Abstract
<jats:p>Background. Metabolic syndrome is associated with an increased risk of cognitive impairment and dementia. Chronic hyperglycemia, glycemic variability, and insulin resistance contribute to neuroinflammation, accumulation of amyloid-β (Aβ) protein, and cognitive dysfunction; however, the traditional marker HbA1c does not reflect glycemic fluctuations or episodes of hypoglycemia. The purpose of the study was to assess the impact of glycemic variability on Aβ oligomer levels, cognitive function, and sleep disturbances in patients with metabolic syndrome. Materials and methods. The study included 100 patients with metabolic syndrome (50 men and 50 women) aged 18–79 (mean of 55.27 ± 1.26) years with a mean body mass index of 33.34 ± 0.62 kg/m2. All participants underwent clinical and anthropometric examination, as well as extended laboratory blood testing with evaluation of carbohydrate and lipid levels, hepatic and renal function, inflammatory and hormonal parameters. Glycemic variability was assessed using the Time in range index. Levels of amyloid-β oligomers in cerebrospinal fluid were determined, as well as Aβ42/Aβ40 ratio. Cognitive function and sleep parameters were evaluated using standardized neuropsychological tests and validated questionnaires. Results. The study detected cognitive impairment in 48.0 % of patients with metabolic syndrome according to the Montreal Cognitive Assessment, with predominant involvement of memory (19.0–37.0 %), executive functions (up to 42.0 %), and information processing speed (70.0–88.0 %). Higher levels of C-reactive protein, fasting plasma glucose, and HbA1c correlated with memory decline, whereas gonadotropic hormone levels correlated with executive dysfunction. Sleep disturbances contributed to reduced information processing speed. The study revealed disturbances of amyloid metabolism in the overall cohort of patients with metabolic syndrome, including reduced Aβ1–42 levels in 35.0 % and a pathological Aβ42/Aβ40 ratio in 8.0 % of cases; in type 2 diabetes mellitus, the prevalence of these changes increased to 44.6 and 12.5 %, respectively. Lower Aβ1–42 levels correlated with sleep disturbances, increased liver enzyme activity, and cortisol levels, whereas higher follicle-stimulating and luteinizing hormones corresponded to higher Aβ oligomer levels. Glycemic variability and hypoglycemic episodes were associated with reduced Aβ1–42 levels and a lower Aβ42/Aβ40 ratio. Conclusions. The study demonstrated a high prevalence of mild cognitive impairment in patients with metabolic syndrome. Memory impairment was associated with markers of inflammation and glycemic control, whereas alterations in Aβ oligomer profiles were linked to sleep disturbances, liver function parameters, and hormonal balance.</jats:p>