Progression of Subjective Cognitive Decline to MCI or Dementia in Relation to Biomarkers for Alzheimer Disease A Meta-analysis

Background and Objectives The risk of mild cognitive impairment (MCI) or dementia in individuals with subjective cognitive decline (SCD) and biomarkers indicating Alzheimer disease (AD) pathology in comparison with individuals with SCD without biomarker evidence for AD is critical to delineate the potential role of biomarker assessment in this group. We performed a meta-analysis of studies on this topic. Methods Three databases (PubMed, PsycINFO, and Cochrane) were searched from inception to May 7, 2021. Search strings included the terms: subjective cognitive decline, biomarker, amyloid, tau, risk, Alzheimer, mild cognitive impairment, and dementia. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane guidelines, 2 researchers independently performed literature search, data collection, and data extraction. We summarized odds ratios (ORs) in random-effects meta-analyses and calculated sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs), and likelihood ratios. The primary outcome was the OR of progression from SCD to MCI or dementia in cases with biomarkers indicative of AD pathology relative to the chance of progression in cases with biomarkers indicating no AD pathology. Results Of 4,147 studies screened, 8 studies were selected. The risk of bias analysis revealed a low risk of bias in all studies. The prevalence of abnormal biomarkers ranged between 15.6% and 35.9% for amyloid, 11.1% and 33.6% for phosphorylated tau (p-tau), 12.3% and 46.3% for total tau (t-tau), and 7.8% and 24.4% for full AD pathology (amyloid pathology with either increased p-tau or t-tau). The chance of clinical progression was increased in cases of amyloid pathology only (OR 5.89, 95% CI 2.33-14.90), elevated p-tau (OR 3.99, 95% CI 2.34-6.85), elevated t-tau (OR 2.26, 95% CI 1.14-4.48), and full AD pathology (OR 11.36, 95% CI 1.97-65.41). The latter showed a PPV of 59.7% (95% CI 48.8%-69.3%) and an NPV of 89.4% (95% CI 86.7%-91.7%), whereas amyloid pathology only showed a PPV of 28.2% (95% CI 23.7%-32.2%) and an NPV of 94.9% (95% CI 93.4%-96.2%). Discussion Individuals with SCD and full AD pathology have a substantially increased risk of developing MCI or dementia in comparison with individuals with SCD without AD pathology.