Alzheimer's, Dementia & Mental Health
Mayo Clinic Finds More Seniors With Mild Cognitive
Impairment Than Assumed
Another study finds help for these pre-Alzheimer's
patients; another finds diabetes treatment seems to fight brain-damaging
plaque associated with AD
July
29, 2008 Mayo Clinic researches have found more cases of mild
cognitive impairment among older senior citizens than expected, but the
good news from another study reports a compound called AL-108 appears to
improve memory for these MCI patients. There was also good news on
reducing the plaques associated with Alzheimers with insulin and
anti-diabetes medicine. The studies were among those presented yesterday
at the 2008 Alzheimer's Association International Conference (ICAD 2008)
in Chicago.
● A Phase II trial, of the compound
AL-108, targeted early abnormal brain changes in a protein called "tau"
in a condition related to Alzheimer's called mild cognitive impairment
(MCI). The researchers saw improvement on various measures of memory.
● Another study examined brains of people
with Alzheimer's: half of whom had diabetes and half did not. The
researchers found that people in the study who took a combination of
insulin and oral anti-diabetes medications had fewer Alzheimer's-related
brain changes (amyloid plaques) than all the others in the study. This
could be a pathway for developing new treatments.
● The new study from the Mayo Clinic
showed higher than expected rates of MCI in a large, older population.
People with MCI have ongoing memory problems, but they do not have other
losses such as confusion, attention problems, and difficulty with
language.
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Read the latest news on
Alzheimer's, Dementia & Mental Health |
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People with MCI are much more likely to get
Alzheimer's than the general population.
"We are making progress. It is very important that
we have as many drugs as possible in the pipeline for Alzheimer's, and
that we explore every available avenue for treatments," said Ralph
Nixon, MD, PhD, of the Alzheimer's Association's Medical and Scientific
Advisory Council.
"However, the population is aging, and we need to
make significant advances soon in treatment and prevention of
Alzheimer's or it will become an overwhelming epidemic, wiping out our
healthcare resources and devastating Medicare."
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From the Alzheimers Association
●
What is Alzheimer's
Warning signs, diagnosis, treatments, risk factors, stages
and more.
●
The Year in Science
Advances in Alzheimer research.
●
CareSource
Online services to help you with care planning and decision
making. |
Dr. Nixon is Professor of Psychiatry and Cell
Biology, Vice Chairman of Research in the Department of Psychiatry, and
Director of the Silberstein Institute at New York University School of
Medicine. Dr. Nixon is also Director of Research and the Center for
Dementia Research at the Nathan S. Kline Institute for Psychiatric
Research.
Rates of Cognitive Impairment Higher Than
Anticipated
As the field of Alzheimer's research moves toward
earlier treatment and ultimately prevention, it becomes necessary to
identify patients at the earliest point in the disease. Mild Cognitive
Impairment (MCI) is the term used to describe the intermediate state
between normal aging and the very earliest features of Alzheimer's, but
its frequency in the population is not known.
Ronald C. Petersen, MD, PhD, and colleagues at Mayo
Clinic, Rochester, MN, are conducting the Mayo Clinic Study of Aging,
which is a longitudinal study of people ages 70 to 89 from Olmsted
County, Minnesota.
One of the goals of the Study is to follow healthy
subjects over time to detect the earliest point of cognitive impairment.
In 2004, the researchers recruited 1,786 people who were found to be
cognitively normal, and reevaluated them a year later. All subjects
underwent a baseline evaluation including an interview of the subject
and their study partner by a nurse, a cognitive assessment, and a
neurological exam by a physician.
Individuals in the study developed MCI at a rate of
about 5.3 percent per year, and this rate was higher with advanced age
about 3.5 percent per year for 70-79 year olds and about 7.2 percent per
year for 80-89 year olds.
Men were nearly twice as likely to develop MCI as
women.
"The rate of new MCI cases in this group was
considerably higher than anticipated," Petersen said.
"If we extrapolate Alzheimer's incidence rates to
MCI, we would expect perhaps 1 to 2 percent per year, but our findings
were substantially higher than that."
"These results underscore the urgency of developing
new and better strategies to create disease modifying therapies for
Alzheimer's. In addition, for public health purposes, we need to know
how many people are cognitively impaired and potentially on the road to
Alzheimer's," Petersen added.
AL-108 Trial (Phase IIa) Shows Promise of
Tau-Targeted Therapies in MCI
MCI can be divided into two broad subtypes.
Amnestic MCI (aMCI) significantly affects memory, while nonamnestic MCI
does not. Other functions, such as language and attention span, may be
impaired in either subtype. Persons with aMCI convert to Alzheimer's at
a much higher rate than the normal aging population.
Donald Schmechel, MD, Adjunct Professor of Medicine
(Geriatrics), Professor of Psychiatry, and Associate Professor of
Neurobiology of Duke University Medical Center, Durham, NC, and
colleagues conducted a Phase IIa clinical trial of AL-108 (Allon
Therapeutics), an experimental therapy designed to combat
neurofibrillary tangles (NFT).
NFT are one of the early key abnormal brain changes
in aMCI and Alzheimer's. AL-108 is a nasal spray formulation of an eight
amino acid peptide, known as NAPVSIPQ, derived from the neuroprotective
protein Activity-Dependent Neuroprotective Protein.
The trial was a double-blind, randomized,
placebo-controlled study to evaluate the safety, tolerability and effect
of two doses of AL-108 after 12 weeks of treatment (low dose=5 mg daily,
high dose=15 mg twice daily).
The study was open to men and women, age 55-85
years (inclusive, mean age=69.4) with Mini-Mental State Exam scores ≥24,
self-reported memory complaint corroborated by spouse or companion, and
Wechsler Memory Scale III (WMS-III) age-adjusted Logical Memory II score
≤5. One hundred forty-four (144) subjects were randomized at 16 centers
in the U.S. Cognitive tests were conducted four weeks prior to drug
administration, and then at baseline, four, eight, 12, and 16 weeks.
The primary endpoint is a change from baseline at
Week 12 in a composite score that focuses on measures of memory.
Secondary efficacy endpoints include analysis of the change in the
individual cognitive tests as a function of both treatment and length of
treatment.
High dose AL-108 gave a statistically significant
improvement in the delayed match-to-sample test (DMTS 12s). After four
weeks, a 34.2 percent change from baseline (p=0.067, versus placebo) was
seen; by Week 16, a 62.4 percent improvement from baseline was observed
(p=0.038, versus placebo), showing a durable response four weeks after
treatment ended.
An improvement on the digit span forward test of
the high dose group became statistically significant at Week 8, with an
11.2 percent change from baseline (p=0.032, versus placebo), and
remained significant at Week 16 with an 11.7 percent change from
baseline (p=0.052, versus placebo).
The low dose AL-108 was not different from placebo.
AL-108 was well tolerated with similar rates of adverse events (AEs) in
placebo and AL-108 treated subjects. The most common AE was headache
which occurred at a rate expected in this patient population. No serious
AEs were associated with AL-108.
"Twelve weeks of AL-108 treatment given
intranasally by spray resulted in a statistically significant,
dose-dependent and durable improvement on measures of short-term memory,
including visual, verbal, and auditory working memory, which is a type
of memory function that deteriorates throughout the progression of
Alzheimer's," Schmechel said.
"This makes AL-108 the first drug to validate in
humans the importance of the tangle' or tau' pathway in Alzheimer's.
Based on these results in MCI, there are plans for further development
of AL-108 in Alzheimer's," Schmechel added.
Insulin and Diabetes Drugs May Reduce
Alzheimer's Brain Lesions
Several large-scale studies have shown that people
with diabetes have a higher risk of developing Alzheimer's than persons
without diabetes. At the same time, previous research showed that some
people with diabetes had fewer Alzheimer's-associated brain lesions than
non-diabetics.
Michal Schnaider Beeri, PhD, of the Mount Sinai
School of Medicine, New York, and colleagues hypothesized that the
treatment of diabetes with insulin and other drugs may have helped
reduce the observable brain damage attributed to Alzheimer's. At ICAD
2008, they reported the results of a study examining the brains of 124
persons with diabetes and 124 without diabetes, of comparable age, sex,
and dementia severity, from the Mount Sinai School of Medicine Brain
Bank.
Diabetic subjects were classified according to
their recorded lifetime anti-diabetic medications:
> none (29),
> insulin only (49),
> diabetes medications other than insulin only (28), or
> concomitant use of both insulin and any oral anti-diabetic
medications (18).
Densities of Alzheimer's-associated brain lesions,
known as amyloid plaques and neurofibrillary tangles, were assessed in
several brain regions.
The researchers found that diabetic subjects who
were treated with both insulin and oral hypoglycemic agents had
significantly fewer amyloid plaques (as much as 80 percent) than people
in all the other categories. These other groups of subjects did not
differ from each other in their Alzheimer's-related brain
characteristics.
"These results suggest that the combination of
insulin and oral anti-diabetes medications may beneficially influence
Alzheimer's-related brain changes," Beeri said. "This also points to
biological pathways in the brain, such as insulin signaling, that might
be a focus for developing new treatment strategies."
Editors Notes:
About ICAD
The 2008 Alzheimer's Association International Conference on
Alzheimer's Disease (ICAD 2008) is the largest gathering of
international leaders in Alzheimer research and care ever convened. At
ICAD 2008, more than 5,000 researchers from 60 countries 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 2008 will be held in Chicago at McCormick
Place, Lake Side Center from July 2631.
About the Alzheimer's Association
The Alzheimer's Association, the nonprofit world leader in
Alzheimer's 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.
>> Ronald C. Petersen, "The Mayo Clinic study of
aging: Incidence of mild cognitive impairment." (Funders: National
Institute on Aging; Robert H. and Clarice Smith and Abigail Van Buren
Alzheimer's Disease Research Program of the Mayo Clinic)
>> Donald E. Schmechel. "A phase 2,
double-blind, placebo-controlled study to evaluate the safety,
tolerability, and effect on cognitive function of AL-108 after 12 weeks
of intranasal administration in subjects with mild cognitive
impairment." (Funder: Allon Therapeutics)
>> Michal Schnaider Beeri. "Combination of
insulin with other diabetes medication is associated with lower
Alzheimer's neuropathology." (Funder: National Institute on Aging)
