Detecting At-Risk Alzheimer’s Disease Cases

Abstract

Abstract. While APOE ε4 is the major genetic risk factor for Alzheimer's disease (AD), amyloid dysmetabolism is an initial or early event predicting clinical disease and is an important focus for secondary intervention trials. To improve identification of cases with increased AD risk, we evaluated recruitment procedures using pathological CSF concentrations of A␤ 42 (pA␤) and APOE ε4 as risk markers in a multi-center study in Norway. In total, 490 subjects aged 40-80 y were included after response to advertisements and media coverage or memory clinics referrals. Controls (n = 164) were classified as normal controls without first-degree relatives with dementia (NC), normal controls with first-degree relatives with dementia (NCFD), or controls scoring below norms on cognitive screening. Patients (n = 301) were classified as subjective cognitive decline or * Correspondence to: Lene Pålhaugen, P.B. 1000, N-1478 Lørenskog, Norway. Tel.: +47 95832775; E-mail: lene. palhaugen@gmail.com. 98 T. Fladby et al. / Detecting At-Risk AD Casesmild cognitive impairment. Subjects underwent a clinical and cognitive examination and MRI according to standardized protocols. Core biomarkers in CSF from 411 and APOE genotype from 445 subjects were obtained. Cases (both self-referrals (n = 180) and memory clinics referrals (n = 87)) had increased fractions of pA␤ and APOE ε4 frequency compared to NC. Also, NCFD had higher APOE ε4 frequencies without increased fraction of pA␤ compared to NC, and cases recruited from memory clinics had higher fractions of pA␤ and APOE ε4 frequency than self-referred. This study shows that memory clinic referrals are pA␤ enriched, whereas self-referred and NCFD cases more frequently are pA␤ negative but at risk (APOE ε4 positive), suitable for primary intervention.

Prescreening for European Prevention of Alzheimer Dementia (EPAD) trial-ready cohort: impact of AD risk factors and recruitment settings

“…As low memory scores were the best predictor for amyloid positivity in the memory clinic setting, memory tests may form a useful prescreen in this situation. An explanation for the discrepancy with previously reported associations of these factors with amyloid status could be the non-standardised test data and could possibly show better predictive effects with the use of tailored sensitive tests and questionnaires [9,11,32,[34][35][36][37].…”

Screening for Alzheimer’s Disease: Cognitive Impairment in Self-Referred and Memory Clinic-Referred Patients

“…Between January 2013 and January 2017, we recruited participants with self-reported cognitive reduction and healthy controls. For further description of the DDI cohort and methods, see Fladby et al [ 23 ]. All participants were examined following a standard protocol.…”

“…A case report form developed for DDI [ 23 ] included assessment protocol for SCD (see below), medical history from participant and informant, physical and neurological examinations, as well as the 15-item Geriatric Depression Score (GDS) [ 25 ]. Educational levels were classified in the following categories [ 26 ]: 0 = Primary school (7–8 y), 1 = High School (9–11 y), 2 = College (12 y), 3 = Bachelor degree (13–15 y), 4 = Master or equivalent = 16 –17 y, 5 = Higher university degree/PhD (18–20 y).…”

Effects of Purified Anthocyanins in People at Risk for Dementia: Study Protocol for a Phase II Randomized Controlled Trial

“…Participants are being recruited from referrals to geriatric, psychiatric, neurology, cardiology, or memory outpatient clinics at two university hospitals and from advertisements in newspapers, radio, and on various social media. Furthermore, participants are recruited from the observational Dementia Disease Initiation study ( 31 ) and by actively reaching out to general practitioners in the areas.…”