Thirty-three inpatients (22 females, 11 males, aged 79.4 ± 9.5 years) were investigated in this prospective cohort study to study the prevalence of polyneuropathy (PNP) and dementia in geriatric inpatients. Clinical and electrodiagnostic investigations, routine laboratory, including thyroid parameters, folic acid, vitamin B(12), homocysteine, neopterin, fibrinogen and glycosylated hemoglobin were measured in serum, the mini-mental state examination and computed tomographic scanning were performed in each patient. PNP was found clinically and electrodiagnostically in 96% of patients. Age was the most precipitating factor for PNP, and was significantly correlated to electrodiagnostic changes in the nerves investigated in both, upper and lower extremities, while clinical symptoms were confined only to the feet. Correlation was seen between homocysteine and the amplitude of the sural nerve (surAmpl) (rs = -0.406, p = 0.029) as well as the sural nerve conduction velocity (surNCV) (rs = -0.389, p = 0.037), and between neopterin and the grade of denervation (rs = 0.445, p = 0.014) in our patients. Neopterin and fibrinogen did not correlate significantly, but there was a trend to higher fibrinogen concentrations in patients with higher neopterin levels (rs = 0.344, p = 0.062). A trend of a correlation was seen between higher homocysteine concentrations and the number of changes in electrodiagnostic measurements (rs = 0.354, p = 0.055). Twenty-one of the 33 patients (64%) were demented, 9 (27%) presented clinically as mild cognitive impairment, 3 (9%) were not demented. Vascular risk factors were found in 83%: hypertension in 58%, hypercholesterinemia in 39%, cardiac disease in 36%, diabetes mellitus (DM) in 21%, peripheral arterial disease (PAD) in 9%. A significant correlation was found between homocysteine and folic acid concentrations (rs = -0.401, p = 0.028). Falls were reported in 48% of cases, indicating PNP as a risk factor in this group of patients. In conclusion, PNP was found very common with a high coincidence with dementia and a female preponderance, suggesting an influence on daily life (falls) in our subjects studied. PNP correlated significantly with markers for vascular disease as well as immune activation (homocysteine and neopterin) similar to earlier findings in patients with neurodegenerative disorders, suggesting common therapeutic options in patients with PNP and dementia.