Criteria for Assessment of Cognitive Impairment in Clinical Trials

Neuropsychological research methods are used to evaluate cognitive functions (CF). Tests used in clinical neuropsychology, in most cases, describe one or more aspects of cognitive domains that are theoretical «constructs» in which several cognitive processes are involved. Neuropsychological tests measure CFs regardless of the medical condition of the test subject. This allows for determination of even minor changes in CFs, including in clinical trials, which is of fundamental importance in studying the efficacy and safety of a given therapy. This article deals with specific aspects of using neuropsychological and screening testing of cognitive functions in individual domains on the basis of foreign experience. It discusses the criteria for selection and application of individual tools, their features, and choice of criteria for evaluating the results of testing in clinical studies in cases of CFs deterioration in various medical conditions accompanied by cognitive impairment. When planning clinical trials, it should also be taken into account that mixed anxiety-depressive disorders are likely to cause forgetfulness, and this calls for differential diagnosis and should be registered in clinical research protocols. The use of subscales and combinations of components of different tools are encouraged based on the objectives of the clinical study, and the tools of neuropsychological research and cognitive function assessment should be validated taking into account the specificity and sensitivity of the method, using statistical analysis methods for specific purposes and tasks. Such a multifaceted approach to the study of cognitive impairments will significantly increase the level of clinical trials conducted and, consequently, will make it possible to put up for sale efficacious and safe medicines for the treatment of cognitive impairment.

1. Олефир ЮВ. Результаты проведенного анализа и обобщения материалов по безопасности клинических исследований. Безопасность и риск фармакотерапии. 2017;(1):5–10. [Olefir YuV. The results of the analysis of materials on the safety of clinical trials. Bezopasnost i risk farmakoterapii=Safety and Risk of Pharmacotherapy. 2017;(1):5–10 (In Russ.)]

2. Горячев ДВ, Тельных МЮ, Бунятян НД. Регуляторные подходы к оценке биоаналогов для лечения ревматических заболеваний. Ведомости Научного центра экспертизы средств медицинского применения. 2017;(3):155–63. [Goryachev DV, Telnykh MYu, Bunyatyan ND. Regulatory approaches to evaluation of biosimilars for treatment of rheumatic diseases. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya=Тhе Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2017;(3):155–63 (In Russ.)]

3. Захаров ВВ. Когнитивные нарушения в неврологической практике. Трудный пациент. 2005;3(5):4–9. [Zakharov VV. Cognitive disorders in neurological practice. Trudny patsient=Difficult Patient. 2005;3(5):4–9 (In Russ.)]

4. Дамулин ИВ. Сосудистая деменция: некоторые патогенетические, диагностические и терапевтические аспекты. Русский медицинский журнал. 2008;16(5):253–8. [Damulin IV. Vascular dementia: some pathogenetic, diagnostic and therapeutic aspects. Russkiy meditsinskiy zhurnal=Russian Medical Journal. 2008;16(5):253–8 (In Russ.)]

5. Larrabee GJ, Crook TH. Estimated prevalence of age-associated memory impairment derived from standardized tests of memory function. Int Psychogeriatr. 1994;6(1):95–104.

6. Lezak MD, Howieson DB, Bigler ED, Tranel D. Neuropsychological assessment. 5th ed. New York; Oxford University Press: 2012.

7. Carson N, Leach L, Murphy KJ. A re-examination of Montreal Cognitive Assessment (MoCA) cutoff scores. Int J Geriatr Psychiatry. 2018;33(2):379–88. https://doi.org/10.1002/gps.4756

8. Kessels RPC, Brands AMA. Neuropsychological assessment. In: Biessels GJ, Luchsinger JA, eds. Diabetes and the Brain. Totowa, NJ: Humana Press; 2009. P. 77−102.

9. Vincent AS, Roebuck-Spencer TM, Fuenzalida E, Gilliland K. Test-retest reliability and practice effects for the ANAM General Neuropsychological Screening battery. Clin Neuropsychol. 2017;32(3):479–94. https://doi.org/10.1080/13854046.2017.1368716

10. Webber TA, Soble JR. Utility of various WAIS-IV Digit Span indices for identifying noncredible performance validity among cognitively impaired and unimpaired examinees. Clin Neuropsychol. 2018;32(4):657–70. https://doi.org/10.1080/13854046.2017.1415374

11. Mitrushina MN, Boone KB, Razani J, D’Elia LF. Handbook of normative data for neuropsychological assessment. New York: Oxford University Press; 2005.

12. Vanderploeg RD, ed. Clinician’s guide to neuropsychological assessment. 2nd ed. Hillsdale, NJ: Lawrence Erlbaum; 2000.

13. Folstein MF, Folstein SE, McHugh PR. «Mini-mental state». A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.

14. Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Neurology. 2001;56(9):1133–42.

15. Tsoi KK, Chan JY, Hirai HW, Wong SY, Kwok TC. Cognitive tests to detect dementia: a systematic review and meta-analysis. JAMA Intern Med. 2015;175(9):1450–8. https://doi.org/10.1001/jamainternmed.2015.2152

16. Lin JS, O’Connor E, Rossom RC, Perdue LA, Burda BU, Thompson M, et al. Screening for cognitive impairment in older adults: an evidence update for the U.S. Preventive Services Task Force. Report No. 14-05198-EF-1. Rockville (MD); 2013

17. Stein J, Luppa M, Maier W, Tebarth F, Heser K, Scherer M, et al. The assessment of changes in cognitive functioning in the elderly: age- and education-specific reliable change indices for the SIDAM. Dement Geriatr Cogn Disord. 2012;33(2–3):73–83. https://doi.org/10.1159/000336864

18. Stein J, Luppa M, Maier W, Wagner M, Wolfsgruber S, Scherer M, et al. Assessing cognitive changes in the elderly: reliable change indices for the Mini-Mental State Examination. Acta Psychiatr Scand. 2012;126(3):208–18. https://doi.org/10.1111/j.1600-0447.2012.01850.x

19. Stein J, Luppa M, Luck T, Maier W, Wagner M, Daerr M, et al. The assessment of changes in cognitive functioning: age-, education-, and gender-specific reliable change indices for older adults tested on the CERAD-NP battery: results of the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe). Am J Geriatr Psychiatry. 2012;20(1):84–97. https://doi.org/10.1097/JGP.0b013e318209dd08

20. Skinner J, Carvalho JO, Potter GG, Thames A, Zelinski E,Crane PK et al. The Alzheimer´s Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-Plus): an expansion of the ADAS-Cog to improve responsiveness in MCI. Brain Imaging Behav. 2012;6(4):489–501. https://doi.org/10.1007/s11682-012-9166-3

21. Karin A, Hannesdottir K, Jaeger J, Annas P, Segerdahl M, Karlsson P, et al. Psychometric evaluation of ADAS-Cog and NTB for measuring drug response. Acta Neurol Scand. 2014;129(2):114–22. https://doi.org/10.1111/ane.12153

22. Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385(9984):2255–63. https://doi.org/10.1016/S0140-6736(15)60461-5

23. Cedarbaum JM, Jaros M, Hernandez C, Coley N, Andrieu S, Grundman M, et al. Rationale for use of the Clinical Dementia Rating Sum of Boxes as primary outcome measure for Alzheimer’s disease clinical trials. Alzheimers Dement. 2013;9(1 Suppl):45–55. https://doi.org/10.1016/j.jalz.2011.11.002

24. Wessels AM, Dowsett SA, Sims JR. Detecting treatment group differences in Alzheimer’s disease clinical trials: a comparison of Alzheimer’s disease Assessment Scale – Cognitive Subscale (ADAS-Cog) and the Clinical Dementia Rating – Sum of Boxes (CDR-SB). J Prev Alzheimers Dis. 2018;5(1):15–20. https://doi.org/10.14283/jpad.2018.2

25. Langbaum JB, Hendrix SB, Ayutyanont N, Chen K, Fleisher AS, Shah RC, et al. An empirically derived composite cognitive test score with improved power to track and evaluate treatments for preclinical Alzheimer’s disease. Alzheimers Dement. 2014;10(6):666–74. https://doi.org/10.1016/j.jalz.2014.02.002

26. McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005;65(12):1863–72. https://doi.org/10.1212/01.wnl.0000187889.17253.b1

27. Mormile MEE, Langdon JL, Hunt TN. The role of gender in neuropsychological assessment in healthy adolescents. J Sport Rehabil. 2018;27(1):16–21. https://doi.org/10.1123/jsr.2016-0140

28. Plourde V, Hrabok M, Sherman EMS, Brooks BL. Validity of a computerized cognitive battery in children and adolescents with neurological diagnoses. Arch Clin Neuropsychol. 2018;33(2):247–53. https://doi.org/10.1093/arclin/acx067