Flash VEP-P2 latency delay in Alzheimer's disease and cognitive impairment: a systematic review and meta-analysis

The flash visual evoked potential P2 component (FVEP-P2) has been investigated as a potential neurophysiological measure of cognitive impairment, but its biological and clinical significance remains uncertain. However, evidence remains fragmented. This systematic review and meta-analysis aimed to quantitatively synthesize evidence on FVEP-P2 latency alterations across the cognitive impairment continuum, including mild cognitive impairment (MCI) and major neurocognitive disorders (dementia).

We systematically searched PubMed, Embase, Web of Science, and Cochrane Library until July 28, 2025. Standardized mean differences (SMDs) for FVEP-P2 latency were pooled from 21 studies (n = 1,778) using a random-effects model to compare AD, mild cognitive impairment (MCI), and VaD groups against healthy controls (HC). Subgroup and sensitivity analyses explored heterogeneity sources.

Twenty-one studies involving 1,778 participants were included. FVEP-P2 latency was significantly prolonged in patients with AD compared with healthy controls (18 comparisons, SMD = 1.55, 95% CI 1.05-2.05, I² = 88.9%). Exploratory analyses also suggested prolonged latency in VaD (four comparisons; SMD = 1.44, 95% CI 0.35-2.53; I² = 92.2%), MCI (two comparisons; SMD = 1.50, 95% CI 0.26-2.74; I² = 53.8%), and PDD (one comparison; SMD = 1.44, 95% CI 0.63-2.25). In a restricted exploratory analysis excluding six selected AD comparisons, the association remained statistically significant and directionally consistent (SMD = 1.32, 95% CI 0.83-1.82; I² = 84%). The ≥ 75-year subgroup showed lower heterogeneity (I² = 41%), although differences between age subgroups were not statistically significant (p = 0.56). Funnel plot asymmetry and Egger's test suggested potential small-study effects in the AD analysis.

Prolonged FVEP-P2 latency was observed in AD, with preliminary findings suggesting similar alterations in other forms or stages of cognitive impairment. These findings do not establish a specific neurobiological mechanism or diagnostic role. Further studies are needed to clarify the biological basis and clinical value of FVEP-P2 latency.