Decline in cerebral glucose utilisation and cognitive function with aging in Down's syndrome

Area of Science:

• Neuroscience
• Medical Imaging
• Genetics

Background:

• Down's syndrome (Trisomy 21) is associated with an increased risk of cognitive decline and dementia.
• Cerebral metabolic rate for glucose (CMRglc) is a key indicator of brain function.
• Age-related changes in brain metabolism are not well understood in Down's syndrome.

Purpose of the Study:

• To investigate age-related differences in cerebral glucose metabolism in individuals with Down's syndrome.
• To compare brain metabolism and cognitive function between young and older adults with Down's syndrome.
• To assess if healthy individuals experience similar age-related metabolic changes.

Main Methods:

• Positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose was used to measure CMRglc.
• Study included young (19-33 years) and older (>35 years) subjects with Down's syndrome (Trisomy 21).
• Control groups of young (20-35 years) and older (45-64 years) healthy men were included for comparison.

Main Results:

• Older Down's syndrome subjects showed a 23% decrease in mean hemispheric CMRglc compared to younger subjects.
• Significant reductions in regional CMRglc (rCMRglc) were observed across all lobar regions in older Down's syndrome individuals.
• No significant age-related differences in CMRglc or rCMRglc were found in healthy control groups.
• Older Down's syndrome subjects exhibited significant reductions in language, visuospatial ability, attention, and memory.

Conclusions:

• Significant age-related declines in cerebral glucose metabolism occur in Down's syndrome, but not in healthy controls.
• These metabolic changes in Down's syndrome are associated with widespread cognitive impairments, irrespective of dementia diagnosis.
• The findings highlight distinct neurobiological aging processes in Down's syndrome.