Alzheimer's, Dementia & Mental Health
Normal Senior Citizens with Amyloid Plaques Show
Changes Associated with Alzheimer’s
Discovery may open door for therapies to prevent
developing Alzheimer ’s disease
March 30, 2011 - Senior citizens with normal mental
abilities, but with brain deposits of amyloid beta – the primary
constituent of the plaques found in the brains of Alzheimer's disease
patients, also had changes in brain structure similar to those seen in
Alzheimer's patients. The research, published early in the online
edition of the Annals of Neurology, may help identify individuals
who could be candidates for therapies to prevent the development of
dementia.
"Our findings support the theory that Alzheimer's
disease begins many years before symptoms appear and that amyloid plaque
is an early sign of this process," says Keith Johnson, MD, Massachusetts
General Hospital (MGH) Imaging, senior author of the study.
"We see that when amyloid deposits are present,
even in cognitively normal individuals, the degenerative changes of
Alzheimer's are underway. Long-term studies to track these changes and
observe how they evolve are ongoing."
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Alzheimer's, Dementia & Mental Health |
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Definitive diagnosis of Alzheimer's disease
requires finding amyloid plaques and neurofibrillary tangles in the
brain at autopsy. In recent years it has been possible to detect amyloid
in living brains by PET scanning with an imaging agent known as
Pittsburgh Compound B (PiB).
Plaques have been observed in the brains of
apparently healthy individuals, as well as those with dementia, but
whether the presence of plaques indicates the early stages of
Alzheimer's disease is not yet known.
High-resolution magnetic resonance imaging studies
have identified characteristic changes in brain structure – thinning of
key cortical regions and reduced volume of structures such as the
hippocampus – in persons with mild cognitive impairment, in individuals
known to carry gene mutations that directly cause Alzheimer's disease
and in diagnosed Alzheimer's patients.
A recent study reported similar brain changes in
some cognitively normal elderly, but did not distinguish those who had
amyloid deposits from those who did not.
The current study involved 87 cognitively normal
older individuals and 32 patients diagnosed with mild Alzheimer's –
matched for age, gender and education – who had enrolled in the
long-term Harvard Aging Brain Study. Participants underwent both
high-resolution MR imaging of brain structure and PET scanning with PiB
to detect amyloid plaques. The results showed that those cognitively
normal individuals who had amyloid plaques also had structural changes.
These were similar to but less pronounced than the neurodegenerative
changes seen in the symptomatic patients.
Structural changes were most evident in areas
comprising what is called the default network, which is known to be
affected early in the course of Alzheimer's disease.
"If amyloidosis – deposits of amyloid plaques – in
the brains of clinically normal people is associated with
Alzheimer's-like neurodegeneration, then amyloidosis itself may signify
'preclinical' AD," say Johnson, an associate professor of Radiology at
Harvard Medical School.
"We need to learn more about how long it takes a
normal person with amyloid to develop AD, whether there are critical
'second hit' factors that convert amyloidosis to Alzheimer's disease,
and if there are measures that can halt the process of neurodegeneration."
Notes:
Alex Becker, PhD, of MGH Imaging, is lead author of
the Annals of Neurology report. Additional co-authors are Jeremy
Carmasin, Jacqueline Maye, Bruce Fischl, MD, and Douglas Greve, PhD, MGH
Imaging; Trey Hedden, PhD and Deepti Putcha, Martinos Center for
Biomedical Imaging at MGH; Dorene Rentz, PsyD, Gad Marshall, MD, and
Reisa Sperling, MGH and Brigham and Women's Neurology; Randy Buckner,
PhD, MGH Psychiatry; Stephen Salloway, MD, Brown University; and Donald
Marks, MD, Tufts University School of Medicine. The study was supported
by grants from the National Institutes of Health, Massachusetts
Alzheimer's Disease Research Center, Howard Hughes Medical Institute,
the Alzheimer's Association and the Charles Farnsworth Trust.
Celebrating the 200th anniversary of its founding
in 1811, Massachusetts General Hospital (www.massgeneral.org)
is the original and largest teaching hospital of Harvard Medical School.
The MGH conducts the largest hospital-based research program in the
United States, with an annual research budget of nearly $700 million and
major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, reproductive
biology, regenerative medicine, reproductive biology, systems biology,
transplantation biology and photomedicine.
