Skip to main navigation menu Skip to main content Skip to site footer

No. 3 (2024)

ORIRGINAL RESEARCH

Predictors of Progression of Cognitive Deficits in First-Degree Relatives of Patients with Alzheimer’s Disease

Published 2024-09-30

  • N.D. Selezneva
    • ,
  • I.F. Roshchina
    • ,
  • I.V. Kolykhalov
    • ,
  • S.I. Gavrilova

N.D. Selezneva
Federal State Budgetary Scientific Institution “Mental Health Research Center“

I.F. Roshchina
Federal State Budgetary Scientific Institution “Mental Health Research Center”; Moscow State University of Psychology and Education

I.V. Kolykhalov
Federal State Budgetary Scientific Institution “Mental Health Research Center”

S.I. Gavrilova
Federal State Budgetary Scientific Institution “Mental Health Research Center”

Abstract

The aim of the study was to establish predictors of cognitive impairment progression in first-degree relatives of patients with Alzheimer’s disease (AD) with subjective complaints of memory loss, who did not receive drug therapy over a 15-year follow-up period.

Study participants. The observation cohort included 66 first-degree relatives of patients with AD (treated at the "Mental Health Reserch Center"), who complained of memory loss (subjective cognitive decline — SCD) (Yu.J. Hong and Jae-H. Lee, 2017; N.D. Selezneva et al., 2021) and agreed to routine psychometric and in-depth neuropsychological examination and subsequent participation in a long-term observation programme, but refused to use any methods of drug and non-drug preventive intervention.

Methods: clinical follow-up, neuropsychological, psychometric, statistical. For psychometric assessment, the following psychometric scales and tests were used: routine clinical practice psychometric scales and tests (Mini-Mental State Examination (MMSE); Montreal Cognitive Assessment (MoCA); Clock Drawing Test (CDT)), as well as the following scales and tests: Global Deterioration Scale (GDS); Ten-Word Memory Test; Boston Naming Test (BNT); Wechsler Memory Scale-Revised (WMS-R, subtest 6); Five Geometric Figures Memory Test; Benton Visual Retention Test (BVRT); Mattis Dementia Rating Scale: Verbal Fluency (DRS) subtest and H. Munsterberg Test. An in-depth neuropsychological examination was based on the results of the express method for assessing mnestic-intellectual functions in old age.

Study design: an open 15-year observational study of the dynamics of cognitive functioning in first-degree relatives of patients with AD with subjective complaints of memory loss – SCD. Cognitive functioning indicators on day 0 of the study were compared with similar indicators after 15 years.

Results. For an unfavorable course of SCD, i.e. accompanied by its conversion to mild cognitive impairment syndrome MCI (ICD-10 rubric F06.7 — Mild cognitive disorder) or to dementia, presumably caused by AD (Dementia in Alzheimer’s disease with early onset, ICD-10 rubric F00.0; Dementia in Alzheimer’s disease with late onset, ICD-10 rubric F00.1), a common significant feature was a later age of relatives at baseline. The significant signs for conversion from SCD to MCI were lower baseline scores on the tests of delayed 10-word recall, memorization of 5 figures, and the Benton test, and for the conversion from SCD to dementia — significantly lower baseline scores (on 10 of 12 psychometric scales and tests (MMSE, MoCA, delayed word recall, forward digit repetition, reverse digit repetition, memorization of geometric shapes, sound associations, categorical associations, and the Benton and Munsterberg tests), as well as significantly worse baseline scores on 10 subtests and the total score on the еxpress method of neuropsychological assessment of mnestic-intellectual functions in the elderly, developed by I.F. Roshchina et al. (2022).

Conclusion. The obtained results indicate the need for an in-depth clinical and neuropsychological examination of the structure of mental activity of first-degree relatives of patients with AD with subjective complaints of memory loss to assess the long-term prognosis and the earliest preventive drug and non-drug interventions in relatives with a negative prognosis.

Keywords

1st degree relatives of patients with Alzheimer’s disease, subjective cognitive decline, minimal cognitive dysfunction

PDF (Русский)

References

  1. Jack C.R. Jr., Bennett D.A., Blennow K., Carrillo M.C., Dunn B., Haeberlein S.B. et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease // Alzheimers Dement – 2018. – Vol. 14 (4). – Pp. 535–562. – https://doi.org/10.1016/j.jalz.2018.02.018
  2. Sperling R.A., Aisen P.S., Beckett L.A., Bennett D.A., Craft S., Fagan A.M. et al. Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease // Alzheimers Dement. – 2011. – Vol. 7 (3). – Pp. 280–292. – https://doi.org/10.1016/j.jalz.2011.03.003
  3. Gauthier S., Rosa-Neto P., Morais J.A., Webster C. World Alzheimer Report 2021: Journey through the diagnosis of dementia. – London, England: Alzheimer’s Disease International, 2021. – 6 p.
  4. Коровайцева Г.И., Щербатых Т.В., Селезнева Н.Д., Гаврилова С.И., Голимбет В.Е., Воскресенская Н.И., Рогаев Е.И. Генетическая ассоциация между аллелями гена аполипопротеина Е (АРОЕ) и различными формами болезни Альцгеймера // Генетика. – 2001. – № 37 (4). – С. 529–535. –https://doi.org/10.1023/A:1016610727938
  5. Селезнева Н.Д., Рощина И.Ф., Гаврилова С.И. Профилактика нарастания когнитивного дефицита при синдроме мягкого когнитивного снижения у родственников 1-й степени родства пациентов с болезнью Альцгеймера: проспективное мультидисциплинарное исследование // Современная терапия психических расстройств. – 2022. – № 4. – С. 16–24. – https://doi.org/10.21265/PSYPH.2022.10.80.003
  6. Селезнева Н.Д., Рощина И.Ф., Гаврилова С.И. Эффективность нейрометаболической терапии при додементных когнитивных расстройствах у родственников 1-й степени родства пациентов с болезнью Альцгеймера: трехлетнее проспективное исследование // Современная терапия психических расстройств. – 2023. – № 2. – С. 10–19. – https://doi.org/10.21265/PSYPH.2023.20.37.002
  7. Селезнева Н.Д., Гаврилова С.И. Лечение Церебролизином снижает риск перехода синдрома мягкого когнитивного снижения в деменцию у родственников 1-й степени родства пациентов с болезнью Альцгеймера: проспективное сравнительное исследование // Журнал неврологии и психиатрии имени С.С. Корсакова. – 2023. – № 123 (8). – С. 90–97. – https://doi.org/10.17116/jnevro202312308190
  8. Dubois B., Hampel H., Feldman H.H., Scheltens P., Aisen P., Andrieu S. et al. Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria // Alzheimers Dement. – 2016. – Vol. 12 (3). – Pp. 292–323. – https://doi.org/10.1016/j.jalz.2016.02.002
  9. Albert M.S., DeKosky S.T., Dickson D., Dubois B., Feldman H.H., Fox N.C., et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease // Alzheimers Dement. – 2011. – Vol. 7 (3). – Pp. 270–279. – https://doi.org/10.1016/j.jalz.2011.03.008
  10. Albert M., Zhu Y., Moghekar A., Mori S., Miller M.I., Soldan A. et al. Predicting progression from normal cognition to mild cognitive impairment for individuals at 5 years // Brain. – 2018. – Vol. 141 (3) – Pp. 877–887. – https://doi.org/10.1093/brain/awx365
  11. Knopman D.S., Jack C.R., Wiste H.J., Weigand S.D., Vemuri P., Lowe V.J. et al. Selective worsening of brain injury biomarker abnormalities in cognitively normal elderly persons with β-amyloidosis // JAMA. Neurol. – 2013. – Vol. 70 (8). – Pp. 1030–1038. – https://doi.org/10.1001/jamaneurol.2013.182
  12. Edmonds E.C., Delano-Wood L., Galasko D.R., Salmon D.P., Bondi M.W. Subtle cognitive decline and biomarker staging in preclinical Alzheimer’s disease // J Alzheimers Dis. – 2015. – Vol. 47 (1). – Pp. 231–242. – https://doi.org/10.3233/JAD-150128
  13. Petersen R.C., Lopez O., Armstrong M.J. et al. Practice guideline update summary: Mild cognitive impairment // Neurology. – 2018. – Vol. 90 (3). – Pp. 126–135. – https://doi.org/10.1212/WNL.0000000000004826
  14. Manly J.J., Jones R.N., Langa K.M. et al. Estimating the prevalence of dementia and mild cognitive impairment in the US: The 2016 health and retirement study harmonized cognitive assessment protocol project // JAMA Neurol. – 2022. – Vol. 79 (12). – Pp. 1242– 1249. – https://doi.org/10.1001/jamaneurol.2022.3543
  15. Rabinovici G.D., Gatsonis C., Apgar C. et al. Association of amyloid positron emission tomography with subsequent change in clinical management among medicare beneficiaries with mild cognitive impairment or dementia // JAMA. – 2019. – Vol. 321 (13). – Pp. 1286– 1294. – https://doi.org/10.1001/jama.2019.2000
  16. Bhamra M.S., Ashton N.J. Finding a pathological diagnosis for Alzheimer’s disease: Are inflammatory molecules the answer? // Electrophoresis. – 2012 Dec. – Vol. 33 (24). – Pp. 3598–3607. – https://doi.org/10.1002/elps.201200161
  17. Jarvik L.F., La Rue A., Gokhman I. et al. Middle-aged children of Alzheimer parents, a pilot study: Stable neurocognitive performance at 20-year follow-up // J Geriatr Psychiatry Neurol. – 2005. – Vol. 18. – Pp. 187–191. – https://doi.org/10.1177/0891988705281862
  18. Small G.W., Ercoli L.M., Silverman D.H. et al. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer’s disease // Proc Natl Acad Sci USA. – 2000. – Vol. 97. – Pp. 6037–6042. – https://doi.org/10.1073/pnas.090106797
  19. Elias M.F., Beiser A., Wolf P.A., Au R., White R.F., D’Agostino R.B. The preclinical phase of Alzheimer disease: a 22-year prospective study of the Framingham Cohort // Arch Neurol. – 2000. – Vol. 57. – Pp. 808–813. – https://doi.org/10.1001/archneur.57.6.808
  20. Backman L., Jones S., Berger A.K., Laukka E.J., Small B.J. Cognitive impairment in preclinical Alzheimer’s disease: А meta-analysis // Neuropsychology. – 2005. – Vol. 19. – Pp. 520–531. – https://doi.org/10.1037/0894-4105.19.4.520.
  21. Kawas C.H., Corrada M.M., Brookmeyer R., Morrison A., Resnick S.M., Zonderman A.B. et al. Visual memory predicts Alzheimer’s disease more than a decade before diagnosis // Neurology. – 2003. – Vol. 60. – Pp. 1089–1093. – https://doi.org/10.1212/01.wnl.0000055813.36504.bf
  22. Snowdon D.A., Kemper S.J., Mortimer J.A., Greiner L.H., Wekstein D.R., Markesbery W.R. Linguistic ability in early life and cognitive function and Alzheimer’s disease in late life findings from the Nun Study // JAMA. – 1996. – Vol. 275. – Pp. 528–532. – https://doi.org/10.1111/j.1749-6632.2000.tb06347.x
  23. La Rue A., Hermann B., Jones J.E., Johnson S., Asthana S. and Sager M.A. Effect of parental family history of Alzheimer’s disease on serial position profiles // Alzheimers Dement. – 2008. – Vol. 4 (4). – Pp. 285–290. – https://doi.org/10.1016/j.jalz.2008.03.009
  24. Yu. J. Hong and Jae-H. Lee. Subjective cognitive decline and Alzheimer’s disease spectrum disorder // Dement Neurocogn Disord. – 2017 Jun. – Vol. 16 (2). – Pp. 40–47. – https://doi.org/10.12779/dnd.2017.16.2.40
  25. Селезнева Н.Д., Гаврилова С.И., Рощина И.Ф., Пономарева Е.В. Цитиколин в лечении когнитивной недостаточности у родственников 1-й степени родства пациентов с болезнью Альцгеймера: влияние ApoE генотипа // Журнал неврологии и психиатрии имени С.С. Корсакова. – 2021. – № 121 (10), вып. 2. – С. 30–36. – https://doi.org/10.17116/jnevro202112110230
  26. Petersen R.C., Smith G.E., Waring S.C., Ivnik R.J., Tangalos E.G., Kokmen E. Mild cognitive impairment: clinical characterization and outcome // Arch Neurol. – 1999. – Vol. 56. – Pp. 303–308. – https://doi.org/10.1001/archneur.56.3.303
  27. Reisberg B., Ferris S.H., de Leon M.J., Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia // Am J Psychiatry. – 1982. – Vol. 139 (9). – Pp. 1136–1139. – https://doi.org/10.1176/ajp.139.9.1136
  28. Folstein M.F., Folstein S.E. and Mchugh P.R. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician // J Psychiat Res. – 1975. – Vol. 12. – Рp. 189–198. – https://doi.org/10.1016/0022-3956(75)90026-6
  29. Nasreddine Z.S., Phillips N.A., Bédirian V., Charbonneau S., Whitehead V., Collin I., Cummings J.L., Chertkow H. The Montreal cognitive assessment, MoCA: A brief screening tool for mild cognitive impairment // J Am Geriatr Soc. – 2005. – Vol. 53 (4). – Pp. 695– 699. – https://doi.org/10.1111/j.1532-5415.2005.53221.x
  30. Нейропсихологическая диагностика. Классические стимульные материалы / Авт.-сост. Е.Ю. Балашова, М.С. Ковязина. – М.: Генезис, 2022. – 84 c.
  31. Kaplan E.F., Goodglass H., Weintraub S. The Boston Naming Test. – 2nd ed. – Philadelphia: Lea & Febiger, 1983. – 120 p.
  32. Wechsler D. Manual for the Wechsler adult intelligence scale. – NY: Psychological Corp., 1955. – 230 p.
  33. Shulman K.I., Shedletsky R. and Silver I.L. The challenge of time: Сlock-drawing and cognitive function in the elderly // International Journal of Geriatric Psychiatry. – 1986. – Vol. 1. – Рp. 135–140.
  34. Рубинштейн С.Я. Экспериментальные методики патопсихологии и опыт применения их в клинике. Практическое руководство. Стимульный материал: в 2 кн. – М.: Психотерапия, 2010. – 224 с.
  35. Benton A.L. A Visual retention test for clinical use // Archives of Neurology and Psychiatry // 1945. – Vol. 54 (3). – Pp. 212–216. – https://doi.org/10.1001/archneurpsyc.1945.02300090051008
  36. Belaus A., Fernández L.A., Farías-Sarquis Ya., Adrián M., Bueno M. Mattis dementia rating scale // Rev Chil Neuropsicol. – 2015. – Vol. 10 (1). – Рp. 8–13. – https://doi.org/10.5839/rcnp.2015.10.01.03
  37. Райгородский Д.Я. Практическая психодиагностика. Методики и тесты. – Самара: Бахрах-М, 2011.
  38. Рощина И.Ф., Сюняков Т.С., Осипова Н.Г., Курмышев М.В., Савилов В.Б., Андрющенко А.В. Оценка эффективности нейрокогнитивной реабилитации пациентов с мягким когнитивным снижением в условиях ограничений во время пандемии COVID-19 // Психиатрия. – 2022. – №. 20 (4). – С. 36–43. – https://doi.org/10.30629/2618-6667-2022-20-4-36-43
  39. Стрижицкая О.Ю. Когнитивный резерв как психологический и психофизиологический ресурс в период старения // Вестник Санкт-Петербургского университета. Сер. 16: Психология. Педагогика. – 2016. – № 2. – С. 79–87. – https://doi.org/10.21638/11701/spbu16.2016.209
  40. Fisher P., Jungwirth S., Zehetmayer S. et al. Conversion of subtypes of mild cognitive impairment to Alzheimer›s disease // Neurology. – 2007 Jan 23. – Vol. 68 (4). – Pp. 88– 291. – https://doi.org/10.1212/01.wnl.0000252358.03285.9d
  41. Farias S.T., Mungas D., Reed B.R. et al. Progression of mild cognitive impairment to dementia in clinic vs community based cohorts // Arch Neurol. – 2009 Sep. – Vol. 66 (9). – Pp.1151–1157. – https://doi.org/10.1001/archneurol.2009.106
  42. Tschanz J.T., Welsh-Bohmer K.A., Lyketsos C.G. et al. Conversion to dementia from mild cognitive disorder: the Cache County Study // Neurology. – 2006. – Vol. 67 (2). – Pp. 229–234. – https://doi.org/10.1212/01.wnl.0000224748.48011.84
  43. Ravaglia G., Forti P., Montesi F., Lucicesare A., Pisacane N., Rietti E., Dalmonte E., Bianchin M., Mecocci P. Mild cognitive impairment: epidemiology and dementia risk in elderly Italian population // J Am Geriatr Soc. – 2008 Jan. – Vol. 56 (1). – Pp. 51–58. – https://doi.org/10.1111/j.1532-5415.2007.01503.x
  44. Лурия А.Р. Основы нейропсихологии. – СПб.: Питер, 2023. – 384 с.

Downloads

Download data is not yet available.