ROCHESTER, Minn. — Unravelling a medical mystery that had patients hopping from one false diagnosis to another, a team of Mayo Clinic neurologists have identified what appears to be an unrecognized, early-onset variant of Alzheimer's disease.
As described, the constellation of biological and cognitive deficits known as Progressive Dysexecutive Syndrome does not affect memory in the traditional sense, or even produce bouts of strange behavior. Instead, the afflicted can find themselves unable juggle information, finish a project or even make a sandwich.
Two of the signature features of the illness are apathy and having been fired for incompetence at a job that once came easy.
The findings, first reported last week in an article in the journal Brain Communications, describe 55 cases of the previously-unknown brain disorder, one capable of striking a person in their 50s. In drawing up the new definition, the Mayo authors hope to spare patients distress, cost and potential harms of wrong treatments, while allowing them to more quickly tap into resources, illness-specific counseling and better planning for life with a progressive illness.
An illness with no name
"We started seeing a lot of young-onset cases for which there was not a good case definition," says Dr. David Jones, assistant professor of neurology at Mayo Clinic and lead author of the study.
"The symptoms weren't clearly defined, there was no diagnostic criteria for them, but we kept finding that they have Alzheimer's disease and that it took them a really long time for them to get a diagnosis."
Looking back over patient records, the 55 patients shared cerebral-spinal fluid biomarkers for Alzheimer's and pathology findings within brain tissue obtained via autopsy but not the normal genetic signature of the illness. Imaging results showed a unique syndrome, as well.
Whereas Alzheimer's patients have characteristic atrophy in the deep-brain region known as the hippocampus, these patients were showing inactivity across the top of their head, an area responsible for executive functioning known as the parietal lobes.
The review found the patients had an mean age of onset of 54 and were not diagnosed until the age of 57.
"A lot of times people with this condition will say they have memory trouble," Jones says. "But if you dig in and see what problems they are having, it's usually problems at work with completing tasks — especially if there's a new computer program they have to learn. It takes them a lot longer to do their normal day-to-day work, and they start having job performance issues."
Of course, there isn't a person over a certain age who hasn't felt challenged by new software. But the Mayo team found these deficits could interfere with a host of low-tech skills as well, like keeping a calendar, following a recipe or scheduling other workers.
In this way, Jones says, early-onset Alzheimer's resembles a computer with too many programs opened on its desktop, one now running low on RAM. The researchers outlined liabilities in three specific, background-level cognitive actions: working memory, cognitive flexibility and cognitive inhibition.
"Working memory is where you temporarily store information and manipulate it in order to put out a new result," says Jones. Cognitive flexibility, on the other hand, may sound like learning to look at an issue differently, but with early-onset Alzheimer's, "it is difficulty switching between tasks, loading something into working memory, or holding a rule." Cognitive inhibition means being able to filter out irrelevant information.
"These individuals usually have very intact, crystallized intelligence," Jones says. "All the knowledge they've accumulated their entire life is still there, and they can still use it as long as long as they focus on one thing at a time, don't do things in multiple steps and ignore distractions."
Of course, all the above are usually required to hold down a job.
"A lot of times they've lost their jobs by the time they see us," Jones says. "When you test as to why they're not performing as well, it's not their memory in the typical sense, it's executive cognitive function or working memory that's the problem."
Patients with early-onset Alzheimer's can appear as if they have become apathetic, and this can bounce them from one provider to another on an expensive, demoralizing "diagnostic odyssey," Jones says. One such patient had recently lost a close friend prior to his troubles and was misdiagnosed with bereavement syndrome.
"They've always been here," Jones says. "Digging into the literature, the first report of this type of presentation dates back to 1988. ...It's been a long, confusing road for these symptoms. If we can educate providers and the public, that's our goal. We want to help people get a diagnosis right away, start to cope, manage this illness (and) plan the rest of their life."