Rate of progression to dementia in people with MCI and amyloid pathology: a systematic review of longitudinal studies.

Mild Cognitive Impairment (MCI) is heterogeneous and predicting conversion to dementia remains challenging. Amyloid positivity (Aβ+) via PET or CSF is a key Alzheimer's disease (AD) marker, yet longitudinal conversion rates vary considerably. This systematic review summarizes conversion risk to AD in MCI Aβ+ versus Aβ− subjects and considers clinical and public health implications. We identified longitudinal observational studies reporting MCI-to-AD conversion by amyloid status. Extracted data included diagnostic criteria, amyloid assessment, sample characteristics, follow-up duration, and conversion rates. Methodological heterogeneity precluded meta-analysis; data are narratively summarized. Approximately 30 studies (>5,000 MCI participants) showed higher conversion in Aβ+ versus Aβ− subjects. Aβ+ conversion rates ranged widely (30-70% over 2-5 years), while Aβ− rates were generally lower. Notably, many Aβ+ subjects remained clinically stable throughout follow-up. Variability reflected differences in sample characteristics, biomarker thresholds, diagnostic frameworks, and follow-up length. Amyloid positivity associates with higher MCI-to-AD conversion, confirming Aβ's role as an AD biomarker. However, heterogeneous conversion rates and substantial clinical stability among Aβ+ subjects highlight limitations of amyloid status alone for prognosis. Findings underscore the need for multidimensional risk stratification integrating additional biomarkers, cognitive trajectories, and clinical profiles. With emerging anti-amyloid therapies, refined prognostic frameworks are essential for informed decision-making, optimal patient selection, and equitable healthcare resource allocation.