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 -- J.R.R. Tolkien The Children of Hurin
- Alzheimer's Disease -


General Information:

Names:
Wikipedia entry:
Dr. Ray Shahelien entry: 

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Observations:

General Information:


"People with Alzheimer's disease have abnormal clumps (amyloid plaques) and tangled bundles of fibers (neurofibrillary tangles) in their brains. Nerve cells are lost in areas of the brain that are vital to memory and other mental abilities. There also are lower levels of chemicals in the brain that carry complex messages back and forth between nerve cells (neurotransmitters). Alzheimers may disrupt normal thinking and memory by blocking messages between nerve cells."
 
[Typical "official" introduction]
[Not necessarily so.  See Dr. Mirkin & Dr. McDougall and the "Kentucky Nuns Study"]
http://www.connecticutcenterforhealth.com/alzheimers.html

"There is a tragedy looming within Australia's ageing population. As more and more Australians join the ranks of the elderly, more and more will be affected by the burden of dementia... personally and through connections with loved ones. This is the story of a maverick Australian scientist whose theory about Alzheimer's has led to a breakthrough in understanding and a potential new treatment for the disease."
http://www.abc.net.au/catalyst/stories/s1134238.htm

[Interesting info from someone calling herself "Moondragon"
 
- AD intro [typical of intros]
 
"Other disorders can cause symptoms similar to those of Alzheimer's disease. Dementia may result from arteriosclerosis (hardening of the arteries) that slowly cuts off the supply of blood to the brain. The death of brain tissue from a series of minor strokes, or from pressure exerted by an accumulation of fluid in the brain, may cause damage. The presence of small blood clots in vessels that supply the brain, a brain tumor, hypothyroidism, and advanced syphilis can all cause symptoms similar to those of Alzheimer's."
 
-Some interesting speculation as to nutritional and toxic causes
        -Aluminum
        -Zinc deficinency
        -Mercury
        -Immune response
 
[With regard to AD being the result of an immune response, could it be that the statin drugs, which are known to also reduce inflamation are supressing some sort of response by the immune system, and that is why they show positive effects on AD?]
http://www.moondragon.org/health/disorders/alzheimers.html

Are You at Risk of Alzheimer's?

"Alzheimer’s disease begins to damage the brain years before symptoms appear. Why pathological changes occur in the brain leading to such profound damage is not clear. Risk factors are things that increase your chances of developing Alzheimer's disease. Some are preventable, such as exercise, some not, for example genetic factors and age."

"Lets look at some risk factors for Alzheimer's disease..."

[Typical AD info.  Not sure if it represents the latest ideas.]
http://alzheimers.about.com/od/diagnosisissues/a/alz_risk_factor.htm

Misdiagnosis of Alzheimer's Disease

"Because AD is so well-known, it is sometimes an over-diagnosed condition. Other causes of dementia or memory loss symptoms may be overlooked. Other possible diagnoses include normal aging (if very mild symptoms), emotional
problems (such as grief), fatigue, depression, and certain physical medical conditions such as thyroid disease, brain tumors, multi-infarct disease, or Huntington's disease. In its early stages, a correct diagnosis of AD can also be overlooked itself and misdiagnosed as other conditions such as depression, dementia, simple forgetfulness, or senility."
http://www.wrongdiagnosis.com/a/alzheimers_disease/misdiag.htm

What are the risk factors for dementia?
While there is still much to learn about the brain, researchers have highlighted some important factors that affect our risk of developing different types of dementia. Most researchers now believe that our risk of developing dementia depends upon a combination of genetic and environmental factors. We are all at some risk of developing dementia, but
some of us more than others. A person who has some of the risk factors for dementia will not necessarily go on to develop the condition. And avoiding risk factors does not guarantee that you will be healthy, although it makes this more likely.
http://www.alzheimers.org.uk/Facts_about_dementia/Risk_factors/info_amIatrisk.htm

Is it Alzheimer's disease or something else?
10 disorders that may feature impaired memory and cognition

Anna M. Barrett, MD

VOL 117 / NO 5 / MAY 2005 / POSTGRADUATE MEDICINE
http://www.postgradmed.com/issues/2005/05_05/barrett.htm

Alzheimer's Disease Treatment & Prevention:
    See also...
 
       COGNIShunt
        Desferrioxamine & Deferasirox
                    EDTA
       
Herbs
        Iron
       
McDougall
        Mirkin


Can Alzheimer's Disease and Vascular Dementia be Prevented?

"There are various levels of evidence which might show that dementia can be postponed."
NOTE:  This is an Adobe Acrobat "PDF" file
http://www.alzheimers.org.au/upload/Update%20Sheet%20-%20Prevention%20Sept%202004.pdf

Live Discussion: Does Blocking Metal-Aβ Interactions Work?
http://www.alzforum.org/res/for/journal/bush/bush_transcript.asp

[Interesting results from an Altavista search on "alzheimer's disease" "halt progression".]
http://www.altavista.com/web/results?itag=ody&q=%22alzheimer%27s+disease%22+%22halt+the+progression%22&kgs=1&kls=0

Red Wine May Help Prevent Alzheimer's
By LiveScience Staff

"A new study finds that moderate red wine consumption, specifically Cabernet Sauvignon, might help reduce the incidence of Alzheimer's disease.

"Previous Alzheimer's research has indicated similar potential benefits of red wine.

"The new research, done only on mice, will be detailed in the November 2006 issue of the FASEB Journal and will be presented at the Society for Neuroscience Meeting next month in Atlanta.

""This study supports epidemiological evidence indicating that moderate wine consumption, within the range recommended by the FDA dietary guidelines of one drink per day for women and two for men, may help reduce the relative risk for AD [Alzheimer's disease] clinical dementia," write Giulio Maria Pasinetti and Jun Wang of the Mount Sinai School of Medicine."
http://www.livescience.com/humanbiology/060928_red_wine.html

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Natural sources:


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References:


G101 ALZHEIMER'S DISEASE
Gabe Mirkin, M.D.

"The most common cause of senility in North America is Alzheimer's disease, a horrible condition in which a person loses his capacity to reason, think, recognize and function. A study in the New England Journal of Medicine shows that people who have high blood levels of a protein called homocysteine are the ones most likely to suffer Alzheimer's disease(1)."
http://www.drmirkin.com/morehealth/G101.htm

AD Cause Speculation:
[Beta]-Amyloid protein oligomers induced by metal ions and acid pH are distinct from those generated by slow spontaneous ageing at neutral pH

"Amyloid protein (A1–40) aggregation and conformation was examined using native and sodium dodecyl sulfate/polyacrylamide gel electrophoresis, and the results compared with those obtained by atomic force microscopy, and with Congo red binding, sedimentation and turbidity assays. The amount of A aggregation measured was different, depending upon the method used. Incubation for 15 min at pH 5.0 or in the presence of Fe2+, Cu2+ or Zn2+ did not alter the level of A oligomers observed on SDS and native gels. However, the slow aggregation of A to form high molecular mass species over 5 days was inhibited. In contrast, when A aggregation was monitored using a Congo red binding assay or sedimentation assay, a rapid increase in A aggregation was observed after incubation for 15 min at pH 5.0, or in the presence of Fe2+, Cu2+ or Zn2+. The low pH-, Zn2+- or Cu2+-induced A aggregation measured in a turbidity assay was reversible. In contrast, a considerable proportion of the A aggregation measured by native and SDS/PAGE was stable. Atomic force microscopy studies showed that A aged at pH 5.0 or in the presence of Zn2+ produced larger looser rod-shaped aggregates than at pH 7.4. A that had been aged at pH 7.4 was more cytotoxic than A aged at pH 5.0. Taken together, the results suggest that A oligomerizes via two mutually exclusive mechanisms to form two different types of aggregates, which differ in their cytotoxic properties."
http://content.febsjournal.org/cgi/content/full/270/21/4282

CURRENT HYPOTHESES

"We list here a collection of special seminars, on-line journal club discussions, recorded talks and other presentations on the Forum web site that describe a variety of scientific hypotheses about the pathogenesis of Alzheimer's disease."
http://www.alzforum.org/res/adh/cur/default.asp

See also Globulomer

AD Research:
    See also Globulomer

Researchers Identify Brain Protein That Halts Progression Of Alzheimer's

"Researchers have identified a protein in the brain that halts the progression of Alzheimer's disease in human brain tissue. The protein, known as "transthyretin," protects brain cells from gradual deterioration by blocking another toxic protein that contributes to the disease process."
http://www.sciencedaily.com/releases/2004/10/041025131754.htm

Phenserine Shows Potential To Slow Or Stop Progression Of Alzheimer's Disease

"April 4, 2002 - Results reported in an abstract on the transgenic mouse confirmed that Phenserine, a third generation acetylcholinesterase inhibitor (AChE-inhibitor), has the ability to reduce both amyloid precursor protein (APP) and amyloid peptide (amyloid-beta) formation in the brain which could have important potential implications for the treatment of Alzheimer's Disease (AD)."
http://www.seniorjournal.com/NEWS/Alzheimers/04-08-02Phenserine.htm

Protein 'Pump' May Aid in Alzheimer's Prevention
 By Steven Reinberg
HealthDay Reporter

THURSDAY, Oct. 20 (HealthDay News) -- A protein well known to scientists appears to clear the brain of amyloid beta, the main component of the plaques that are found in Alzheimer's patients, according to a new study with mice.

The protein, P-glycoprotein (Pgp), has long been known to obstruct chemotherapy drugs and other drugs used in treating brain disorders. But, by creating drugs that alter the natural levels of Pgp, it may be possible to prevent and treat Alzheimer's disease, the researchers suggest.
http://news.healingwell.com/index.php?p=news1&id=528648

Protein 'Pump' May Aid in Alzheimer's Prevention
In study with mice, it removed dangerous plaques from the brain.

By Steven Reinberg

THURSDAY, Oct. 20 (HealthDay News) -- A protein well known to scientists appears to clear the brain of amyloid beta, the main component of the plaques that are found in Alzheimer's patients, according to a new study with mice.

The protein, P-glycoprotein (Pgp), has long been known to obstruct chemotherapy drugs and other drugs used in treating brain disorders. But, by creating drugs that alter the natural levels of Pgp, it may be possible to prevent and treat Alzheimer's disease, the researchers suggest.

"We found a new way of getting amyloid out of the brain," said lead author John Cirrito, a postdoctorate research fellow at Washington University School of Medicine in St. Louis. "Now there are avenues we can explore to try to find a treatment. Anything you can do to prevent amyloid beta from being produced or helping get it cleared is good."
http://www.healthfinder.gov/news/newsstory.asp?docID=528648

Alzheimer's Plaques in PET Brain Scans Identify Future Cognitive Decline
ScienceDaily (July 11, 2012)
http://www.sciencedaily.com/releases/2012/07/120711210100.htm
http://www.dukehealth.org/health_library/news/alzheimers-plaques-in-pet-brain-scans-identify-future-cognitive-decline
 
[Could be used to test the effectiveness of drugs in clearing or preventing AB.]

Amyloid-β assessed by florbetapir F 18 PET and 18-month cognitive decline: A multicenter study.
Doraiswamy PM, Sperling RA, Coleman RE, Johnson KA, Reiman EM, Davis MD, Grundman M, Sabbagh MN, Sadowsky CH, Fleisher AS, Carpenter A, Clark CM, Joshi AD, Mintun MA, Skovronsky DM, Pontecorvo MJ; For the AV45-A11 Study Group.
Neurology. 2012 Jul 11. [Epub ahead of print]
Source: From the Duke University Medical Center (P.M.D., R.E.C.), Durham, NC; Massachusetts General Hospital (R.A.S., K.A.J.), Harvard Medical School, Boston; Banner Alzheimer's Institute (E.M.R., A.S.F.), Phoenix, AZ; University of Pennsylvania (M.D.D.), Philadelphia; Theorem Clinical Research (M.D.D.), King of Prussia, PA; Global R&D Partners (M.G.), San Diego, CA; University of California (M.G., A.S.F.), San Diego; Banner-Sun Health Research Institute (M.N.S.), Sun City, AZ; Nova SE University (C.H.S.), Ft. Lauderdale, FL; and Avid Radiopharmaceuticals (A.C., C.M.C., A.D.J., M.A.M., D.M.S., M.J.P.), Philadelphia, PA.
Abstract
OBJECTIVES:
Florbetapir F 18 PET can image amyloid-β (Aβ) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting Aβ pathology using florbetapir PET in subjects at risk for progressive cognitive decline.
METHODS:
A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (Aβ+) or negative (Aβ-) for pathologic levels of β-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline.
RESULTS:
In both MCI and CN, baseline Aβ+ scans were associated with greater clinical worsening on the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog (p < 0.01) and Clinical Dementia Rating-sum of boxes (CDR-SB) (p < 0.02). In MCI Aβ+ scans were also associated with greater decline in memory, Digit Symbol Substitution (DSS), and Mini-Mental State Examination (MMSE) (p < 0.05). In MCI, higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog (p < 0.01), CDR-SB (p < 0.03), a memory measure, DSS, and MMSE (p < 0.05). Aβ+ MCI tended to convert to AD dementia at a higher rate than Aβ- subjects (p < 0.10).
CONCLUSIONS:
Florbetapir PET may help identify individuals at increased risk for progressive cognitive decline.
PMID: 22786606 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/22786606

Timeline Maps Brain's Descent Into Alzheimer's
ScienceDaily (July 11, 2012)
http://www.sciencedaily.com/releases/2012/07/120711205859.htm
http://news.wustl.edu/news/Pages/24026.aspx
 
Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease.
Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC; the Dominantly Inherited Alzheimer Network.
N Engl J Med. 2012 Jul 11. [Epub ahead of print]
Source: The authors' affiliations are listed in the Appendix.
Abstract
Background The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. Methods In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to calculate the estimated years from expected symptom onset (age of the participant minus parent's age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes. Results Concentrations of amyloid-beta (Aβ)(42) in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini-Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset. Conclusions We found that autosomal dominant Alzheimer's disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer's disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer's disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817 .).
PMID: 22784036 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/22784036

 

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Updated: July 2, 2012
Inception: July 2, 2012