Enhancing Capacity of Neuroimaging and Biomarkers: Application in Early-stage Alzheimer's Disease with Comorbidities

Closed for proposals

Project Type

Coordinated Research Project

Project Code




Approved Date

12 May 2015



Start Date

15 December 2015

Expected End Date

30 June 2022

Completed Date

18 August 2022

Participating Countries

South Africa
United States of America


1. Dementia poses significant healthcare challenges in the Member States.2. Early detection of the disease is a diagnostic challenge.3. Comorbidities associated with Alzheimer's disease are major confounders for accurate diagnosis and management of the        patients.4. Such comorbidities are often more prevalent in developing countries.5. However, there is limited knowledge concerning effects of comorbidities on PET imaging biomarker expression and its      diagnostic accuracy.6. Limited experience and access to standardized quantitative image interpretation in developing counties, severely constrains      the value of imaging diagnosis.7. Accurate diagnosis of dementia is the first step towards decreasing burden of the disease in the world.8. Due to all these circumstances, there is a need to investigate the value of neuroimaging with modern techniques such a     PET/CT to properly diagnose patients which Mild Cognitive Impairment (MCI) and determine to what extend –if any– the     presence of comorbidities such as HIV, cerebrovascular disease (CVD), and traumatic brain injury (TBI), can impact on the     accurate diagnosis in comparison to patients without comorbidities. Currently, there is limited scientific evidence in this     subset of patients, and therefore gaining information could be of great benefit to many Member States. 


The aim of this CRP is to assess imaging biomarker expression of possible AD patients with and without common comorbidities seen in developing countries (CVD, HIV, TBI) using PET and MRI, and, in a subset of patients, CSF biomarkers. This investigation will elucidate a complex nature of imaging biomarker expression in possible AD patients, which, in turn, will provide unique knowledge of imaging features of AD in a real clinical setting and help clinicians better diagnose dementia using imaging technologies. Through this investigation, common quantitative image interpretation software will be implemented and used in the Core Laboratories, and will be distributed to participating sites and other imaging sites in the Member States to help their day-to-day image interpretation on site beyond this project. These efforts facilitate standardization of functional brain imaging interpretation, improve diagnostic efficacy of functional brain imaging across countries, and contribute to appropriate use of neuroimaging technology.

Specific objectives

To distribute quantitative mapping software used in the two prior specific aims to participating imaging sites in the Member States and provide educational tools to improve day-to-day scan interpretation.

To evaluate differences in imaging biomarker expression between early-stage AD with and without comorbidities.

To refine quantitative brain mapping software in the Core Laboratories to incorporate specific imaging biomarker indices that will be used for data analysis.


All 3 research objectives were achieved:
The study revealed the new finding that cerebrovascular comorbidity modified the pattern of brain metabolism in primary sensorimotor cortex, visual cortex, cerebellum and anterior cingulate.
The CRP contributed to enhancing the knowledge and expertise in neuroimaging, as well as improving collaboration with related disciplines such as neurology and psychiatry.
The utilization of FDG PET in conjunction with advanced image analysis techniques was enhanced at the participating sites.
The meeting was successful, and the objectives were achieved.
Presentations from all research centers and core labs were done.
Discussion of difficulties faced, and way forward was conducted, and recommendations made.
Data was successfully completed and cleaned, and further analyses were initiated.
The group acknowledges the excellent collaboration of all participating centers, and the outstanding support from the IAEA.

The impact of this CRP was very significant. It refined the expression of imaging biomarkers of potential AD patients with and without common comorbidities, provided new and complementary insights on FDG brain metabolism of patients with cerebrovascular comorbidities, improved neuro-imaging software by introducing the data newly acquired by this CRP, increases the skills and knowledge of Nuclear Medicine Physicians in metabolic neuro-imaging and facilitated exchanges and communication with referring physicians such as neurologists and psychiatrists.


Considering the huge burden worldwide represented by Alzheimer Disease, the relevance of this CRP is important since it has revealed the new finding that cerebrovascular comorbidity significantly modified the pattern of brain metabolism of AD patients and highlighted the critical role played by functional and morphological imaging techniques in the early and precise diagnosis of this devastating neuro-degenerative pathological process.

CRP Publications


Professional peer review publication




Paper on Amyloid PET imaging



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