An increasing number of studies are exploring the possibilities of cognitive reserve in Alzheimer’s patients with higher education levels. Specific neural networks have been found in an area of the prefrontal cortex that light up in educated subjects and compensate for neural damage in the beginning stages of the disease, according to research published in the June issue of The Journal of Nuclear Medicine.
Silvia Morbelli, MD, from the department of nuclear medicine at IRCCS AOU San Martino–IST, University of Genoa in Genoa, Italy, and colleagues, traversed the brain using F-18 FDG PET as a means of mapping cognitive reserve in this project involving the European Alzheimer Disease Consortium.
An estimated 20 percent of those deemed cognitively normal who die in old age show all the pathology of Alzheimer’s disease in post-mortem studies. Brain researchers are increasingly attributing this to cognitive reserve.
“Two mechanisms have been described as being part of cognitive reserve, that is, neural reserve and neural compensation,” wrote Morbelli et al. “Neural reserve reflects preexisting brain networks that are more efficient or have greater capacity and may therefore be less susceptible to disruption, whereas neural compensation refers to the adoption of new, compensatory brain networks after disease has affected those networks typically used for particular tasks.”
In this study, researchers interpreted hypo and hyper-metabolism in the brains of both highly educated patients and those who were identified as less educated to find key neural networks that could account for the cognitive function maintained despite onset of disease. F-18 FDG PET scans focused on resting metabolic networks that might allow early-stage (prodromal) Alzheimer’s patients to sustain cognitive functioning in the presence of depressions in brain metabolism in line with Alzheimer’s-typical neurodegeneration.
Results showed higher-educated prodromal patients had “more severe” hypometabolism than those with less schooling, specifically in the left inferior and middle temporal gyri and the left middle occipital gyrus. However, compensation was seen in the right inferior, middle and superior frontal gyri and mainly in relation to the right dorsolateral prefrontal cortex (DLFC). This activity in the right DLFC was not matched in the less educated Alzheimer’s patients, nor healthy controls, which paints an ideal picture of cognitive reserve for highly educated Alzheimer’s patients.
“The present findings suggest that highly educated prodromal [Alzheimer’s] patients can cope better with the disease thanks to neural reserve but also to the recruitment of compensatory neural networks in which the right DLFC plays a key role,” noted the researchers.
A total of 186 patients with mild cognitive impairment showing signs of memory decline and 90 cognitively normal healthy controls were selected for the study. During the course of a two-year follow-up, mild cognitive impairment developed into Alzheimer’s dementia in 64 subjects with a mean age of 72. These subjects comprised the core prodromal Alzheimer’s group for this study.
The demarcation between high and low education was based on the mean of total years that subjects were in school. Higher-educated early-stage Alzheimer’s patients had a mean of about 15 years of education plus or minus two years, and lower-educated early stage Alzheimer’s patients had a mean of seven years of schooling plus or minus one year.
Investigators used data from F-18 FDG PET studies to determine the relationship between hypermetabolism in the DLFC and relevant activity in other regions, including extensive metabolic associations with both sides of the frontotemporal cortex, precuneus and parahippocampal gyrus.
“This finding suggests that metabolic activity within the right DLFC—which is likely to be relatively spared by the disconnection process—can be increased through synaptic trafficking only in [highly educated] prodromal AD patients,” the authors wrote.
The data from this study reveal a functional representation of cognitive reserve in higher educated prodromal AD patients as a result of both neural reserve and neural compensation.