{
  "abstract": "Objective This study aimed to evaluate the cumulative benefits of Food and Drug Administration (FDA)-approved monoclonal antibodies (mABs), administered at FDA-approved dosing regimens in slowing cognitive decline compared with placebo and acetylcholinesterase inhibitor (AChEI), and the dynamic relationships between cognitive decline, amyloid reduction and whole brain volume (WBV) changes in mAB treatment.Methods Five major databases were systematically searched for double-blinded randomised controlled trials of patients with mild cognitive impairment due to Alzheimer’s disease (AD) or mild AD treated with mAB or AChEI for at least 6 months. The primary outcomes were the change in cognitive function measured by Alzheimer’s Disease Assessment Scale—cognitive subscale 14-Item (ADAS-Cog) and Clinical Dementia Rating Scale—Sum of Boxes (CDR-SOB). The secondary outcomes included amyloid burden and WBV changes.Results There were 6479 participants across seven mAB trials, and 4993 participants in nine AChEI trials. Compared with placebo, the pooled percentage of cognitive slowing was 27.6% (95% CI 24.6% to 30.9%), and the pooled progression delay was 5.52 months over 19.5 months (1.40 to 9.65) on CDR-SOB in patients treated with mABs. For cognitive trajectories on ADAS-Cog, mAB progressively attenuated cognitive decline, whereas AChEI exhibited a smaller effect with large uncertainty and eventually provided no benefits. Additionally, the rates of cognitive decline and amyloid reduction stabilised over time, while WBV initially showed a rapid decline but progressively slowed. Finally, WBV decline was not associated with worsening cognitive function. Instead, a 1 cm³ reduction in WBV was linked to a 0.0975-point reduction in CDR-SOB (0.0614 to 0.1336).Conclusions In prodromal to mild AD, mAB therapy provided greater cumulative cognitive benefits than placebo and AChEI, and WBV reduction may reflect a treatment-related process rather than a detrimental sequela.PROSPERO registration number CRD42024628107.",
  "authors": [
    {
      "affiliations": [
        "Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli, Taiwan",
        "Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan"
      ],
      "name": "Yu-Hsuan Lin"
    },
    {
      "affiliations": [
        "Department of Psychiatry, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan",
        "School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan"
      ],
      "name": "Tien-Wei Hsu"
    },
    {
      "affiliations": [
        "Department of Psychiatry, School of Medicine, College of Medicine, National Defense Medical University, Taipei, Taiwan",
        "Department of Psychiatry, Tri-Service General Hospital, Beitou Branch, Taipei, Taiwan"
      ],
      "name": "Yu-Chen Kao"
    },
    {
      "affiliations": [
        "Centre for Chronic Illness and Ageing, Greenwich University, London, UK"
      ],
      "name": "Trevor Thompson"
    },
    {
      "affiliations": [
        "IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, Deakin University, Geelong, Victoria, Australia"
      ],
      "name": "Andre F Carvalho"
    },
    {
      "affiliations": [
        "Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK"
      ],
      "name": "Brendon Stubbs"
    },
    {
      "affiliations": [
        "Institute of Biomedical Sciences and Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan",
        "Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan",
        "Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan"
      ],
      "name": "Ping-Tao Tseng"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan"
      ],
      "name": "Chih-Wei Hsu"
    },
    {
      "affiliations": [
        "Department of Neurology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"
      ],
      "name": "Fu-Chi Yang"
    },
    {
      "affiliations": [
        "Department of Neurology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"
      ],
      "name": "Chia-Kuang Tsai"
    },
    {
      "affiliations": [
        "Department of Pharmacy, Chang Gung Memorial Hospital, Taoyuan, Taiwan"
      ],
      "name": "Chia-Ling Yu"
    },
    {
      "affiliations": [
        "Department of Psychiatry, School of Medicine, College of Medicine, National Defense Medical University, Taipei, Taiwan",
        "Department of Psychiatry, Tri-Service General Hospital, Beitou Branch, Taipei, Taiwan"
      ],
      "name": "Chih-Sung Liang"
    },
    {
      "affiliations": [
        "Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan",
        "Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan"
      ],
      "name": "Yu-Kang Tu"
    }
  ],
  "title": "Cumulative cognitive benefits and brain volume change with anti-amyloid therapies for Alzheimer’s disease",
  "uid": "c54d21c9-88e3-55c0-aeb8-c817e30dcaa8"
}