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Review

Toward the optimized assessment of clinical outcomes in studies of novel treatments for Alzheimer’s disease

, , , ORCID Icon, , , & show all
Pages 863-873 | Received 06 Oct 2022, Accepted 15 Nov 2022, Published online: 29 Nov 2022

References

  • Alzheimer’s Association As. 2019 Alzheimer’s disease facts and figures. Alzheimers Dement. 2019;15(3):321–387.
  • Europe A. Dementia in Europe Yearbook 2019: estimating the prevalence of dementia in Europe. Alzheimer Europe. 2019.
  • Scheltens P, Blennow K, Breteler M, et al. Alzheimer’s disease. Lancet (Lond Engl). 2016;388(10043):505–517.
  • Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–259.
  • Food and Drug Administration. Incorporating clinical outcome assessments into endpoints for regulatory decision making. 2018 https://www.fda.gov/media/132505/download.
  • Grober E, Hall CB, Lipton RB, et al., Memory impairment, executive dysfunction, and intellectual decline in preclinical Alzheimer’s disease. J Int Neuropsychol Soc. 2008;14(2):266–278. .
  • Sperling RA, Aisen PS, Beckett LA, 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;7(3):280–292.
  • Albert MS, DeKosky ST, Dickson D, 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. Focus. 2013;11(1):96–106.
  • McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia 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;7(3):263–269.
  • Alzheimer’s Association. 2021 Alzheimer’s disease facts and figures. Alzheimers Dement. 2021 Mar;17(3):327–406.
  • Dubois B, Hampel H, Feldman HH, et al. Preclinical Alzheimer’s disease: definition, natural history, and diagnostic criteria. Alzheimers Dement. 2016;12(3):292–323.
  • Schindler SE, Bateman RJ. Combining blood-based biomarkers to predict risk for Alzheimer’s disease dementia. Nature Aging. 2021;1(1):26–28.
  • Ribeiro F, de Mendonça A, Guerreiro M. Mild cognitive impairment: deficits in cognitive domains other than memory. Dement Geriatr Cogn Disord. 2006;21(5–6):284–290.
  • Petersen RC, Smith GE, Waring SC, et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56(3):303–308.
  • Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183–194.
  • Petersen RC, Caracciolo B, Brayne C, et al. Mild cognitive impairment: a concept in evolution. J Intern Med. 2014;275(3):214–228.
  • Jak AJ, Bondi MW, Delano-Wood L, et al. Quantification of five neuropsychological approaches to defining mild cognitive impairment. Am J Geriatric Psychiatry. 2009;17(5):368–375.
  • Petersen RC, Lopez O, Armstrong MJ, 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;90(3):126–135.
  • Farias ST, Mungas D, Reed BR, et al. Progression of mild cognitive impairment to dementia in clinic-vs community-based cohorts. Arch Neurol. 2009;66(9):1151–1157.
  • Bruscoli M, Lovestone S. Is MCI really just early dementia? A systematic review of conversion studies. Int Psychogeriatr. 2004;16(2):129–140.
  • Malek-Ahmadi M. Reversion from mild cognitive impairment to normal cognition. Alzheimer Dis Assoc Disord. 2016;30(4):324–330.
  • Brown PJ, Devanand D, Liu X, et al. Functional impairment in elderly patients with mild cognitive impairment and mild Alzheimer's disease. Arch Gen Psychiatry. 2011;68(6):617–626.
  • Hoe J, Hancock G, Livingston G, et al. Changes in the quality of life of people with dementia living in care homes. Alzheimer Dis Assoc Disord. 2009;23(3):285.
  • Feldman H, Woodward M. The staging and assessment of moderate to severe Alzheimer disease. Neurology. 2005;65(6 suppl 3):S10–S17.
  • Winblad B, Gauthier S, Åström D, et al. Memantine benefits functional abilities in moderate to severe Alzheimer’s disease. J Nutr Health Aging. 2010;14(9):770–774.
  • Moran M, Lynch C, Walsh C, et al. Sleep disturbance in mild to moderate Alzheimer’s disease. Sleep Med. 2005;6(4):347–352.
  • Alzheimer’s Association. 2020 Alzheimer’s disease facts and figures. Alzheimers Dement. 2020;16(3):391–460.
  • Franx BAA, Arnoldussen IAC, Kiliaan AJ, et al. Weight loss in patients with dementia: considering the potential impact of pharmacotherapy. Drugs Aging. 2017 Jun;34(6):425–436.
  • Anderson RM, Hadjichrysanthou C, Evans S, et al. Why do so many clinical trials of therapies for Alzheimer’s disease fail? Lancet. 2017;390(10110):2327–2329.
  • Atri A. Current and Future Treatments in Alzheimer’s Disease. Semin Neurol. 2019 Apr;39(2):227–240.
  • Casey DA, Antimisiaris D, O’Brien J. Drugs for Alzheimer’s disease: are they effective? Pharm Ther. 2010;35(4):208.
  • Cummings J, Lee G, Zhong K, et al. Alzheimer’s disease drug development pipeline: 2021. Alzheimers Dementia. 2021;7(1):e12179.
  • Database MC. Decision Memo. National Coverage Determination for Monoclonal Antibodies Directed Against Amyloid for the Treatment of Alzheimer’s Disease. 2022.
  • Ezzati A, Davatzikos C, Wolk DA, et al. Application of predictive models in boosting power of Alzheimer’s disease clinical trials: a post hoc analysis of phase 3 solanezumab trials. Alzheimer's Dementia. 2022;8(1):e12223.
  • Gauthier S, Albert M, Fox N, et al., Why has therapy development for dementia failed in the last two decades? Alzheimers Dement. 2016;12(1):60–64. .
  • Mangialasche F, Solomon A, Winblad B, et al. Alzheimer’s disease: clinical trials and drug development. Lancet Neurol. 2010;9(7):702–716.
  • United States Food and Drug Administration. Guidance for industry. Early Alzheimer’s disease. Developing drugs for the treatment (draft guidance) Feb, 2018.
  • Mintun MA, Lo AC, Duggan Evans C, et al. Donanemab in early Alzheimer’s disease. N Engl J Med. 2021;384(18):1691–1704.
  • Ostrowitzki S, Lasser RA, Dorflinger E, et al. A phase III randomized trial of gantenerumab in prodromal Alzheimer’s disease. Alzheimer’s Res Ther. 2017;9(1):1–15.
  • Banks SJ, Qiu Y, Fan CC, et al. Enriching the design of Alzheimer’s disease clinical trials: application of the polygenic hazard score and composite outcome measures. Alzheimer's Dementia. 2020;6(1):e12071.
  • Giebel CM, Sutcliffe C, Stolt M, et al. Deterioration of basic activities of daily living and their impact on quality of life across different cognitive stages of dementia: a European study. Int Psychogeriatr. 2014 Aug;26(8):1283–1293.
  • McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS‐ADRDA work group* under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology. 1984;34(7):939.
  • Albert MS, DeKosky ST, Dickson D, 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;7(3):270–279.
  • Jack CR Jr, Bennett DA, Blennow K, et al. NIA‐AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–562.
  • Huang L-K, Chao S-P, C-J H. Clinical trials of new drugs for Alzheimer disease. J Biomed Sci. 2020;27(1):1–13.
  • O’Bryant SE, Waring SC, Cullum CM, et al. Staging dementia using clinical dementia rating scale sum of boxes scores: a Texas Alzheimer’s research consortium study. Arch Neurol. 2008;65(8):1091–1095.
  • National Institute for Health and Clinical Excellence Draft scope for the appraisal of donepezil, galantamine, rivastigmine & memantine for the treatment of mild to moderate Alzheimer’s disease issue date: September 2009.
  • Pause BM, Zlomuzica A, Kinugawa K, et al. Perspectives on episodic-like and episodic memory. Front Behav Neurosci. 2013;7:33.
  • Fabrigoule C, Rouch I, Taberly A, et al. Cognitive process in preclinical phase of dementia. Brain. 1998;121(1):135–141.
  • Matsuda O, Saito M. Multiple cognitive deficits in patients during the mild cognitive impairment stage of Alzheimer’s disease: how are cognitive domains other than episodic memory impaired? Int Psychogeriatr. 2009;21(5):970–976.
  • Wechsler D. WAIS-R: Wechsler adult intelligence scale-revised. New York N.Y: Psychological Corporation, [1981] ©1981; 1981.
  • Devanand D, Folz M, Gorlyn M, et al. Questionable dementia: clinical course and predictors of outcome. J Am Geriatr Soc. 1997;45(3):321–328.
  • Hall CB, Ying J, Kuo L, et al. Estimation of bivariate measurements having different change points, with application to cognitive ageing. Stat Med. 2001;20(24):3695–3714.
  • Ueckert S, Plan EL, Ito K, et al., Improved utilization of ADAS-cog assessment data through item response theory based pharmacometric modeling. Pharm Res. 2014;31(8):2152–2165. .
  • Kueper JK, Speechley M, Montero-Odasso M. The Alzheimer’s disease assessment scale–cognitive subscale (ADAS-Cog): modifications and responsiveness in pre-dementia populations. a narrative review. J Alzheimers Dis. 2018;63(2):423–444.
  • Grober E, Sanders AE, Hall C, et al. Free and cued selective reminding identifies very mild dementia in primary care. Alzheimer Dis Assoc Disord. 2010;24(3):284.
  • Delis DC, Kramer JH, Kaplan E, et al. CVLT: California verbal learning test-adult version: manual. San Antonio, TX: Psychological corporation; 1987.
  • Wilson JR, De Fries J, Mc Clearn G, et al. Cognitive abilities: use of family data as a control to assess sex and age differences in two ethnic groups. Int J Aging Hum Dev. 1975;6(3):261–276.
  • Papp KV, Rentz DM, Orlovsky I, et al. Optimizing the preclinical Alzheimer’s cognitive composite with semantic processing: the PACC5. Alzheimer's Dementia. 2017;3(4):668–677.
  • Harrison J, Minassian SL, Jenkins L, et al. A neuropsychological test battery for use in Alzheimer disease clinical trials. Arch Neurol. 2007;64(9):1323–1329.
  • Holtzer R, Verghese J, Wang C, et al. Within-person across-neuropsychological test variability and incident dementia. Jama. 2008 Aug 20;300(7):823–830.
  • Zahodne LB, Manly JJ, MacKay-Brandt A, et al. Cognitive declines precede and predict functional declines in aging and Alzheimer’s disease. PLoS One. 2013;8(9):e73645.
  • Delgado C, Vergara RC, Martínez M, et al. Neuropsychiatric symptoms in Alzheimer’s disease are the main determinants of functional impairment in advanced everyday activities. J Alzheimers Dis. 2019;67(1):381–392.
  • Galasko D, Bennett D, Sano M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer’s disease. the Alzheimer’s disease cooperative study. Alzheimer Dis Assoc Disord. 1997;11(2):S33–9.
  • Dubbelman MA, Jutten RJ, Tomaszewski Farias SE, et al. Decline in cognitively complex everyday activities accelerates along the Alzheimer’s disease continuum. Alzheimers Res Ther. 2020 Oct 29;12(1):138.
  • Burton CL, Strauss E, Bunce D, et al. Functional abilities in older adults with mild cognitive impairment. Gerontology. 2009;55(5):570–581.
  • Allaire JC, Gamaldo A, Ayotte BJ, et al. Mild cognitive impairment and objective instrumental everyday functioning: the everyday cognition battery memory test. J Am Geriatr Soc. 2009 Jan;57(1):120–125.
  • Tabira T, Hotta M, Murata M, et al. Age-related changes in instrumental and basic activities of daily living impairment in older adults with very mild Alzheimer’s disease. Dement Geriatr Cogn Dis Extra. 2020 Jan-Apr;10(1):27–37.
  • Politis AM, Alexopoulos P, Vorvolakos T. May neuropsychiatric symptoms be a potential intervention target to delay functional impairment in Alzheimer’s disease? Int Psychogeriatr. 2020;32(6):689–691.
  • Cahn-Weiner DA, Farias ST, Julian L, et al. Cognitive and neuroimaging predictors of instrumental activities of daily living. J Int Neuropsychol Soc. 2007 Sep;13(5):747–757.
  • Fields JA, Machulda M, Aakre J, et al. Utility of the DRS for predicting problems in day-to-day functioning. Clin Neuropsychol. 2010 Oct;24(7):1167–1180.
  • Giebel CM, Sutcliffe C, Challis D. Activities of daily living and quality of life across different stages of dementia: a UK study. Aging Ment Health. 2015 Jan;19(1):63–71.
  • United States Food and Drug Administration. Guidance for industry. Alzheimer’s disease. Developing drugs for the treatment of early stage disease (draft guidance) Feb, 2013.
  • Pedrosa H, De Sa A, Guerreiro M, et al. Functional evaluation distinguishes MCI patients from healthy elderly people—the ADCS/MCI/ADL scale. J Nutr Health Aging. 2010;14(8):703–709.
  • Pfeffer RI, Kurosaki TT, Harrah CH Jr., et al. Measurement of functional activities in older adults in the community. J Gerontol. 1982 May;37(3):323–329.
  • Ard MC, Galasko DR, Edland SD. Improved statistical power of Alzheimer clinical trials by item-response theory: proof of concept by application to the activities of daily living scale. Alzheimer Dis Assoc Disord. 2013 Apr-Jun;27(2):187–191.
  • Bowling A, Rowe G, Adams S, et al. Quality of life in dementia: a systematically conducted narrative review of dementia-specific measurement scales. Aging Ment Health. 2015 Jan;19(1):13–31.
  • Torisson G, Stavenow L, Minthon L, et al. Reliability, validity and clinical correlates of the Quality of Life in Alzheimer’s disease (QoL-AD) scale in medical inpatients. Health Qual Life Outcomes. 2016;14(1):1–8.
  • Ezzati A, Zammit AR, Katz MJ, et al. Health-related quality of life, cognitive performance, and incident dementia in a community-based elderly cohort. Alzheimer Dis Assoc Disord. 2019 Jul-Sep;33(3):240–245.
  • Bárrios H, Narciso S, Guerreiro M, et al. Quality of life in patients with mild cognitive impairment. Aging Ment Health. 2013;17(3):287–292.
  • Weiss EM, Papousek I, Fink A, et al. Quality of life in mild cognitive impairment, patients with different stages of Alzheimer's disease and healthy control subjects. Neuropsychiatr. 2012;26(2):72–77.
  • Hussenoeder FS, Conrad I, Roehr S, et al. Mild cognitive impairment and quality of life in the oldest old: a closer look. Qual Life Res. 2020 Jun;29(6):1675–1683.
  • Kahle-Wrobleski K, Ye W, Henley D, et al. Assessing quality of life in Alzheimer’s disease: implications for clinical trials. Alzheimers Dement (Amst). 2017;6(1):82–90.
  • Landeiro F, Mughal S, Walsh K, et al. Health-related quality of life in people with predementia Alzheimer’s disease, mild cognitive impairment or dementia measured with preference-based instruments: a systematic literature review. Alzheimer’s Res Ther. 2020 November 18;12(1):154.
  • Ecklund-Johnson E, Torres I. Unawareness of deficits in Alzheimer’s disease and other dementias: operational definitions and empirical findings. Neuropsychol Rev. 2005 Sep;15(3):147–166.
  • Karlawish JH, Casarett D, Klocinski J, et al. The relationship between caregivers’ global ratings of Alzheimer’s disease patients’ quality of life, disease severity, and the caregiving experience. J Am Geriatr Soc. 2001 Aug;49(8):1066–1070.
  • Smith S, Lamping D, Banerjee S, et al. Measurement of health-related quality of life for people with dementia: development of a new instrument (DEMQOL) and an evaluation of current methodology. Health Technol Assess. 2005;9(10):1–iv.
  • Logsdon RG, Gibbons LE, McCurry SM, et al. Quality of life in Alzheimer’s disease: patient and caregiver reports. Aging Ment Health Aging. 1999;5. 21–32.
  • Dean K, Jenkinson C, Wilcock G, et al. The development and validation of a patient-reported quality of life measure for people with mild cognitive impairment. Int Psychogeriatr. 2014 Mar;26(3):487–497.
  • Savaskan E, Bopp-Kistler I, Buerge M. Therapy guidelines for the behavioural and psychological symptoms of dementia. Praxis (Bern 1994). 2014;103(3):135–148.
  • Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. Bmj. 2015 Mar 2;350(mar02 7):h369.
  • Barnes DE, Yaffe K, Byers AL, et al. Midlife vs late-life depressive symptoms and risk of dementia: differential effects for Alzheimer disease and vascular dementia. Arch Gen Psychiatry. 2012 May;69(5):493–498.
  • Modrego PJ, Ferrández J. Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: a prospective cohort study. Arch Neurol. 2004 Aug;61(8):1290–1293.
  • Canevelli M, Adali N, Cantet C, et al. Impact of behavioral subsyndromes on cognitive decline in Alzheimer’s disease: data from the ICTUS study. J Neurol. 2013;260(7):1859–1865.
  • Sundermann EE, Katz MJ, Lipton RB. Sex differences in the relationship between depressive symptoms and risk of amnestic mild cognitive impairment. Am J Geriatric Psychiatry. 2017;25(1):13–22.
  • Pocnet C, Antonietti J-P, Donati A, et al. Behavioral and psychological symptoms and cognitive decline in patients with amnestic MCI and mild AD: a two-year follow-up study. Int Psychogeriatr. 2015;27(8):1379–1389.
  • Lyketsos CG, Lopez O, Jones B, et al. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. Jama. 2002 Sep 25;288(12):1475–1483.
  • Roberto N, Portella MJ, Marquié M, et al. Neuropsychiatric profiles and conversion to dementia in mild cognitive impairment, a latent class analysis. Sci Rep. 2021;11(1):1–9.
  • Van der linde RM, Dening T, Stephan BC, et al. Longitudinal course of behavioural and psychological symptoms of dementia: systematic review. Br J Psychiatry. 2016;209(5):366–377.
  • Ballard CG, O’Brien JT, Coope B, et al. Psychotic symptoms in dementia and the rate of cognitive decline. J Am Geriatr Soc. 1997 Aug;45(8):1031–1032.
  • Cohen-Mansfield J. Behavioral and psychological symptoms of dementia. 2015.
  • Alexopoulos GS, Abrams RC, Young RC, et al. Cornell scale for depression in dementia. Biol Psychiatry. 1988 Feb 1;23(3):271–284.
  • Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997;48(5 Suppl 6):10S–16S.
  • Reisberg B, Borenstein J, Salob SP, et al. Behavioral symptoms in Alzheimer’s disease: phenomenology and treatment. J Clin Psychiatry. 1987;48 Suppl:9–15.
  • Balardy L, Voisin T, Cantet C, et al. Predictive factors of emergency hospitalisation in Alzheimer’s patients: results of one-year follow-up in the REAL. FR Cohort. J Nutr Health Aging. 2005;9(2): 112–116
  • McIlvane JM, Popa MA, Robinson B, et al. Perceptions of illness, coping, and well-being in persons with mild cognitive impairment and their care partners. Alzheimer Dis Assoc Disord. 2008;22(3):284–292.
  • Mohamed S, Rosenheck R, Lyketsos CG, et al. Caregiver burden in Alzheimer disease: cross-sectional and longitudinal patient correlates. Am J Geriatric Psychiatry. 2010;18(10):917–927.
  • Dauphinot V, Delphin-Combe F, Mouchoux C, et al. Risk factors of caregiver burden among patients with Alzheimer’s disease or related disorders: a cross-sectional study. J Alzheimers Dis. 2015;44(3):907–916.
  • Erder MH, Wilcox TK, Chen W-H, et al. A new measure of caregiver burden in Alzheimer’s disease: the caregiver-perceived burden questionnaire. Am J Alzheimer’s Dis Other Dementias®. 2012;27(7):474–482.
  • Hébert R, Bravo G, Préville M. Reliability, validity and reference values of the Zarit Burden Interview for assessing informal caregivers of community-dwelling older persons with dementia. Canadian Journal on Aging / La Revue Canadienne du Vieillissement. 2000;19(4):494–507.
  • Dubois B, Villain N, Frisoni GB, et al. Clinical diagnosis of Alzheimer’s disease: recommendations of the international working group. Lancet Neurol. 2021 Jun;20(6):484–496.
  • Food and Drug Administration. Methods to identify what is important to patients & select, develop or modify fit-for-purpose clinical outcomes assessments. https://www.fda.gov/downloads/Drugs/NewsEvents/UCM620708.pdf.
  • Van Cauwenberghe C, Van Broeckhoven C, Sleegers K. The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med. 2016;18(5):421–430.
  • Sabbagh MN, Perez A, Holland TM, et al. Primary prevention recommendations to reduce the risk of cognitive decline. Alzheimers Dement. 2022 Jan 13;18(8):1569–1579.
  • Assunção SS, Sperling RA, Ritchie C, et al. Meaningful benefits: a framework to assess disease-modifying therapies in preclinical and early Alzheimer’s disease. Alzheimers Res Ther. 2022 Apr 19;14(1):54.
  • Grober E, Lipton RB, Sperling RA, et al. Associations of stages of objective memory impairment with amyloid PET and structural MRI: the A4 study. Neurology. 2022 Mar 29;98(13):e1327–e1336.
  • Sperling RA, Rentz DM, Johnson KA, et al. The A4 study: stopping AD before symptoms begin? Sci Transl Med. 2014 Mar 19;6(228):228fs13.
  • Teunissen CE, Verberk IM, Thijssen EH, et al. Blood-based biomarkers for Alzheimer’s disease: towards clinical implementation. Lancet Neurol. 2022;21(1):66–77.
  • Hampel H, Cummings J, Blennow K, et al. Developing the ATX (N) classification for use across the Alzheimer disease continuum. Nat Rev Neurol. 2021;17(9):580–589.
  • Wesseling H, Mair W, Kumar M, et al. Tau PTM profiles identify patient heterogeneity and stages of Alzheimer’s disease. Cell. 2020;183(6):1699–1713. e13.
  • Food and Drug Administration. FDA grants accelerated approval for Alzheimer’s drug. 2021. Available from: https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug