBP of greater than 20 mm Hg and/or a fall in DBP of greater than 10 mm Hg after 1–10 min’ standing, and a fall in greater than 40 or 20 mm Hg (SBP or DBP) immediately upon standing up [20]. Orthostatic intolerance was defined if participants reported any symptom of autonomic failure associated during the test: dizziness, fatigue, blackouts, nausea, instability, ringing in the ears, vertigo, light-headedness, headache, syncope, confusion, and sweating.

Falls and FOF

During the medical examination, participants answered questions about whether they had fallen during the last 12 months (yes/no) and answered questions in the self-assessment questionnaire about the FOF indoors or outdoors.

Quality of Life

The questionnaire included the Swedish translation of the SF-12 items for rating quality of life. Participant answers were transformed with an established algorithm to provide a physical component score (PCS-12) and a mental component score (MCS-12) [21].

Diabetic Neuropathy Symptom Score

Subjective symptoms of DSP have been classified into a four-item symptom score developed for diabetic neuropathy [22], which is validated, fast and easy to perform, and with a high predictive value. All subjects were asked to answer questions on: (i) unsteadiness in walking, (ii) pain, burning, or aching at legs or feet, (iii) prickling sensations in legs or feet, and (iv) numbness in legs or feet (shown in online suppl. Table S3).

Statistical Analysis

Statistical estimates are presented as estimate (CI 95% lower bound, upper bound). Background and result variables are presented as means (± standard deviation [SD]), and dichotomous data as count (percentage) and compared between sexes using t test and χ2 tests. The participants were categorized into four quartiles according to the increasing UENS and separately for men and women. Due to the uneven distribution of subjects, with a majority of subjects comprised on the left side of the UENS scale, the number of subjects in each quartile showed to be unequal and we defined these groups as quantiles (Q1, Q2, Q3, Q4). Stratification for sex was performed for easier interpretation of sex-specific differences of test of physical function. The characteristics of the study population were explored and described as mean ± SD for continuous, or as proportions for categorical variables for the whole cohort and across the quantiles of UENS. Differences across the various characteristics were examined using χ2 for categorical variables and ANOVA for continuous variables.

The association between UENS (independent variable) and each of the dichotomous dependent variables (i.e., one-leg balance test, balance pad test, autonomic function, pain, walking aid, diabetic neuropathy symptom score [DNSS], falls, and FOF) was examined by logistic regression analysis. Odds ratio (OR) with 95% CIs were compared between the quantiles Q2–Q4 and quantile Q1, adjusted for age and stratified by sex. The association between UENS (independent variable) and continues dependent variables (i.e., Timed Up and Go test, 15 m walking test, step test, and quality of life) were examined with univariate analysis of variance. Estimated marginal means (EMM) (95% CI) for dependent parameters have been defined for each UENS Quantile, adjusted for age and stratified by sex. Pairwise comparisons of the quantiles Q2–Q4 versus Q1 were made, adjusted for multiple comparisons using post hoc Bonferroni test.

Population data of the study are presented in Table 1 with means, SDs, counts, and proportions of the result variables calculated by sex. The female participants were older than the men, with a mean age of 72.2 ± 9.6 years versus 70.6 ± 9.0, years (p < 0.001) and had a lower mean UENS score of 3.8 ± 3.6 versus 4.6 ± 4.0 (p < 0.001). The distribution of UENS scores in age subgroups 59–64, 65–69, 70–74, 75–79, 80–84, 86+, shows increasing UENS score during aging (shown in online suppl. Table S1) and sex difference for each age subgroup. Further, it shows that a substantial part of the elderly was examined at own home, but only a few subjects living in institutionalized care unit were examined with UENS. There is a trend with higher UENS scores in subjects examined at home versus in the clinic in the same age, even if, in many subjects who were visited by research team the UENS could not be performed. Significant sex differences were also seen in tests of physical function, with better performance in males, who had also lower proportion of individuals experiencing pain, falls and FOF, incontinence and constipation, and had a higher quality of life (p < 0.001 in all instances). Physical tests were done during home visits as well but a significant drop-out has been observed for his subgroup due to cognitive and physical restrictions. Test results and participation per examination place and sex are shown in online supplementary Table S4.

Table 1.

Baseline characteristics of study variables

FemaleMalep value
Age, mean (SD), years 72.2 (9.6) 70.6 (9.0) <0.001 
UENS (0–42 points), mean (SD) 3.8 (3.6) 4.6 (4.0) <0.001 
Timed Up and Go, mean (SD), s 10.7 (5.5) 9.9 (3.3) <0.001 
0–15 m-Walk test, mean (SD), s 10.6 (2.9) 10.1 (2.7) <0.001 
Step test, mean (SD), steps 15.3 (4.5) 16.3 (4.4) <0.001 
One-leg balance, fail 60 s, n (%) 1,039 (68.4) 873 (63.4) <0.005 
One-leg balance, fail 45 s, n (%) 977 (64.3) 817 (59.4) <0.01 
One-leg balance, fail 30 s, n (%) 865 (56.9) 709 (51.5) <0.01 
One-leg balance, fail 15 s, n (%) 660 (43.4) 529 (38.4) <0.05 
Balance pad (fail), n (%) 395 (26) 297 (22) 0.006 
Use of walking aids, n (%) 263 (16) 129 (9) <0.001 
Lower limb pain, n (%) 459 (28) 295 (20) <0.001 
Orthostatic hypotension, n (%) 197 (13) 181 (13) 0.96 
Orthostatic intolerance, n (%) 244 (16) 183 (13) 0.038 
Falls last 12 months, n (%) 409 (24) 262 (18) <0.001 
FOF, n (%) 881 (47) 331 (21) <0.001 
Urinary incontinence, n (%) 440 (26) 162 (11) <0.001 
Constipation, n (%) 350 (21) 120 (8) <0.001 
Fecal incontinence, n (%) 216 (13) 121 (8) <0.001 
PCS-12 46.6 (8.7) 48.0 (7.6) <0.001 
MCS-12 52.2 (8.1) 53.3 (7.1) <0.001 
FemaleMalep value
Age, mean (SD), years 72.2 (9.6) 70.6 (9.0) <0.001 
UENS (0–42 points), mean (SD) 3.8 (3.6) 4.6 (4.0) <0.001 
Timed Up and Go, mean (SD), s 10.7 (5.5) 9.9 (3.3) <0.001 
0–15 m-Walk test, mean (SD), s 10.6 (2.9) 10.1 (2.7) <0.001 
Step test, mean (SD), steps 15.3 (4.5) 16.3 (4.4) <0.001 
One-leg balance, fail 60 s, n (%) 1,039 (68.4) 873 (63.4) <0.005 
One-leg balance, fail 45 s, n (%) 977 (64.3) 817 (59.4) <0.01 
One-leg balance, fail 30 s, n (%) 865 (56.9) 709 (51.5) <0.01 
One-leg balance, fail 15 s, n (%) 660 (43.4) 529 (38.4) <0.05 
Balance pad (fail), n (%) 395 (26) 297 (22) 0.006 
Use of walking aids, n (%) 263 (16) 129 (9) <0.001 
Lower limb pain, n (%) 459 (28) 295 (20) <0.001 
Orthostatic hypotension, n (%) 197 (13) 181 (13) 0.96 
Orthostatic intolerance, n (%) 244 (16) 183 (13) 0.038 
Falls last 12 months, n (%) 409 (24) 262 (18) <0.001 
FOF, n (%) 881 (47) 331 (21) <0.001 
Urinary incontinence, n (%) 440 (26) 162 (11) <0.001 
Constipation, n (%) 350 (21) 120 (8) <0.001 
Fecal incontinence, n (%) 216 (13) 121 (8) <0.001 
PCS-12 46.6 (8.7) 48.0 (7.6) <0.001 
MCS-12 52.2 (8.1) 53.3 (7.1) <0.001 

Data presented as means (SD) and number (%) where appropriate.

p values derived from Z tests for continuous variables, χ2 for dichotomous variables.

UENS, Utah Early Neuropathy Scale.

The result variables in relationship to the four quantiles of UENS scores are presented separately for the sexes in Table 2. Increasing UENS score was associated with: higher mean age (ΔQ4–Q1 in females: 8.6 years., in males: 7.8 years.), worse parameters of all physical tests and of physical quality of life with largest decline in Q4, with higher proportion of individuals using walking aids (fivefold increase between Q1 and Q4 in both sexes), with higher proportion of individuals experiencing lower limb pain, experiencing falls and FOF in Q4, and urinary incontinence in both sexes, and additionally in male participants, with orthostatic intolerance, constipation, and fecal incontinence (threefold increase in Q4 in both sexes) (shown in Table 2).

Table 2.

Baseline characteristics of functional parameters and of quality of life in four UENS quantile groups of female and male GAS-study participants

UENS score (points)AllQ1Q2Q3Q4p value*
0–2p3–4p5–6p≥7p
Female participants 
 Participants, n 1,585 681 159 381 364  
 Age, mean (SD), years 72.2 (9.6) 68.3 (8.0) 69.1 (7.4) 71.8 (8.5) 76.9 (9.2) <0.0001 
 Tests of physical function 
  Timed Up and Go, mean (SD), s 10.7 (5.5) 9.6 (4.2) 9.5 (2.6) 10.1 (3.2) 13.0 (7.9) <0.0001 
  0–15 m Walk test, mean (SD), s 10.6 (2.9) 10.1 (2.1) 10.0 (2.2) 10.4 (2.6) 11.8 (4.1) <0.0001 
  Step test (steps), mean (SD), na 15.3 (4.5) 16.4 (4.2) 15.8 (3.9) 15.2 (4.2) 13.3 (4.2) <0.0001 
  One-leg balance, fail 60 s, n (%) 1,004 (67.7) 382 (57.7) 103 (66.0) 260 (71.8) 259 (85.5) <0.0001 
  One-leg balance, fail 45 s, n (%) 942 (63.5) 346 (52.3) 100 (64.1) 245 (67.7) 252 (82.8) <0.0001 
  One-leg balance, fail 30 s, n (%) 830 (56.0) 287 (43.3) 88 (56.4) 220 (60.8) 235 (77.6) <0.0001 
  One-leg balance, fail 15 s, n (%) 625 (42.1) 197 (29.8) 63 (40.4) 171 (47.2) 194 (64.0) <0.0001 
  Balance pad (fail; n, %) 395 (26) 110 (16.6) 26 (16.7) 100 (27.5) 130 (43) <0.0001 
 Non-motor function 
  Use of walking aids, n (%) 263 (16) 34 (5.1) 6 (3.8) 36 (9.6) 91 (26.5) <0.0001 
  Lower limb pain, n (%) 459 (28) 168 (25) 41 (25.9) 97 (25.9) 113 (32.9) <0.0001 
  Orthostatic hypotension, n (%) 197 (13) 79 (12.3) 22 (14.5) 42 (11.9) 48 (16.1) ns 
  Orthostatic intolerance, n (%) 244 (16) 95 (14.6) 25 (16.3) 54 (15.0) 48 (15.5) ns 
  Falls last 12 months, n (%) 409 (24) 133 (19.8) 36 (22.8) 79 (21.1) 110 (32.2) = 0.0001 
  FOF, n (%) 881 (47) 253 (37.7) 65 (41.1) 177 (48) 204 (61.8) <0.0001 
  Urinary incontinence, n (%) 440 (26) 129 (19.3) 32 (20.6) 89 (24.4) 107 (32.2) <0.0001 
  Constipation, n (%) 350 (21) 112 (16.8) 32 (20.5) 73 (19.9) 82 (24.3) 0.029 
  Fecal incontinence, n (%) 216 (13) 73 (11) 17 (10.9) 51 (14) 44 (13.3) 0.455 
  Quality of life: PCS-12 (score), mean (SD) 46.6 49.1 (7.5) 47.5 (7.6) 44.1 (9.6) 47.5 (8.5) <0.0001 
  Quality of life: MCS-12 (score), mean (SD) 52.2 52.3 (7.9) 52.5 (7.8) 52.1 (8.9) 53.1 (7.5) 0.346 
Male participants 
 Participants, n 1,411 487 384 251 289  
 Age, mean (SD), years 70.1 (8.7) 66.7 (7.4) 70.0 (8.0) 71.9 (8.6) 74.5 (9.5) <0.0001 
 Tests of physical function 
  Timed Up and Go, mean (SD), s 9.8 (3.1) 9.1 (2.1) 9.4 (2.4) 10.0 (3.0) 11.4 (4.6) <0.0001 
  0–15 m-Walk test, mean (SD), s 10.1 (2.7) 9.6 (1.9) 9.7 (2.2) 10.3 (2.8) 11.4 (3.5) <0.0001 
  Step test (steps), mean (SD), na 16.3 (4.4) 17.6 (4.2) 16.4 (4.3) 15.6 (4.1) 14.4 (4.5) <0.0001 
  One-leg balance, fail 60 s, n (%) 847 (62.8) 233 (48.5) 239 (64.1) 166 (69.7) 209 (81.3) <0.0001 
  One-leg balance, fail 45 s, n (%) 792 (58.8) 212 (44.2) 216 (57.9) 160 (67.2) 204 (79.4) <0.0001 
  One-leg balance, fail 30 s, n (%) 686 (50.9) 171 (35.6) 189 (50.7) 135 (56.7) 191 (74.3) <0.0001 
  One-leg balance, fail 15 s, n (%) 510 (37.8) 118 (24.6) 133 (35.7) 98 (41.2) 161 (62.6) <0.0001 
  Balance pad, fail, n (%) 281 (20.8) 48 (10.0) 70 (18.7) 53 (22.3) 110 (42.6) <0.0001 
 Non-motor function 
  Use of walking aids, n (%) 96 (6.8) 13 (2.7) 18 (4.7) 17 (6.8) 48 (16.6) <0.0001 
  Lower limb pain, n (%) 285 (20.2) 80 (16.4) 67 (17.4) 53 (21.2) 85 (29.4) <0.0001 
  Orthostatic hypotension, n (%) 176 (13.0) 63 (13.3) 47 (12.6) 36 (14.9) 30 (11.4) ns 
  Orthostatic intolerance, n (%) 180 (13.2) 42 (8.8) 63 (16.7) 34 (14.0) 41 (15.4) 0.004 
  Falls last 12 months (n, %) 239 (17.0) 61 (12.6) 60 (15.6) 43 (17.2) 75 (26.0) <0.0001 
  FOF, n (%) 273 (19.7) 61 (12.8) 75 (19.9) 55 (22.1) 82 (29.1) <0.0001 
  Urinary incontinence, n (%) 131 (9.4) 31 (6.4) 32 (8.5) 26 (10.5) 42 (9.4) 0.001 
  Constipation, n (%) 105 (7.6) 18 (3.8) 34 (9.1) 22 (8.9) 31 (11.0) 0.001 
  Fecal incontinence, n (%) 99 (7.2) 18 (3.8) 25 (6.7) 26 (10.5) 30 (10.7) 0.001 
  QoL: PCS-12 (score), mean (SD) 48.4 (7.6) 50.0 (5.9) 48.5 (7.7) 47.4 (8.4) 46.1 (8.8) <0.0001 
  QoL: MCS-12 (score), mean (SD) 53.4 (7.1) 52.5 (6.4) 53.9 (7.1) 53.8 (7.1) 54.4 (7.7) 0.003 
UENS score (points)AllQ1Q2Q3Q4p value*
0–2p3–4p5–6p≥7p
Female participants 
 Participants, n 1,585 681 159 381 364  
 Age, mean (SD), years 72.2 (9.6) 68.3 (8.0) 69.1 (7.4) 71.8 (8.5) 76.9 (9.2) <0.0001 
 Tests of physical function 
  Timed Up and Go, mean (SD), s 10.7 (5.5) 9.6 (4.2) 9.5 (2.6) 10.1 (3.2) 13.0 (7.9) <0.0001 
  0–15 m Walk test, mean (SD), s 10.6 (2.9) 10.1 (2.1) 10.0 (2.2) 10.4 (2.6) 11.8 (4.1) <0.0001 
  Step test (steps), mean (SD), na 15.3 (4.5) 16.4 (4.2) 15.8 (3.9) 15.2 (4.2) 13.3 (4.2) <0.0001 
  One-leg balance, fail 60 s, n (%) 1,004 (67.7) 382 (57.7) 103 (66.0) 260 (71.8) 259 (85.5) <0.0001 
  One-leg balance, fail 45 s, n (%) 942 (63.5) 346 (52.3) 100 (64.1) 245 (67.7) 252 (82.8) <0.0001 
  One-leg balance, fail 30 s, n (%) 830 (56.0) 287 (43.3) 88 (56.4) 220 (60.8) 235 (77.6) <0.0001 
  One-leg balance, fail 15 s, n (%) 625 (42.1) 197 (29.8) 63 (40.4) 171 (47.2) 194 (64.0) <0.0001 
  Balance pad (fail; n, %) 395 (26) 110 (16.6) 26 (16.7) 100 (27.5) 130 (43) <0.0001 
 Non-motor function 
  Use of walking aids, n (%) 263 (16) 34 (5.1) 6 (3.8) 36 (9.6) 91 (26.5) <0.0001 
  Lower limb pain, n (%) 459 (28) 168 (25) 41 (25.9) 97 (25.9) 113 (32.9) <0.0001 
  Orthostatic hypotension, n (%) 197 (13) 79 (12.3) 22 (14.5) 42 (11.9) 48 (16.1) ns 
  Orthostatic intolerance, n (%) 244 (16) 95 (14.6) 25 (16.3) 54 (15.0) 48 (15.5) ns 
  Falls last 12 months, n (%) 409 (24) 133 (19.8) 36 (22.8) 79 (21.1) 110 (32.2) = 0.0001 
  FOF, n (%) 881 (47) 253 (37.7) 65 (41.1) 177 (48) 204 (61.8) <0.0001 
  Urinary incontinence, n (%) 440 (26) 129 (19.3) 32 (20.6) 89 (24.4) 107 (32.2) <0.0001 
  Constipation, n (%) 350 (21) 112 (16.8) 32 (20.5) 73 (19.9) 82 (24.3) 0.029 
  Fecal incontinence, n (%) 216 (13) 73 (11) 17 (10.9) 51 (14) 44 (13.3) 0.455 
  Quality of life: PCS-12 (score), mean (SD) 46.6 49.1 (7.5) 47.5 (7.6) 44.1 (9.6) 47.5 (8.5) <0.0001 
  Quality of life: MCS-12 (score), mean (SD) 52.2 52.3 (7.9) 52.5 (7.8) 52.1 (8.9) 53.1 (7.5) 0.346 
Male participants 
 Participants, n 1,411 487 384 251 289  
 Age, mean (SD), years 70.1 (8.7) 66.7 (7.4) 70.0 (8.0) 71.9 (8.6) 74.5 (9.5) <0.0001 
 Tests of physical function 
  Timed Up and Go, mean (SD), s 9.8 (3.1) 9.1 (2.1) 9.4 (2.4) 10.0 (3.0) 11.4 (4.6) <0.0001 
  0–15 m-Walk test, mean (SD), s 10.1 (2.7) 9.6 (1.9) 9.7 (2.2) 10.3 (2.8) 11.4 (3.5) <0.0001 
  Step test (steps), mean (SD), na 16.3 (4.4) 17.6 (4.2) 16.4 (4.3) 15.6 (4.1) 14.4 (4.5) <0.0001 
  One-leg balance, fail 60 s, n (%) 847 (62.8) 233 (48.5) 239 (64.1) 166 (69.7) 209 (81.3) <0.0001 
  One-leg balance, fail 45 s, n (%) 792 (58.8) 212 (44.2) 216 (57.9) 160 (67.2) 204 (79.4) <0.0001 
  One-leg balance, fail 30 s, n (%) 686 (50.9) 171 (35.6) 189 (50.7) 135 (56.7) 191 (74.3) <0.0001 
  One-leg balance, fail 15 s, n (%) 510 (37.8) 118 (24.6) 133 (35.7) 98 (41.2) 161 (62.6) <0.0001 
  Balance pad, fail, n (%) 281 (20.8) 48 (10.0) 70 (18.7) 53 (22.3) 110 (42.6) <0.0001 
 Non-motor function 
  Use of walking aids, n (%) 96 (6.8) 13 (2.7) 18 (4.7) 17 (6.8) 48 (16.6) <0.0001 
  Lower limb pain, n (%) 285 (20.2) 80 (16.4) 67 (17.4) 53 (21.2) 85 (29.4) <0.0001 
  Orthostatic hypotension, n (%) 176 (13.0) 63 (13.3) 47 (12.6) 36 (14.9) 30 (11.4) ns 
  Orthostatic intolerance, n (%) 180 (13.2) 42 (8.8) 63 (16.7) 34 (14.0) 41 (15.4) 0.004 
  Falls last 12 months (n, %) 239 (17.0) 61 (12.6) 60 (15.6) 43 (17.2) 75 (26.0) <0.0001 
  FOF, n (%) 273 (19.7) 61 (12.8) 75 (19.9) 55 (22.1) 82 (29.1) <0.0001 
  Urinary incontinence, n (%) 131 (9.4) 31 (6.4) 32 (8.5) 26 (10.5) 42 (9.4) 0.001 
  Constipation, n (%) 105 (7.6) 18 (3.8) 34 (9.1) 22 (8.9) 31 (11.0) 0.001 
  Fecal incontinence, n (%) 99 (7.2) 18 (3.8) 25 (6.7) 26 (10.5) 30 (10.7) 0.001 
  QoL: PCS-12 (score), mean (SD) 48.4 (7.6) 50.0 (5.9) 48.5 (7.7) 47.4 (8.4) 46.1 (8.8) <0.0001 
  QoL: MCS-12 (score), mean (SD) 53.4 (7.1) 52.5 (6.4) 53.9 (7.1) 53.8 (7.1) 54.4 (7.7) 0.003 

aHigher value indicates better function. Analysis of variance (ANOVA) or Pearson χ2 was used to calculate p value for the difference across the UENS quartiles.

*p value is for difference across the quartiles of UENS.

Age-adjusted ORs for failed physical tests and for non-motor symptoms were calculated separately for sexes across the quantiles of UENS (shown in Table 3). In these models, female subjects in the highest quantile (Q4) compared to the bottom quantile (Q1) had higher risk of failing one-leg balance 60 s test (OR: 2.1; 95% CI: 1.4–3.2; Nagelkerke R2 for the model: 0.278) and Foam pad balance test (OR: 1.8 95% CI: 1.3–2.6; R2 = 0.283). In male participants, the higher risk of failed one-leg balance test 60 s was observed already in the Q3 versus the Q1 (OR 2.1; 95% CI: 1.1–4.1; R2 = 0.45), and for the failed Foam pad balance test in the Q4 (OR 4.6 95% CI: 3.2–6.7, R2 = 0.40).

Table 3.

ORs calculated in female and male subgroups for each dichotomous, dependent variable for UENS quantiles 2–4 versus quantile 1 as a reference category, adjusted for age

Q1Q2Q3Q4
Female participants OR OR (95% CI) OR (95% CI) OR (95% CI) 
 Use of walking aids 0.7 (0.3–1.7) 1.11 (0.7–1.8) 2.4 (1.6–3.8)*** 
 Lower limb pain 1.1 (0.7–1.6) 1.1 (0.8–1.5) 1.6 (1.2–2.1)** 
 Orthostatic hypotension 1.2 (0.7–2.0) 0.9 (0.6–1.4) 1.3 (0.8–1.9) 
 Orthostatic intolerance 1.2 (0.7–1.9) 1.0 (0.7–1.5) 1.1 (0.7–1.6) 
 Falls last 12 months 1.2 (0.8–1.8) 1.0 (0.8–1.4) 1.8 (1.3–2.4)** 
 FOF 1.1 (0.8–1.6) 1.3 (1.0–1.7)* 1.8 (1.4–2.4*** 
 Urinary incontinence 1.0 (0.7–1.6) 1.2 (0.9–1.6) 1.5 (1.1–2.1)* 
 Constipation 1.3 (0.8–2.0) 1.2 (0.8–1.6) 1.5 (1.1–2.1) 
 Fecal incontinence 1.0 (0.5–1.7) 1.3 (0.9–1.8) 1.1 (0.7–1.7.) 
 One-leg balance (fail 60 s) 1.3 (0.8–1.9) 1.3 (0.9–1.8) 2.1 (1.4–3.2)*** 
 One-leg balance (fail 45 s) 1.5 (1.0–2.2)* 1.3 (0.9–1.8) 2.2 (1.5–3.2)*** 
 One-leg balance (fail 30 s) 1.6 (1.1–2.4)* 1.4 (1.1–1.9)* 2.2 (1.6–3.2)*** 
 One-leg balance (fail 15 s) 1.5 (1.0–2.3)* 1.5 (1.1–2.1)** 2.0 (1.5–2.9)*** 
 Balance pad (fail) 0.9 (0.5–1.5) 1.4 (0.9–1.9) 1.8 (1.3–2.6)** 
 EMM (95% CI) EMM (95% CI) EMM (95% CI) EMM (95% CI) 
 Timed Up and Go (s) 10.2 (9.9–10.6) 9.9 (9.2–10.6) 9.9 (9.4–10.4) 11.7 (11.2–12.3)*** 
 15 m-Walking test (s) 10.4 (9.7–10.6) 10.2 (9.7–10.6) 10.3 (10.0–10.6) 11.2 (10.9–11.5)** 
 Step test (steps) 15.8 (15.5–16.1) 15.5 (14.9–16.1) 15.4 (15.0–15.8) 14.5 (14.0–14.9) *** 
 Quality of life: PCS-12 score 48.6 (47.8–49.3) 47.2 (46.6–48.4) 47.5 (46.6–48.4) 44.3 (43.3–45.3)*** 
 Quality of life: MCS-12 score 52.6 (52.0–53.3) 52.8 (51.5–54.1) 52.0 (51.1–52.8) 52.1 (51.1–53.0) 
Male participants OR OR (95% CI) OR (95% CI) OR (95% CI) 
 Use of walking aids 0.9 (0.5–1.6) 1.4 (0.7–2.6) 4.2 (2.5–6.9)*** 
 Lower limb pain 1.06 (0.7–1.5) 1.4 (0.9–2.1) 2.3 (1.6–3.3)*** 
 Orthostatic hypotension 0.9 (0.6–1.3) 1.1 (0.7–1.8) 0.9 (0.5–1.4) 
 Orthostatic intolerance 1.9 (1.3–2.9)* 1.6 (1.1–2.7)* 2.0 (1.2–3.2)** 
 Falls last 12 months 1.1 (0.8–1.7) 1.3 (0.9–2.0) 2.5 (1.7–3.6)*** 
 FOF 1.3 (0.9–1.9) 1.6 (1.1–2.3)* 2.4 (1.7–3.5)*** 
 Urinary incontinence 1.0 (0.6–1.6) 1.3 (0.8–2.2) 2.2 (1.4–3.5)** 
 Constipation 1.8 (1.1–3.0)* 1.9 (1.1–3.4)* 2.6 (1.5–4.6)** 
 Fecal incontinence 1.5 (0.8–2.7) 2.7 (1.5–4.8)** 3.0 (1.7–5.4)*** 
 One-leg balance (fail 60 s) 1.3 (0.9–1.7) 2.5 (1.1–4.1)* 2.5 (1.7–3.8)*** 
 One-leg balance (fail 45 s) 1.2 (0.9–1.6) 1.6 (1.1–2.3)* 2.7 (1.8–4.0)*** 
 One-leg balance (fail 30 s) 1.3 (0.9–1.8) 1.4 (0.9–2.0) 2.9 (2.0–4.3)*** 
 One-leg balance (fail 15 s) 1.2 (0.6–1.7) 1.1 (0.8–1.8) 2.8 (1.9–4.1)*** 
 Balance pad (fail) 1.3 (0.9–1.8) 1.7 (1.1–2.5)* 4.6 (3.2–6.7)*** 
 EMM (95% CI) EMM (95% CI) EMM (95% CI) EMM (95% CI) 
 Timed Up and Go (s) 9.6 (9.3–9.8) 9.4 (9.2–9.7) 9.8 (9.4–10.1) 10.8 (10.5–11.2)*** 
 15 m walking test (s) 9.9 (9.7–10.1) 9.7 (9.4–9.9) 10.1 (9.8–10.4) 11.1 (10.7–11.4)*** 
 Step test (Steps) 17.0 (16.6–17.3) 16.4 (16.0–16.8) 16.0 (15.5–16.5)* 15.2 (14.7–15.7)*** 
 Quality of life: PCS-12 (score) 49.4 (48.7–50.1) 48.4 (47.7–49.2) 47.7 (46.7–48.7)* 46.8 (45.8–47.8)*** 
 Quality of life: MCS-12 (score) 53.1 (52.5–53.8) 53.8 (53.1–54.5) 53.4 (52.5–54.3) 53.4 (52.5–54.3) 
Q1Q2Q3Q4
Female participants OR OR (95% CI) OR (95% CI) OR (95% CI) 
 Use of walking aids 0.7 (0.3–1.7) 1.11 (0.7–1.8) 2.4 (1.6–3.8)*** 
 Lower limb pain 1.1 (0.7–1.6) 1.1 (0.8–1.5) 1.6 (1.2–2.1)** 
 Orthostatic hypotension 1.2 (0.7–2.0) 0.9 (0.6–1.4) 1.3 (0.8–1.9) 
 Orthostatic intolerance 1.2 (0.7–1.9) 1.0 (0.7–1.5) 1.1 (0.7–1.6) 
 Falls last 12 months 1.2 (0.8–1.8) 1.0 (0.8–1.4) 1.8 (1.3–2.4)** 
 FOF 1.1 (0.8–1.6) 1.3 (1.0–1.7)* 1.8 (1.4–2.4*** 
 Urinary incontinence 1.0 (0.7–1.6) 1.2 (0.9–1.6) 1.5 (1.1–2.1)* 
 Constipation 1.3 (0.8–2.0) 1.2 (0.8–1.6) 1.5 (1.1–2.1) 
 Fecal incontinence 1.0 (0.5–1.7) 1.3 (0.9–1.8) 1.1 (0.7–1.7.) 
 One-leg balance (fail 60 s) 1.3 (0.8–1.9) 1.3 (0.9–1.8) 2.1 (1.4–3.2)*** 
 One-leg balance (fail 45 s) 1.5 (1.0–2.2)* 1.3 (0.9–1.8) 2.2 (1.5–3.2)*** 
 One-leg balance (fail 30 s) 1.6 (1.1–2.4)* 1.4 (1.1–1.9)* 2.2 (1.6–3.2)*** 
 One-leg balance (fail 15 s) 1.5 (1.0–2.3)* 1.5 (1.1–2.1)** 2.0 (1.5–2.9)*** 
 Balance pad (fail) 0.9 (0.5–1.5) 1.4 (0.9–1.9) 1.8 (1.3–2.6)** 
 EMM (95% CI) EMM (95% CI) EMM (95% CI) EMM (95% CI) 
 Timed Up and Go (s) 10.2 (9.9–10.6) 9.9 (9.2–10.6) 9.9 (9.4–10.4) 11.7 (11.2–12.3)*** 
 15 m-Walking test (s) 10.4 (9.7–10.6) 10.2 (9.7–10.6) 10.3 (10.0–10.6) 11.2 (10.9–11.5)** 
 Step test (steps) 15.8 (15.5–16.1) 15.5 (14.9–16.1) 15.4 (15.0–15.8) 14.5 (14.0–14.9) *** 
 Quality of life: PCS-12 score 48.6 (47.8–49.3) 47.2 (46.6–48.4) 47.5 (46.6–48.4) 44.3 (43.3–45.3)*** 
 Quality of life: MCS-12 score 52.6 (52.0–53.3) 52.8 (51.5–54.1) 52.0 (51.1–52.8) 52.1 (51.1–53.0) 
Male participants OR OR (95% CI) OR (95% CI) OR (95% CI) 
 Use of walking aids 0.9 (0.5–1.6) 1.4 (0.7–2.6) 4.2 (2.5–6.9)*** 
 Lower limb pain 1.06 (0.7–1.5) 1.4 (0.9–2.1) 2.3 (1.6–3.3)*** 
 Orthostatic hypotension 0.9 (0.6–1.3) 1.1 (0.7–1.8) 0.9 (0.5–1.4) 
 Orthostatic intolerance 1.9 (1.3–2.9)* 1.6 (1.1–2.7)* 2.0 (1.2–3.2)** 
 Falls last 12 months 1.1 (0.8–1.7) 1.3 (0.9–2.0) 2.5 (1.7–3.6)*** 
 FOF 1.3 (0.9–1.9) 1.6 (1.1–2.3)* 2.4 (1.7–3.5)*** 
 Urinary incontinence 1.0 (0.6–1.6) 1.3 (0.8–2.2) 2.2 (1.4–3.5)** 
 Constipation 1.8 (1.1–3.0)* 1.9 (1.1–3.4)* 2.6 (1.5–4.6)** 
 Fecal incontinence 1.5 (0.8–2.7) 2.7 (1.5–4.8)** 3.0 (1.7–5.4)*** 
 One-leg balance (fail 60 s) 1.3 (0.9–1.7) 2.5 (1.1–4.1)* 2.5 (1.7–3.8)*** 
 One-leg balance (fail 45 s) 1.2 (0.9–1.6) 1.6 (1.1–2.3)* 2.7 (1.8–4.0)*** 
 One-leg balance (fail 30 s) 1.3 (0.9–1.8) 1.4 (0.9–2.0) 2.9 (2.0–4.3)*** 
 One-leg balance (fail 15 s) 1.2 (0.6–1.7) 1.1 (0.8–1.8) 2.8 (1.9–4.1)*** 
 Balance pad (fail) 1.3 (0.9–1.8) 1.7 (1.1–2.5)* 4.6 (3.2–6.7)*** 
 EMM (95% CI) EMM (95% CI) EMM (95% CI) EMM (95% CI) 
 Timed Up and Go (s) 9.6 (9.3–9.8) 9.4 (9.2–9.7) 9.8 (9.4–10.1) 10.8 (10.5–11.2)*** 
 15 m walking test (s) 9.9 (9.7–10.1) 9.7 (9.4–9.9) 10.1 (9.8–10.4) 11.1 (10.7–11.4)*** 
 Step test (Steps) 17.0 (16.6–17.3) 16.4 (16.0–16.8) 16.0 (15.5–16.5)* 15.2 (14.7–15.7)*** 
 Quality of life: PCS-12 (score) 49.4 (48.7–50.1) 48.4 (47.7–49.2) 47.7 (46.7–48.7)* 46.8 (45.8–47.8)*** 
 Quality of life: MCS-12 (score) 53.1 (52.5–53.8) 53.8 (53.1–54.5) 53.4 (52.5–54.3) 53.4 (52.5–54.3) 

Estimated marginal means (EMM; 95% CI) calculated for each continuous, dependent variable for UENS quantiles 2–4 versus quantile 1 as a reference category, adjusted for age.

ns, nonsignificant.

*p = 0.05–0.01; **p = 0.009–0.001; ***p < 0.0005.

The risk of using walking aids increased in both sexes, especially in males in Q4 (OR 4.2; 95%: 2.5–6.9; R2 = 0.77), as well as experiencing lower limb pain, falls, and of a FOF was higher in the Q4 versus Q1 UENS. Additionally, only male participants had significantly higher risk for constipation in UENS Q2, Q3, and Q4, higher risks for fecal incontinence in Q3 and Q4, and for orthostatic intolerance in Q2, Q3, and Q4 versus Q1.

Age-adjusted EMM of continuous parameters of physical tests differed between the highest and lowest UENS quantiles in both sexes. Pairwise comparison of Q2–Q4 versus Q1 showed significantly slower Timed Up and Go and 15 m-Walking test and Step test results in Q4, both in female and male subjects. Scores of physical, but not of mental domain, of SF-12 quality-of-life tool were lower in Q4 versus Q1 in both sexes (shown in Table 3).

Subjective neuropathic symptoms assessed with DNSS were absent in 73% of female (score 1: 18.6%; score 2: 5.7%, score 3: 2.0%, score 4: 0.8%) and in 75% of male subjects (score 1: 15.1%; score 2: 6.1%, score 3: 1.9%, score 4: 0.7%). As many as 53% of male and 51% female subjects with UENS-Q4 had DNSS score = 0. Since DNSS defines PN as present if score is ≥1, we defined it as dependent variable in logistic regression analysis with adjustment for age. OR for DNSS ≥1 in female subjects with UENS-Q4 was 3.5 (95% CI: 2.6–4.8; p < 0.0001), in male subjects with Q3 was 2.0 (95% CI: 1.4–2.9; p < 0.00001), and with Q4 was 5.7 (95% CI: 4.0–8.1; p < 0.00001) (shown in online suppl. Table S5).

The principal findings of this study are that mild signs of PN are common in a community-dwelling population of adults, ages 60 years and older, particularly among the participants above 80 years old. In general, PN seems to be more pronounced and develops earlier in male participants, while the female participants with the most extensive signs had the highest proportions of associated symptoms. Participants with the highest scoring UENS quantiles (Q4) performed the worst during tests of physical function, and this was mirrored in their higher frequency of using walking aids, of falling, and of having experienced FOF, however, only half of them experienced subjective sensory discomfort common in distal neuropathy, according to DNNS. The Q4 groups were also more likely to report other manifestations of neuropathy, like bowel or urinary symptoms, and pain. These participants report lower quality-of-life scores in physical domains. UENS scores showed a trend to higher values in those elderly participants who chose a home visit of research team.

When comparing the extents of PN found in our cohort to other studies having used UENS, we observed that our participants’ UENS scores were noticeably lower, including in highest quantiles [11, 23, 24]. Previous studies using the UENS are mostly conducted in younger study populations and often with manifest polyneuropathy determined or suspected per clinical diagnosis in the context of epidemiological investigation of disease etiology, or in the context of neurophysiological studies. Thus, the reliability of UENS as a test for PN in our population could have its limitations. Considering that our cohort consists of unselected community-dwelling older adults and that no active inclusion selection has been made regarding neuropathic symptomatology, the comparatively lower scores could be an expected finding. Since no exclusion criteria were applied in our analyses except not having been examined with UENS, and most participants scored lower than often seen in clinical polyneuropathy, our participants likely have different and possibly multiple causes for their somatosensory deficits. We could, however, observe in subjects examined at home that fewer were able to be examined with UENS, and a trend toward a higher UENS scores. Fewer older adults were able to be examined with physical test during home visits as well, suggesting a selection bias despite efforts to include subjects who could not visit research clinic. As expected, a substantial part of the elderly denied to participate or did not answer the invitation, suggesting that institutionalized patients are overrepresented in this group. However, the threshold to receive a place in senior care-institutions in Sweden is very high, requiring a serious cognitive, not only physical decline. Otherwise, a frequent home care visits are offered as a primary choice. Concerning this, in most of these subjects the correct estimation of UENS scale would be difficult and making physical test probably impossible. Additionally, multimorbidity would make it difficult to differentiate early PN from other conditions.

UENS design, it is not always possible to discern whether a participant’s higher UENS scores are caused by a axonal or demyelinating distal neuropathy, rhizopathy, or a mild spinal stenosis. Further, central nerve system and peripheral nerve degeneration might occur parallelly affecting physical function in a similar way. A separate, not primarily neurological, explanation of incident falls and reduced walking speed with unpleasant sensory phenomena in the older adult could be knee osteoarthritis, which can present as weakness, unsteadiness, and pain in the lower limb. This could be interpreted by participant and physician as neuropathic in origin in the context of our study. Some patients with osteoarthritis describe their pain in neuropathic terms, and abnormal remodeling subchondral nerve fibers are speculated to contribute to this neuropathic-like pain in more advanced osteoarthritis [25].

An increase of UENS points from Q1 to Q4 resulted in significant worse physical function as monitored with five gait and balance tests as well as higher odds of FOF and falls. Our results suggest that UENS scores at Q4 level are strongly associated with fundamental aspects of gait and balance function such as gait speed, leg weight-shift and movement velocity, turning and chair transfers, standing with small base of support or on nonsolid surface with limited vision. We believe these findings are related to UENS ability to monitor lower limb sensory loss in early PN. It is well-known that intact sensory input from lower limb is essential for gait and balance function, and it is reflected in our results. Also, motor examination of hallux weakness may contribute to associations with impaired balance performance [26]. Higher odds for falls are not surprising given significant impairments in physical function with increased UENS scores. Declining physical function is clearly a marker of frailty, closely related to the “geriatric syndromes.” It is also well-known that older adults with FOF often limit their activities of daily living, which in turn leads in the long term to decline in physical function and increase the risk for development of sarcopenia and frailty [27, 28]. Interestingly in our study, FOF was significantly associated with increasing UENS scores from Q1 to Q3. Moreover, FOF was the only one significant dependent variable that female and male had in common at UENS Q3 scores level. Thus, very low scores of UENS could be a red flag for a broad variety of consequences of neuropathy or other common conditions in older adults. Both balance and gait are complex sensorimotor tasks characterized by robustness, where smaller deficits in sensory input can lead to compensatory motor recruitment. It is possible that the causal relationship is complex and includes loss of sensory nerve function, atrophy of musculoskeletal tissue, and behavioral patterns of physical inactivity, as a result of self-reinforcing inactivity related to pain, unsteadiness, and FOF. It is also possible that impaired static balance control and gait speed are partly explained by subcortical vascular changes, due to impaired use of their sensory, visual, and vestibular input. As vascular degenerative disease of brain can deal the same risk factors as peripheral PN, then a part of physical and autonomous symptoms can have central or mixed mechanism. As muscle mass and muscular strength decrease with age due to reduction in cross-sectional area of the muscle fibers, there is evidence that a decline in muscular strength in lower limb muscles occurs in poorer cognitive performance [29]. However, in a general population, there is evidence of shared susceptibility to peripheral and central nervous system degeneration [9]. Therefore, screening of older people with UENS may be of importance for early identifying of individuals predisposed to develop “geriatric syndrome.” That in turn may facilitate early implementation of physical training and other fall preventive actions, such as recently highlighted significances of feet- and footwear-related influence on fall risk among community-dwelling older adults [30].

Previous experimental investigations of how PN affects balance have shown that in PN higher ankle torques are needed to remain stable during one-leg balance, and weight is quickly displaced from one foot to the other, but more motoric output is needed to keep their balance. The study participants with PN initiate their balance strategies as fast as controls but with worse results. These phenomena and the resulting fall tendency were seen even when participants with PN themselves decided which foot to stand on and when to start the test [31]. The fall risk in PN is exemplified in a case-control study of older adults regarding PN as a risk factor for falls, where the PN group had substantially larger proportions of having fallen or of near-falls and shorter times on one-leg balance tests. In-group comparison of PN participants showed those who had fallen had less vibration sense and even shorter times in one-leg balance testing than those that had not fallen [32]. In our study, the quantiles with the most extensive signs of PN had increased odds of having failed the balance tests, and on average performed worse on the Step test, an active balance test, as well.

From our results, one can infer qualitatively an association between the processes measured by the UENS and dysautonomic phenomena, which are observed already in Q3 of men but only in Q4 of women. This sex difference remains significant after correction for age which could be a result of other factors leading to orthostatic intolerance, fecal incontinence and constipation [33], and opens for discussion if this association is causative or just reflecting common etiologies. Urinary and fecal incontinence have different sex-dependent mechanisms in younger elderly as well as constipation which increases in frequency already in perimenopause in females. Therefore, increasing odds of dysautonomic symptoms in men in Q3 could suggest their common etiological mechanism with PN. Sex differences were observed for UNSE score in majority of age-categories (online suppl. Table S1). We expected women to age healthier than men also in the peripheral nervous system, as a possible parallel to the sex differences seen in cardiovascular and metabolic health. Strotmeyer et al. [34] reported differences in proportions detecting monofilament 10 g and 1.4 g, and electroneurographic amplitudes and velocities, between people with diabetes and people without diabetes by sex. In this large cohort, more women have a retained sense of pressure in the feet, detect vibrations, and had better neurophysiological parameters than men, regardless of diabetes status. In females, OLS in best leg showed to differ already in UENS Q2 irrespectively of how long the stance last, i.e., in subjects with very mild signs of neuropathy (shown in Table 3). Contrary in males, UENS in Q3 identified failing balance with stance time of at least 45 s, probably due to physical differences between sexes but also due to differences in number of subjects in the quantiles.

Studies into quality of life among those affected by peripheral neuropathies have shown that quality of life related to physical function is lower among those with neuropathy compared to a general population and while comparing the quality of life among subjects with diabetes with or without PN [35, 36]. The effects seen in the latter comparison were mediated by the subjects’ results on physical function testing. Even if the effect sizes are not directly comparable between SF-12 in our study, SF-36 or EQ-5D, and the populations studied are different, we could observe a significantly lower physical quality of life, as per SF-12, in our participants with UENS score in Q4.

When discussing a possible weakness of the study we are aware that the diagnose of PN would be more specific using nerve conduction studies, allowing to differentiate between different kinds of PN, as distal symmetrical polyneuropathy, mononeuropathy, lumbar/cervical radiculopathy or plexopathy, which all could have overlapped symptomatology. Though, our aim was to estimate an epidemiological survey over poorly examined phenomenon on a population level and its functional impact. The attempt to divide a study population into quartiles resulted in a unequal number of participants per group. This was due to the uneven distribution of subjects, with a majority comprised on the left side of the UENS scale. However, that UENS score segmentation was important from the clinical point of view, even if number of participants could affect results of regression analysis in each quantile.

A major strength of our study is its external validity and a good reliability of the physical tests, with similar tests previously shown to have acceptable to high levels of reliability [37]. Good Aging in Skåne is a large population study with both rural and urban populations sampled. Participants can be seen in their homes if they cannot visit the research clinics, which increase the representativity. As not all tests could be administered at home, this cross-sectional study’s results might underestimate effects if PNs are more extensive and more disabling in the frailer population.

Early signs of PN are very common in an unselected population of older adults. In 20–25% of our study population subjects, the highest UENS scores coincide with slower walking speeds, a loss of balance, falls, FOF, lower limb pain, and other sensory discomfort. At least half of them lacks typical sensory discomfort in legs which affects self-awareness of the disease. A higher proportion of these older adults use walking aids, presumably to counteract unsteadiness, to prevent falls, and to preserve physical function. Especially males, with early signs of PN, have increased risk for having autonomic dysfunction in the form of orthostatic intolerance, fecal, and urinary incontinence. This study adds to a growing body of observational evidence that peripheral nerve dysfunction is common among older adults, and that it could be a common cause of worse health, and loss of physical function, and a push for increased recognition of this patient group’s unmet needs [38‒40].

Ethical approval was obtained by the Regional Ethics Committee at Lund University, Lund, Sweden (LU 744-00). Participants provided written informed consent prior to taking part in the study.

The authors have no conflicts of interest to declare.

The Good Aging in Skåne (GÅS-SNAC) project, part of the Swedish National Study on Aging and Care, was supported by the Swedish Ministry of Health and Social Affairs, the county Region Skåne, the Medical Faculty at Lund University, and the Swedish Research Council (Grant No. 2013-8604, 2017-01613, 2021-01437).

W.B. contributed to data analysis, data interpretation, writing, and editing of the manuscript. B.L. contributed to data interpretation and reviewing of the manuscript, and S.E. contributed to funding, data collection, data interpretation, and reviewing of the manuscript. A.S.-L. contributed to the concept, data collection, data analysis, data interpretation, writing, and editing of the manuscript.

The data that support the findings of this study are not publicly available due to privacy reasons but are available from (W.B.) upon reasonable request.

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