Title : Cognitive impairment resting-state fMRI markers in elderly
Background: Neurodegenerative diseases, associated to aging, cause profound changes in brain's structure and function. Alzheimer Disease (AD) as one of the most common type of dementia, is accompanied by a generalized loss of neurons and connections in the brain. Resting state fMRI functional connectivity (FC rs-fMRI) analysis is broadly used to detect brain network differences in neurodegenerative diseases such as AD. Here, we analysis data from three groups of elderlies: a cognitively normal group, other with amnesic mild cognitive impairment and another diagnosed with AD; to identify FC rs-fMRI patterns characteristic of cognitive impairment and dementia.
Methods: Forty-five subjects were included: 14 patients with dementia, 17 patients with MCI and 14 controls. All patients received an extensive neuropsychological battery and brain MRI scanning. The study was approved by the Ethical Committee of the Cuban Center for Neuroscience. Written informed consent was provided by all subjects or their caregiver. Imaging was performed on a 3.0 Tesla Siemens Allegra scanner (Siemens AG, Erlangen, Germany) using a standard head coil. Resting state functional scans consisted of 240 T2*-weighted echo planar imaging (EPI) volumes (repetition time 3000 ms; echo time 60 ms; ip angle 90°; 32 axial slices; matrix 64 x 64; voxel size 3.3 x 3.4 x 4 mm). Additionally, a high-resolution T1-weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) image (repetition time 2700 ms; echo time 3.97 ms; inversion time 950 ms; flip angle 8°; 256 axial slices; matrix 256 x 192; voxel size 1 mm isotropic) was acquired. Data analyses were performed using the Functional Connectivity Toolbox (CONN) for Matlab (https://www.nitrc.org/frs/) to identify large-scale patterns of temporal signal-intensity coherence, interpreted as functional connectivity, in the sample of subjects (Beckmann et al., 2005). Preprocessing consisted of motion correction and spatial smoothing using an 8 mm full-width-at-half-maximum Gaussian kernel. fMRI volumes were registered to the subject's high-resolution T1weighted scan. Subsequently, a roi to roi analysis was performed for each subjects and between subjects group (dementia patients; MCI patients and controls), using the resting state networks atlas provided by the CONN. Spatial maps of the group independent component analysis (ICA) were used in a linear model t against each individual fMRI data set. After this dual regression, spatial maps of all subjects were collected into single 4-dimensional files for each original independent component.
Results: Within the Default Mode Network (DMN), two regions of lower FC were found in dementia compared with controls within the precuneus and the PCC (p<0.001 uncorrected). No regions of FC changes were found within the DMN when comparing MCI patients with controls or dementia patients.
Conclusions: In a nutshell, these results show clinically meaningful changes in FC rsfMRI in dementia patients, specifically related to regions of the DMN. More studies in larger samples are necessary to further determine FC differences between dementia patients, MCI patients and normal elderly.
Cuban demographic situation, regarding dementia, behaves similar to that of developed countries, being the Cuban population the oldest of Latin America. The prevalence of dementia syndrome (DS) in Cuban elderly population is high (6.4 - 10.2 per 1,000); that is, 1.1% of the total population, figure that will reach 260,000 people by 2030 (Llibre et al, 2014). Dementia is the leading cause of disability in elderly and the largest contributor to dependency, need for care, economic overload and psychological stress in the caregiver. The prodromal stage of AD, also referred as mild cognitive impairment (MCI) due to AD is the stage in which obvious symptoms of brain dysfunction, occurs. Furthermore, it is necessary that a clinician evaluate the AD primary underlying pathophysiology in individuals meeting the criteria for MCI.
A few decades ago, with advances in neuroscience and the introduction of neuroimaging studies, various groups of researchers have performed researches based on supported theories that cognitive-behavioral alterations appear early in the disease Alzheimer's.
The present investigation has been conducted by researchers from the Cuban Center of Neuroscience. The preliminary results declared are from a study that correlates neuropsychological-behavioral variables with functional magnetic resonance imaging fMRI studies in patient’s whit mild cognitive impairment (MCI) and Mild Alzheimer's Disease.
In this sense, we intend that our preliminary results would be of interest to the audience with whom we wish to collaborate and expand scientific interactions.
The methodology used in our research meets the requirements of a high scientific level study and provides a widely standardized design in the processing of neuroimaging data. Likewise, neuropsychological evaluation protocols are widely employed in big data studies, which adds value to the proposed methodology.
Other benefits would be:
- To attend this High-level scientific meeting will permit me to address the implications of our ageing population for society, policy, and the health and social care systems,
- It will allow discussions on scientific and technical challenges of the next decade and bring together leading experts from wider scientific community.
- It will promote collaborative paradigms to study cognitive aging.
- It will discuss knowledge on the field of biomedical research.