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Multicenter Study
. 2017;60(1):97-105.
doi: 10.3233/JAD-170231.

Detecting At-Risk Alzheimer's Disease Cases

Tormod Fladby  1   2 , Lene Pålhaugen  1   2 , Per Selnes  1   2 , Knut Waterloo  3   4 , Geir Bråthen  5   6 , Erik Hessen  1   7 , Ina Selseth Almdahl  1   2 , Kjell-Arne Arntzen  3   8 , Eirik Auning  9 , Carl Fredrik Eliassen  1   7 , Ragna Espenes  3   4 , Ramune Grambaite  1 , Gøril Rolfseng Grøntvedt  5   6 , Krisztina Kunszt Johansen  1 , Stein Harald Johnsen  3   8 , Lisa Flem Kalheim  1   2 , Bjørn-Eivind Kirsebom  3   4 , Kai Ivar Müller  10   11 , Arne Exner Nakling  12   13 , Arvid Rongve  14   15 , Sigrid Botne Sando  5   6 , Nikias Siafarikas  9 , Ane Løvli Stav  1   2 , Sandra Tecelao  16 , Santiago Timon  1 , Svein Ivar Bekkelund  10   11 , Dag Aarsland  1   13   17
Affiliations
Multicenter Study

Detecting At-Risk Alzheimer's Disease Cases

Tormod Fladby et al. J Alzheimers Dis. 2017.

Abstract

While APOEɛ4 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 Aβ42 (pAβ) and APOEɛ4 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 mild 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 pAβ and APOEɛ4 frequency compared to NC. Also, NCFD had higher APOEɛ4 frequencies without increased fraction of pAβ compared to NC, and cases recruited from memory clinics had higher fractions of pAβ and APOEɛ4 frequency than self-referred. This study shows that memory clinic referrals are pAβ enriched, whereas self-referred and NCFD cases more frequently are pAβ negative but at risk (APOEɛ4 positive), suitable for primary intervention.

Keywords: Alzheimer’s disease; amyloid; apolipoprotein E4; biomarkers; cerebrospinal fluid; mild cognitive impairment; subjective cognitive decline.

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Figures

Fig.1
Fig.1
Initially 577 subjects were considered for inclusion, whereof 87 did not fulfill inclusion criteria or withdrew before finishing the assessment program. 465 subjects were staged, as either normal controls (NC), normal controls with first degree relative (NCFD), controls with abnormal cognitive screening results (ACS), subjective cognitive decline (SCD) or mild cognitive impairment (MCI). At the time of analysis, APOE genotyping was available for 445 subjects, whereof 202 were APOE ɛ4 positive. Cerebrospinal fluid data was available for 411 subjects, whereof 96 subjects had pathological levels of Aβ42.
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