Alzheimer' s Disease: A Summary
of Research Findings -Part XVII
(3/31/21)-A British study of 493,888 people over the age of 57 over a period of 18 years concluded that there was an increased risk of developing Alzheimer’ disease if they ate any meats that were treated by smoking, salting or the addition of chemical preservatives.
The lead author of the study, the results of which were published in the American Journal of Clinical Nutrition was Hulfeng Zhang, a doctoral student at the University of Leeds.
The study found that for each ounce per day increase
in processed meat was accompanied by a 52% increased relative risk of Alzheimer
and a 44% relative rate increase of any form of dementia.
(9/16/20)-Using data on 6,582 men and women, age 50 and older, British researchers who examined their cognitive ability over an 11- year period, published their results in a recent edition of The International Journal of Epidemiology.
About 7 percent of the group developed dementia. They concluded that people with normal weight were 27 percent less inclined to develop dementia than the overweight group. Those who were even more overweight were 31 percent more inclined to develop dementia.
The differential was even greater for women who were overweight by about 34.6 percent.
The study controlled for age, sex, APOE4 (a gene known to increase the risk for Alzheimer’s disease), education, marital status, smoking and other known dementia risks.
Yixuan Ma, a student at University College London, the lead author of the study stated it did not prove cause and effect.
(8/5/20)-Researchers at Harvard University examined data from seven large studies with a total of 49,202 individuals aged 65 and older. The studies followed the men and women for at least 15 years, and included in person exams and in many cases genetic data, brain scans and risk factor for cardiovascular disease.
The data also included a separate assessment for Alzheimer’s disease. The results of the study were published in the journal Neurology. Dr Albert Hofman, chairman of the department of epidemiology at the Harvard School of Public Health was the lead author of the study.
The researchers concluded that the incidence of Alzheimer’s has steadily fallen at a rate of 16% per decade.
The risk of a person developing dementia over a lifetime is now 13% lower than it was in 2010. The researchers also concluded that men and women have equal dementia rates.
(9/28/17)- Yet another once-promising treatment for Alzheimer’s disease has come up short in the final stage of development, this time adding Wall Street drama to the familiar disappointment that has plagued the drug industry for decades.
A pill called intepirdine,
developed by the biotech startup Axovant Sciences
Inc., failed to blunt the symptoms of Alzheimer’s in a large clinical trial.
The drug was never seen as a cure, but the company had hoped it would delay the
worst symptoms of the disease, giving patients a few more months of health
before needing around-the-clock care.
The company announced that the drug had failed to meet the goals of the trial, since the subjects in the study did not show signs of improved cognition or daily living.
Axovant will stop pursuing the drug’s use for the treatment of Alzheimer’s disease.
(6/26/17)- According to new data from the Centers for Disease Control
and Prevention, Alzheimer’s deaths increased by 55 percent among all Americans
between 1999 and 2014.
But they increased 99
percent for African-Americans and 107 percent for
Latinos. While striking, that’s likely to be an
underestimate because some independent studies have found that Alzheimer’s
deaths are underreported on death certificates by approximately six times
because death is often attributed to more immediate causes, like pneumonia."
(6/13/17)-
As per a Centers for
Disease Control and Prevention (CDC) “it is estimated that total health and
long-term care costs for persons with Alzheimer’s and other dementias in the
United States will total $259 billion in 2017, more than two thirds of which is
expected to be covered by public sources such as Medicare and Medicaid.”
Most of the care for those who do not live in long-term facilities is done by family members or other unpaid caregivers— “in 2015, caregivers of persons with dementia, including Alzheimer’s provided 18.2 billion hours of unpaid assistance.”
(5/28/17)- A
total of 93,541 Alzheimer’s deaths occurred in the United States in 2014 at an
age-adjusted (to the 2000 standard population) rate of 25.4 deaths per 100,000
population, a 54.5% increase compared with the 1999 rate of 16.5 deaths per
100,000. Most deaths occurred in a nursing home or long-term care facility.
The percentage of Alzheimer’s decedents who died in a medical facility (e.g., hospital) declined from 14.7% in 1999 to 6.6% in 2014, whereas the percentage who died at home increased from 13.9% in 1999 to 24.9% in 2014.
(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 aging.
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 disease (72%).
(11/5/10)- The following is taken from an email sent by Physicians First Watch
"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 certificates.
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 facilities.
(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 present.
- 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 cases.
- 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
cognitive decline.
- 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
protein (APP).
- 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 disease development.
- Depression is probably prodromal.
- Even on autopsy, it might be difficult to arrive at a
definitive diagnosis.
- 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
wine.
- 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 impairment.
- 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 biloba.
- 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
for Alzheimer's.
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 PartIV-Alternative
Treatment.
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
See:Alzheimer's
Harold Rubin, MS, ABD, CRC, Guest Lecturer
updated March 31, 2021
e-mail: harold.rubin255@gmail.com or allanrubin4@gmail.com
http://www.therubins.com