In his search for ways to prevent Alzheimer’s disease, Rhode Island Hospital neuropsychologist Peter J. Snyder, PhD, didn’t want o rely solely on the memory and learning tasks that have been used for more than 50 years to detect cognitive impairment. Instead, Snyder was on the hunt for a fresh, scientifically sound approach that identifies the arly stages of the underlying disease process. Snyder found what he was looking for in the pattern separation task, developed by neuropsychologist Craig E.L. Stark, PhD, of the University of California at Irvine. The task assesses how well study participants can tell whether either of a pair of pictures they previously saw on a computer was moved, even slightly. The test measures the ability to store and retrieve memories — processes that involve a subregion of the hippocampus — and may help to detect brain changes
that occur very early in the Alzheimer’s disease process.
“I think it has great potential” to uncover how the
disease process unfolds, says Snyder, also a neurology professor
at Brown University.
His colleagues in the international Dominantly Inherited
Alzheimer’s Network (DIAN), which is funded by the National
Institute on Aging and directed by John C. Morris, MD, of the
Washington University School of Medicine in St. Louis, will use
the test in a new clinical trial launched to evaluate three drugs
for preventing Alzheimer’s.
Stark is just one of many psychologists who are assuming
broader roles in Alzheimer’s research, as the focus shifts from
finding treatment for symptoms to stopping the disease process
before symptoms begin. In fact, neuropsychologists have been
critical in the design and performance of several pivotal trials,
says DIAN principal investigator Randall Bateman, MD, also of
the Washington University School of Medicine.
New and different techniques
Using several effective methods to find early signs of
Alzheimer’s disease is important, says Glenn Smith, PhD,
a clinical neuropsychologist working on early detection of
Alzheimer’s at the Mayo Clinic in Minnesota, and a member of
the APA’s Committee on Aging. “The more ways you measure
something, the more accurately it’s measured,” he says.
He points to data from the Alzheimer’s Disease
Neuroimaging Initiative (ADNI), a large-scale study
launched in 2003 to find biomarkers, including behaviors in
standardized tasks, that are most effective in detecting early
signs of Alzheimer’s. Funded by the federal government, the
pharmaceutical industry and several private foundations, the
study’s principal investigator is Michael W. Weiner, MD, of the
Veterans Affairs Medical Center at the University of California,
A recent ADNI data analysis led by Bruno Jedynak, PhD,
of Johns Hopkins University showed a somewhat surprising
result: The Rey Auditory Verbal Learning Test, a memory task
commonly used in clinical practice, indicated abnormalities
earlier in the course of neurodegenerative disease than six other
biomarkers, including the well-publicized amyloid-beta seen
on positron-emission tomography (PET) scanning and tau
proteins found in cerebrospinal fluid.
Role of vascular changes
Amyloid plaques and neurofibrillary tangles have been
considered Alzheimer’s defining features, but some researchers
are probing whether changes in the brain’s blood vessels play
a role in the disease process. In his lab at Columbia University,
neuropsychologist Adam Brickman, PhD, and colleagues are
using MRI to examine vascular abnormalities in the brain that
might be harbingers of Alzheimer’s disease.
Brickman says vascular changes in the brain — measured
with neuroimaging — may predict which healthy adults
will develop Alzheimer’s and the severity of their symptoms
when they do. His lab uses MRI scanning to measure
various structural brain changes, including white matter
hyperintensities — distributed bright patches seen on one type
of MRI scan that Brickman says are signs of damage to small
His lab also studies amyloid formation related to white
matter hyperintensities, strokes and microbleeds, which are tiny
specks of blood that have seeped from leaky vessels in the brain.
“These three types of pathology in the brain seem to occur with
higher prevalence among people with Alzheimer’s, and they also
seem to predict the types of symptoms we see in Alzheimer’s
disease,” Brickman says.
Clarifying the relationship between Alzheimer’s and vascular
disease in the brain — whether they occur independently of each
other, or they interact, or if one causes the other — could lead to
some basic, low-tech prevention strategies, says Brickman.
“We know how to prevent vascular disease a lot better than
we know how to prevent plaques and tangles,” he notes. “It’s
with lifestyle factors, medication, hypertension control and
Long-standing public health campaigns that have