Alzheimer's disease strikes people with Down syndrome

EDITOR’S NOTE: This is another installment of a series exploring issues faced by families who care for special needs adults.

Although Grace Pollack of Sun City was born with Down syndrome, she was a big help in raising her nieces and nephews over the past 26 years.

Lately, Grace, 60, no longer recognizes the children she once considered her own because, in addition to Down syndrome, Grace also has Alzheimer’s disease — the progressive and fatal brain disorder that causes memory loss and problems with thinking and other behaviors.

For Grace, it manifested in her inability to do tasks she did for the past 25 years, and led to a need for 24-hour supervision, said her sister and brother-in-law, Polly and Leo Levenson.

“She is very different now — we could not have done this without help 26 years ago (while raising our children),” Leo said. “She used to be able to use the microwave, and now she can’t get a cup of water.”

According to researchers, Grace’s case is not unique.

There appears to be a strong link between the two diseases, which puts those with Down at a risk of between 35 percent and 100 percent chance of developing Alzheimer’s after age 40, which compares with about 10 percent of the general population of those 65 and older and nearly 50 percent of those 85 years and older developing Alzheimer’s.

Dr. Marwan Sabbagh, medical director of Banner Sun Health Research Institute, said the Alzheimer’s genetic marker affects 100 percent of Down patients who are 40 and older, leading to the development of the disease in all of those patients.

Sabbagh said those with Down, whose life expectancy used to be quite low, now can live into their late 50s to 70s.

“As they break north of 40, though, they tend to have a lot of cognitive decline,” Sabbagh said. “That’s how we first found the mutation to identify (Alzheimer’s in Down).”

Sabbagh said one of the key proteins found in Alzheimer’s patients — beta amyloid — is found on the gene on chromosome 21 — whose over-expression causes Down.

Dr. Lynn Nadel, a regents professor with the department of psychology at the University of Arizona, has studied the connection for the past five years in about 25 patients. He said he has found those with Down have between a 35 percent to 45 percent of developing Alzheimer’s, but 100 percent of them develop the tangles and plaques in the brain associated with Alzheimer’s.

“They seem to involve problems with some of the same brain systems and hence, cognitive functions,” Nadel said.
Nadel’s work with Down-Alzheimer’s patients at the University of Arizona concentrates on neuropsychological research, where he is trying to connect the cognitive impairments to underlying neural systems. He is not utilizing drug interventions at this time.

“We are also trying to relate cognitive impairments to particular patterns of gene expression, and beginning to track cognitive function by re-testing people every year or two,” Nadel said.

This work has been awarded funding from the Arizona Alzheimer’s Consortium — the statewide collaboration of seven research institutions and 140 scientists.

“As patients with Down syndrome are living to older ages, there is almost no other group with a greater sense of urgency to find that prevention therapy, since by the time patients with Down are 40, all of them have one of the abnormalities we see with patients with Alzheimer’s, which is amyloid plaque,” said Dr. Eric Reiman, director of the consortium and chief scientific officer of Banner Research and executive director of Banner Alzheimer’s Institute. “And many develop the characteristics of the progressive memory disease of Alzheimer’s.”

Reiman said the consortium is interested in targeting high risk groups, such as those with Down syndrome and families with a genetic factor that contributes to early onset Alzheimer’s. Many researchers, he said, believe targeting these high risk groups will be key in finding early detection and preventative therapies, not just in high risk, but the general population.

“Those with Down have the extra chromosome, which places them at a very extreme high risk,” Reiman said. “We share the urgency of the problem, and want to find a demonstrative, effective and preventive (therapies).”
While those with Down’s have a high probability of developing Alzheimer’s, studying and tracking progress provides its own sets of challenges.

“One major challenge is indeed that they are at serious risk for Alzheimer’s disease,” Nadel said. “Another is that many individuals with Down syndrome are not capable of completely independent living, so that when their parents are no longer around, or able to help, their problems are compounded.”

Sabbagh said he is utilizing some of the same medications he uses on the general population to also treat those with Down, in order to slow the progression of the disease.

“I’m trying to get an indication for treatment for those Down patients,” Sabbagh said. “What has been plaguing the field for those with Down has much to do with methodology,” Sabbagh said. “How do you study those with Down?”

“Everybody with Down is starting off at a different baseline,” Sabbagh said. “We have a standard memory test for the unimpaired, but not for those with Down. Some are starting off with their IQs in the 50s, or 70s, or 30s and 40s. Everyone is a little bit different.”

Researchers agree that Down patients would make ideal test subjects because of the high probability of developing Alzheimer’s disease.

But there are ethical concerns.

“If you had a pool where you were 100 percent sure they were going to get Alzheimer’s diease, wouldn’t you want to study them to determine how to stop development?” Sabbagh said. “They would be an important group to study.”

“Such individuals raise serious issues of informed consent when one wants to test them, or scan their brains,” Nadel said.

Research with Down patients can help both the Down and the general population, Nadel said.

“Obviously the costs associated with helping individuals with Down syndrome and Alzheimer’s disease are enormous, so anything that helps them and improves their status and outcome will benefit society as a whole in terms of reducing costs,” Nadel said. “But what we learn about aging, and about cognitive impairment, from the study of Down syndrome and Alzheimer’s disease will likely have a big impact on our understanding of these things in a typical population.”

To help with Down syndrome/Alzheimer’s disease research, Nadel is developing a neuropsychological test battery to help identify those with Down who are most likely to actually develop early Alzheimer’s.

“Once we can do this, we can target this select group for treatments — behavioral and/or pharmacological,” he said. “We are using this to help us figure out exactly what kinds of cognitive and neural impairments are at the root of the mental retardation in Down syndrome; what genes on C-21 are or are not associated with better or worse outcomes in Down syndrome and what sorts of interventions can make a difference in cognitive function.”

Sabbagh said when a person with Down begins to develop Alzheimer’s, it becomes apparent very quickly. So caregivers should note any behavioral changes.

“When you have someone who is low baseline to moderately impaired in daily life already, the margin to fall down from functional to low functioning is low,” Sabbagh said. “Basically they can go from daily living — grooming, dressing and doing their day programs to no longer volunteering, and then no longer personal care. It becomes very apparent, but may not measure on a memory test.”

“They may go from being able to do a workshop before and now not be able to use the tools, so we tend to measure more on function versus formal memory,” Sabbagh said.

Joy Slagowski may be reached at 623-876-2514 or jslagowski@yourwestvalley.com.

DID YOU KNOW?

>> For information on Dr. Marwan Sabbagh’s research with Down syndrome and Alzheimer’s disease, call the Banner Sun Health Research Institute at 623-876-5328.
>> For information on Dr. Lynn Nadel’s research, or to be a participant, contact Jamie Eddin, Down Syndrome Research Group, University of Arizona at jedgin@email.arizona.edu.