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To estimate the association of rs11218343 in the sortilin-related receptor 1 (SORL1) gene with cognitive performance in the elderly and with Alzheimer's disease (AD) in the Russian population.A sample included 586 elderly people (mean age 70.9±5.7 years) without AD diagnosis and 100 patients with late-onset AD (mean age 72.1±7.8 years) from the Tomsk population. SORL1 rs11218343 was genotyped using PCR and MALDI-TOF mass spectrometry. Cognitive performance in the sample of elderly without AD was assessed by Montreal Cognitive Assessment (MoCA) test.Allele frequencies of the SORL1 polymorphism were not significantly different between the elderly without AD and AD patients. However mean MoCA score in the carriers of the rare allele (19.00±6.61) was significantly lower than in homozygotes for the common variant (22.25±3.89) (F=4.97; p=0.026).The rare variant in SORL1 gene previously associated with AD in genome-wide association studies and meta-analyses was associated with lower total МоСА scores in the random sample of elderly people that suggests declined cognitive functions in the carriers of this variant in elderly.Цель исследования. Изучение связи rs11218343 гена сортилинподобного рецептора 1 (SORL1) с показателями состояния когнитивных функций у пожилых людей из российской популяции с диагнозом 'болезнь Альцгеймера' (БА) и без такового. Материал и методы. Выборка включала 586 пожилых пациентов (средний возраст 70,9±5,7 года) без БА и 100 пациентов с поздним началом БА (средний возраст 72,1±7,8 года) из популяции Томска. Генотипирование rs11218343 гена SORL1 проводили с помощью ПЦР и масс-спектрометрии. Нейропсихологическое тестирование проводили по Монреальской шкале оценки когнитивных функций (МоСА). Результаты. Частота аллелей rs11218343 гена SORL1 в изученных группах обследованных не достигала степени статистической достоверности. Однако средние значения общего балла по МоСА в контрольной выборке пожилых пациентов (без БА) у носителей редких аллелей отличались (были ниже) от гомозигот с частыми их вариантами (19,00±6,61 и 22,25±3,89; р0,026). Заключение. Редкий вариант в гене SORL1 связан с низкими показателями МоСА, о чем свидетельствует снижение когнитивных функций у носителей редкого аллеля в пожилом возрасте.

Understanding regional differences in cognitive performance is important for interpretation of data from large multinational clinical trials.Data from Durham and Cabarrus Counties in North Carolina, USA and Tomsk, Russia (n = 2972) were evaluated. The Montreal Cognitive Assessment (MoCA), Trail Making Test Part B (Trails B), Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Test (WLM) delayed recall, and self-report Alzheimer's Disease Cooperative Studies Mail-In Cognitive Function Screening Instrument (MCFSI) were administered at each site. Multilevel modeling measured the variance explained by site and predictors of cognitive performance.Site differences accounted for 11% of the variation in the MoCA, 1.6% in Trails B, 1.7% in WLM, and 0.8% in MCFSI scores. Prior memory testing was significantly associated with WLM. Diabetes and stroke were significantly associated with Trails B and MCFSI.Sources of variation include cultural differences, health conditions, and exposure to test stimuli. Findings highlight the importance of local norms to interpret test performance.