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

Abstract

Background and Objectives:The risk of mild cognitive impairment (MCI) or dementia in individuals with subjective cognitive decline (SCD) and biomarkers indicating Alzheimer’s disease (AD) pathology in comparison to individuals with SCD without biomarker evidence for AD is critical to delineate the potential role of biomarkers assessment in this group. We performed a meta-analysis of studies on this topic.Methods:Three data bases (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 PRISMA and Cochrane guidelines, two researchers independently performed literature search, data collection and data extraction. We summarized odds ratios (OR) in random-effects meta-analyses and calculated sensitivity, specificity, positive and negative predictive values (PPV, NPV), and likelihood ratios. The primary outcome was the OR of progressing 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:Out of 4147 studies screened, eight studies were selected. The risk of bias analysis revealed low risk of bias in all studies. The prevalence of abnormal biomarkers ranged between 15,6%-35,4% for amyloid, 11,1%-33,7% for p-tau, 12,4%-46,3% for t-tau and 7,8%-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 a 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 a 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.Systematic Review Registration:Prospero CRD42020175282.