PET Detects Increased Cognitive Reserve Levels in Very Educated Pre-Alzheimer’s Patients

Highly educated individuals with mild cognitive impairment that later progressed to Alzheimer’s disease (AD) better deal with the disease than individuals with a lower level of education in the same setting, according to new research conducted by investigators from a number of leading European institutions.

In the study, neural reserve and neural compensation were both shown to play a role in determining cognitive reserve, as seen by positron emission tomography (PET) imaging. The study’s findings were published in the June 2013 issue of the Journal of Nuclear Medicine. Cognitive reserve refers to the hypothesized capacity of an adult brain to cope with brain damage in order to maintain a relatively preserved functional level.

Determining the brain adaptation processes underlying this process remains a critical question, and researchers of this study sought to examine the metabolic basis of cognitive reserve in individuals with higher (more than 12 years) and lower (less than 12 years) levels of education who had mild cognitive impairment that progressed to AD, also known as prodromal AD.

“This study provides new insight into the functional mechanisms that mediate the cognitive reserve phenomenon in the early stages of Alzheimer’s disease,” said Silvia Morbelli, MD, the from the department of nuclear medicine at IRCCS AOU San Martino-IST, University of Genoa (Italy; www.unige.it), and lead author of the study. “A crucial role of the dorsolateral prefrontal cortex was highlighted by demonstrating that this region is involved in a wide frontotemporal and limbic functional network in patients with Alzheimer’s disease and high education, but not in poorly educated Alzheimer’s disease patients.”

In the study, 64 patients with prodromal AD and 90 control subjects, which were taken from the brain PET project chaired by Flavio Nobili, MD, in Genoa (Italy), of the European Alzheimer Disease Consortium, underwent brain 18F-flurodeoxygluxoce (FDG) PET scans. Individuals were split into a subgroup with a low level of education (42 control subjects and 36 prodromal AD patients) and a highly educated subgroup (40 controls and 28 prodromal AD patients). Brain metabolism was compared between education-matched groups of patients and controls, and then, between highly and poorly educated prodromal Alzheimer’s disease patients.

Higher metabolic activity was shown in the dorsolateral prefrontal cortex for prodromal AD patients. More extended and significant correlations of metabolism within the right dorsolateral prefrontal cortex and other brain regions were found with highly educated than less educated prodromal AD patients or even highly educated controls.

This evidence suggests that neural reserve and neural compensation are turned on in highly educated prodromal AD patients. Researchers concluded that assessment of the implication of metabolic connectivity in cognitive reserve additionally validate that adding a comprehensive evaluation of resting 18F-FDG PET brain distribution to standard inspection may allow a more complete comprehension of AD pathophysiology and possibly may increase 18F-FDG PET diagnostic sensitivity.

“This work supports the notion that employing the brain in complex tasks and developing our own education may help in forming stronger ‘defenses’ against cognitive deterioration once Alzheimer knocks at our door,” noted Dr. Morbelli. “It’s possible that, in the future, a combined approach evaluating resting metabolic connectivity and cognitive performance can be used on an individual basis to better predict cognitive decline or response to disease-modifying therapy.”

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