PREVENT‐AD cohort: from normal to impaired cognition, who are declining and why? Preliminary results

Abstract

AbstractBackgroundThe StoP‐Alzheimer Center follows a cohort of cognitively normal participants at risk of developing Alzheimer’s disease (AD) due to their parental history (PREVENT‐AD cohort). Cognitive impairments were detected in 17% of the cohort (66 out of 386) mostly after between 4 to 6 years of follow‐up, at an average age of 70 ± 7 years of age.MethodWe looked at various variables at baseline (demographics, blood results, medical history, cognition, genetic variants, AD pathology, mood) to describe the differences between the participants who maintained a normal cognition versus those who declined.ResultDifference in ApoE4 status was not as important as expected with 39.4% ApoE4 carriers in the decliner group compared to 38.2% in the normal group (Table 1). Despite a normal cognition at baseline, we found subtle but significant lower cognitive performance in the decliner group on the MoCA (‐1 pt) and the Repeatable Battery for the Assessment of Neuropsychological Status (‐5 pts). Systolic blood pressure and glycosylated hemoglobin were slightly more elevated in the decliner group (132 mmHg versus 128 mmHg and 5.6% versus 5.4% respectively). When asked about their past medical history, more participants were treated for hypertension, hyperlipidemia and diabetes in the decliner group. At the level of brain AD pathology measured by PET, the decliner group presented higher levels (standard uptake values) of amyloid and tau. Overall, 27% of the decliner group were amyloid AND tau positive compared to 7% in the normal group. The decliner group also showed lower smell identification performances at baseline when compared to the group who didn’t decline.ConclusionMain differences between the groups at baseline are related to AD pathology, vascular risk factors and cognitive and smell identification capacities. Other available variables such as brain structure, cerebrospinal fluid proteins, additional cognitive tests, lifestyle questionnaires, and genetics variants need to be analyzed along with trajectories and change over time. As a growing number of participants are declining cognitively and are still followed annually with multimodal evaluations, we trust that further investigations will help better understand the development of cognitive impairment.