Mind Over Matter, Language Skills May Ward Off Alzheimer’s

Time.com | Tiffany Sharples | July 9, 2009

Adding to the deep body of research associating mental acuity with a lower risk of Alzheimer’s disease, a study published online on July 8 by the journal Neurology suggests that people who possess sophisticated linguistic skills early in life may be protected from developing dementia in old age — even when their brains show the physical signs, like lesions and plaques, of memory disorders.

That discrepancy is not unheard of: many elderly patients develop the brain lesions, plaques and tangled neurological-tissue fibers that are indicative of dementia and Alzheimer’s disease, but not all of them exhibit the memory loss and confusion that typically characterize these disorders. In fact, the number of such patients may be greater than researchers first thought.

In a November 2008 study, a team of scientists used a new positron emission tomography (PET) brain-imaging technique developed by Drs. William Klunk and Chester Mathis of the University of Pittsburgh to image the brains of live patients — a leap forward in a field that long had to rely on postmortem analyses of brain tissue to confirm diagnoses after the fact — and showed that some 21% of patients with physical signs of dementia suffered no outward symptoms of cognitive impairment.

The leading theory to explain this fortunate disconnect is the brain-reserve hypothesis, which suggests that people who have more cognitive ability and more neural tissue to start with — sharper minds, broadly — may be better able to withstand the ravages of age. “In some ways, you could think of it like a trained athlete who might be able to resist some atherosclerosis of the heart,” explains Dr. Bradley Hyman, director of the Massachusetts Alzheimer’s Disease Research Center and a professor of neurology at Harvard Medical School.

Past studies have shown that patients who have so-called asymptomatic Alzheimer’s disease — those who have the hallmark brain lesions and plaques of Alzheimer’s disease but no memory loss — also have enlarged neurons, compared with patients who suffer cognitive impairment. Dr. Diego Iacono, a neuropathology fellow at Johns Hopkins School of Medicine and the future director of the Brain Bank at Sweden’s Karolinska Institute, conducted several such studies in predominantly male populations, but his latest research, the study published in Neurology, demonstrates the same patterns in an entirely female population — of nuns.

The Nun study (www.healthstudies.umn.edu/nunstudy/faq.jsp) may not be familiar to most people outside of élite neurology circles, but to dementia researchers, it’s a gold mine. The long-term data on more than 600 nuns from Minnesota has revealed a great many insights about the effects of aging and the development of Alzheimer’s disease and dementia. And yet it was not in the Nun study’s core data that its director, Dr. David Snowdon, first discovered a fascinating correlation between the sisters’ language skills, based on essays they had written in their 20s when they first entered the convent (Snowdon discovered the essays in the convent’s archives), and the likelihood that they would develop Alzheimer’s later in life. The correlation was striking: the young women who had more sophisticated language skills — defined as the density of ideas per every 10 written words — were far less likely to suffer from Alzheimer’s or dementia five, six or seven decades later.

Iacono effectively picked up where Snowdon left off. Iacono and his colleagues discovered that not only did nuns who avoided dementia later in life have 20% higher linguistic scores as young women, compared with peers who developed symptoms of cognitive decline, but that the relationship held up even in nuns whose brains showed all the physical signs of Alzheimer’s. “There is a special group of people who have comparable amount of plaques and tangles — the typical marks of the disease — without the cognitive impairment,” says Iacono. “[It appears that] people with higher linguistic scores were protected even in the face of higher pathology.”

The finding adds to a collection of studies suggesting that the greater one’s initial mental fitness — measured variously as higher educational achievement or high IQ, for example — the better it may be safeguarded in old age. “It’s broadly consistent with the notion that if someone starts out with the ability, however their brain is organized, to have a greater set of skills in language and performing other complicated tasks, then maybe that brain is more resistant [later in life],” says Harvard’s Hyman.

How exactly the brain builds up resistance to Alzheimer’s is, of course, the central question driving legions of researchers. Are some people’s brains capable of building detours around damaged neural circuits? Is there a gene that may help certain people rebuild and repair damaged brain tissue better than others can? Iacono suggests that’s a strong possibility, pointing to the presence of one particular gene, APOE2, in 30% of patients with asymptomatic Alzheimer’s. The next step in his research, he says, is to understand how this gene works.

What researchers are increasingly discovering is that the human brain may contain much more plasticity than they thought. Understanding how it recovers from injury or compensates for damaged tissue may shed light not only on memory disorders, but also on other conditions, such as Parkinson’s or Lou Gehrig’s disease, Hyman suggests. “That kind of mental flexibility would be an important component to recovery from any kind of damage.”

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