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

  • STATUS
    Recruiting
  • End date
    Jun 30, 2022
  • participants needed
    125
  • sponsor
    Neil M Rofsky, MD, MHA
Updated on 3 February 2021
oophorectomy
positron emission tomography
alzheimer's disease
cognitive decline
amyloid
amyloidosis
flortaucipir
mental deterioration

Summary

The investigators will conduct tau positron emission tomography (PET) scans on 125 adults using the radiopharmaceutical Flortaucipir F18 ([18F]AV-1451). This will allow the investigators 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. Autopsy studies, as well as magnetic resonance imaging (MRI) studies 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. Magnetic resonance image studies of AD consistently reveal volumetric loss in the hippocampus using both cross-sectional and longitudinal approaches. The primary symptom of early-stage AD is memory impairment possibly accompanied by deficits in attentional control. Normal aging, however, is also marked by cognitive decline, as well as structural brain changes. 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.

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. 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. Understanding the impact of tau deposits and its interactions with amyloid deposition allows the investigators 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. 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.

Details
Condition Dementia, Alzheimer's Disease, Cognitive Impairment, Cognitive Dysfunction, Cognitive Decline, Cognitive Impairments, Mental Deterioration, neurocognitive disturbance, alzheimer, dementia alzheimer's type
Treatment positron emission tomography, [18F]AV-1451
Clinical Study IdentifierNCT04080544
SponsorNeil M Rofsky, MD, MHA
Last Modified on3 February 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 38 yrs and 96 yrs?
Gender: Male or Female
Do you have any of these conditions: Dementia or Alzheimer's Disease or Cognitive Decline?
Do you have any of these conditions: Mental Deterioration or Cognitive Impairment or Alzheimer's Disease or Dementia or alzheimer or Cognitive Dysfunction or dementia alzheimer's type or ...?
Do you have any of these conditions: Alzheimer's Disease or alzheimer or Dementia or Cognitive Impairments or dementia alzheimer's type or Cognitive Dysfunction or Mental Deterioration or...?
Participated in Wave 2 of the DLBS and Amyloid PET studies
Subjects must indicate that they are not currently pregnant if they are women of child-bearing potential. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: 1) Has not undergone a hysterectomy or bilateral oophorectomy; or 2) Has not been naturally post-menopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
Volumetric Brain MRI Image (T-1 Weighted MPRage) collected as part of DLBS Wave 3 protocol
Completed at least 9 years of formal education, or the equivalent of freshman year of high school
Fluent English speakers
Tolerate laying 20 minutes on a flat table for the PET scan
Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria

Mini-Mental State Examination (MMSE) score lower than 22; all DLBS participants at the time of initial Wave 1 enrollment between 2008 - 2014 had an MMSE score of 26 or above, indicating normal cognitive function. However, in the time interval between Wave 1 and Wave 3, it is possible that mental capacity may have deteriorated. The investigators will exclude all participants in Wave 3 testing who have an MMSE lower than 22
Taking some types of sedatives, benzodiazepines, or anti-psychotics
Currently undergoing chemotherapy or radiation for cancer
New history of substance abuse
Has a history of drug or alcohol dependence within the last year, or prior prolonged history of dependence
Recreational drug use in past six months
Central nervous systems disease or brain injury that would preclude participation in the study
Psychiatric or neurological disorder that would preclude participation in this study
Has clinically significant hepatic, renal, pulmonary, metabolic or endocrine disturbances which pose safety risk
Has a current clinically significant cardiovascular disease that poses a safety risk
Has a current clinically significant infectious disease or a medical comorbidity which poses a safety risk
Has either: 1) Screening electrocardiogram (ECG) with corrected QT Interval (QTc) > 450 millisecond (msec) if male, or QTc > 470 msec if female; or 2) A history of additional risk factors for Torsades de Pointes (TdP) (e.g., hypokalemia, family history of Long QT syndrome) or are taking drugs that are known to cause QT prolongation (a list of prohibited and discouraged medications is provided by the Sponsor); Patients with a prolonged QTc interval in the setting of intraventricular conduction block (examples right bundle branch block or left bundle branch block), may be enrolled with sponsor approval
Has received or will receive investigational medication within the 30 days of PET/CT scan
Has received or will receive a radiopharmaceutical for imaging or therapy within 24 hours of PET/CT scan
Is a participant who, in the opinion of the investigator(s), is otherwise unsuitable for a study of this type
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