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Alzheimer's, Dementia & Mental Health
IVIg Headlines Alzheimer's Treatments at
International Conference
Therapies show promise, address
multiple aspects of the disease
July 19, 2006 – In April of last year,
SeniorJournal.com published a story, " IVIg Therapy May Improve
Cognitive Function in Alzheimer's Patients," that became one of the most
read stories the Website had ever published (see story in sidebar). Yesterday, IVIg was a hot
topic again at a conference in Madrid sponsored by the Alzheimer's
Association. It was, however, among several drugs showing promise in
the battle against Alzheimer's that were discussed at the conference.
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IVIg Therapy May Improve Cognitive Function in
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April 12, 2005 - In what could prove to be an
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physician-scientists say the results of an initial (Phase I) clinical
study provide encouraging evidence that antibodies derived from human
plasma can capture the beta-amyloid protein in blood and exert positive
effects on patients' thinking abilities.
Read more...
Diabetes Drug Shows Promise in Treating Alzheimer’s
In
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July 17, 2006 – It’s a small study but the results
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Brain Injections May Be Way to Stop Alzheimer’s
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April 18, 2005 – In a report being released today,
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injection of anti-beta-amyloid that inhibited the development of the
plaque without producing the serious side-effects seen in prior attempts
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Alzheimer's Dementia Drug Approved for Parkinson's
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Exelon gains FDA approval as first to treat this
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June 28, 2006 – Exelon (rivastigmine tartrate), a
drug already used to treat mild-to-moderate dementia associated with
Alzheimer's disease, got the nod yesterday from the Food and Drug
Administration to become the first medication available for the
treatment of this condition when associated with Parkinson's disease. It
is estimated that about 0.2 percent to 0.5 percent of senior citizens
over age 65 are affected by Parkinson's dementia and experience such
symptoms as impairments in executive function, memory and attention.
Read more...
Read more
on
Alzheimer's, Dementia & Mental Health |
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“The world’s population is growing rapidly larger
and older, and Alzheimer’s diagnoses will sharply increase,” said Steven
Ferris, Ph.D., a member of the Alzheimer’s Association’s Medical &
Scientific Advisory Council. “We desperately need major breakthroughs in
new therapies to reduce disability and suffering, and control costs.
Therefore, it is very important that we have a diverse drug pipeline and
investigate all viable options that might slow progression or prevent
the disease.”
Ferris is Friedman Professor in the Department of
Psychiatry at New York University (NYU) School of Medicine, and Director
of the Alzheimers Disease Center at NYU's Silberstein Institute.
Following are summaries of some of the
presentations on Alzheimer's treatments presented at the 10th
International Conference on Alzheimer's Disease and Related Disorders (ICAD).
● IVIg may promote removal of beta amyloid -
Antibodies provide lasting benefits in Alzheimer’s
Intravenous immunoglobulin (IVIg) is a purified mixture of human
antibodies that has proven effective in several immune system disorders.
It also may promote removal of beta amyloid from the body.
Beta amyloid is an abnormal protein that collects
in the brain and is considered central to the progression of
Alzheimer’s.
In a previous study, IVIg treatment for six months
improved or stabilized cognitive test results of eight patients with
mild to moderate Alzheimer’s (mean age 75). When therapy was stopped,
the IVIg treated patients rapidly declined.
Norman R. Relkin, M.D., Ph.D., from Weill Cornell
Medical College, New York City, and colleagues resumed their IVIg trial
as a low dose, open label study for an additional nine months with the
eight previously-treated patients. Participants received IVIg at a dose
of 1g/kg/2 weeks for 3 months followed by 0.4g/kg/2 weeks for 6 months.
Subjects were maintained on stable doses of their regular Alzheimer’s
drugs during the study. Mental status was assessed every three months.
The researchers found that participants’ cognitive
status remained stable throughout the first three months of follow-up
treatment and trended upward in the majority of cases (six out of eight)
during the remaining six months.
This is the first study to demonstrate that IVIg
can have lasting benefits in Alzheimer’s when administered over a year
or more.
“This study suggests that IVIg can exert long-term
benefits for the treatment of cognitive decline in Alzheimer’s,” Relkin
said. “In our eight participants, we observed that spinal fluid beta
amyloid levels were reduced by more than a third over 18 months. This is
consistent with the movement of amyloid out of the central nervous
system and into the blood stream where it can be cleared from the body.
That is a very positive sign.”
(To
learn more about IVIg, click here to story
from 2005.)
● Anti-inflammatory drug may be effective in
Alzheimer’s
Research has uncovered signs of inflammation in brain regions affected
by Alzheimer's, and observational studies have shown that groups of
people who take large doses of nonsteroidal anti-inflammatory drugs
(NSAIDs) have a reduced likelihood of developing Alzheimer's. However,
clinical trials of anti-inflammatory compounds in Alzheimer’s have so
far been unsuccessful.
Triflusal, a medication used as an antiplatelet
agent in prevention of cerebral and myocardial infarction, also has been
shown to have potent anti-inflammatory effects in the central nervous
system. Teresa Gomez-Isla, M.D., from Hospital Santa Creu i Sant Pau,
Barcelona, Spain, and colleagues have completed preliminary research
demonstrating that triflusal lowered the probability of progression to
Alzheimer’s in a group of people with amnestic mild cognitive impairment
(MCI). Amnestic MCI means memory impairment but not dementia, and having
it increases the risk of progression to Alzheimer’s.
A total of 257 study subjects (129=triflusal,
128=placebo) were randomized to receive placebo or triflusal (900 mg per
day) for 18 months. A very slow rate of recruitment forced a premature
cessation of the study after an average follow-up of 13 months. Over the
course of this time, 41 participants developed dementia (16=triflusal,
25=placebo), a rate of 16% per year. Triflusal therapy was well
tolerated.
The researchers found that the probability of
progression to dementia was significantly lower in the treated group
than in the placebo group (hazard ratio, 2.10; 95 percent confidence
interval, 1.10 to 4.01; p=0.024; adjusted analysis by baseline ADAS-cog
and geographical zone).
“MCI represents a critical point for early
intervention in Alzheimer’s disease,” said Gomez-Isla. “However, because
this trial was prematurely halted, these results should be interpreted
with great caution. Nonetheless, the effect of Triflusal in this study
is a hopeful signal to continue this research.”
● Lithium may have therapeutic role in Alzheimer’s
Lithium is believed to inhibit GSK-3, a common enzyme that is involved
in producing tau tangles, which are hallmark lesions in the brains of
people with Alzheimer’s.
Peter Annas, Ph.D., from AstraZeneca R&D
Sodertalje, Sweden, and colleagues conducted a 10-week
placebo-controlled study of 71 Alzheimer patients (33 treatment, 38
placebo) to investigate whether lithium could inhibit GSK-3 in humans
and improve the cognitive symptoms of Alzheimer’s. The effect of lithium
on the tangle producing process was measured assessing levels of key
enzymes and various forms of tau in blood and cerebrospinal fluid. The
effect on the Alzheimer’s symptoms was measured through three well
established tests of thinking and memory (ADAS-cog, MMSE and NPI).
Though not statistically significant, initial
results showed a 30 percent improvement (defined as a reduction of 4
points or more on the ADAS-Cog scale) in the lithium group as compared
to a 10 percent improvement in the placebo group. Other results are
forthcoming.
“A 10-week study is quite short when compared to
conventional Alzheimer studies,” said Annas. “Our preliminary results
warrant additional studies with more potent GSK3 inhibitors.”
● Memantine may reduce Alzheimer’s tau tangles
Memantine, a moderate affinity N-methyl-D-aspartate receptor antagonist,
is approved for treatment of moderate to severe Alzheimer’s. It appears
to work by regulating the activity of glutamate, one of the brain’s
specialized messenger chemicals involved in information processing,
storage, and retrieval. In studies using rat brains, memantine has been
shown to inhibit and reverse the formation of tau tangles.
To investigate if this is also true in people,
Malin Degerman Gunnarsson, M.D., and colleagues from the Department of
Public Health/Geriatrics, Uppsala, Sweden, evaluated several chemical
markers in cerebrospinal fluid (CSF) in 11 Alzheimer’s patients taking
memantine therapy. Nine of the subjects also were taking cholinesterase
inhibitors, which are approved for treatment of mild to moderate
Alzheimer’s.
After one year, the researchers found a
statistically significant reduction of p-tau, the abnormally
phosphorylated tau associated with Alzheimer’s tangles, in CSF. No
statistically significant difference of total tau or ß-amyloid was
found.
“The results may reflect the effects of memantine
on a key abnormality in the Alzheimer’s brain,” concluded Gunnarsson.
“However, studies in larger number of patients are needed.”
“The diversity of therapies in the pipeline for
Alzheimer’s, as represented by the wide variety of studies reported at
ICAD this year, is very exciting,” said Khalid Iqbal, Ph.D., co-founder
of ICAD and co-chair of the Scientific Program Committee. “While the
‘amyloid cascade’ may be the most popular theory of the Alzheimer’s and
deserves significant attention, it is extremely important that we pursue
a wide variety of avenues to treat and prevent this devastating
disease.”
● About ICAD
The 10th International Conference on Alzheimer's Disease and Related
Disorders (ICAD), presented by the Alzheimer's Association, is the
largest gathering of Alzheimer researchers in history. At ICAD 2006,
more than 5,000 researchers will share groundbreaking information and
resources on the cause, diagnosis, treatment and prevention of
Alzheimer’s and related disorders. As a part of the Association’s
research program, ICAD serves as a catalyst for generating new knowledge
about dementia and fostering a vital, collegial research community. ICAD
2006 will be held at IFEMA Feria de Madrid, Centro de Convenciones,
North Section - Hall 9 and 10, IFEMA Convention Center, Madrid, Spain.
● About the Alzheimer’s Association
The Alzheimer’s Association, the nonprofit world leader in Alzheimer
research and support, is the first and largest U.S. voluntary health
organization dedicated to finding prevention methods, treatments and an
eventual cure for Alzheimer’s. For more than 25 years, the
donor-supported Alzheimer’s Association has provided reliable
information and care consultation; created supportive services for
families; increased funding for dementia research; and influenced public
policy changes. For more information, call (800) 272-3900 or visit
www.alz.org.
Presentations:
● Norman R. Relkin – Intravenous
Immunoglobulin (IVIG) Maintains Cognition over 18 Months in Patients
with Alzheimer’s Disease (AD) (Funders: NIH, Baxter BioScience,
Citigroup Foundation, Harvey Goodstein Charitable Trust)
● Teresa Gomez-Isla – A Randomized, Double-Blind, Placebo
Controlled-Trial of Triflusal in Mild Cognitive Impairment (Funder:
Uriach Lab)
● Peter Annas – A Randomised, Single-Blind, Placebo-Controlled,
Multicentre Study to Investigate the Pharmacodynamic Effects of Lithium
on GSK-3 Activity in Patients with Mild Alzheimer’s Disease (Funder:
AstraZeneca R&D Södertälje, Sweden)
● Malin Degerman Gunnarsson – Reduction of Hyperphosphorylated-Tau by
Memantine Treatment of Alzheimer’s Disease (Funders: Alzheimer
Foundation of Sweden, Lundbeck)
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