Dementia’s Signs May Come Early

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7/19/13 1:2ementias Signs May Come Early - NYTimes.com

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July 17, 2013

Dementias Signs May Come EarlyBy PAM BELLUCKThe man complained of memory problems but seemed perfectly normal. No specialist he visited

detected any decline.

He insisted that things were changing, but he aced all of our tests, said Rebecca Amariglio, a

neuropsychologist at Brigham and Womens Hospital in Boston. But about seven years later, he

began showing symptoms of dementia. Dr. Amariglio now believes he had recognized a cognitive

change so subtle he was the only one who could identify it.

Patients like this have long been called the worried well, said Creighton Phelps, acting chief of th

dementias of aging branch of the National Institute on Aging. People would complain, and we

didnt really think it was very valid to take that into account.

But now, scientists are finding that some people with such complaints may in fact be detecting

early harbingers of Alzheimers.

Studies presentedWednesday at anAlzheimers Association conferencein Boston showed that

people with some types of cognitive concerns were more likely to have Alzheimers pathology in

their brains, and to develop dementia later. Research presented by Dr. Amariglio, for example,

found that people with more concerns about memory and organizing ability were more likely to

have amyloid, a key Alzheimers-related protein, in their brains.

And, in a significant shift highlighted at the conference, leading Alzheimers researchers are

identifying a new category called subjective cognitive decline, which is peoples own sense that

their memory and thinking skills are slipping even before others have noticed.

The whole field now is moving to this area, and saying Hey, maybe there is something to this, anmaybe we should pay attention to these people, said Dr. Ronald C. Petersen, chairman of the

advisory panel to the federal governments new National Alzheimers Project.

Dr. Petersen, director of the Mayo Clinics Alzheimers center, said preliminary results of a Mayo

study of healthy older adults in Minnesota suggested something similar.
http://www.alz.org/aaic/_releases_2013/wed_130pm_decline.asphttps://www.alz.org/aaic/http://aspe.hhs.gov/daltcp/napa/https://www.alz.org/aaic/http://www.alz.org/aaic/_releases_2013/wed_130pm_decline.asphttp://topics.nytimes.com/top/reference/timestopics/people/b/pam_belluck/index.html


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Lo and behold, those who had a concern about their memory in fact had more likelihood of later

developing mild cognitive impairment, an early phase of dementia, he said. He said study

participants with memory concerns were 56 percent more likely to be given a diagnosis of such

impairment, even when results were adjusted for factors like education, genetic risk and

psychiatric issues like anxiety and depression.

These people are sensing something, and theres some biological signals that correlate, Dr.

Petersen said. I think its real.

Experts emphasize that many people with such complaints will not develop dementia. Some

memory decline reflects normal aging, they say, and some concerns reflect psychological angst.

People who forget what they wanted in the kitchen or the names of relatively unfamiliar people ar

probably aging normally. People who forget important details of recent events, get lost in familiar

places or lose track of book or television plots may not be, especially if they have more problems

than others their age.

And much remains unknown about subjective concerns. In some studies, like Dr. Amariglios,

highly educated people noticed changes more readily, but in other studies, less educated people

did. Some studies suggest people who worry more about memory deficits have more dementia ris

but it is unclear if the worry reflects the changes they sense or if worrying itself increases risk.

People with family histories of dementia could be reporting problems simply because they know

about the disease and its genetic component. And, while a study presented Wednesday found sligh

correlations between subjective concerns and the highest-risk genetic mutation, ApoE4, thatrelationship remains unclear.

Experts are not yet suggesting doctors regularly screen people for subjective cognitive decline

because much more research is needed and no effective dementia treatment now exists.

Dr. Richard Caselli, a neurology professor at the Mayo Clinic in Arizona, said that when patients

cited cognitive problems, he ruled out reversible things, but did not recommend testing for

Alzheimers because if we do a scan and say, Hey, we found some amyloid in your brain, theres

really nothing you can do.

But subjective screening has value now for clinical trials, experts say, because it can help pinpoint

people at higher risk for dementia to better determine if treatments can delay or prevent

Alzheimers.

Major studies like theAlzheimers Disease Neuroimaging Initiative are adding subjective memory
http://www.adni-info.org/


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complaint categories. So will an important trial to see if an anti-amyloid drug can prevent dement

in cognitively normal people with amyloid in their brains.

People have been interested in this subjective concern for a long time, but we didnt have a way t

say is this normal, said Dr. Reisa Sperling, who runs Brigham and Womens Alzheimers program

and is helping lead the coming anti-amyloid study.

Not long ago, most experts considered subjective concerns unmeasurable or related to depression

or anxiety. Frank Jessen, a researcher at the German Center for Neurodegenerative Diseases, said

his first study on the topic, submitted to journals around 2004, got rejected everywhere, but in

2012, the same study with more years of data was accepted by Neurology, a major journal.

In November, a working group of leading experts was formed, headed by Dr. Jessen. The name

subjective cognitive decline was chosen after some debate, with some experts preferring other

terms.

Dr. Jessen said in diseases from arthritis to Parkinsons, people often feel something is wrong

before others notice. In most phases of dementia, family members and friends see deficits, but the

disease has usually stolen the persons ability to recognize them. But at the subjective phase,

studies suggest family members may miss problems; the person may feel his mind working harde

but he still functions well.

One of Dr. Casellis patients, Roger Siegel, 84, has noticed problems for at least five years, and sai

he now remembers about 30 percent of what he would like to, and has trouble concentrating. I

take a shower and wonder did I wash that leg, he said. In books, many times I forget which

character is which.

Recently, he bought six packages of pie filling instead of one because I asked somebody where

would I find it and the answer was Aisle 6, so I wrote down 6, but by the time I got to the aisle, I

picked up six of the thing.

Neither his wife nor Dr. Caselli perceive these difficulties.

I know Im losing my mind, Mr. Siegel said, but according to Caselli, Im fine.

Dr. Caselli said Mr. Siegel has been saying he is declining for years, and was given a diagnosis at

another clinic of mild cognitive impairment three years ago based on his subjective complaints,

when he had no evidence of decline and I told him so.
http://www.dzne.de/en/research-institute-for-neurodegenerative-diseases.html


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But recently fine-grained cognitive measures showed he had slight decline on his tests, and so m

possibly be at a very early stage of a very slowly progressive degenerative syndrome, Dr. Caselli

said.

The working group aims to develop standardized subjective cognitive tests so when treatments

become available doctors can eventually use them as a cheap and noninvasive way to help

identify people at greater risk, said Dr. Petersen. We cant do M.R.I.s and scanning on everyone,

he said.

Current tests range from an eight-page assessment in Dr. Amariglios research to one question

included in a broader University of Kentucky study of dementia. But Richard Kryscio, a

biostatistician and study leader, said those reporting memory changes since their last visit were 2

times as likely to develop mild cognitive impairment or dementia years later, and autopsies of

participants who died found more Alzheimers plaques and tangles in people with subjective

cognitive concerns.

Experts say the goal is a test identifying which subjective concerns are potentially worrisome, sinc

not all are.

Sharon Atkinson-Mallory, 70, of Belmont, Mass., a participant in Dr. Amariglios study of people

without symptoms, said she had occasional trouble putting names to faces and remembering why

she entered a room. But Ms. Atkinson-Mallory, a psychotherapist, maintains a practice, exercises

pursues a genealogy hobby, and considers her issues similar to those of others her age.

Carol Miller, 61, of Rochester, Minn., part of the Mayo Clinics study of cognitively healthy adults,

seems more concerned. A registered nurse who retired after being laid off a few years ago, she has

forgotten cardiovascular and neurological vocabulary that once I would recall very easily, she

said. I dont trust myself as a safe R.N. because I dont have the knowledge anymore.

When shopping for blueberry filling for her daughters birthday cake, she twice reached the

checkout counter having forgotten it. And twice she has left the stove on. I couldve burned the

house down, she said. That was scary, like Wow, whats the deal there?

Still, she said, so far they tell me Im normal.


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Dementia’s Signs May Come Early