COBRA: A prospective multimodal imaging study of dopamine, brain structure and function, and cognition

Abstract

Cognitive decline is a characteristic feature of normal human aging. Previous work has demonstrated marked interindividual variability in onset and rate of decline. Such variability has been linked to factors such as maintenance of functional and structural brain integrity, genetics, and lifestyle. Still, few, if any, studies have combined a longitudinal design with repeated multimodal imaging and a comprehensive assessment of cognition as well as genetic and lifestyle factors. The present paper introduces the Cognition, Brain, and Aging (COBRA) study, in which cognitive performance and brain structure and function are measured in a cohort of 181 older adults aged 64 to 68 years at baseline. Participants will be followed longitudinally over a 10-year period, resulting in a total of three equally spaced measurement occasions. The measurement protocol at each occasion comprises a comprehensive set of behavioral and imaging measures. Cognitive performance is evaluated via computerized testing of working memory, episodic memory, perceptual speed, motor speed, implicit sequence learning, and vocabulary. Brain imaging is performed using positron emission tomography with [(11)C]-raclopride to assess dopamine D2/D3 receptor availability. Structural magnetic resonance imaging (MRI) is used for assessment of white and gray-matter integrity and cerebrovascular perfusion, and functional MRI maps brain activation during rest and active task conditions. Lifestyle descriptives are collected, and blood samples are obtained and stored for future evaluation. Here, we present selected results from the baseline assessment along with a discussion of sample characteristics and methodological considerations that determined the design of the study. This article is part of a Special Issue entitled SI: Memory & Aging.

Better together: Left and right hemisphere engagement to reduce age-related memory loss

“…These findings drew attention to brain maintenance hypothesis [15]. According with the maintenance notion the brain of the old individuals whose cerebral anatomy is relatively preserved is more likely to exhibit functional brain activation patterns that appears similar to those of young subjects [92][93][94][95][96][97]. Moreover, less structural brain change is associated with better memory performance in old age.…”

Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

“…We have previously reported the COBRA design, recruitment procedure, imaging protocols, and details of the cognitive and lifestyle battery (28). Here we restrict the presentation to methodological details directly relevant to the present results.…”

“…Each cognitive ability (i.e., episodic memory, working memory, and perceptual speed) was evaluated with three separate tasks (verbal, numerical, and figural). Episodic memory was tested with word recall, number-word recall, and object-position recall; working memory was tested with letter-string updating, numerical 3-back, and spatial updating; and speed was tested with letter comparison, number comparison, and figure comparison (28). For each task, summary scores were computed across the total number of blocks or trials.…”

“…Here we present results from the Cognition, Brain, and Aging (COBRA) study that include assessment of episodic memory, working memory, and processing speed, in combination with [ 11 C]raclopride PET and MRI of 181 healthy adults between 64 and 68 y of age (28). The main analyses concerned caudate D2DR-cognition associations, as this striatal region has been implicated in cognitive functioning (11,12,29,30).…”

Dopamine Transporter And Transmission Of Psychopathological Risk. A Review Of Gene-Environment Interplay

“…Dopamine is an important monoamine, released predominantly from the ventral tegmental area (VTA) of the brain, that acts as a neuromodulator and is involved in a variety of cognitive, affective, and motivational processes, including reward (Schultz, Carelli, & Wightman, 2015), aggression (Schlüter et al, 2013), and cognitions (Nevalainen et al, 2015). Genetic studies have also evidenced that the release of dopamine is associated with behavioural exploration, increasing the motivation to explore and facilitating cognitive-behavioural processes functional in exploration (DeYoung, 2013), which are central processes in the middle-childhood.…”