Study finds connection between age-related cognitive decline and dopamine levels

June 8, 2015 by Christopher Packham, Medical Xpress report
Ball-and-stick model of the dopamine molecule, a neurotransmitter that affects the brain's reward and pleasure centers. Credit: Jynto/Wikipedia

(Medical Xpress)—Scientists broadly regard cognitive decline as a natural condition of aging. However, research has not yet established the mechanisms for age-related differences in brain function between younger and older people. Among the changes that occur with normal aging is the decline of the dopamine system. A group of researchers recently explored the connection between the dopamine system and cognitive function in older and younger adults, and they have published their results in the Proceedings of the National Academy of Sciences.

Previous studies demonstrated that neurons in mice with healthy systems exhibit classic bursting activity and that mice induced with dopamine deficiency display a complete lack of neuron bursting activity. In the dopamine-deficient mice, the researchers successfully increased bursting activity by administering a dopamine agonist, and these findings directly influenced the current human study.

The brain dynamics of high-functioning young adults are characterized by greater brain signal variability than that of . The brains of healthy young people typically express more signal variability across trials and time relative to older subjects. As a marker of this function of variability, the researchers examined the effects of amphetamine on blood oxygen level-dependent (BOLD) signal variability, which is easily monitored in brain regions via fMRI.

A group of 40 younger participants and 22 older participants underwent fMRI scanning on two occasions, one week apart: During one session, a physician administered a placebo; for the other session, participants were administered low-dose amphetamine. During the fMRI, participants performed a letter n-back task (blocked design) chosen for its cognitive load on working memory.

Additionally, the researchers investigated the effect of session order on cognitive effect of low-dose amphetamine. Some participants received placebo during the first session and amphetamine during the second; other participants received amphetamine first followed by placebo the second week.

The results of the experiment are in line with the hypothesis that age differences in brain signal variability reflect age-induced changes in the neuromodulation of dopamine. The researchers found that the majority of the older adults in the study showed increased BOLD variability on amphetamine, particularly those subjects with the lowest levels of BOLD variability during the placebo stage. The experiment also showed improved reaction mean times on amphetamine. It's notable that amphetamine effectively increased BOLD variability in older adults in specific brain regions observed in previous studies to show reduced signal variability during aging. These include the dorsolateral prefrontal cortex, posterior parietal, and primary visual cortices.

Under placebo, young adults expressed more signal variability in all task conditions than the older adults. But the researchers noted that under amphetamine, signal variability in older adults increased dramatically, whereas the effect on was far more modest. Additionally, the effect of increased signal variability appeared to increase with increasing task difficulty.

Older adults who received amphetamine during the first session tended to show the greatest improvements in speed and test performance. Conversely, those who received amphetamine during the second session, and therefore had already practiced the working memory test on placebo, showed either performance improvements in the presence of modest BOLD signal variability, or no effect at all. The authors note, "The subsequent administration of a DA agonist (AMPH) when participants are in a more practiced state (as in the placebo-AMPH group) may then have productive or counterproductive effects... Conversely, those who receive AMPH with limited task practice arguably reflect a purer example of the influence of AMPH alone." Thus, the researchers hope that future studies of aging and brain dynamics will continue to account for drug administration order as an important influence on results.

The researchers conclude that the resulting data provide strong evidence for -related changes in BOLD signal variability related to aging and working memory. The were able to match or even surpass the younger adult levels of BOLD variability in response to dopamine agonism. In turn, this reinforces the theorized connection between the manipulation of dopamine levels, brain dynamics and age.

Explore further: Signal variability and cognitive performance in the aging human brain

More information: "Amphetamine modulates brain signal variability and working memory in younger and older adults." PNAS 2015 ; published ahead of print June 1, 2015, DOI: 10.1073/pnas.1504090112

Abstract
Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI–based blood oxygen level-dependent (BOLD) signal variability (SDBOLD) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SDBOLD levels in the presence of AMPH. Drug session order greatly moderated change–change relations between AMPH-driven SDBOLD and reaction time means (RTmean) and SDs (RTSD). Older adults who received AMPH in the first session tended to improve in RTmean and RTSD when SDBOLD was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SDBOLD decreased (for RTmean) or no effect at all (for RTSD). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.

Related Stories

Signal variability and cognitive performance in the aging human brain

April 9, 2015
As we age, the physical make up of our brains changes. This includes changes in neural processing in grey matter, but also in the deterioration of structural connections in the brain, which allow communication between distinct ...

Study finds which brain skills are more likely to last over a lifetime

January 9, 2015
Research from the Center for Vital Longevity (CVL) at The University of Texas at Dallas has shed new light on which cognitive processes tend to be preserved with age and which ones decline.

Researchers discover how cocaine, amphetamines disrupt the brain's normal functioning

May 11, 2015
In a major advance in the field of neuropsychiatry, researchers in the Vollum Institute at Oregon Health & Science University have illuminated how cocaine and amphetamines disrupt the normal functioning of the dopamine transporter ...

Young vs. old: Who performs more consistently?

August 6, 2013
Sometimes it's just not your day: First you can't remember where you put your car keys, then you forget about an important meeting at work. On days like that, our memory seems to let us down. But are there actually "good" ...

Study finds cardiorespiratory fitness contributes to successful brain aging

April 27, 2015
Cardiorespiratory fitness may positively impact the structure of white matter in the brains of older adults. These results suggest that exercise could be prescribed to lessen age-related declines in brain structure.

Dopamine leaves its mark in brain scans

November 21, 2014
Researchers use functional magnetic resonance imaging (fMRI) to identify which areas of the brain are active during specific tasks. The method reveals areas of the brain, in which energy use and hence oxygen content of the ...

Recommended for you

New technique helps uncover changes in ALS neurons

June 22, 2018
Northwestern Medicine scientists have discovered that some neurons affected by amyotrophic lateral sclerosis (ALS) display hypo-excitability, using a new method to measure electrical activity in cells, according to a study ...

Broken shuttle may interfere with learning in major brain disorders

June 22, 2018
Unable to carry signals based on sights and sounds to the genes that record memories, a broken shuttle protein may hinder learning in patients with intellectual disability, schizophrenia, and autism.

Watching stem cells repair spinal cord in real time

June 22, 2018
Monash University researchers have restored movement and regenerated nerves using stem cells in zebra fish where the spinal cord is severely damaged.

Scientists discover fundamental rule of brain plasticity

June 21, 2018
Our brains are famously flexible, or "plastic," because neurons can do new things by forging new or stronger connections with other neurons. But if some connections strengthen, neuroscientists have reasoned, neurons must ...

Waking up is hard to do: Prefrontal cortex implicated in consciousness

June 21, 2018
Philosophers have pondered the nature of consciousness for thousands of years. In the 21st century, the debate over how the brain gives rise to our everyday experience continues to puzzle scientists. To help, researchers ...

Researchers find mechanism behind choosing alcohol over healthy rewards

June 21, 2018
A new study links molecular changes in the brain to behaviours that are central in addiction, such as choosing a drug over alternative rewards. The researchers have developed a method in which rats learn to get an alcohol ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

gettingwell
not rated yet Jun 22, 2015
Interesting study! However, as is usually done, the researchers focused on effects and not causes. I didn't see questionnaires or investigation into possible historical causative factors for reduced dopamine levels, leaving the researchers with age as the only correlated-but-not-causative explanation.

http://surfaceyou...ealself/

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.