Deborah Brauser

March 31, 2017

VIENNA, Austria — Education, as a proxy for cognitive reserve, appears neuroprotective during early stages of the aging process but becomes less beneficial in later stages — and can even have a negative effect in patients with late amnestic mild cognitive impairment (aMCI) or mild Alzheimer's dementia (AD), new research suggests.

The study of more than 500 participants showed that those with normal cognition who were younger than age 65 years had significantly positive correlations between education level and resting-state functional connectivity (rsFC) in the right precentral, left superior frontal, left middle frontal, and left inferior temporal gyrus.

No significant relationships were found in the older participants with normal cognition or in those who had early aMCI.

However, those with late aMCI or mild AD had negative correlations in several brain areas, "showing a more disrupted resting-state functional network," lead author, Yeshin Kim, MD, Samsung Medical Center, Seoul, Republic of Korea, told attendees here at the International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD) 2017.

After the presentation, session co-chair Jacques Hugon, MD, PhD, Memory Center, University of Paris Diderot, France, told Medscape Medical News that the study "is good confirmation about the theory that cognitive reserve works well with people with higher education."

"But once the lesion starts to be very important, the cognitive reserve seems to be not so protective and the benefit falls off," said Dr Hugon.

"Capacity…to Endure Neuropathology"

Cognitive reserve “reflects the capacity of the brain to endure neuropathology to minimize clinical manifestations," write the investigators.

"It is well known that in AD patients with higher cognitive reserve, there is more severe brain atrophy compared with AD patients with lower cognitive reserve," added Dr Kim. "However, it is not well known how resting-state functional networks are affected by cognitive reserve in each cognitive stage."

The investigators enrolled 526 participants at Samsung Medical Center and placed them into one of the following six subgroups:

  • Young/normal cognition (n = 46; 59% women; mean age, 57 years);

  • Older/normal cognition (n = 70; 44% women; mean age, 71.7 years);

  • Early aMCI (n = 57; 56% women; mean age, 69.6 years);

  • Late aMCI (n = 141; 58% women; mean age, 70.6 years);

  • Mild AD (n = 173; 67% women; mean age, 71.2 years; Clinical Dementia Rating [CDR] score < 2); and

  • Moderate-to-severe AD (n = 39; 77% women; mean age, 72.5 years; CDR > 2).

The mean number of years of education for each group was 12.5, 11.8, 10.4, 11.2, 8.9, and 8.6 years, respectively.

"We constructed a total of 4005 functional network connections by calculating the signal correlations between 90 nodes," report the researchers. They also used a machine-learning method to find correlations between rsFC and each group's educational level.

After adjustment for age, sex, and gray matter volume, the young/normal cognition group had higher network efficiency for those with higher vs lower education (P = .01). No significant association was found in the older/normal cognition group.

In participants with late aMCI, significantly negative correlations (together, P = .04) were found for those with higher education in the following brain areas:

  • Left middle frontal and orbital;

  • Left lingual;

  • Left caudate;

  • Left putamen; and

  • Right thalamus.

And the patients with mild AD and higher education had negative correlations with network efficiency (P = .02) in the following regions:

  • Superior frontal;

  • Superior orbital;

  • Left insula; and

  • Right postcentral.

The moderate-to-severe AD group had no significant associations between education and rsFC but may have been underpowered because of its small number of participants.

"We have seen before that as soon as patients start to decline, those with very high cognitive reserve decline much more rapidly than other patients," commented Dr Hugon, who was not involved with the research.

He noted that a recent study compared levels of amyloid-β (Aβ) in individuals with low education vs those with high education. "When cognitive problems started, people with high education had very low Aβ. So it seems that the cognitive reserve was protective at that point."

However, "once they started to decline, the decline was sharper as the protection went away."

Dr Kim and Dr Hugon have disclosed no relevant financial relationships.

International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD) 2017. Symposium 14, Presentation 14. Presented March 30, 2017.

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