Table 2.
Included studies
| Study | Country | Study design | Population n | Diagnostic criteria | Diagnostic use | Female: N (%) | Mean age | Follow up | ||
| (centers) | (source, date) | MCI due to AD | AD dementia | CSF | PET | (SD)* | ||||
| Prognostic factors | ||||||||||
| Cullen 2021 [28] •• | BioFINDER Sweden Multiple (n = NR) ADNI USA, Canada | Retrospective cohort BioFINDER Dates: July 2008 to June 2019 ADNI Dates: Sep 2005 and Dec 2019 | BioFINDER MCI: n = 340 ADNI MCI: n = 543 | BioFINDER Petersen criteria (Petersen 2004) ADNI NR | BioFINDER DSM-5 criteria ADNI NINCDS-ADRDA criteria (McKhann 1984) | NR | NR | BioFINDER 54 (36.5) ADNI 42 (51.2) | BioFINDER 71.36 (5.47) ADNI 71.51 (7.59) | 4 y |
| Janelidze 2020 [51] •• | Sweden (Multicenter: n = 2) USA (Single center n = 1) | Prospective cohort (Swedish BioFINDER study and Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program) Dates: NR | MCI: n = 125 | Petersen criteria (Petersen 2004) | As reported in BIOFINDER | NR | NR | 48 (38.4) | Range: 63-76 | 4.9 y |
| Lee 2012 [25] •• | South Korea Multicenter (n = 56) | Prospective cohort (Nationwide hospital-based cohort from Clinical Research Center for Dementia of South Korea) Dates: 2006 to 2010 | MCI: n = 504 | Petersen criteria (Winbland 2004) | NINCDS-ADRDA criteria (McKhann 1984) | NR | NR | 325 (64.5) | 70.8 (NR) | 1.47 y (Range: 5.5 mo to 5 y) |
| LoBue 2018 [27] •• | Canada, USA Multiple (n = 34) | Retrospective cohort (ADNI) Dates: Sep 2005 to Jun 2015 | MCI: n = 2719 | Peterson 2005 | NINCDS/ADRDA criteria (McKhann 1984) | NR | NR | 1342 (49.4) | NR | Median: 4 y (IQR 2 to 5 y) |
| Mouchet 2021 [35] •• | USA Multiple (n = NR) | Prospective cohort (NACC UDS) Dates: Sep 2005 to Feb 2019 | MCI: n = 830 | Albert 2011 | McKhann 2011 | NR | NR | 483 (58.2) | 78.5 (8.8) | Mean 3.6 y (SD: 2.5; Range: 0–11) |
| Palmqvist 2021 [29] • | ADNI: USA, Canada Multiple (n = NR) BioFINDER: Sweden Multiple (n = NR) | Retrospective cohort ADNI Dates 2003 to 2019 BioFINDER Dates: 2010 to 2014 | BioFINDER MCI: n = 148 ADNI MCI: n = 86 | BioFINDER Petersen 2004 ADNI Subjective memory concern; abnormal memory function score MMSE score between 24 and 30, CDR = 0.5, preserved cognition and functional performance | BioFINDER NINCDS/ADRDA criteria (McKhann 2011) were Aβ-positive according to the Aβ PET scan (Landau 2012) ADNI NINCDS/ADRDA criteria (McKhann 2011) | NR | Yes | BioFINDER 283 (52.1) ADNI 168 (49.4) | NR | 4 y |
| Pichet Binette 2022 [20] • | USA Unclear (n = NR) | Retrospective cohort NCT01028053 Dates: 2009 to 2014 | MCI: n = 110 | Peterson 2005 | McKhann 2011 | Y | Y | 52 (47.3) | NR | 3 y |
| Pyun 2017 [26] •• | Canada, USA Multicenter (n = NR) | Retrospective cohort (ADNI) Dates: 2003 to 25th May 2017 | MCI: n = 258 | Presence of objective memory impairment but without meeting the criteria for dementia | As described in ADNI | NR | NR | 101 (39.1) | Median: 74.1 (IQR: 69.5–78.5) | Up to 3 y; Median 24 mo |
| Richard 2012 [23] •• | Canada, USA Multiple (n > 50) | Retrospective cohort (ADNI) Dates: 2003 to Jun 2011 | MCI: n = 397 | As reported in the ADNI | As reported in the ADNI | NR | NR | 141 (35.5) | NR | Average: 2.7 y (SD 1.0) |
| Spalletta 2012 [34] • | Italy Multiple (n = 3) | Prospective cohort (Italian memory clinics) Dates NR | Mild AD dementia: n = 119 | NA | NINCDS-ADRDA criteria (McKhann 1984) | NR | NR | 67 (56.3) | 74.7 (6.3) | 1 y |
| Spencer 2019 [31] •• | Canada, USA Multiple (n = NR) | Retrospective cohort (ADNI) Dates: Aug 2005 and Sep 2007 | MCI: 185 | MMSE score between 24 and 30, a CDR rating of 0.5, both a subjective memory complaint and an objective memory impairment, intact ADL, and absence of dementia | Diagnosis of dementia at follow-up was determined by the study clinician. Criteria as described in the ADNI | NR | NR | 63 (34) | NR | Mean 4.3 y (SD: 2.8) |
| Therriault 2021 [30] •• | Canada, USA Multiple (n = NR) | Retrospective cohort (ADNI) Dates: NR to 2020 | MCI: n = 604 | CDR of 0.5, with the memory box score of at least 0.5, with preserved general cognitive performance | As reported in ADNI | NR | NR | 257 (42.5) | 72.2 (7.47) | Median 4.1 y (SD:1.34)* |
| Tosto 2014 [36] •• | Canada, USA Multicenter (n = NR) | Retrospective cohort (ADNI) Dates: NR | MCI:N=332 | Aged between 55 and 90 y; a memory symptom; objective evidence of abnormal memory; CDR score of 0.5, with a Memory Box score of at least 0.5; MMSE score between 24 and 30 (inclusive); preserved general cognition | NA | NR | NR | 118 (35) | 74.6 (7.4) | 48 mo |
| Van Loenhoud 2022 [52] • | Netherlands Single (n = 1) | Retrospective cohort (Amsterdam Dementia Cohort) Dates: 2000 and 2019 | MCI: n = 274 | Albert 2011 | McKhann 2011 | Y | Y | 130 (47.4) | 67.1 (7.4) | Median 2.3 y* |
| Wolfsgruber 2017 [33] •• | Germany Multiple (n = NR) | Retrospective cohort (German DCN) Dates: NR | MCI: n = 134 | Bondi 2014 | Dubois 2016 | Y | Y | 62 (46.3) | 65.5 (8.1) | 27.0 (0.95) mo |
| Xue 2020 [32] •• | Canada, USA Multiple (n > 50) | Retrospective cohort (ADNI) Dates: From 2003 | MCI: n = 193 | MMSE score between 24 and 30; CDR score of 0.5; objective memory loss preserved ADL, and the absence of dementia | NINCDS-ADRDA criteria (had MMSE scores between 20-26 and a CDR of 0.5 or 1.0) | NR | NR | 63 (32.6) | 74.4 (7.5) | NR |
| Budd Haeberlein 2022 [7] •• (Associated publication Salloway 2022 [37] | EMERGE: Multiple (n = 180) ENGAGE: Multiple (n = 181) | Two Phase 3 RCTs: EMERGE &ENGAGE Enrolment occurred from Aug 2015 to Jul 2018, and the trials were terminated early (Mar 21, 2019) based on a futility analysis. | eAD EMERGE Placebo: n = 548 Low dose: n = 543 High dose: n = 547 ENGAGE Placebo: n = 545 Low dose: n = 547 High dose: n = 555 | MCI due to AD or mild AD dementia, CDR of 0.5, objective evidence of cognitive impairment at screening, MMSE score of 24 to 30 | MCI due to AD or mild AD dementia, CDR of 0.5, objective evidence of cognitive impairment at screening, MMSE score of 24 to 30 | NR | Y | eAD EMERGE Placebo: 290 (53) Low dose: 269 (50) High dose: 284 (52) ENGAGE Placebo: 287 (53) Low dose: 284 (52) High dose: 292 (53) | eAD EMERGE Placebo: 70.8 (7.4) Low dose: 70.6 (7.4) High dose: 70.6 (7.5) ENGAGE Placebo: 69.8 (7.7) Low dose: 70.4 (7.0) High dose: 70.0 (7.7) | 78 weeks |
| Mintun 2021 [9] •• | Canada, USA Multiple (n = 56) | Phase 2 RCT: TRAILBLAZER-ALZ (donanemab versus placebo) | eAD Donanemab: n = 131 Placebo: n = 126 | Dubois 2007 | Dubois 2007 | NR | ✓ | Donanemab: 68 (51.9) Placebo: 65 (51.6) | Donanemab: 75.0 (5.6) Placebo: 75.4 (5.4) | 72 wk |
| Ostrowitzki 2017 [39] ••• | Worldwide Multiple (n = 128) | Phase 3 RCT: Scarlet RoAD (gantenerumab versus placebo) | Prodromal AD Placebo: n = 266 105 mg: n = 271 255 mg: n = 260 | Dubois 2007 | NA | ✓ | ✓ | NR | Placebo: 69.5 (7.5) 105 mg: 70.3 (7.0) 255 mg: 71.3 (7.1) | 2 y |
| Sevigny 2016 [38] •• | USA Multiple (n = 33) | Phase 1b RCT: PRIME (placebo versus multiple dose aducanumab) Oct 2012 to Jan 2014 | eAD Placebo: n = 40 1 mg/kg: n = 31 3 mg/kg: n = 32 6 mg/kg: n = 30 10 mg/kg: n = 32 | Derby 2013 Dubois 2010 | McKhann 2011 | NR | ✓ | Placebo: 23 (58) 1 mg/kg: 13 (42) 3 mg/kg: 17 (53) 6 mg/kg: 15 (50) 10 mg/kg: 15 (47) | Placebo: 72.8 (7.2) 1 mg/kg: 72.6 (7.8) 3 mg/kg: 70.5 (8.2) 6 mg/kg: 73.3 (9.3) 10 mg/kg: 73.7 (8.3) | 54 wk |
| Swanson 2021 [8] ••• | Worldwide Multiple (n = 169) | Phase 2b RCT: BAN2401-G000-201 (placebo versus multiple dose lecanemab) | Patients with MCI due to AD or mild AD dementia Dates: NR | eAD Placebo: n = 245 Lecanemab: n = 609 | NIAA-AA | NIAA-AA | ✓ | Placebo: 137 (58) 2.5 mg/kg biweekly: 26 (50) 5 mg/kg Monthly: 24 (50) 5 mg/kg Biweekly 48 (54) 10 mg/kg Monthly 110 (45) 10 mg/kg Biweekly 64 (42) | Median (range) Placebo: 72 (50–89) 2.5 mg/kg biweekly: 71 (50–86) 5 mg/kg Monthly: 71 (55–84) 5 mg/kg Biweekly 72 (52–87) 10 mg/kg Monthly 71 (53–90) 10 mg/kg Biweekly 73 (51–88) | 18 mo |
AD, Alzheimer’s Disease; ADL, Activities of daily living; ADNI, Alzheimer’s Disease Neuroimaging Initiative; CDR, The Clinical Dementia Rating; DCN, German Dementia Competence Network; DSM, Diagnostic and Statistical Manual of Mental Disorders; IQR, interquartile range; MCI, mild cognitive impairment; mo, month; MoCA, The Montreal Cognitive Assessment; MMSE, Mini-Mental State Examination; MSCI, Moderate/Severe Cognitive Impairment; NACC, National Alzheimer’s Coordinating Center; NIA-AA, National Institute on Aging and the Alzheimer’s Association criteria; NINCDS/ADRDA, National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association; NR, not reported; PET, positron emission tomography; SD, standard deviation; UDS, uniform data set; wk, week; y, year. *Unless otherwise stated. •low risk of bias •• moderate risk of bias ••• high risk of bias.