New Lessons About Education Levels and Dementia Risk

Damian McNamara

February 13, 2019

Contrary to the popular belief that higher education guards against dementia, new research suggests it has little, to no, protective effect.

In a unique study that included annual cognitive assessments in older adults and neuropathologic autopsy results, investigators found that while there was a link between higher education levels and better cognitive function before old age, it did not reduce dementia risk or slow the rate of cognitive decline.  

"What it tells us is that education does not appear to provide much protection against these dementias of old age," principal investigator Robert S. Wilson, PhD, of Rush Alzheimer's Disease Center and the Departments of Neurological Sciences and Behavioral Sciences at Rush University Medical Center, Chicago, Illinois, told Medscape Medical News.

The only protection it offers, added Wilson, is that it provides better educated individuals with a higher baseline level of cognitive function so they have a longer way to go before they reach the threshold for dementia diagnosis.

The study was published February 6 in Neurology.

Mixed Results

Previous studies examining the potential link between higher education and lower risk of dementia have garnered mixed results.  

"Thus, it remains uncertain whether education moderates pathologic influences on cognitive change," the researchers note.

To look at this question, Wilson and colleagues took a "clinical-pathologic" approach that combined clinical assessment over time and brain autopsy at death.  

The study included 2899 individuals from two longitudinal studies — the Religious Orders Study and The Memory and Aging Project. Inclusion criteria required the absence of dementia at baseline and a valid cognitive score at baseline plus at least one follow-up evaluation.

At the start of the study, participants had an average age of 78, an average of 16.3 years of education, and no prior dementia diagnosis. They were followed for an average of 8 years.

All participants underwent annual cognitive testing that included different cognitive domains associated with clinical dementia, as well as measures of episodic memory, semantic memory, working memory perceptual speed, and visuospatial ability.

Of the total cohort, 696 individuals developed incident dementia during the study. The current analysis was based on results from 752 individuals who died during the study and underwent brain autopsy, and 405 participants who developed dementia, died, and also underwent brain autopsy.

"Nearly everyone who died in the study had a brain autopsy and a uniform neuropathological examination to quantify different pathologies related to dementia and cognitive decline in old age," Wilson said.

Diminishing Effect?

Investigators divided participants into three education groups: low (12 years or less of schooling; n = 546), medium (13-16 years; n = 1,029) and high (17+ years; n = 1324).

Results showed a higher level of education was significantly associated with younger age at baseline (P < .001). Both of these factors — more education and younger age at baseline — were associated with higher baseline level of global cognition (both P < .001). Women presented with a higher baseline level of cognition compared to men (P = .003).

The investigators calculated global cognition using a mixed-effects model that took education, sex, and baseline age into consideration. They found this composite measure decreased a mean of 0.073 unit per year, a significant finding (P < .001).

In addition, the level of global cognition at study entry increased by 0.052 units for each additional year of education (P < .001). In contrast, education was not significantly related to linear rate of change in global cognition (P = .438).

The results also showed that medium and high education classifications were significantly associated with higher baseline level of global cognition compared to low education (both P < .001). Again, neither education group was related to global cognitive change.

"Generally we got the results most people have — that education is very strongly related to level of cognitive function when you begin old age, but it doesn't seem to be related to your overall rate of decline," Wilson said.

"Then we asked a further question: Of people who started out cognitively healthy but who later developed dementia, does education have anything to do with when their cognitive decline starts to accelerate, or the rate of acceleration or rate of decline after that point?" Wilson said.

No Impact on Cognitive Reserve

To address these questions, the investigators performed another mixed-effects model. They found global cognition decreased a mean of 0.059 unit annually until a mean of 1.8 years before a dementia diagnosis. After this point, the mean rate of decline accelerated to a loss of 0.373 unit per year, "a more than 6-fold increase," they note.

"We asked a similar question about death," Wilson said. "There is a thing called 'terminal decline' – that is during the last few years of life, there tends to be a very strong acceleration in the rate of cognitive decline."

In the group of participants who died after at least 4 years of follow-up, the global cognitive score decreased a mean of 0.038 unit per year until a mean of 3.4 years before death. After this point, the mean rate of decline accelerated more than 8-fold to 0.312 unit per year.

These findings do not support the belief that education adds to cognitive reserve "because a higher level of education was associated with earlier onset of residual terminal cognitive decline in all models," the researchers note.

The researchers also found education modified associations between three neurodegenerative markers — TDP-43 pathology, hippocampal sclerosis, and tau-tangle density — and onset of accelerated terminal cognitive decline. The changes, however, were in the opposite direction predicted by the cognitive reserve hypothesis.

"The concept of cognitive reserve was introduced to account for nonpathologic influences on cognition, but we found a direct association of higher education with lower likelihood of gross and microscopic cerebral infarcts," the researchers note. "These associations were not particularly strong, which may explain why they have not been identified in some previous clinical-pathologic research."

"Education is not going to help [physicians] predict whether the person will experience cognitive decline," Wilson added. Education is the most common way most researchers evaluate cognitive reserve. "A popular belief is that education is a marker of cognitive reserve, and we're saying it's not a very good marker."

"We argue that may be because educational experiences are so remote by the time you're old," Wilson said.

Opportunities for Intervention?

In other words, educational levels from decades earlier are less likely to confer a robust protection on cognitive reserve. It's possible the relationship is more indirect.

Activities associated with higher education levels — routinely reading books or remaining intellectually active later in life — may be more likely to boost cognitive reserve.

"People who report reading more than others do seem to be able to tolerate more of this pathology," Wilson said. "They do seem to decline less rapidly in old age."

For this reason, researchers looking for modifiable factors to forestall cognitive decline "might want to look at more current activities," he added.

A potential limitation of the study is inclusion of a relatively well-educated cohort with a mean of 16.3 years. Further research in less-educated groups is warranted, Wilson said.

Generalizability of the results remains unknown because participants were selected for the research. Inclusion of a broad range of postmortem neurodegenerative and cerebrovascular markers was a strength of the research.

Going forward, Wilson would like to study other factors that could contribute to cognitive reserve. Conscientiousness is a personality trait with some associations, he said, and another possibility is purpose in life or the ability to find meaning in day-to-day activities.

"Those seem to be associated with better cognitive functioning, regardless of pathology," he said. "We're trying to get a better understanding of those mechanisms, and whether they offer opportunities for intervention."

Surprising Findings

Commenting on the findings for Medscape Medical News, Thomas R. Vidic, MD, a Fellow of the American Academy of Neurology and neurologist at the Elkhart Clinic in Elkhart, Indiana, said he was surprised by the finding "simply because the standard teaching had been that better education leads to better cognitive reserve, although we had no data to support that."

The current study helps researchers and clinicians "establish what works and what doesn't work" regarding Alzheimer's disease.

Alzheimer's disease is a major problem, but we are still working with limited information, including retrospective studies," Vidic added. "Through prospective studies of this type, we can begin to increase our knowledge base to better understand this disease."

Wilson reports he receives research support through multiple NIH grants. Vidic has disclosed no relevant financial relationships. The study was funded by the NIH and the Illinois Department of Public Health.

Neurology. Published online February 6, 2019. Abstract

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