Disease: A Summary of Research Findings -Part XVII
(11/26/16)- The results of a study, published recently online by the journal
JAMA International Medicine, that was funded by the National Institute on Aging
concluded that dementia rates are declining, even though the population is
The study found that the dementia rate in Americans 65 and older fell by 24%
over 12 years, to 8.8 percent in 2012 from 11.6 percent in 2000. In 2000,
people received a diagnosis of dementia at an average age of 80.71; in 2012,
the average was 82.4.
The study included 21,000 Americans 65 and older across all races, education
and incomes in the study known as the Health and Retirement Study. The study
required participants to recall 10 nouns immediately and after a delay; to
serially subtract 7 from 100, and to count backwards from 20.
(10/8/16)- 56% of persons aged
90 years or more with Alzheimer’s disease use psychotropic drugs whereas the
same figure was 48% among younger persons with Alzheimer’s disease and 38%
among those aged 90 years or more but without Alzheimer’s disease.
Psychotropic drugs include
antipsychotics, antidepressants and benzodiazepines and related drugs which are
used for anxiety and insomnia in short-term treatment. On the contrary, persons
aged 90 years or more with Alzheimer’s disease used less frequently
anti-dementia drugs (63%) when compared with younger persons with the same
(11/5/10)- The following is taken from an email sent by Physicians First
"Contrary to epidemiological studies suggesting that docosahexaenoic
acid (DHA) might lower risk for Alzheimer disease, a randomized trial in has found that DHA does not slow cognitive decline in
patients with AD.
Researchers randomized some 400 adults with mild-to-moderate AD to receive
DHA (2 g daily) or placebo for 18 months. At the end of treatment, there was no
difference between the groups in the rate of cognitive decline, as measured by
the Alzheimer's Disease Assessment Scale and the
Clinical Dementia Rating sum of boxes.
Given their findings, the authors conclude that "there is no basis for
recommending DHA supplementation" for patients with AD.
(1/28/09)- Researchers at Vanderbilt University concluded that long term
usage of antipsychotic drugs pose a substantial risk to the elderly and the
young. The results of the study were published in a recent edition of the New
England Journal of Medicine.
The study also found that the risk of death increased for patients receiving
larger doses of these drugs. Wayne Ray, a professor of preventive medicine at
Vanderbilt was the lead investigator for the study.
The drugs involved in the study were Zyprexa made by Eli Lilly & Co.,
Risperdal made by J&J, Seroquel made by AstraZeneca PLC and .Clozaril, made by Novartis AG..
Researchers for the study reviewed the medical records of about 277,000
Tennessee Medicaid enrollees for the years 1990 to 2004. About 46,000 of them
were taking atypical antipsychotic drugs and 44,000 were taking typical
antipsychotic drugs. About 187,000 were not taking any of the drugs. Patients
ranged in age from 30 to 74 years, with the average age being 46.
The researchers concluded that among patients taking the antipsychotic
drugs, there were about three sudden cardiac deaths for every 1,000
patient-years. The death rate was about half that level for the control group
of patients who were not taking any antipsychotic medications.
The study also found that the risk of death increased for patients receiving
larger doses of both kinds of drugs.
(1/13/09)-The dementia antipsychotic withdrawal trial
)DART-AD) long-term follow-up of a randomized placebo controlled trial
study appeared in The Lancet Neurology, Early Online Publication, 9
January 2009. It was conducted by Clive Ballard et al "for the DART-AD
investigators". These researchers looked at mortality in patients with
Alzheimer's disease (AD) who are prescribed antipsychotics. They were interested
in mortality data from a long-term placebo-controlled trial.
Between October 2001, and December 2004, patients with AD who resided in
care facilities in the UK were enrolled into a randomized, placebo-controlled,
parallel, two-group treatment discontinuation trial. Participants were randomly
assigned to continue with their antipsychotic treatment (thioridazine,
chlorpromazine, haloperidol, trifluoperazine, or
risperidone) for 12 months or to switch their medication to an oral placebo.
The primary outcome was mortality at 12 months. An additional follow-up
telephone assessment was done to establish whether each participant was still
alive 24 months after the enrolment of the last participant (range 24?54 months). Causes of death were obtained from death
The results indicated a reduction in survival in the patients who continued
to receive antipsychotics compared with those who received placebo. The
researchers concluded that there is an increased long-term risk of mortality in
patients with AD who are prescribed antipsychotic medication. These results
further highlight the need to seek less harmful alternatives for the long-term
treatment of neuropsychiatric symptoms in nursing homes.
Usually, antipsychotics are prescribed when a demented patient is agitated. It should be
noted that The Physicians' Desk Reference (PDR) labels these
medications with a blackbox warning indicating an
increased risk of death and/or strokes in these patients. We recently reviewed
a book, The Nursing Home Guide by Dr. Joshua D. Schor
(look in our index under books) who expressed an approach well worth quoting.
"Do I personally prescribe antipsychotics? Of course I do, but I do so
cautiously and only after talking to staff and family. I do follow the rules of
trying to wean the medications at least twice a year, unless there is a very
compelling reason not to...If you get in a tussle with the physician, ask him
or her to provide documentation that the proposed drug works and see what they
say." (p. 139-140) The need for long-term care
patient advocacy is an essential factor in enhancing quality of life in care
(5/24/06)- The February 2006 issue of the Archives of General Psychiatry
published a study that indicated that Alzheimer's patients with a lifetime
history of depression have increased plaques and tangles in the hippocampus
section of the brain and more rapid cognitive decline into dementia than those
who did not have depression. Present treatment outcomes for
this type of patient is less favorable.
(7/3/02)-After writing 16 articles on various aspects of Alzheimer's
disease, it would seem helpful to our readers to summarize what is known about
the disease as reflected in the many peer reviewed studies published in the
research literature. More detailed information on many of the items listed
below can be found in the various articles in this series.
These conclusions are subject to future research findings, but represent the
most recent state of knowledge in the field.
- Alzheimer' s disease is the most
prevalent neurodegenerative disease and is considered nonreversible at
- Alzheimer' s disease involves
progressive deterioration in intellectual abilities, namely loss of
memory, and, finally, in loss of mental and physical function.
- Behavioral symptoms associated with Alzheimer'
s disease include delusional thinking, suspiciousness,
hallucinations, agitation, violence and verbal outbursts. Many of these
symptoms may be amenable to pharmacological intervention.
- Roughly 7% of the population over 65 years of age has Alzheimer' s disease. (Common number used is 4 million
in the United States.
- There are two types of Alzheimer's disease; early onset
and late onset.
- Early onset familial cases of Alzheimer's disease are attributable
to mutations on chromosome 21 or to presenilin 1
gene on chromosome 14, or presenilin 2 on
chromosome 1. Accumulated evidence indicates that all these familial Alzheimer' s disease genes can induce death in neuronal
cells or augment their vulnerability to other insults.
- Familial Alzheimer' s disease
(early onset) is extremely rare, occurring in 5-10% of Alzheimer's disease
- The role of genes in late onset may be to
increase/modify the risk of developing Alzheimer' s disease by affecting
factors involved in the formation of plaques and tangles or other
Alzheimer' s disease related pathologies in the brain.
- Plaques are known to contain the B-amyloid
protein as the major pathologic constituent. The neurofibrillary tangles
are linked to a pathological relevant proteinaceous constituent known as
the tau protein.
- The incidence of Alzheimer's disease rises with age
over 65 at about 5% every 5 years.
- Mortality rates rise with increasing levels of
- Risk factors for Alzheimer' s
disease include increased age, the presence of apolipoprotein E- alleles,
familial aggregation of cases and Down's syndrome. However, risk factors
are not direct causes of the disease.
- A large body of data supports the hypothesis that
amyloid B-protein plays a causal role in development of
Alzheimer's disease, but is not sufficient to cause the disease. Beta
amyloid is a fragment of a much larger protein known as amyloid-precursor
- Risk for Alzheimer's disease is known to be influenced
by multiple genetic and environmental factors and aging. High fat diet may
substantially elevate the risk of developing Alzheimer's disease.
- Cerebrovascular disease intensifies the presence and
severity of Alzheimer's disease. In general, vascular disease is
associated with cognitive impairment.
- Alzheimer's disease pathology commonly includes the
occurrence of large numbers of neuritic plaques
and fibrillary tangles.
- The onset of Alzheimer's disease is insidious and can
be dated only within broad limits.
- People with mild cognitive impairment have an increased
risk of developing Alzheimer's disease.
- The preclinical phase of Alzheimer's disease is the
subject of intensive investigation. Cognitive symptoms and brain
abnormalities (medial temporal lobe atrophy) are present many years before
a clinical diagnosis.
- Medial temporal lobe atrophy, especially the
hippocampus and parahippocampal gyrus regions,
plays an important role in the storage of new information and may be sites
of change preceding the expression of Alzheimer's disease symptoms.
- Women appear at higher risk for Alzheimer'
s disease than men. One in eight men, and almost one in four women,
will suffer at least some of their lifetime from Alzheimer's disease.
- Lower levels of education increases risk of Alzheimer's
- Depression is probably prodromal.
- Even on autopsy, it might be difficult to arrive at a
- Head injury, a risk factor, may interact with ApoE gene, which is involved in various aspects of
neurodegeneration and repair.
- Presence of ApoE4 gene, a variant of the ApoE lipoprotein, part of the bodies cholesterol
transport system, does not invariably lead to Alzheimer'
s disease. It is associated with increased serum total cholesterol
levels, and with increased risk of artherosclerosis
and coronary heart disease.
- Exposure to aluminum in the water supply may enhance
the risk of Alzheimer's disease.
- Hypertension and other vascular symptoms appear to
predispose to Alzheimer's disease.
- Potential protective factors include the use of
non-steroid anti-inflammatory drugs to treat arthritis as well as estrogen
use by post-menopausal women.
- Beta amyloid induces a local inflammatory reaction that
contributes to the progression of Alzheimer's disease.
- Other protective factors include physical activity and
diet with high levels of B6, B12, and folate, and moderate amounts of
- The higher fraction of people who survive to 80 and
beyond will drive up the frequency of the disease in coming years.
- There is no biological or chemical threshold beyond
which Alzheimer's disease can be said to begin.
- Only about one-third of identical twins are concordant
for Alzheimer's disease.
- Alzheimer's disease is characterized by cognitive
deficits that involve cholinergic pathways. Cholinergic pathways comprise
neurons that release the neurotransmitter acetylcholine, which originate
in the reticular core of the brainstem and basal forebrain. Enhance the
amount of cholinergic activity and this should lead to improvement in the
efficiency of working memory.
- At this time, there is no known cure for this disease.
- Anticholinesterase inhibitors may retard the
development of cognitive loss in individuals with mid
to moderate dementia.
- Alzheimer's disease medicines work to slow down the
symptom progression rather than substantially improving memory function.
- The four cholinesterase inhibitors presently being used
are tacrine (Cognex,
Parke-Davis), donepezil HCP (Aricept. Eisai/Pfizer), rivastigmine
(Exelon, Novartis) and. galantami ne hydrobromide (Reminyl, Shire
Pharamaceutical and Johnson & Johnson). Tacrine and donepezil are classified as short-acting
or reversible agents since when binding to acetylcholinesterase enzyme (AChE) it is hydrolyzed within minutes. Rivastigmine is classified as an intermediate-acting
or pseudo-irreversible agent due to its long inhibition on AChE of up to 10 hours.Galantamine
also is classified as acetylcholinesterase inhibitor. It also appears to
act on nicotine receptors in the brain. Both the acetylcholine and
nicotine receptors have been suggested as areas related to cognitive
- There are free radical scavengers that have been
proposed as effective in the treatment of cognitive disorders, but there
continues to be questions about their effectiveness. Included in this
group is Vitamin E, Selegiline (Eldepryl, Somerset etc.), and extract of Ginkgo
- Eating nuts, leafy green vegetables and other foods
rich in antioxidants such as vitamin E may reduce the risk of Alzheimer's
disease according to two recent studies. The studies suggest that
vitamin-rich foods-not supplements-impart the beneficial effects. Intake
of Vitamin C appeared to offer some protection also, but the results were
not as clear cut as were the results for Vitamin E. More definitive
studies on this are still required.
- Many drugs are in different clinical trial levels,
hoping for approval, since more effective drugs are needed and there is a
large cohort group that can use this medication.
See: Alzheimer’s Disease-PartI-Medications
See: Alzheimer’s Disease Part II- Selegiline and AD.
See: Alzheimer's Disease
Part III- Use of Gingko Biloba in
memory problems of Alzheimer patients.
See: Alzheimer's Disease
See: Alzheimer's Disease
Part V-Possible New Drugs for Alzheimer's Disease Treatment.
See: Alzheimer's Part VI -Early Diagnosis.
See: Alzheimer's Part VII -New Medication-Metrifonate
Disease PartVIII --
Implications of Longer Life Expectancies
See: Alzheimer's Part IX-Ethical Care
See: Alzheimer's Disease Part X-Estrogen and
See: Alzheimer's Disease Part XI-Pocket Smell
See: Alzheimer's Disease Part XII-MAO-B
See: Alzheimer's Disease Part XIII-Critical
Flicker Fusion Threshold Test
See: Alzheimer's Disease Part XIV-Donepezil
See" Alzheimer's Disease Part XV-Cerebroylsin
See: Alzheimer's Disease Part XVI-MCI
See: Alzheimer's Disease Part XVIII-NO
See: Alzheimer's Disease Part XIX-Vitamin E
See: Alzheimer's Disease-Part XX-Clinical
See: Alzheimer's Disease Part XXI-The Brain
See Dementia with Lewy Bodies- Part XXII-by Gourete Broderick
See: Alzheimer's Disease-Part XXIII-HMG
See: Alzheimer's Disease-Part XXIV-A Prequel
See: Alzheimer's Disease-Part XXV-Psychosis
See: Alzheimer's Disease-Part XXVI-Amyloid-beta
See: Alzheimer's Disease-Part XXVII- AD and
See: Alzhemeir's Disease-Part XXVIII - Insulin
AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A
NURSING HOME SEE OUR ARTICLE "HOW TO SELECT A NURSING HOME"
Harold Rubin, MS, ABD, CRC, Guest Lecturer
updated November 26, 2016
e-mail: email@example.com or firstname.lastname@example.org
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