News reports of research into Alzheimer's disease Jan - June 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.
June
More evidence that mental exercise helps prevent or postpone dementia
Another study provides support for the idea that mentally demanding
activities can help stave off dementia. The study involved 469 people aged 75
and older. Over the course of the study, dementia developed in 124 of the
participants (Alzheimer's disease in 61,
vascular dementia in 30, mixed dementia in 25, and other
types of dementia in 8). Those who participated at least twice weekly in
reading, playing
games (chess, checkers, backgammon or cards), playing
musical instruments, and dancing were significantly less likely to develop
dementia. Although the evidence on crossword puzzles was not quite statistically
significant, those who did crossword puzzles four days a week had a much lower
risk of dementia than those who did one puzzle a week. Most physical activities,
like group exercise or team games, had no significant impact. The only exception
- ballroom dancing - possibly occurred because of the mental demands of
remembering dance steps, responding to music and coordinating with a partner.
Although the study was careful to include only those who showed no signs of
dementia at the start, it cannot be ruled out that people in pre-clinical stages
of dementia may be less likely to participate in mentally demanding activities.
The study was published in the June 19 issue of the New
England Journal of Medicine.
Full reference
Effects of Alzheimer's disease may be influenced by education
New findings from the Religious Orders Study (ROS), a long-running
prospective study of aging and cognitive function in Catholic clergy, provides
evidence that formal education may provide a cognitive reserve or a
"neuroplasticity" that can reduce the effect of AD brain abnormalities on
cognitive function in later life. A post-mortem study of the brains of 130
participants who had all undergone cognitive testing some months before death,
found that the relationship between cognitive performance and the number of
amyloid plaques in the brain (characteristic of Alzheimer’s) changed with level
of formal education. The more years education you had, the less effect the same
number of plaques had on actual cognitive performance. For example, an
84-year-old woman in the most highly educated group (postgraduate work after
college) might score 98.1 (on a scale where the average participant scores 100)
in the absence of any plaques. The same age woman with the least education (some
college attendance) would score 96.8. In the presence of about 18 plaques (more
than the number required for a diagnosis of Alzheimer’s), the more highly
educated woman's score would drop about two points, to 96.2, while the score of
the woman with less formal education would drop more than 14 points, to 82. It’s
worth noting that this considerable difference was observed in a population
where even the least educated had some college attendance; presumably the
difference would be even more marked in the general population.
The research was published in the June 24 issue of
Neurology.
Full reference
http://www.eurekalert.org/pub_releases/2003-06/rpsl-rrf062303.htm
No benefit from Rofecoxib or Naproxen
A study of 351 patients with mild to moderate Alzheimer’s
compared the effects of treatment with a selectivecyclooxygenase
(COX) -2 inhibitor (rofecoxib) or a traditionalnonselective
NSAID (naproxen) against that of a placebo. The trial lasted a
year. No benefit was found for either treatment.
The report appeared in the Journal of the
American Medical Association.
Full reference
http://www.eurekalert.org/pub_releases/2003-06/gumc-uoc060203.htm
Buildup of amyloid plaques linked to gene inhibition
Examination of genetically engineered mice and of brain tissue
from deceased Alzheimer's patients has found that the buildup of
amyloid plaques in the brain dramatically inhibits six genes
known to be important for the formation of new memories. The
finding suggests a new approach to the treatment of Alzheimer’s
disease, combining amyloid-lowering treatment with other
strategies designed to block the effect of amyloid on these
genes.
The results were reported in the June 15 issue of the
Journal of Neuroscience.
Full reference
http://www.eurekalert.org/pub_releases/2003-06/uosf-sla062503.htm
New diagnostic marker for Alzheimer's disease
A mouse study has unexpectedly revealed that a protein that
senses changes in calcium levels can be used to estimate the
extent of cognitive deficits caused by toxic amyloid peptides
found in Alzheimer brains. The discovery came about when
researchers found that those mice with learning and memory
deficits had not only the expected high level of amyloid
peptides in their brains, but also had very low levels of a
protein called calbindin that binds calcium and regulates
functions in granule cells, located in the dentate gyrus (a
region that plays an important role in memory formation).
Examination of autopsy brain tissue from Alzheimer sufferers has
confirmed this finding. It is hoped that this will prove a
valuable diagnostic marker.
The findings were reported in the
Proceedings of the National Academy of Sciences.
Full reference
http://www.eurekalert.org/pub_releases/2003-07/uoc--bcs071003.htm
Exelon more effective than thought
Exelon ® (rivastigmine tartrate) is one of the drugs used to treat the
symptoms of mild-to-moderate Alzheimer’s. A new study suggests that the effects
of Exelon might be more significant than was thought — it may be able to delay
progression of the disease. The study found that 26 weeks after discontinuing
treatment , those who had been on Exelon showed less cognitive decline than
patients who had previously taken a placebo.
The study appeared in the June issue of Archives of
Neurology.
Full reference
http://www.eurekalert.org/pub_releases/2003-06/iu-mms061703.htm
May 2003
Insulin-degrading enzyme may affect risk of Alzheimer’s disease
A new mouse study suggests that low levels of insulysin, an
enzyme that degrades insulin, could increase the risk for
Alzheimer's, and points to a new mechanism linking diseases like
diabetes and Alzheimer's — the competition of multiple
substrates, such as insulin and amyloid-beta, for a limiting
amount of the insulysin enzyme. The insulysin enzyme, it seems,
also degrades amyloid-beta peptides, and even a partial decrease
in insulysin activity was found to raise amyloid-beta peptide
levels in the brain.
The study was published online before print in
Proceedings of the National Academy of Sciences.
Full reference
http://www.eurekalert.org/pub_releases/2003-05/uots-iem050603.htm
Cholesterol not a risk factor for Alzheimer's
Previously, the long-running, large-scale Framingham study found people with
elevated levels of homocysteine in the blood had nearly double the risk of
developing Alzheimer’s disease (AD). The study now clarifies the inconclusive
results from previous studies regarding whether plasma cholesterol levels are
associated with increased risk of Alzheimer disease (AD). They found that, after
adjustment for age, sex, APOE
genotype,smoking, body mass index, coronary heart disease,and diabetes, there
was no significant association between ADrisk and cholesterol level.
The study was reported in the May 12 issue of the
Archives of Internal Medicine.
Full reference
http://archinte.ama-assn.org/cgi/content/abstract/163/9/1053
For women over 65, Combined Hormone Therapy increases risk of dementia
Much to the researchers’ surprise and disappointment, a
four-year experiment involving 4,532 women at 39 medical
centers, has found that combined hormone therapy (involving both
estrogen and progestin) doubles the risk of Alzheimer's disease
and other types of dementia in women who began the treatment at
age 65 or older, although the risk is still small : for every
10,000 women 65 and older who take hormones, 23 of the predicted
45 cases of dementia a year, will be attributable to the
hormones. The study also found that the combined hormone therapy
produced no improvement in general cognitive function, and in
fact had adverse effects on cognition among some women. This
supports an earlier study suggesting that, while estrogen is
helpful to cognitive function in postmenopausal women, the
benefits can be cancelled out by progestin / progesterone. The
study also confirmed previous research showing that the
combination therapy increased the risk of stroke - previous
research has indicated that risk factors for stroke are also
risk factors for cognitive decline.
The study was published in the May 28 issue of the
Journal of the American Medical Association.
Full reference
2
3
http://www.eurekalert.org/pub_releases/2003-05/wfub-chr052203.htm
April 2003
A new approach to slowing the progression of Alzheimer’s
Researchers have discovered the molecules that play a
critical role in making the brain think it is under attack from
the amyloid plaques characteristic of Alzheimer’s disease.
Microglial cells detect beta amyloid plaques and gear up to
fight them as foreign invaders. However, for some unknown
reason, they don’t follow through on the attack, but remain
inflamed. It is this inflammation that causes a lot of the
problem. Research has now shown that the microglial cells at
least four different receptor proteins to bind to the amyloid.
Each one of these receptor proteins act together at the same
time to drive the inflammation. This discovery suggests a new
approach to treating Alzheimer’s — finding a means to block
these receptors.
The study was published in the April issue of the
Journal of Neuroscience.
Full
reference
http://www.eurekalert.org/pub_releases/2003-04/cwru-mti042903.htm
New Drug for Moderate-to-Severe Alzheimer's
Four drugs — donepezil (marketed as ARICEPT®), galantamine
(Reminyl®), rivastigmine (Exelon®),and tacrine (Cognex®) — are
approved for treatment of mild-to-moderate Alzheimer's disease
in the U.S., but there are no approved treatments for severe AD.
Now an industry-sponsored study has examined memantine for this
use. The study involved 252 patients with moderate-to-severe AD,
over a period of28 weeks. Patients were evaluated on 7 tests of
cognition, functional capacity, and behavior. Outcomes were
significantly better with memantine than with placebo on 4 of
these scales, and no significant adverse events were noted. It
is not clear yet how clinically meaningful these small
improvements are. Memantine has been approved for use in Europe.
The report appeared in the April 3 issue of the
New England Journal of Medicine.
Full reference
http://www.eurekalert.org/pub_releases/2003-04/nyum-dsp032603.htm
ARICEPT® helpful in treating patients with severe Alzheimer's
A new analysis from the Moderate to Severe Alzheimer's Disease Study (MSAD),
previously published in Neurology in August 2001, suggests that ARICEPT® may
also be helpful to those with more advanced Alzheimer’s. The study involved 145
patients with severe Alzheimer's disease who were residing in the community or
in assisted living settings. Patients requiring total nursing care were
ineligible. ARICEPT®-treated patients showed cognitive improvement ; improved or
stable global function; less decline on activities of daily living; fewer
behavioral disturbances. Some 10% had to drop out because of adverse reactions.
The data were presented at the American Academy of Neurology (AAN) 55th Annual
Meeting.
http://www.eurekalert.org/pub_releases/2003-04/ei-nsf040303.htm
Cholesterol-lowering drugs shown to decrease predictor of Alzheimer's
In a recent study, cholesterol-lowering medications known as statins lowered
brain cholesterol levels in Alzheimer’s patients by 21.4%. Brain cholesterol is
involved in the formation of amyloid plaques. The findings from this research
provide information about the safety and efficacy of a reasonable dose of a
statin on the reduction of brain cholesterol, and pave the way for research to
find out what effect statins have on the cognitive impairment of people with
Alzheimer’s.
The report appeared in the April issue of the Archives of
Neurology.
Full reference
http://www.eurekalert.org/pub_releases/2003-04/uots-cds041703.htm
DHEA supplement shows no effect on Alzheimer's
The supplement dehydroepiandrosterone, or DHEA, had no effect
on Alzheimer's patients who took the supplement for six months.
A transient benefit on cognitive performance occurred at three
months, but was not statistically significant. Of the 58 people
who started the study, 46 completed three months of treatment
and 33 completed six months of treatment. The small size of the
study and the high number of people who dropped out may limit
the findings of the study.
The study was published in the April 8 issue of
Neurology.
Full
reference
http://www.eurekalert.org/pub_releases/2003-04/aaon-dss033103.htm
March 2003
Activity in the mediotemporal lobe lower in elderly with poor memory
An imaging study has revealed that, although
there is no difference on standard MRI scans,scans showing the amount of
oxygen (and thus activity) find that elderly persons with a poor memory
have less activity in the mediotemporal lobe when storing new
information than elderly persons with a normally functioning memory.This
more sensitive scan may help early diagnosis of Alzheimer's. You can see
an image of the brain scans at
www.nwo.nl/news.
The research was done as part of a doctoral thesis by Dr Sander
Daselaar.
http://www.eurekalert.org/pub_releases/2003-03/nofs-svp032103.htm
http://www.nwo.nl/NWOHome.nsf/pages/NWOP_5KRH7V?OpenDocument&g=NWO&n=ACPP_4WMESE&rc=1
High-dose vitamin regime may help slow Alzheimer's
A preliminary study suggests that a regime of high
doses of folic acid, B12 and B6 reduces levels of homocysteine in people with
mild to moderate Alzheimer’s. A larger study, recruiting 400 participants from
all over the U.S., is to be undertaken to assess whether such a vitamin regime
can slow the progression of Alzheimer's disease. In the meantime, it is not
advised that people take high doses of these vitamins, as there are possible
side-effects, including peripheral nerve damage.
The report was published in the March /April issue of the
American Journal of Geriatric Psychiatry.
Full
reference
http://www.eurekalert.org/pub_releases/2003-03/gumc-cvs031403.htm
Common painkillers may help protect against Alzheimer’s disease
Observations that people who take
anti-inflammatory medications over several years have a lower risk of later
developing Alzheimer's disease have received support from an exciting new study
which has revealed that common over-the-counter pain medications (such as
ibuprofen and naproxen) bind to amyloid plaques, and may help dissolve existing
plaques and prevent the formation of new ones. Amyloid plaques are one of the
definitive hallmarks of Alzheimer's disease.
The findings are reported in the March 31 issue of
Neuroscience.
Full reference
http://www.eurekalert.org/pub_releases/2003-03/uoc--urd031203.htm
Gene transfer reduces levels of key Alzheimer's disease protein
An animal study has found that a molecule that naturally degrades of the
protein beta-amyloid (the substance in the amyloid plaques indicative of
Alzheimer’s) appears to reduce the levels of that protein by nearly 50% when
delivered by gene therapy.
The findings appear in the March 15 issue of the Journal
of Neuroscience.
Full reference
http://www.eurekalert.org/pub_releases/2003-03/si-gtr032003.htm
February 2003
Alzheimer patients who scored well on memory tests show unique compensatory brain activity
A study of 12 healthy older adults and 11 older
patients with probable early-stage Alzheimer's compared their performance in a
series of semantic and episodic memory tasks on a computer screen, using PET
scans. Overall, Alzheimer's patients performed less accurately on the semantic
and episodic tasks compared to the normal controls. However, the range of scores
was quite large in the Alzheimer group, with some performing poorly and others
performing within the normal range. For those patients who did better on the
memory tasks, researchers found that their prefrontal network activity was more
expansive compared to the error-prone patients. This additional activity was
happening in the right frontal and temporoparietal areas. It was a unique neural
pattern not found in the controls either. This provides the most direct evidence
to date that Alzheimer's patients can use additional neural resources in the
prefrontal cortex to compensate for losses attributable to the degenerative
process of the disease.
The study was published in the February 1 issue of the
Journal of Neuroscience.
Full reference
http://www.eurekalert.org/pub_releases/2003-02/bcfg-apw013103.htm
January 2003
Verbal memory tests predict dementia
The Longitudinal Aging Study
Amsterdam tested the memories of a large group of elderly people
on two occasions, two years apart. Performance on the memory
tests was then compared between those who developed dementia
during those two years and those who did not. It was found that
those who later were found to have dementia were scarcely better
at remembering word pairs clearly linked in meaning (for
example, pipe - cigar) than word pairs without such a link (for
example nail - butter), on the first test. (those who not have
dementia two years later did, as is usual, benefit from such a
link in meaning). In addition, those in the early stage of
dementia did not benefit from the repeated presentation of
words. The results suggest a means by which elderly people in
the early stages of dementia can be identified, which is
important because the drugs used to inhibit dementia only work
in the earliest stages of the disease.
This was revealed in doctoral research by the neuropsychologist
Pauline Spaan from the University of Amsterdam.
http://www.eurekalert.org/pub_releases/2003-01/nofs-mtp012403.htm
