Executive dysfunction is the earliest sign of preclinical Alzheimer’s disease detected by regional Ab‐PET SUVr in the precuneus and posterior cingulate cortex

Abstract

AbstractBackgroundAmyloid (Aβ) deposition occurs many years or even decades before the appearance of cognitive decline (preclinical Alzheimer’s disease (pAD)). The diagnosis of pAD is based on biomarker positivity using diagnostic tests such as amyloid‐PET that can provide regional quantification of Aβ deposition in the brain. The precuneus and posterior cingulate gyri are thought to represent the earliest brain regions affected by AD pathology. The present study sought to explore the associations of amyloid‐PET standardized uptake value ratio (SUVr) positivity with global, executive, and memory‐specific domain involvement in pAD.MethodNinety‐nine clinically‐normal, aged participants with Montreal Cognitive Assessment (MoCA) scores ≥ 23 that had undergone amyloid‐PET scanning were analyzed. The participants were divided into two groups based on SUVr in the posterior cingulate and precuneus gyri (SUVR≥1.17). Between group differences in MoCA, Trail Making Test (TMT), and California Verbal Learning Test‐II (CVLT‐II) scores were analyzed using two‐sided independent t test.ResultThe sample included 45 participants in the pAD group and 54 participants in the healthy control group that did not differ in age or education. Statistically significant between group differences were seen for TMT B, TMT B‐A and MoCA (p = 0.006, 0.001 and 0.034, respectively). No significant differences were seen between groups in delayed recall measures on the CVLT‐II.ConclusionWhile the prevailing view in the field suggests that early memory change is the hallmark of AD, the present data demonstrate that changes in executive function may be the earliest signs of pAD. Ongoing and future efforts at developing more sensitive tests for preclinical executive function deficits may serve as the most sensitive, low cost, non‐invasive clinical biomarkers of pAD.