Clinical trial NCT04437290: University of Washington Alzheimer's Disease Research Center (UW ADRC) Imaging & Biomarker Core
Official title: University of Washington Alzheimer's Disease Research Center (UW ADRC) Imaging & Biomarker Core
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Alzheimer Disease
Keywords: mild cognitive impairment
dementia
tau
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: Ellison Foundation
First posted: 2020-06-18
Enrollment: 300
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with preclinical, prodromal, or mild dementia due to Alzheimer's disease, based on amyloid biomarker evidence

Brief summary: This is a cross-sectional, observational study that characterizes research participants with Alzheimer's disease (AD) for their patterns of brain degeneration with the investigational tau positron emission tomography (PET) radiotracer \[18F\] MK-6240. The goal is to describe the topographic pattern of involvement of cerebral brain regions (topographic phenotyping) in early stage AD participants using tau PET in a sub-cohort of the University of Washington Alzheimer's Disease Research Center (ADRC) Clinical Cohort, and to make this phenotype information available to affiliated research studies at the University of Washington and to the general scientific community via the National Alzheimer's Coordinating Center.

Detailed description: Memory loss and dementia, including Alzheimer's disease (AD), are heterogeneous in terms of pattern of symptoms and brain atrophy, likely due to underlying variability in AD biological processes, as well as comorbidity (separate diseases that co-occur with AD). The correspondence between clinical findings and underlying cause is imperfect, though, and the field has benefitted tremendously from development of biomarkers that can be used for diagnosis, for estimation of the biological burden of pathology, and/or for tracking disease trajectories. For example, in the National Institute on Aging-Alzheimer's Association (NIA-AA) research framework, biomarkers of Amyloid beta, phosphorylated Tau, and Neurodegeneration (A/T/N) standardize the separation of cases with Alzheimer pathophysiology from those without it.

A sub-cohort of UW ADRC Clinical Core participants who have amyloid deposition (A+ by cerebrospinal fluid \[CSF\] or amyloid PET) and mild degrees of cognitive impairment will be investigated for their specific pattern of tau deposition with tau PET. Additionally, participants who are thought to be resilient to Alzheimer disease, e.g. 85 years or older and normal cognition, or A+ by CSF or amyloid PET and normal cognition, will also be investigated for their specific pattern of tau deposition with tau PET.

The ADRC Imaging and Biomarker Core will conduct and analyze these scans, and store the data in the Integrated Brain Imaging Center at the University of Washington Medical Center campus, which is directed by the PI, Dr. Grabowski. It will also use other data collected by ADRC Cores (such as neuropsychology testing) to perform other analysis, such as estimating resilience measures (i.e. the ability of the brain to function well in spite of the presence of AD).

This sub-cohort will aid in the investigation of Alzheimer's disease and related dementias (ADRD) by providing a means to better understand the relationships between the spatial patterns of tau deposition, neurodegeneration in the brain, cognitive symptoms, and resilience. It will provide a ready source of potential participants to the larger research community. By standardizing and supporting the collection imaging and CSF for research participants with Alzheimer's disease and related dementias under the ADRC, we promote research synergism and productivity across UW studies of AD and related disorders.

Eligibility criteria: Inclusion Criteria:

1. Amnestic MCI or Amnestic multimodal MCI or dementia primarily attributed to AD, by consensus diagnosis in the ADRC Clinical Core;
2. Evidence of A+ T+ Alzheimer disease by CSF evaluation (e.g. low amyloid beta(AB)42 or 42/40 ratio and elevated p-181-tau); or evidence of A+ Alzheimer disease by amyloid PET.
3. Age of presentation for first evaluation \> 55 years;
4. Sporadic onset, defined by not from a known autosomal dominant AD family and not more than 1 first degree relative with dementia onset before age 65;
5. Clinical Dementia Rating scale (CDR) score 0.5 or 1.0;
6. English competency sufficient to complete cognitive testing battery to the satisfaction of ADRC neuropsychologist;
7. MRI scan in the Clinical Core, with additional selection for topographic diversity, based on the MRI imaging.

Exclusion Criteria:

1. History of symptomatic cerebrovascular disease (CVD) or CVD evaluated to contribute significantly to cognitive impairments;
2. Parkinsonism, or meeting revised McKeith criteria for possible or probable Dementia with Lewy bodies;
3. Contraindication to MRI scanning (e.g. metal implants, severe claustrophobia);
4. Premorbid history of neurologic disease that may contribute to cognitive impairment (e.g. multiple sclerosis, epilepsy, brain tumor);
5. History of developmental dyslexia or other developmental disorder affecting validity of cognitive tests. These exclusion criteria minimize comorbidity;
6. Pregnancy or breast-feeding.

Primary outcomes:
measure: tau PET SUVR image
timeFrame: Day 1
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Washington
name: Thomas J Grabowski, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lohith TG, Bennacef I, Vandenberghe R, Vandenbulcke M, Salinas CA, Declercq R, Reynders T, Telan-Choing NF, Riffel K, Celen S, Serdons K, Bormans G, Tsai K, Walji A, Hostetler ED, Evelhoch JL, Van Laere K, Forman M, Stoch A, Sur C, Struyk A. Brain Imaging of Alzheimer Dementia Patients and Elderly Controls with 18F-MK-6240, a PET Tracer Targeting Neurofibrillary Tangles. J Nucl Med. 2019 Jan;60(1):107-114. doi: 10.2967/jnumed.118.208215. Epub 2018 Jun 7.
citation: Pascoal TA, Shin M, Kang MS, Chamoun M, Chartrand D, Mathotaarachchi S, Bennacef I, Therriault J, Ng KP, Hopewell R, Bouhachi R, Hsiao HH, Benedet AL, Soucy JP, Massarweh G, Gauthier S, Rosa-Neto P. In vivo quantification of neurofibrillary tangles with [18F]MK-6240. Alzheimers Res Ther. 2018 Jul 31;10(1):74. doi: 10.1186/s13195-018-0402-y.
citation: Koole M, Lohith TG, Valentine JL, Bennacef I, Declercq R, Reynders T, Riffel K, Celen S, Serdons K, Bormans G, Ferry-Martin S, Laroque P, Walji A, Hostetler ED, Briscoe RJ, de Hoon J, Sur C, Van Laere K, Struyk A. Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. Mol Imaging Biol. 2020 Feb;22(1):173-180. doi: 10.1007/s11307-019-01367-w.