The EMIF-AD PreclinAD study: study design and baseline cohort overview

Abstract

BackgroundAmyloid pathology is the pathological hallmark in Alzheimer’s disease (AD) and can precede clinical dementia by decades. So far it remains unclear how amyloid pathology leads to cognitive impairment and dementia. To design AD prevention trials it is key to include cognitively normal subjects at high risk for amyloid pathology and to find predictors of cognitive decline in these subjects. These goals can be accomplished by targeting twins, with additional benefits to identify genetic and environmental pathways for amyloid pathology, other AD biomarkers, and cognitive decline.MethodsFrom December 2014 to October 2017 we enrolled cognitively normal participants aged 60 years and older from the ongoing Manchester and Newcastle Age and Cognitive Performance Research Cohort and the Netherlands Twins Register. In Manchester we included single individuals, and in Amsterdam monozygotic twin pairs. At baseline, participants completed neuropsychological tests and questionnaires, and underwent physical examination, blood sampling, ultrasound of the carotid arteries, structural and resting state functional brain magnetic resonance imaging, and dynamic amyloid positron emission tomography (PET) scanning with [18F]flutemetamol. In addition, the twin cohort underwent lumbar puncture for cerebrospinal fluid collection, buccal cell collection, magnetoencephalography, optical coherence tomography, and retinal imaging.ResultsWe included 285 participants, who were on average 74.8 ± 9.7 years old, 64% female. Fifty-eight participants (22%) had an abnormal amyloid PET scan.ConclusionsA rich baseline dataset of cognitively normal elderly individuals has been established to estimate risk factors and biomarkers for amyloid pathology and future cognitive decline.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0406-7) contains supplementary material, which is available to authorized users.

Retinal thickness as a potential biomarker in patients with amyloid‐proven early‐ and late‐onset Alzheimer's disease

“…Controls were subjects with subjective cognitive decline, defined as subjective cognitive complaints without objective cognitive impairment on neuropsychological evaluation, no signs of neurodegeneration on neuroimaging, and absence of amyloid pathology based on CSF and/or amyloid-PET. In addition, controls were enrolled through the EMIF-AD PreclinAD twin study at our center (n = 39) [27] . One sibling of each monozygotic twin pair was selected to avoid genetic dependency.…”

Optical coherence tomography angiography in preclinical Alzheimer’s disease

“…[16][17][18] Exclusion criteria for the EMIF-AD study were: uncontrolled diabetes mellitus, alcohol consumption >35 units (1 unit=10 mL or 8 g of pure alcohol) per week, stroke with physical impairment, neurodegenerative disorders and/or cancer with a terminal life expectancy. 20…”

Decline in cognitively complex everyday activities accelerates along the Alzheimer’s disease continuum

“…The ADC is a memory-clinic cohort comprised of patients of the Alzheimer Center Amsterdam [ 24 ]. In the EMIF-AD PreclinAD Study, cognitively normal subjects aged 60 years and older were included [ 25 ]. The EMIF-AD 90+ Study focused on people aged 90 years and older who were either cognitively normal or who had some cognitive impairment [ 26 ].…”

“…Amyloid status was assessed at baseline using either amyloid positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) using local procedures, such as described in more detail elsewhere [ 25 – 30 ]. PET scans, using 11 C-Pittsburgh compound-B (PiB) in HABS, 18 F-florbetapir in ADNI, and one of 11 C-PiB, 18 F-flutemetamol, 18 F-florbetapir, or 18 F-florbetaben in the ADC and EMIF cohorts, were judged either using standard uptake volume ratios (ADNI, NACC), distribution volume ratios (HABS), or visual rating by independent nuclear medicine physicians (ADC, both EMIF studies).…”