Multi-modal imaging correlates of astroglial activation, ß-amyloid deposition and neuronal activity as markers of cognitive impairment in AD


Study ID: 20371
Short Title: Astroglial activation, ß-amyloid deposition and neuronal activity
Organisation: Solent NHS Trust
Location: Solent NHS Trust
Condition: Alzheimer's Disease
Main Specialty: Dementias
Expected End Date: 15/02/2018
Postcode: PO3 6AD
Contact Name: Solent Research
Contact Email: research@solent.nhs.uk
Active: Yes

Inclusion Criteria

Inclusion criteria for AD subjects


1. Subjects who meet the National Institute on Aging¬Alzheimer’s Association (NIA¬AA) core clinical criteria for probable Alzheimer's disease dementia


2. Clinical Dementia Rating (CDR) score of 0.5 or 1.0 and memory box score of 0.5 or greater


3. Age 50 or above


4. Mini Mental State Examination (MMSE) score ≥21


5. Females must not be pregnant or lactating, and specified contraceptive precautions must be followed


6. Subjects on symtpomatic (cholinesterase inhibitor or memantine) therapy for AD must be on a stable dose for at least 6 weeks prior to baseline


7. Subjects must have partners/caregivers able to monitor for, and report, any adverse events to the study team throughout the course of study


8. Subjects must be able to provide and confirm informed consent


Inclusion criteria for healthy controls


1. Cognitively normal without significant chronic disease diagnoses affecting cerebral, cardiovascular, respiratory, renal or hepatic functions


2. Within normal limits (i.e. > ¬1.5 SD below normal) according to age¬ and education¬adjusted norms on all domains of the RBANS

Exclusion Criteria

Exclusion criteria for all subjects


1. Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the patient’s AD


2. History of stroke within 12 months of screening


3. Poorly controlled seizure disorder


4. History of diabetes or abnormal (6.2 mmol/l or greater) fasting plasma glucose on two separate measures


5. Any psychiatric diagnosis or symptoms, (e.g. hallucinations, major depression or delusions) that could interfere with study procedures in the subject


6. Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants, e.g. in skull, and cardiac devices other than those approved as safe for use in MR scanners


7. Contraindications to PET scanning, including exposure to significant ionising radiation within 12 months of screening as a part of other research protocols or known hypersensitivity to any of the ligands used


8. Severe visual or hearing impairment or language barriers that would prevent the subject from performing neuropsychometric tests accurately


9. Inability to lie on the scanner for sufficient length of the scan

Study summary:

With PET (a special type of imaging) we have previously shown that Alzheimer’s disease (AD) subjects have significantly increased accumulation of an abnormal protein called amyloid in the brain. In this research, we propose a proof­of­concept study to characterise the brain uptake of a novel astroglial (brain cell) activation imaging marker called [11C]BU99008 in a population of patients with mild to moderate AD. We will define the relationships between brain uptake of this marker, amyloid deposition (measured with a different marker called [18F]florbetaben) and brain glucose metabolism (measured by uptake of another PET tracer, [18F]FDG). The potential clinical significance of astroglialactivation measured in this way will be explored by testing for relationships with measures of brain and memory performance, measures of activities of daily living and measures of brain activity.

Primary objective To test whether the uptake of [11C]BU99008 is increased in the brains of people with mild to moderate AD relative to age­matched healthy volunteers

Secondary objectives 1. To assess the relationship between [11C]BU99008 uptake and reduction in glucose metabolism in the brain 2. To assess whether [11C]BU99008 binding in the brain corresponds to amyloid accumulation.


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