News reports of research into Alzheimer's disease July - December 2003
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There's a glossary of terms used in Alzheimer's research.
Disclaimer:
This section began as an offshoot of my
gathering of news items about memory. I am not a medical expert. My
background is in psychology. The information I have gathered here should
not be taken as providing any advice.
December
Low blood pressure risk factor for Alzheimer's
A long-term study of 488 adults over 75 (the Bronx Aging Study) found that
122 participants developed dementia (65 Alzheimer’s, 28 vascular dementia,29
other), and that the relative risk of dementia increased as a function of
decreases in blood pressure (diastolic and mean arterial). Low diastolic BP
significantly increased the risk of developing Alzheimer’s, but not vascular
dementia. Those with mildly to moderately raised systolic BP had a reduced risk
of developing Alzheimer’s. The risk of developing dementia was higher in those
who had persistently low BP over 2 years.
The report appeared in the December 23 issue of Neurology.
Full reference
Distress-prone people more likely to develop Alzheimer's disease
The Religious Orders Study has found that those who most often
experience negative emotions like depression and anxiety were
twice as likely to develop Alzheimer's disease as those who were
least prone to experience negative emotions. A person’s tendency
to experience psychological distress has been shown to be a
stable personality trait throughout adulthood. Proneness to
stress was specifically associated with a decline in episodic
memory (measured by asking participants to recall a list of
words or a story) — an area particularly problematic for those
with Alzheimer's. Episodic memory ability declined 10 times
faster in those high in proneness to distress than in those low
in this response. This result was not altered when participants’
engagement in cognitively stimulating activities. Examination of
the brains of those who have died during the long-term study
appears to rule out the possibility that proneness to distress
is an early sign of Alzheimer's disease rather than a risk
factor, although more research is needed to confirm this.
The study was published in the December 9 issue of
Neurology.
Full reference
http://www.eurekalert.org/pub_releases/2003-12/aaon-pm120203.htm
Late-life Alzheimer's begins in midlife
A new model of human brain aging identifies midlife breakdown
of myelin, a fatty insulation with very high cholesterol content
that wraps tightly around axons (part of the neurons) and
enables messages to pass along the “wiring” of the brain
speedily, as a possible key to the onset of Alzheimer's disease
later in life. Imaging studies and examination of brain tissue
shows that the brain's wiring develops until middle age and then
begins to decline as the breakdown of myelin triggers a
destructive domino affect. It is suggested that genetic factors
coupled with the brain's own developmental process of increasing
cholesterol and iron levels in middle age help degrade the
myelin. The complex connections that take the longest to develop
and allow humans to think at their highest level are among the
first to deteriorate as the brain's myelin breaks down in
reverse order of development. The model suggests that the best
time to address the inevitability of myelin breakdown is when it
begins, in middle age. Possible preventive therapies include
cholesterol- and iron-lowering medications, anti-inflammatory
medications, diet and exercise programs and possibly hormone
replacement therapy designed to prevent menopause rather than
simply ease the symptoms. Education and cognitively stimulating
activities may also stimulate the production of myelin.
The report was published in the January edition of
Neurobiology of Aging.
Full
reference
http://www.eurekalert.org/pub_releases/2003-12/uoc--mbc122303.htm
Hippocampal damage seen in those with alcoholic memory disorder and those with Alzheimer's
A comparison between the brains of five men with alcoholic Korsakoff's
syndrome and the brains of men with Alzheimer's disease as well as the brains of
healthy men, found that the brains of all Korsakoff's patients and Alzheimer's
patients were comparable in significant volume loss in the hippocampus. Greater
hippocampal damage (for Korsakoff's patients) and smaller hippocampal size (for
Alzheimer’s) was correlated with poorer memory performance. It is suggested
that, although there are of course a number of differences between these
disorders, the nature of the memory impairment may be the same. Awareness of the
similarities may help detection of both disorders.
The study was published in the December 23 issue of
Neurology.
Full reference
http://www.eurekalert.org/pub_releases/2003-12/aaon-seu121503.htm
Clioquinol slowed progression of cognitive decline in Alzheimer's patients
A new clinical trial has found that the drug Clioquinol slowed
the progression of cognitive decline in a group of 36 patients
with moderate to severe Alzheimer’s, over a period of 24 weeks.
PBT-1 (Clioquinol) is a chemical that binds zinc and copper, and
has been shown to lower the levels of beta-amyloid and the
associated toxicity in the brains of transgenic mice used as a
model of Alzheimer's disease.
The trial was reported in the December 15 issue of the
Archives of Neurology.
Full reference
http://www.eurekalert.org/pub_releases/2003-12/aaft-cto121503.htm
November 2003
Dietary supplement helps Alzheimer’s
A three-month study of 55 elderly patients with mild or
moderate Alzheimer’s found that those given EV-1, a dietary
supplement containing, among other things, the putative
antioxidant ingredient of red wine, showed no deterioration
during the trial. The supplement is designed to interfere with a
defective mitochondrial cycle thought to contribute to the
metabolic disturbances associated with late onset Alzheimer’s.
The Krebs tricarboxylic acid cycle is fuelled by glucose and
regulates levels of reactive oxygen species in the body. EV-1
contains glucose, a compound called malate that primes or
maintains the Krebs cycle, and resveratrol - the antioxidant
component of red wine that is thought to soak up reactive oxygen
species. More studies are needed to confirm this result.
The findings were presented in November at the annual meeting of
the Society for Neuroscience (SFN) in New Orleans.
http://gateways.bmn.com/news/story?day=031121&story=1
Program helps physical and behavioral well-being of Alzheimer's patients
A controlled trial of 153 community-dwelling patients diagnosed with
Alzheimer’s examined the effectiveness of a home-based exercise program combined
with caregiver training in behavioral management techniques in reducing
functional dependence and delay institutionalization. The program resulted in
improved physical health and less depression. Specifically, after three months,
those receiving the training were more likely to exercise at least 60 minutes a
week, to have fewer days of restricted activity, to have improved scores for
physical role functioning, and improved Cornell Depression Scale for Depression
in Dementia scores, and have less institutionalization due to behavioral
disturbance.
The study was reported in the Journal of the American
Medical Association.
Full reference
October 2003
Conflicting results about benefit of anti-inflammatory drugs
It’s long been known that patients regularly taking
nonsteroidal anti-inflammatory drugs, such as ibuprofen and
naproxen, seem to have less risk of developing Alzheimer's. It’s
been suggested that this might mean that Alzheimer's is a
product of inflammation in the brain, and that damage happens
when the microglia, the brain's immune cells, become overactive
and attack healthy neurons. A new study of autopsy brain tissue,
and of in vitro rat cultures indicates that, on the contrary,
what’s happening is that, as microglia age, they lose their
ability to protect the brain. Moreover, the latest study into
the effects of anti-inflammatory drugs found no benefit for
those suffering from Alzheimer’s. Indeed, it is possible that
such drugs might exacerbate the problem. It is speculated that
microglia may have the potential to both protect and attack
neurons. The key may lie in the way microglia interact with
beta-amyloid protein.
http://www.sciam.com/article.cfm?chanID=sa004&articleID=00079718-699A-1F98-A99A83414B7F0103
September 2003
Brief telephone questionnaire screens for early signs of dementia
Researchers have developed a brief telephonic questionnaire that helps
distinguish between persons with early signs of dementia and persons with normal
cognitive function. The questionnaire provides a way to reach out to persons
with dementia whose impairment otherwise may go undetected until substantial
cognitive deterioration has occurred. The questionnaire consists of a test of
delayed recall and 2 questions that ask whether the person needs help with
remembering to take medications or with planning a trip for errands. It is
estimated that of 100 people who score positive on this test, 42 will actually
have cognitive impairment. In other words, this does not provide a diagnosis of
Alzheimer’s, but provides evidence that further evaluation is required. The rate
of false positives compares favorably to other types of screening tests. A
further study is underway to confirm the validity and reliability of the test.
The report was published in the August issue of the
Journal of Clinical Outcomes Management.
Full reference
http://www.eurekalert.org/pub_releases/2003-09/twc-btq091603.htm
Cancer drug may help against Alzheimer's too
The drug Gleevec, approved for treatment of chronic myelogenous
leukemia (CML) over two years ago, has been found to reduce the
level of beta-amyloid in immature rat neurons and cultured human
cells. The drug also significantly reduced the levels of amyloid
peptides in live guinea pigs (who have amyloid peptides
comparable to those found in humans). While still preliminary,
the work may indicate a new approach to treating Alzheimer’s.
The report was published in the
Proceedings of the National Academy of Sciences.
Full
reference
http://www.sciam.com/article.cfm?chanID=sa003&articleID=00014A83-AC91-1F78-AC9183414B7F0000
August 2003
New toxic protein found
New research has found up to 70 times more small, soluble
aggregated proteins called "amyloid b-derived diffusible
ligands" (ADDLs) in the brain tissue of individuals with
Alzheimer's disease compared to that of normal individuals. This
supports a recent theory in which ADDLs accumulate at the
beginning of Alzheimer's disease and block memory function by a
process predicted to be reversible. ADDLs have the ability to
attack the memory-building activity of synapses, points of
communication where neurons exchange information, without
killing neurons. While both are a form of amyloid beta, ADDLs
differ significantly from the amyloid fibrils (plaques) that are
diagnostic of Alzheimer's. ADDLs are much, much smaller than
fibrils. Unlike fibrils, ADDLs are soluble and diffuse between
brain cells until they find vulnerable synapses. The discovery
of ADDLs may help explain the poor correlation between plaques
and neurological deficits.
The findings were published online by the Proceedings of the
National Academy of Sciences during the week of August 18.
Full reference
http://www.eurekalert.org/pub_releases/2003-08/nu-tpc081803.htm
Anti-inflammatories lower Alzheimer disease–related protein levels in mice
Following earlier research showing three commonly used
nonsteroidal anti-inflammatory drugs (NSAIDs) were capable of
selectively lowering the levels of Abeta42 (an isoform of the
amyloid beta protein) in mice, investigation of 20 commonly used
NSAIDs found 8 FDA-approved drugs successfully lowered Abeta42
levels in mice at doses achievable in humans.
The report was published in the August 1 issue of the Journal of
Clinical Investigation.
Full reference
http://www.eurekalert.org/pub_releases/2003-08/joci-fds072503.htm
July 2003
Higher education or larger brain size may protect against dementia
More findings from the Nun Study, a longitudinal study of aging and
Alzheimer's disease. It was found that nuns who completed 16 or more years
of formal education or whose head circumference was in the upper two-thirds
were four times less likely to be demented than those with both smaller head
circumferences and lower education. (Head circumference is a good indicator
of the volume or size of the brain.) It was not that these nuns were less
likely to have the brain abnormalities characteristic of Alzheimer's
disease, but that the larger brain size and more education provided extra
reserve, allowing them to function normally in the presence of such brain
abnormalities.
The study was published in the June issue of the
Journal of Clinical and Experimental Neuropsychology.
Full reference
http://www.eurekalert.org/pub_releases/2003-07/uosf-heo071003.htm
Anti-inflammatories offer some protection against developing Alzheimer's
A review of 9 observational studies that examined the role of NSAID use in
preventing Alzheimer's disease found the pooled relative risk of Alzheimer's
disease among users of NSAIDs was 0.72. Therisk was 0.95 among short term users
(< 1 month), 0.83 among intermediate term (mostly < 24 months) and 0.27 for long
term (mostly> 24 months) users. The pooled relative risk in 8 studies of aspirin
use was 0.87. It was concluded that NSAIDs offer some protection against the
development of Alzheimer's disease.
The report appeared in the July 19 issue of the British
Medical Journal.
Full reference
Imaging techniques help distinguish between Alzheimer's and vascular dementia
A combination of magnetic resonance imaging (MRI) and MR
spectroscopy has enabled researchers to differentiate between
Alzheimer’s and dementia caused by poor blood flow (vascular
dementia). Comparison of the brains of those with Alzheimer’s,
those who had suffered subcortical ischemic vascular dementia
(SIVD), and those belonging to cognitively normal older adults,
also found significant differences in the chemical signature of
various brain regions, leading researchers to suggest that in
patients with SIVD, there may only be neuronal dysfunction
rather than neuronal loss, offering hope for recovery of
neuronal function in these areas. More research is needed to
confirm these results.
The study appeared in the August 12 issue of
Neurology.
Full reference
High cholesterol risk factor for the development of Alzheimer-related amyloid deposits
A review of autopsy cases of patients over 40 years old found that high blood
cholesterol levels were correlated with the presence of amyloid deposits in the
brain in the youngest subjects (aged 40-55).
The report appeared in the July 22 issue of Neurology.
Full reference
