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

Abstract

BACKGROUND:

Amyloid 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.

METHODS:

From 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.

RESULTS:

We 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.

CONCLUSIONS:

A rich baseline dataset of cognitively normal elderly individuals has been established to estimate risk factors and biomarkers for amyloid pathology and future cognitive decline.

• Authors: Elles Konijnenberg, Stephen F Carter, Mara Ten Kate, Anouk den Braber, Jori Tomassen, Chinenye Amadi, Linda Wesselman, Hoang-Ton Nguyen, Jacoba A van de Kreeke, Maqsood Yaqub, Matteo Demuru, Sandra D Mulder, Arjan Hillebrand, Femke H Bouwman, Charlotte E Teunissen, Erik H Serné, Annette C Moll, Frank D Verbraak, Rainer Hinz, Neil Pendleton, Adriaan A Lammertsma, Bart N M van Berckel, Frederik Barkhof, Dorret I Boomsma, Philip Scheltens, Karl Herholz, Pieter Jelle Visser
• Journal: Alzheimer's research & therapy (Alzheimers Res Ther) Vol. 10 Issue 1 Pg. 75 (08 04 2018) ISSN: 1758-9193 [Electronic] England
• PMID: 30075734 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Twin Study)

Chemical References

• Amyloid beta-Peptides
• Aniline Compounds
• Apolipoproteins E
• Benzothiazoles
• flutemetamol

Topics

• Age Factors
• Aged
• Aged, 80 and over
• Alzheimer Disease (cerebrospinal fluid, complications, diagnostic imaging, genetics)
• Amyloid beta-Peptides (metabolism)
• Aniline Compounds (pharmacokinetics)
• Apolipoproteins E (genetics)
• Benzothiazoles (pharmacokinetics)
• Carotid Arteries (diagnostic imaging)
• Cognition Disorders (etiology)
• Cohort Studies
• Female
• Humans
• Imaging, Three-Dimensional
• International Cooperation
• Magnetic Resonance Imaging
• Magnetoencephalography
• Male
• Middle Aged
• Neuropsychological Tests
• Positron-Emission Tomography
• Tomography, Optical Coherence