Individualised computerised cognitive training (iCCT) for community-dwelling people with mild cognitive impairment (MCI): results on cognition in the 6-month intervention period of a randomised controlled trial (MCI-CCT study).
Community-dwelling
Computerised cognitive training
Mild cognitive impairment
Non-pharmacological intervention
Randomised controlled trial
Journal
BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723
Informations de publication
Date de publication:
15 Oct 2024
15 Oct 2024
Historique:
received:
21
05
2024
accepted:
23
09
2024
medline:
16
10
2024
pubmed:
16
10
2024
entrez:
15
10
2024
Statut:
epublish
Résumé
Computerised cognitive training (CCT) can improve the cognitive abilities of people with mild cognitive impairment (MCI), especially when the CCT contains a learning system, which is a type of machine learning (ML) that automatically selects exercises at a difficulty that corresponds to the person's peak performance and thus enables individualised training. We developed one individualised CCT (iCCT) with ML and one basic CCT (bCCT) for an active control group (CG). The study aimed to determine whether iCCT in the intervention group (IG) resulted in significantly greater enhancements in overall cognitive functioning for individuals with MCI (age 60+) compared with bCCT in the CG across a 6-month period. This double-blind randomised controlled study was conducted entirely virtually. The 89 participants were community-dwelling people with a psychometric diagnosis of MCI living in Germany. The iCCT stimulates various cognitive functions, especially working memory, visuo-constructional reasoning, and decision-making. The bCCT includes fewer and simpler tasks. Both CCTs were used at home. At baseline and after 6 months, we assessed cognitive functioning with the Montreal Cognitive Assessment (MoCA). A mixed-model ANCOVA was conducted as the main analysis. Both CCTs led to significant increases in average global cognition. The estimated marginal means of the MoCA score increased significantly in the CG by an average of 0.9 points (95% CI [0.2, 1.7]) from 22.3 (SE = 0.25) to 23.2 (SE = 0.41) points (p = 0.018); in the IG, the MoCA score increased by an average of 2.2 points (95% CI [1.4, 2.9]) from 21.9 (SE = 0.26) to 24.1 (SE = 0.42) points (p < 0.001). In a confound-adjusted multiple regression model, the interaction between time and group was statistically significant (F = 4.92; p = 0.029). The effect size was small to medium (partial η By using a multi-tasking CCT three times a week for 30 min, people with MCI living at home can significantly improve their cognitive abilities within 6 months. The use of ML significantly increases the effectiveness of cognitive training and improves user satisfaction. ISRCTN14437015; registered February 27, 2020.
Sections du résumé
BACKGROUND
BACKGROUND
Computerised cognitive training (CCT) can improve the cognitive abilities of people with mild cognitive impairment (MCI), especially when the CCT contains a learning system, which is a type of machine learning (ML) that automatically selects exercises at a difficulty that corresponds to the person's peak performance and thus enables individualised training.
METHODS
METHODS
We developed one individualised CCT (iCCT) with ML and one basic CCT (bCCT) for an active control group (CG). The study aimed to determine whether iCCT in the intervention group (IG) resulted in significantly greater enhancements in overall cognitive functioning for individuals with MCI (age 60+) compared with bCCT in the CG across a 6-month period. This double-blind randomised controlled study was conducted entirely virtually. The 89 participants were community-dwelling people with a psychometric diagnosis of MCI living in Germany. The iCCT stimulates various cognitive functions, especially working memory, visuo-constructional reasoning, and decision-making. The bCCT includes fewer and simpler tasks. Both CCTs were used at home. At baseline and after 6 months, we assessed cognitive functioning with the Montreal Cognitive Assessment (MoCA). A mixed-model ANCOVA was conducted as the main analysis.
RESULTS
RESULTS
Both CCTs led to significant increases in average global cognition. The estimated marginal means of the MoCA score increased significantly in the CG by an average of 0.9 points (95% CI [0.2, 1.7]) from 22.3 (SE = 0.25) to 23.2 (SE = 0.41) points (p = 0.018); in the IG, the MoCA score increased by an average of 2.2 points (95% CI [1.4, 2.9]) from 21.9 (SE = 0.26) to 24.1 (SE = 0.42) points (p < 0.001). In a confound-adjusted multiple regression model, the interaction between time and group was statistically significant (F = 4.92; p = 0.029). The effect size was small to medium (partial η
CONCLUSIONS
CONCLUSIONS
By using a multi-tasking CCT three times a week for 30 min, people with MCI living at home can significantly improve their cognitive abilities within 6 months. The use of ML significantly increases the effectiveness of cognitive training and improves user satisfaction.
TRIAL REGISTRATION
BACKGROUND
ISRCTN14437015; registered February 27, 2020.
Identifiants
pubmed: 39407328
doi: 10.1186/s12916-024-03647-x
pii: 10.1186/s12916-024-03647-x
doi:
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
472Informations de copyright
© 2024. The Author(s).
Références
Inui Y, Ito K, Kato T. Longer-term investigation of the value of 18F-FDG-PET and magnetic resonance imaging for predicting the conversion of mild cognitive impairment to Alzheimer’s disease: a multicenter study. J Alzheimer’s Dis. 2017;60(3):877–87.
doi: 10.3233/JAD-170395
Hu M, Wu X, Shu X, Hu H, Chen Q, Peng L, et al. Effects of computerised cognitive training on cognitive impairment: a meta-analysis. J Neurol. 2019;268:1680–8.
pubmed: 31650255
doi: 10.1007/s00415-019-09522-7
Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, et al. Mild cognitive impairment. Lancet. 2006;367(9518):1262–70.
pubmed: 16631882
doi: 10.1016/S0140-6736(06)68542-5
Nygard L. Instrumental activities of daily living: a stepping-stone towards Alzheimer’s disease diagnosis in subjects with mild cognitive impairment? Acta Neurol Scand Suppl. 2003;179:42–6.
pubmed: 12603250
doi: 10.1034/j.1600-0404.107.s179.8.x
Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183–94.
pubmed: 15324362
doi: 10.1111/j.1365-2796.2004.01388.x
Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, et al. Mild cognitive impairment- beyond controversies, towards a consensus: report of the international working group on mild cognitive impairment. J Intern Med. 2004;256(3):240–6.
pubmed: 15324367
doi: 10.1111/j.1365-2796.2004.01380.x
Petersen RC, Lopez O, Armstrong MJ, Getchius TSD, Ganguli M, Gloss D, 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):126–35.
pubmed: 29282327
doi: 10.1212/WNL.0000000000004826
Kasper S, Bancher C, Eckert A, Forstl H, Frolich L, Hort J, et al. Management of mild cognitive impairment (MCI): the need for national and international guidelines. World J Biol Psychiatry. 2020;21(8):579–94.
pubmed: 32019392
doi: 10.1080/15622975.2019.1696473
Yao S, Liu Y, Zheng X, Zhang Y, Cui S, Tang C, et al. Do nonpharmacological interventions prevent cognitive decline? a systematic review and meta-analysis. Transl psychiatry. 2020;10(1):19.
pubmed: 32066716
doi: 10.1038/s41398-020-0690-4
Heser K, Wagner M, Wiese B, Prokein J, Ernst A, König H-H, et al. Associations between dementia outcomes and depressive symptoms, leisure activities, and social support. Dement Geriatr Cogn Disord extra. 2014;4(3):481–93.
doi: 10.1159/000368189
Guure CB, Ibrahim NA, Adam MB, Said SM. Impact of physical activity on cognitive decline, dementia, and its subtypes: meta-analysis of prospective studies. Biomed Res Int. 2017;2017:13.
doi: 10.1155/2017/9016924
Cheng S-T. Cognitive reserve and the prevention of dementia: the role of physical and cognitive activities. Curr Psychiatry Rep. 2016;18(9):85.
pubmed: 27481112
pmcid: 4969323
doi: 10.1007/s11920-016-0721-2
Levy S-A, Smith G, De Wit L, DeFeis B, Ying G, Amofa P, et al. Behavioral interventions in mild cognitive impairment (MCI): lessons from a multicomponent program. Neurotherapeutics. 2023;19(1):117–31.
doi: 10.1007/s13311-022-01225-8
Xu Z, Sun W, Zhang D, Chung VC-H, Sit RW-S, Wong SY-S. Comparative effectiveness of interventions for global cognition in patients with mild cognitive impairment: a systematic review and network meta-analysis of randomized controlled trials. Front Aging Neurosci. 2021;13: 653340.
pubmed: 34220484
doi: 10.3389/fnagi.2021.653340
Hou J, Jiang H, Han Y, Huang R, Gao X, Feng W, et al. Lifestyle influence on mild cognitive impairment progression: a decision tree prediction model study. Neuropsychiatr Dis Treat. 2024:271–80.
Caffò AO, Spano G, Tinella L, Lopez A, Ricciardi E, Stasolla F, et al. The prevalence of amnestic and non-amnestic mild cognitive impairment and its association with different lifestyle factors in a South Italian elderly population. Int J Environ Res Public Health. 2022;19(5): 3097.
pubmed: 35270789
doi: 10.3390/ijerph19053097
Wang L-Y, Pei J, Zhan Y-J, Cai Y-W. Overview of meta-analyses of five non-pharmacological interventions for Alzheimer’s Disease. Front Aging Neurosci. 2020;12: 594432.
pubmed: 33324194
doi: 10.3389/fnagi.2020.594432
Straubmeier M, Behrndt E-M, Seidl H, Özbe D, Luttenberger K, Gräßel E. Non-pharmacological treatment in people with cognitive impairment—results from the randomized controlled German day care study. Dtsch Arztebl Int. 2017;114(48):815–21.
pubmed: 29249224
Faucounau V, Wu YH, Boulay M, De Rotrou J, Rigaud AS. Cognitive intervention programmes on patients affected by mild cognitive impairment: a promising intervention tool for MCI? J Nutr Health Aging. 2010;14(1):31–5.
pubmed: 20082051
doi: 10.1007/s12603-010-0006-0
Ge S, Zhu Z, Wu B, McConnell ES. Technology-based cognitive training and rehabilitation interventions for individuals with mild cognitive impairment: a systematic review. BMC Geriatr. 2018;18(1):213.
pubmed: 30219036
pmcid: 6139138
doi: 10.1186/s12877-018-0893-1
Zhang H, Huntley J, Bhome R, Holmes B, Cahill J, Gould RL, et al. Effect of computerised cognitive training on cognitive outcomes in mild cognitive impairment: a systematic review and meta-analysis. BMJ Open. 2019;9(8): e027062.
pubmed: 31427316
pmcid: 6701629
doi: 10.1136/bmjopen-2018-027062
Contreras-Somoza LM, Irazoki E, Toribio-Guzmán JM, de la Torre-Díez I, Diaz-Baquero AA, Parra-Vidales E, et al. Usability and user experience of cognitive intervention technologies for elderly people with MCI or dementia: a systematic review. Front Psychol. 2021;12:636116.
pubmed: 33967901
pmcid: 8100576
doi: 10.3389/fpsyg.2021.636116
Gates NJ, Vernooij RW, Di Nisio M, Karim S, March E, Martinez G, et al. Computerised cognitive training for preventing dementia in people with mild cognitive impairment. Cochrane Database Syst Rev. 2019;3:CD012279.
pubmed: 30864747
Chapman SB, Aslan S, Spence JS, Hart JJ Jr, Bartz EK, Didehbani N, et al. Neural mechanisms of brain plasticity with complex cognitive training in healthy seniors. Cereb Cortex. 2015;25(2):396–405.
pubmed: 23985135
doi: 10.1093/cercor/bht234
Adolphe M, Pech M, Sawayama M, Maurel D, Delmas A, Oudeyer P-Y, et al. Exploring the potential of artificial intelligence in individualized cognitive training: a systematic review. 2023.
Tolks D, Schmidt JJ, Kuhn S. The role of AI in serious games and gamification for health: scoping review. JMIR Serious Games. 2024;12:12(e48258).
pubmed: 38224472
doi: 10.2196/48258
Eun S-J, Kim EJ, Kim JY. Development and evaluation of an artificial intelligence–based cognitive exercise game: a pilot study. J Environ Public Health. 2022;2022:15.
doi: 10.1155/2022/4403976
Faria AL, Almeida Y, Branco D, Câmara J, Cameirão M, Ferreira L, et al. NeuroAIreh@b: an artificial intelligence-based methodology for personalized and adaptive neurorehabilitation. Front Neurol. 2024;14:14.
doi: 10.3389/fneur.2023.1258323
Park J-H. Effects of personalized cognitive training using mental workload monitoring on executive function in older adults with mild cognitive impairment. Brain Neurorehabil. 2023;16(3): e21.
pubmed: 38047099
pmcid: 10689865
doi: 10.12786/bn.2023.16.e21
Book S, Jank M, Pendergrass A, Graessel E. Individualised computerised cognitive training for community-dwelling people with mild cognitive impairment: study protocol of a completely virtual, randomised, controlled trial. Trials. 2022;23(1):1–13.
doi: 10.1186/s13063-022-06152-9
Altman DG, Bland JM. Treatment allocation by minimisation. BMJ. 2005;330(7495): 843.
pubmed: 15817555
doi: 10.1136/bmj.330.7495.843
R Core Team. R: a language and environment for statistical computing. : R Foundation for Statistical Computing; 2019. Available from: https://www.R-project.org/ .
Luttenberger K, Donath C, Uter W, Graessel E. Effects of multimodal nondrug therapy on dementia symptoms and need for care in nursing home residents with degenerative dementia: a randomized-controlled study with 6-month follow-up. J Am Geriatr Soc. 2012;60(5):830–40.
pubmed: 22468985
doi: 10.1111/j.1532-5415.2012.03938.x
Graessel E, Stemmer R, Eichenseer B, Pickel S, Donath C, Kornhuber J, et al. Non-pharmacological, multicomponent group therapy in patients with degenerative dementia: a 12-month randomised, controlled trial. BMC Med. 2011;9(1): 129.
pubmed: 22133165
doi: 10.1186/1741-7015-9-129
Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695–9.
pubmed: 15817019
doi: 10.1111/j.1532-5415.2005.53221.x
Freitas S, Simoes MR, Alves L, Santana I. Montreal cognitive assessment: validation study for mild cognitive impairment and Alzheimer disease. Alzheimer Dis Assoc Disord. 2013;27(1):37–43.
pubmed: 22193353
doi: 10.1097/WAD.0b013e3182420bfe
Sala G, Inagaki H, Ishioka Y, Masui Y, Nakagawa T, Ishizaki T, et al. The psychometric properties of the Montreal Cognitive Assessment (MoCA). Swiss J Psychol. 2020;79(3–4):155–61.
doi: 10.1024/1421-0185/a000242
Freitas S, Prieto G, Simões MR, Santana I. Scaling cognitive domains of the montreal cognitive assessment: an analysis using the partial credit model. Arch Clin Neuropsychol. 2015;30(5):435–47.
pubmed: 25944337
doi: 10.1093/arclin/acv027
O’Caoimh R, Timmons S, Molloy DW. Screening for mild cognitive impairment: comparison of “MCI specific” screening instruments. J Alzheimer’s Dis. 2016;51(2):619–29.
doi: 10.3233/JAD-150881
Ciesielska N, Sokolowski R, Mazur E, Podhorecka M, Polak-Szabela A, Kedziora-Kornatowska K. Is the Montreal Cognitive Assessment (MoCA) test better suited than the Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI) detection among people aged over 60? Meta-analysis. Psychiatria Polska. 2016;50(5):1039–52.
pubmed: 27992895
doi: 10.12740/PP/45368
Thomann AE, Berres M, Goettel N, Steiner LA, Monsch AU. Enhanced diagnostic accuracy for neurocognitive disorders: a revised cut-off approach for the montreal cognitive assessment. Alzheimer’s Res Ther. 2020;12(1):39.
doi: 10.1186/s13195-020-00603-8
Bruijnen CJWH, Dijkstra BAG, Walvoort SJW, Budy MJJ, Beurmanjer H, De Jong CAJ, et al. Psychometric properties of the Montreal Cognitive Assessment (MoCA) in healthy participants aged 18–70. Int J Psychiatry Clin Pract. 2020;24(3):293–300.
pubmed: 32271127
doi: 10.1080/13651501.2020.1746348
Folstein M, Folstein S, Mc HP. “Mini-Mental State”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.
pubmed: 1202204
doi: 10.1016/0022-3956(75)90026-6
Arevalo-Rodriguez I, Smailagic N, Roque IFM, Ciapponi A, Sanchez-Perez E, Giannakou A, et al. Mini-Mental State Examination (MMSE) for the detection of Alzheimer’s disease and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2015;3:CD010783.
Tombaugh TN, McIntyre NJ. The mini-mental state examination: a comprehensive review. J Am Geriatr Soc. 1992;40(9):922–35.
pubmed: 1512391
doi: 10.1111/j.1532-5415.1992.tb01992.x
Creavin ST, Wisniewski S, Noel-Storr AH, Trevelyan CM, Hampton T, Rayment D, et al. Mini-Mental State Examination (MMSE) for the detection of dementia in clinically unevaluated people aged 65 and over in community and primary care populations. Cochrane Database Syst Rev. 2016;2016(1):CD011145.
pubmed: 26760674
Zhang S, Qiu Q, Qian S, Lin X, Yan F, Sun L, et al. Determining appropriate screening tools and cutoffs for cognitive impairment in the Chinese elderly. Front Psychiatry. 2021;12: 773281.
pubmed: 34925100
doi: 10.3389/fpsyt.2021.773281
Salis F, Costaggiu D, Mandas A. Mini-mental state examination: optimal cut-off levels for mild and severe cognitive impairment. Geriatrics. 2023;8(1): 12.
pubmed: 36648917
doi: 10.3390/geriatrics8010012
Kroenke K, Spitzer RL, Williams JBW. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606–13.
pubmed: 11556941
pmcid: 1495268
doi: 10.1046/j.1525-1497.2001.016009606.x
Kroenke K, Spitzer RL, Williams JBW, Löwe B. The patient health questionnaire somatic, anxiety, and depressive symptom scales: a systematic review. Gen Hosp Psychiatry. 2010;32(4):345–59.
pubmed: 20633738
doi: 10.1016/j.genhosppsych.2010.03.006
Gilbody S, Richards D, Barkham M. Diagnosing depression in primary care using self-completed instruments: UK validation of PHQ-9 and CORE-OM. Br J Gen Pract. 2007;57(541):650–2.
pubmed: 17688760
pmcid: 2099671
Lippert T, Maas R, Fromm MF, Luttenberger K, Kolominsky-Rabas P, Pendergrass A, et al. Impact of sedating drugs on falls resulting injuries among people with dementia in a nursing home setting. Gesundheitswesen. 2020;82(1):14–22.
pubmed: 31962367
Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173(6):676–82.
pubmed: 21330339
doi: 10.1093/aje/kwq433
Graessel E, Jank M, Greiner S, Stemmler M. First validation of the Computerized Cognitive Test Battery (CCTB) on the Short Cognitive Performance Test (SKT) and the Montreal Cognitive Assessment (MoCA) in terms of convergent and divergent validity in individuals aged 60 years and older. Erlangen: Open FAU; 2024. 77 p.
Wechsler D. Wechsler adult intelligence scale–fourth edition (WAIS-IV)–Deutsche Version. Petermann F, editor. Frankfurt/Main: Pearson Assessment; 2012.
Lehfeld H, Schläfke S, Hoerr R, Stemmler M. SKT short cognitive performance test and activities of daily living in dementia. Geropsych (Bern). 2014;27(2):75–80.
doi: 10.1024/1662-9647/a000104
Henik A, Tzelgov J. Is three greater than five: the relation between physical land semantic size in comparison tasks. Mem Cognition. 1982;10(4):389–95.
doi: 10.3758/BF03202431
Raven JC, Court JH. Manual for Raven’s progressive matrices and vocabulary scales. London: H.K. Lewis; 1986.
Laugwitz B, Held T, Schrepp M, editors. Construction and evaluation of a User Experience Questionnaire. Berlin, Heidelberg: Springer Berlin Heidelberg; 2008.
Schrepp M. User Experience Questionnaire Handbook. 2023. 16 p.
Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale: Erlbaum Associates; 1988.
Yu J-T, Xu W, Tan C-C, Andrieu S, Suckling J, Evangelou E, et al. Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020;91(11):1201–9.
pubmed: 32690803
doi: 10.1136/jnnp-2019-321913
Field A. Discovering statistics using IBM SPSS Statistics. 6 th ed. London: SAGE Publications Limited; 2024.
Pituch KA, Stevens JP. Applied multivariate statistics for the social sciences: analyses with SAS and IBM’s SPSS. 6th ed. New York: Routledge; 2015. p. 814.
doi: 10.4324/9781315814919
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH: E 9: Statistical principles for clinical trials - Step 5 - Note for guidance on statistical principles for clinical trials (CPMP/ICH/363/96). European Medicines Ageny; 1998. Available from: https://www.ema.europa.eu/en/ich-e9-statistical-principles-clinical-trials-scientific-guideline#current-version-8451 .
World Health Organization. ICD-10: international statistical classification of diseases and related health problems: tenth revision. Geneva: World Health Organization; 2004.
Canevelli M, Adali N, Voisin T, Soto M, Bruno G, Cesari M, et al. Behavioral and psychological subsyndromes in Alzheimer’s disease using the Neuropsychiatric Inventory. Int J Geriatr Psychiatry. 2013;28(8):795–803.
pubmed: 23147419
doi: 10.1002/gps.3904
German Federal Statistical Office. Verteilung der Bevölkerung in Deutschland nach höchstem Schulabschluss im Jahr 2023: Statista; 2024. Available from: https://de.statista.com/statistik/daten/studie/1988/umfrage/bildungsabschluesse-in-deutschland/ .
Thomann AE, Goettel N, Monsch RJ, Berres M, Jahn T, Steiner LA, et al. The montreal cognitive assessment: normative data from a German-speaking cohort and comparison with international normative samples. J Alzheimer’s Dis. 2018;64(2):643–55.
doi: 10.3233/JAD-180080
Pinto TC, Machado L, Bulgacov TM, Rodrigues-Júnior AL, Costa ML, Ximenes RC, et al. Is the Montreal Cognitive Assessment (MoCA) screening superior to the Mini-Mental State Examination (MMSE) in the detection of mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) in the elderly? Int Psychogeriatr. 2019;31(4):491–504.
pubmed: 30426911
doi: 10.1017/S1041610218001370
Tan JP, Li N, Gao J, Wang LN, Zhao YM, Yu BC, et al. Optimal cutoff scores for dementia and mild cognitive impairment of the montreal cognitive assessment among elderly and oldest-old Chinese population. J Alzheimer’s Dis. 2015;43(4):1403–12.
doi: 10.3233/JAD-141278
Berg J-L, Durant J, Leger GC, Cummings JL, Nasreddine Z, Miller JB. Comparing the electronic and standard versions of the montreal cognitive assessment in an outpatient memory disorders clinic: a validation study. J Alzheimers Dis. 2018;62(1):93–7.
pubmed: 29439349
doi: 10.3233/JAD-170896
Zeng B, Tang C, Wang J, Yang Q, Ren Q, Liu X. Pharmacologic and nutritional interventions for early Alzheimer’s disease: a systematic review and network meta-analysis of randomized controlled trials. J Alzheimer’s Dis. 2024(Preprint):1–14.