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Cognitive Decline and Alzheimer's Disease in the Dallas Lifespan Brain Study

2019-09-12 02:34:41 | BioPortfolio

Summary

We will conduct tau positron emission tomography (PET) scans on 125 adults using the radiopharmaceutical flortaucipir F18 ([18F]AV-1451). This will allow us to determine tau deposition across adults of different ages and assess the relationship of current tau burden to cognitive function and amyloid deposition collected over the previous 10-year interval.

Description

Alzheimer's disease (AD) is a highly prevalent disorder of dementia in older adults. AD neuropathology is marked by the presence of amyloid plaques and tau neurofibrillary tangles (Khachaturian, 1985). Autopsy studies (Trojanowski et al., 1997), as well as magnetic resonance imaging (MRI) studies (Jack et al., 1997; Convit et al., 1993; Killiany et al., 1993) in living persons, have established that the neurodegenerative changes in AD begin in medial temporal lobe structures and later progress to adjacent temporal, parietal and frontal neocortical regions (Braak & Braak, 1991; Price et al., 2001). Magnetic resonance image studies of AD consistently reveal volumetric loss in the hippocampus using both cross-sectional and longitudinal approaches (Jack et al., 1997; Convit et al., 1993; Killiany et al., 1993). The primary symptom of early-stage AD is memory impairment (Mohs et al., 1998; Storandt et al., 2002) possibly accompanied by deficits in attentional control (Balota & Faust, 2001). Normal aging, however, is also marked by cognitive decline (Park & Reuter-Lorenz, 2009; Reuter-Lorenz & Park, 2014), as well as structural brain changes (Raz & Rodrigue, 2006). Autopsy data had shown in the past that about 30% of older adults with no obvious cognitive impairment show some degree of the neuropathology typically associated with dementia at autopsy (Bennett et al., 2006; Kemper, 1994).

Importantly, the recent ability to image beta-amyloid and tau deposits in vivo using positron emission tomography (PET) scanning has revolutionized our understanding of early stages of AD. Evidence suggests that amyloid deposits may be detected 10 - 15 years before memory symptoms appear. These findings are leading to the ability to diagnose AD years before symptoms begin (see Jack et al., 2013 for a review). Much less is known about the impact and developmental course of tau deposition as compared to beta-amyloid because the ligand to image tau was only recently invented. There is increasing evidence that tau is particularly toxic to the brain and is a later precursor of AD than amyloid deposits. Additional research on beta-amyloid and tau deposition in aging is crucial, as much work suggests that treatment of AD may be most effective when implemented early in the time course of the disease (Sperling et al., 2011). Understanding the impact of tau deposits and its interactions with amyloid deposition allows us to see the development of early markers of AD, which are important in understanding the trajectory of the disease. An important approach to understand the amyloid/tau puzzle and its relationship to AD is a large-scale longitudinal study of normal aging that integrates extensive neuroimaging and cognitive assessments along with tau imaging. A key aspect in understanding pathological aging is the need to be able to clearly differentiate normal aging from early pathology. The present Tau imaging study described here is an important component of the Dallas Lifetime Brain Study (DLBS).

The Dallas Lifespan Brain Study (DLBS) began in 2008 and was designed to utilize the new in vivo imaging techniques to address uncertainty regarding how AD pathology relates to the developmental process of aging and cognition, fueled in part by the partial overlap of pathological markers and decline in mnemonic function observed in a substantial proportion of 'normal' aged individuals (Mohs et al., 1998; Whalley, 2002). A total of 296 participants were recruited for Wave 1 from 2008 to 2014 to the DLBS and they received cognitive testing, structural and functional MRI, as well as a scan for beta amyloid using the radioligand AV-45 (florbetapir F 18, also known as "[18F]AV-45"). A total of 183 returning participants were tested four years later in Wave 2, and they received the same battery as in Wave 1. In addition, 60 of these were also scanned with Flortaucipir F 18 (also known as "[18F]AV-1451"). [18F]AV-1451 is a newly-developed Phase II ligand that measures tau deposit in the human brain and this drug was provided to the DLBS by Avid Radiopharmaceuticals.

The objective of the current study is to test 125 DLBS participants with [18F]AV-1451 (Flortaucipir F 18) at the University of Texas Southwestern Medical Center (UTSW). The inclusion of tau imaging in Wave 3 will allow the investigators to relate tau deposition in the brain to the 10-year history of amyloid deposition and cognitive decline in the DLBS participants and understand the independent and joint contributions of tau to cognitive decline and early AD at different ages.

Study Design

Conditions

Alzheimer Disease

Intervention

[18F]AV-1451, Positron Emission Tomography

Status

Not yet recruiting

Source

University of Texas Southwestern Medical Center

Results (where available)

View Results

Links

Published on BioPortfolio: 2019-09-12T02:34:41-0400

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Medical and Biotech [MESH] Definitions

An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower.

An imaging technique that combines a POSITRON-EMISSION TOMOGRAPHY (PET) scanner and a CT X RAY scanner. This establishes a precise anatomic localization in the same session.

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An imaging technique using a device which combines TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON and TOMOGRAPHY, X-RAY COMPUTED in the same session.

The creation of a visual display of the inside of the entire body of a human or animal for the purposes of diagnostic evaluation. This is most commonly achieved by using MAGNETIC RESONANCE IMAGING; or POSITRON EMISSION TOMOGRAPHY.

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