R.T. GAIFUTDINOV¹, S.K. PERMINOVA², V.V. TIMONIN³

 ¹Kazan State Medical University, Kazan

²City Clinical Hospital No. 7, Kazan

³Almetyevsk Interdistrict Multidisciplinary Hospital, Almetyevsk

Contact details:

Gaifutdinov R.T. — PhD (Medicine), Associate Professor of the Department of Neurology, Neurosurgery and Medical Genetics

Address: 49 Butlerov St., Kazan, 420012, tel.: +7-917-263-90-07, e-mail: Gaifutdinov69@mail.ru

Cognitive function impairment is one of the main disabling manifestations of vascular and degenerative brain pathology. The main cause of vascular dementia is cerebral microangiopathy (CMA) caused by arterial hypertension. The existing gender differences in the age of onset of cerebral vascular pathology in men increasingly draw researchers’ attention to the problem of age-related decline in gonadal function. The high association of metabolic risk factors for cardiovascular diseases with age-related hypogonadism (AHG) and the prospects of its correction determined our interest in the study of cognitive functions in adult men.

The purpose was to investigate the structure and severity of cognitive disorders in patients with CMA and AHG.

Material and methods. We performed an in-depth neuropsychological testing of 171 men aged 45 to 60 years with complaints of memory and attention impairment against the background of CMA and 52 practically healthy individuals without cerebral complaints (control group). Based on clinical and laboratory assessment of sexual function, patients with CMA were divided into groups: group 1 with AHG (74 persons) and group 2 without it (77 persons).

Results. The examined men did not differ in age, education, behavioral disorders, stress level, Apo E 4 allele carrier both in the main and comparison groups; the manifestations of metabolic syndrome and CMA in men with AHG were more expressed than in men with normal gonadal function. Psychometric studies revealed impairment of frontal-executive functions both in isolation and in combination with other cognitive disorders (multifunctional type of moderate cognitive disorders) significantly more often in hypogonadal men.

Conclusions. Complaints of cognitive decline in men with cerebral microangiopathy should promote the efforts of physicians to search for AHG in order to correct it and prevent cognitive impairment in the future.

Key words: cognitive disorders, cerebral microangiopathy, age-related hypogonadism.

REFERENCES

1. Gusev E.I., Bogolepova A.N. Kognitivnye narusheniya pri tserebrovaskulyarnykh zabolevaniyakh. 6-e izd., dop. [Cognitive impairment in cerebrovascular diseases. 6th ed., supplemented]. Moscow: MEDpress-inform, 2023. 240 p.
2. WHO fact sheet “Dementia”, 15 March 2023, available at: https://www.who.int/news-room/fact-sheets/detail/dementia
3. GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health, 2022, vol. 7 (2), rr. 105–125. DOI: 10.1016/S2468-2667(21)00249-8
4. Grinberg L.T., Nitrini R., Suemoto C.K. et al. Prevalence of dementia subtypes in a developing country: a clinicopathological study. Clinics (San Paulo), 2013, vol. 68, rr. 1140–1145. DOI: 10.6061/clinics/2013(08)13
5. Levin O.S. Diagnostika i lechenie kognitivnykh narusheniy i dementsii v klinicheskoy praktike [Diagnostics and treatment of cognitive impairment and dementia in clinical practice]. Moscow: MEDpress-inform, 2019. 448 p.
6. Petersen R.C., Lopez O., Armstrong M.J. et al. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology, 2018, vol. 90 (3), rr. 126–135. DOI: 10.1212/WNL.0000000000004826
7. Yakhno N.N., Zakharov V.V., Lokshina A.B. Mild cognitive impairment syndrome in cerebrovascular insufficiency. Nevrol. Psikhiatr, 2005, vol. 105, no. 2, pp. 13–17 (in Russ.).
8. Patnode C.D., Perdue L.A., Rossom R.C. et al. Screening for Cognitive Impairment in Older Adults: An Evidence Update for the U.S. Preventive Services Task Force. Rockville (MD): Agency for Healthcare Research and Quality (US); 2020 Feb. (Evidence Synthesis, No. 189.), available at: https://www.ncbi.nlm.nih.gov/books/NBK554654//
9. Kivipelto M., Helkala E.L., Laakso M.P., Hänninen T., Hallikainen M., Alhainen K. et al. Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ, 2001, vol. 322 (7300), rr. 1447–1451. DOI.: 10.1136/bmj.322.7300.1447
10. Alzheimer,s Association, 2016. Alzheimer’s Disease Facts and Figures. Alzheimer’s Dement, 2016, vol. 12, pp. 459–509.

11. Zekry D., Houw J.J., Gold G. Mixed dementia: epidemiology, diagnosis, and treatment. J. Am. Geriatr. Soc, 2002, vol. 50, pp. 1431–1438.
12. Sharvadze G.G., Kurbatov D.G., Poddubskaya E.A., Mamedov M.N. Androgen deficiency and cardiovascular diseases: current issues of comorbidity in clinical practice. Ratsional’naya farmakoterapiya v kardiologii, 2010, vol. 6, no. 4, pp. 532–538 (in Russ.).
13. Goodman-Gruen D., Barrett-Connor E. Sex differences in the association of endogenous sex hormone levels and glucose tolerance status in older men and women. Diabetes Care, 2000, vol. 23 (7), rr. 912–918.
14. Burden of disease in Russia from 1980 to 2016: a systematic analysis of the global burden of disease. Lancet, 2016 (in Russ.), available at: https://www.thelancet.com/pb-assets/Lancet/pdfs/S0140-6736(18)314855_russian.pdf
15. Gorpinchenko I.I., Spiridonenko V.V. Men in the 21st century: problems of late hypogonadism. Zdorov’e muzhchiny, 2016, vol. 4, no. 59, pp. 13–17 (in Russ.).
16. Vertkin A.L., Arinina E.N., Kolosova E.S. et al. Gender approaches to the treatment of cardiovascular pathology: men in the spotlight. RMZh, 2008, no. 16 (special issue), pp. 17–21 (in Russ.).
17. Araujo A.B., O’Donnell A.B., Brambilla D.J. et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J. Clin. Endocrinol. Metab, 2004, vol. 89 (12), rr. 5920–5926.
18. Lebedeva N.B., Gofman V.V., Mel’nikova V.A., Dymova O.I., Ustyuzhanina O.F. Prevalence of hypogonadism in middle-aged men and its association with the risk of cardiovascular diseases. Klinicheskaya meditsina, 2020, vol. 98, no. 2, pp. 130–136 (in Russ.). DOI: 10.30629/0023-2149-2020-98-2-130-136
19. Zitzmann M., Erren M., Kamischke A. et al. Endogenous progesterone and the exogenous progestin norethisterone enanthate are associated with a proinflammatory profile in healthy men. J. Clin. Endocrinol. Metab, 2005, vol. 90 (12), rr. 6603–6608.
20. Heufelder A.E., Saad F., Bunck M.C. et al. Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. J. Androl, 2009, vol. 30 (6), rr. 726–733.
21. Wardlaw J.M., Smith C., Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol, 2013, vol. 12, rr. 483–497. DOI: 10.1016/S1474-4422(13)70060-7
22. Dobrynina L.A., Gadzhieva Z.Sh., Kalashnikova L.A. et al. Neuropsychological profile and vascular risk factors in patients with cerebral microangiopathy. Annaly klinicheskoy i eksperimental’noy nevrologii, 2018, vol. 12, no. 4, pp. 5–15 (in Russ.). DOI: 10.25692/ACEN.2018.4
23. Kalinchenko S.Yu. Obsledovanie muzhchin [Examination of men]. Moscow: Prakticheskaya meditsina, 2016. 160 p.
24. Nieschlag E., Swerdloff R., Behre H.M. et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. J. Androl, 2006, vol. 27 (2), pp. 135–137. DOI: 10.2164/jandrol.05047
25. European guidelines for the prevention of cardiovascular diseases in clinical practice (2016 revision). Kardiovaskulyarnaya terapiya i profilaktika, 2017, vol. 16, no. 6, pp. 7–68 (in Russ.). DOI: 10.15829/1728-8800-2017-6-7-68
26. Holmes T.N., Rahe R.H. The social readjustment rating scale. J. Psych. Res,1967, vol. 11, pp. 213–218.
27. Nasreddine Z.S., Phillips N.A., Bédirian V. et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J. Am. Geriatr. Soc, 2005, vol. 53, rr. 695–699. DOI: 10.1111/j.1532-5415.2005.53221
28. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5TM). Arlington, 2013. 992 r.
29. Sachdev P., Kalaria R., O‘Brien J. et al. Internationlal Society for vascular behavioral and cognitive disorders. Diagnostic criteria for vascular cognitive disorders: a VASCOG statement. Alzheimer Dis. Assoc. Disord, 2014, vol. 28, rr. 206–218. DOI: 10.1097/WAD.0000000000000034
30. Litvinov I.V., Emelin A.Yu., Lobzin V.Yu. et al. Otsenka kognitivnykh funktsiy v klinicheskoy praktike: diagnosticheskie testy i shkaly: uchebnoe posobie [Assessment of cognitive functions in clinical practice: diagnostic tests and scales: a tutorial]. Saint Petersburg, 2021, 144 s.
31. Luriya A.R. Vysshiye korkovyye funktsii cheloveka [Higher cortical functions of man]. Moscow: Pub. Moscow University, 1969. 503 p.
32. Sunderland T., Hill J.L., Mellow A.M. et al. Clock drawing in Alzheimer’s disease. A novel measure of dementia severity. J. Am. Geriatr. Soc, 1989, vol. 37, rr. 725–729. DOI: 10.1111/j.1532-5415.1989.tb02233
33. Petersen R.C. Conceptual overview. In: Petersen R.C. (ed.) Mild Cognitive Impairment: Aging to Alzheimer’s Disease. New York: Oxford University Press, Inc, 2003. 14 r.
34. Jockenhovel F. Male hyrogonadism. Auflage-Bremen: Uni-Med, 2004. 185 r.
35. Cai Z., Li H. An updated review: androgens and cognitive impairment in older men. Front. Endocrinol. (Lausanne), 2020, vol. 11, rr. 586–909. DOI: 10.3389/fendo.2020.586909