Unraveling the bidirectional link between cancer and dementia and the impact of cancer therapies on dementia risk: A systematic review and meta-analysis

Observational studies on the cancer-dementia relationship have yielded controversial results. This study systematically reviews the evidence to clarify this association. We searched Embase, Global Health, Ovid Medline, and APA PsycInfo. Colorectal and lung cancers showed the greatest risk reduction for all-cause dementia (ACD) and Alzheimer's disease (AD), respectively, while melanoma and colorectal cancers had the largest reduction in vascular dementia (VaD). Prostate cancer survivors on androgen deprivation therapy (ADT) had a higher risk of ACD/AD, while breast cancer patients on tamoxifen had a lower AD risk. Chemotherapy was linked to a reduced AD risk. ACD patients saw a 30% risk reduction for bladder, colorectal, and lung cancers, while AD patients had a ≈ 35% reduction for bladder and lung cancers. Our study urges clinicians to monitor cognitive function in cancer patients, especially those on ADT, tamoxifen, or chemotherapy and highlights the need for research into cancer-dementia mechanisms. HIGHLIGHTS: Cancer survivors have an 8% to 14% lower risk of dementia, while those with dementia have a 25% lower cancer risk. Colorectal and non-melanoma skin cancers were associated with reduced risks of all-cause dementia (ACD; 16%/9%), Alzheimer's disease (AD; 13%/5%), and vascular dementia (VaD; 24%/9%). Lung cancer reduced AD risk by 17%, and melanoma reduced VaD risk by 27%. ACD and AD patients had lower risks of lung (30%/36%), bladder (32%/34%), breast (26%/20%), and colorectal (31%/28%) cancers. Tamoxifen and chemotherapy reduced AD risk, while androgen deprivation therapy increased ACD risk.