1229 replies to this topic

[tham]

Latest data from the Cache County Study :

Spouses Who Care for Partners With Dementia at Sixfold Higher
Risk of Same Fate: Stress of Caregiving May Be to Blame.

http://www.scienceda...00505091630.htm

http://www.medscape....warticle/721365



Loneliness and Risk of Alzheimer's.

http://archpsyc.ama-...t/full/64/2/234


Living with a partner reduces risk of Alzheimer's.

http://esciencenews....risk.alzheimers



Links between life events, traumatism and dementia.

http://www.ncbi.nlm....t_uids=17099599


" The essence of the phenomenon, the lived experience of dementia, is
that the persons with dementia and their spouses live in a heteronomous
existence in which they are lost and are strangers in their own world.
The result of this is a life without coherence and a new but unknown
meaning that can make them feel uncertain and puts them in a quandary.
Whatever those with dementia and their spouses do, they have no real
influence over their situation, which leads to feelings of awkwardness,
perplexity, and futility. "

http://www.ncbi.nlm....t_uids=15359077



Predictors of cognitive decline and mortality of aged people.

" At 10 years, the decline associated with APOE4 (RR 3.3),
slightly elevated serum ionized calcium (RR 3.3), and feelings
of loneliness (RR 3.0). "

http://www.ncbi.nlm....t_uids=15031312

Edited by tham, 07 May 2010 - 07:56 PM.

[tham]

"Type 3 Diabetes".

" Post-mortem brain studies show that insulin expression is
inversely proportional to the Braak stage of AD progression. "

http://www.ncbi.nlm....t_uids=20030463



ALA, ALCAR, Alpha GPC, DHA, PS.

http://www.ncbi.nlm....t_uids=19185780


" C-reactive protein (CRP), an inflammatory biomarker and
stroke-recurrence predictor, responds favorably to krill oil
(a phospholipid-DHA/EPA-astaxanthin complex). "

http://www.ncbi.nlm....t_uids=19364191

http://www.jacn.org/...nt/full/26/1/39


http://www.thorne.co...ext/13/2/85.pdf

[tham]

This looks like one powerful supplement and would definitely
help dementia.

http://www.medicinal...supplement.html

[mentatpsi]

This looks like one powerful supplement and would definitely
help dementia.

http://www.medicinal...supplement.html

It might help reduce risk of developing dementia, but once the condition sets in I do not believe such minimal efforts will "cure" the degradation.

Of particular interest is Bacopa (link from my blog), which might aid more so than antioxidant measures. Additionally, have you noticed the arguably extremely low quantities of said herbs in that formulation? It doesn't seem standardized or anything...

[tham]

When it comes to a difficult disease like dementia with a
very complex pathophysiology and etiology, tantamount to
a condition like cancer, one of course is not hoping for a
single magic bullet-type cure, realistically.

Improving, reducing, ameliorating, or at least palliating/slowing
down the degeneration is what one hopes to achieve with
supplements, herbs or other measures.

The doses of most of the herbs in the above formula are small
because there are 22 of them. They add up to 540 mg, just enough
for a 500 mg capsule. Thus with 6 caps a day, one would get
3,240 mg a day.

They are not standardized extracts because the manufacturer likely
wants it that way to be in line with a whole-herb holistic principle,
wherein one would be obtaining the entire works of the countless
antioxidants in each herb, rather than just a few with an extract.

This holistic principle is in line with the whole-herb formulations in
many Western, Chinese and Indian herbal products.

Examples are the famous Indian herbal pastes,
Maharishi Amrit Kalash and Chyavanprash.


http://www.maharishi...t_Kalash_1.html


http://www.ncbi.nlm....t_uids=12510173

http://www.ncbi.nlm....t_uids=12018521


http://www.sciencedi...f22490c5d8132a1


http://www.ncbi.nlm....st_uids=8415133

http://www.ncbi.nlm....st_uids=1357573

http://www.ncbi.nlm....st_uids=2246098

http://www.ncbi.nlm....t_uids=11522125

http://www.ncbi.nlm....t_uids=11491581

http://www.ncbi.nlm....t_uids=17559639

http://www.ncbi.nlm....t_uids=15234748

http://www.ncbi.nlm....st_uids=8538064



http://www.banyanbot...hyavanprash.asp


http://ecam.oxfordjo...ent/full/neq021


" Effect of chyawanprash in the prevention of dementia. "

http://www.ijp-onlin...3027_055030.pdf



Your recommendation of Bacopa is well substantiated. It has
been discussed above.

http://www.imminst.o...o...st&p=405753


Its cognitive-improving together with restlessness/agitation and
anxiety-reducing properties would make it well suited for dementia.

http://www.favorfine.../hhbacopa.shtml

http://www.himalayah...er/h_bacopa.htm


This Himalaya product, Mentat, also looks a good whole-herb
formula based around Bacopa and Centella asiatica. It's been
selling here for many years. Also known as BR-16A in India.

I am also considering giving it to my father ( or at least hoping
to give to him - getting it past my brother and then the nursing
home people, the two main "barriers", are another matter ! ) .

The price of their many herbal formulas here in Malaysia has gone
up substantially over the years. A 100-tablet bottle of Mentat or
Bacopa, for example, used to cost M$8 to M$10 in the mid-1990s.
It now costs M$40 for a 60-tablet bottle.


http://www.himalayah...ucts/mentat.htm


http://www.ncbi.nlm....st_uids=8045602

http://www.ncbi.nlm....st_uids=1597339

http://www.ncbi.nlm....st_uids=1816096

http://www.ncbi.nlm....t_uids=16691632

http://www.ncbi.nlm....st_uids=8045603

http://www.ncbi.nlm....t_uids=15233467

http://www.ncbi.nlm....st_uids=8055293

Edited by tham, 10 May 2010 - 10:51 AM.

[chrwe]

As much as I would like to do anything to prevent cognitive decline, I find myself hesitant to swallow stuff that has not been monitored in any way (and could contain anything)

[tham]

Mentat, BR-16A.

http://www.ijp-onlin...4752_132907.pdf


Herbs in Mentat.


Brahmi (Bacopa monnieri) and Mandukarpani (Centella asiatica).

http://www.indiaoz.c...bs_Brahmi.shtml

http://www.indiaoz.c...dukaparni.shtml

http://www.indianjps...1144_133651.pdf


Withania somnifera (Ashwagandha, Indian ginseng).

http://www.jstage.js...128/8/1159/_pdf

http://www.ncbi.nlm....t_uids=10884056

http://www.ncbi.nlm....t_uids=16553605



Evolvulus alsinoides, synonymous Convolvolus pluricalis.
Sanskit Shankapushpi, highly rated in Ayurvedic medicine.

http://www.indiaoz.c...nkapushpi.shtml

http://www.ayurveday...hankhpushpi.asp

http://www.jcimjourn...ID=jcim20091101

http://www.ncbi.nlm....t_uids=19610035

http://www.ncbi.nlm....t_uids=17639556

http://www.ncbi.nlm....t_uids=17128592



Nardostachys jatamansi.

http://www.indiaoz.c...Jatamansi.shtml

http://www.ncbi.nlm....t_uids=18512329

http://www.ncbi.nlm....t_uids=16579738



Tinospora cordifolia.

http://www.indiaoz.c...s_Guduchi.shtml

http://www.ijp-onlin...0852_133008.pdf


Acorus calamus (Sweet flag).

http://www.ncbi.nlm....t_uids=15500267


Celastrus paniculatus.

http://informahealth...880200903127391

http://www.ncbi.nlm....t_uids=12120811


Emblica officinalis (Amla, Indian gooseberry).

http://www.jstage.js...27/10/1701/_pdf

Edited by tham, 11 May 2010 - 06:57 PM.

[tham]

Replacement of the missing links to the Indian journals above.
They appear to place the links to their PDF files in a volatile cache.


Mentat, BR-16A.

http://ijp-online.co...st=Handu;type=2

http://ijp-online.co...=Ramteke;type=2

http://ijp-online.co...=Andrade;type=2


Bacopa monnieri and Centella asiatica.

http://www.indianjps...;aulast=Andrade

http://www.indianjps...=Andrade;type=2



Tinospora cordifolia.

http://ijp-online.co...Ashutosh;type=2

http://ijp-online.co...st=Singh;type=2


Against HIV :

http://ijp-online.co...=Kalikar;type=2


Antihistaminic, mast cell stabilizing properties.

http://ijp-online.co...=Sunanda;type=2


In diabetes :

http://www.indianjme...ulast=Purandare


Antidepressant activity :

http://www.ijpsonlin...=Dhingra;type=0


Immunomodulatory activity :


http://www.jpgmonlin...3;aulast=Thatte

[Sillewater]

Brain. 2010 May;133(Pt 5):1342-51. Epub 2010 Apr 12.
Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice.
Pan X, Gong N, Zhao J, Yu Z, Gu F, Chen J, Sun X, Zhao L, Yu M, Xu Z, Dong W, Qin Y, Fei G, Zhong C, Xu TL.

Department of Neurology, Zhongshan Hospital & Shanghai Medical College, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
Abstract
Reduction of glucose metabolism in brain is one of the main features of Alzheimer's disease. Thiamine (vitamin B1)-dependent processes are critical in glucose metabolism and have been found to be impaired in brains from patients with Alzheimer's disease. However, thiamine treatment exerts little beneficial effect in these patients. Here, we tested the effect of benfotiamine, a thiamine derivative with better bioavailability than thiamine, on cognitive impairment and pathology alterations in a mouse model of Alzheimer's disease, the amyloid precursor protein/presenilin-1 transgenic mouse. We show that after a chronic 8 week treatment, benfotiamine dose-dependently enhanced the spatial memory of amyloid precursor protein/presenilin-1 mice in the Morris water maze test. Furthermore, benfotiamine effectively reduced both amyloid plaque numbers and phosphorylated tau levels in cortical areas of the transgenic mice brains. Unexpectedly, these effects were not mimicked by another lipophilic thiamine derivative, fursultiamine, although both benfotiamine and fursultiamine were effective in increasing the levels of free thiamine in the brain. Most notably, benfotiamine, but not fursultiamine, significantly elevated the phosphorylation level of glycogen synthase kinase-3alpha and -3beta, and reduced their enzymatic activities in the amyloid precursor protein/presenilin-1 transgenic brain. Therefore, in the animal Alzheimer's disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms, which are likely to include the suppression of glycogen synthase kinase-3 activities. These results suggest that, unlike many other thiamine-related drugs, benfotiamine may be beneficial for clinical Alzheimer's disease treatment.

[tham]

This study identifies two hereditary middle age risk factors
for the development of dementia in later years, independent
of Apo E epsilon4.

1. High blood pressure
2. The inflammatory cytokines, IL-1beta, IL-6 and TNF alpha.

Pentoxifylline (Trental), which knocks down all three cytokines,
may thus be a preventative drug.

http://www.ncbi.nlm....t_uids=19884614



Dietary fats.

" Saturated fats and cholesterol may exacerbate Abeta induced
cerebrovascular disturbances by enhancing exposure of vessels
of circulating Abeta. However, presently there is no evidence to
support this contention. Rather, SFA and cholesterol appear to
more broadly compromise BBB (blood-brain barrier) integrity with
the consequence of plasma protein leakage into brain, including
lipoprotein associated Abeta.

The latter findings are consistent with the concept that AD is a
dietary-fat induced phenotype of vascular dementia, reflecting
the extraordinary entrapment of peripherally derived lipoproteins
endogenously enriched in Abeta.

Rather than being the initiating trigger for inflammation in AD,
accumulation of extracellular lipoprotein-Abeta may be a secondary
amplifier of dietary induced inflammation, or possibly, simply be
consequential. "

http://www.ncbi.nlm....t_uids=19896503

[tham]

Thiamine derivatives.

TTFD (fursultiamine) is a Japanese synthetic derivative of
allithiamine, the form found in garlic.

http://commons.wikim...derivatives.svg


TTFD has a mild effect on dementia, probably by increasing thiamine
levels in the brain. However, it appears only benfotiamine is able to
reduce the amyloid plaques as given in Sillewater's post above.

http://www.ncbi.nlm....st_uids=8815393


http://www.ncbi.nlm....t_uids=15328496

http://lib.bioinfo.pl/meid:143830


Sulbutiamine. Arcalion (by Servier of France) has been selling
OTC in Malaysia for many years. About M$10 for a strip of 10 tabs.

I gave it to my father years ago, just one tab a day, and he stopped
after a few tabs, complaining it caused headaches. I'm considering
giving it to him again now that he has dementia.


http://www.ncbi.nlm....t_uids=17675917

http://www.ncbi.nlm....st_uids=4059305

http://www.ncbi.nlm....t_uids=15951087



http://www.absolutea...cs/Sulbutiamine

http://www.raysaheli...lbutiamine.html

http://www.narcomund...s/sulbutiamine/

http://www.freepaten...om/5863925.html


Seems quite popular.





http://relentlessimp...ne-amazing.html



Review of thiamine and its derivatives.

http://ecam.oxfordjo...ent/full/3/1/49


Ecological Formulas makes allithiamine.

http://www.fubaoheal...LITHIAMINE.html

Edited by tham, 13 May 2010 - 11:56 AM.

[tham]

" The facilitation of central glutamatergic transmission is a likely
explanation for the ability of sulbutiamine to improve memory.
In addition to its action on cholinergic and glutamatergic
transmission, the administration of sulbutiamine reduces the
release of dopamine in the prefrontal cortex, which increases
the density of D1 dopamine receptors through a compensatory
mechanism. The modulation of dopaminergic transmission may
also contribute to the ability of sulbutiamine to improve memory. "

http://en.wikipedia....anism_of_action


http://www.ncbi.nlm....t_uids=10996447


http://www.ncbi.nlm....t_uids=11704349

http://www.ncbi.nlm....t_uids=15857571


Hydergine's mechanism of action.

http://www.ncbi.nlm....st_uids=2869188

[Blue]

Disappointing result for ibuprofen which as noted earlier in this thread by Prophet is somewhat similar to oleocanthal.

BACKGROUND AND AIMS: Epidemiological studies have examined the association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Alzheimer's disease (AD). Recently, a variety of experimental studies indicates that a subset of NSAIDs, such as ibuprofen or flurbiprofen, also have Abeta-lowering properties in both AD transgenic mice and cell cultures of peripheral, glial and neuronal origin. In this trial, we evaluated whether the non-selective NSAID ibuprofen slows disease progression in patients with mild to moderate AD. METHODS: This was a 12-month multicenter, randomized, double-blind, placebo-controlled, parallel group trial. Participants with mild-moderate AD (Mini-Mental State Examination score >15, <26; Clinical Dementia Rating= 0.5-1), 65 years or older, with reliable caregivers, were recruited between April 2003 and September 2004. Seven AD Outpatient Treatment Centers screened 530 patients, 132 of whom were enrolled. Intervention consisted of 400 mg ibuprofen twice a day or placebo, together with 20 mg once a day of esomeprazol, or placebo. The primary measure was any one-year change in the Alzheimer Disease Assessment Scale- Cognitive (ADAS-Cog) subscale score. Secondary measures included changes in MMSE, CDR, Basic and Instrumental Activities of Daily Living scales, and Neuropsychiatric Inventory (NPI). RESULTS: Fifty-one patients (77%) in the ibuprofen vs 46 (70%) in the placebo group completed the protocol (p>0.20). In intention-to- treat analysis, ADAS-Cog score worsening was similar in the two groups (p=0.951, treatment difference= 0.1, CI -2.7; 2.9). No differences were found for any secondary outcomes. In a subsample of genotyped patients, ApoE epsilon4 carriers treated with ibuprofen (n=27) were the only group without significant cognitive decline. CONCLUSIONS: Ibuprofen, if used for relatively short periods of time and although well tolerated thanks to gastroprotection, does not seem to be effective in tertiary prevention of mild-moderate AD. Our results suggest the need to examine whether differences in the response to NSAIDs exist, based on ApoE epsilon4 carrier status.
http://www.ncbi.nlm....pubmed/19448381

Edited by Blue, 15 May 2010 - 10:10 AM.

[tunt01]

strange, i thought there was decent data out there on ibuprofen being effective in preventing alzheimer's. maybe it depends on APOE4 carrier status and is only effective in prevention, rather than those already diagnosed.

either way, treating Abeta oligomers seems like an interesting approach. i've temporarily given up trying to rationalize the MUFA:PUFA:SFA allocation of the fat component of my diet, and merely look to EVOO as a good way to get the polyphenols which can prevent alzheimer's, cardiovascular disease, etc.

[Lufega]

Centella asiatica extract selectively decreases amyloid beta levels in hippocampus of Alzheimer's disease animal model.

Dhanasekaran M, Holcomb LA, Hitt AR, Tharakan B, Porter JW, Young KA, Manyam BV.

Department of Neurology, Scott and White Clinic, Texas A & M University System HSC College of Medicine, Texas, USA.
Abstract

PSAPP mice expressing the 'Swedish' amyloid precursor protein and the M146L presenilin 1 mutations are a well-characterized model for spontaneous amyloid beta plaque formation. Centella asiatica has a long history of use in India as a memory enhancing drug in Ayurvedic literature. The study investigated whether Centella asiatica extract (CaE) can alter the amyloid pathology in PSAPP mice by administering CaE (2.5 or 5.0 g/kg/day) starting at 2 months of age prior to the onset of detectable amyloid deposition and continued for either 2 months or 8 months. A significant decrease in amyloid beta 1-40 and 1-42 was detectable by ELISA following an 8 month treatment with 2.5 mg/kg of CaE. A reduction in Congo Red stained fibrillar amyloid plaques was detected with the 5.0 mg/kg CaE dose and long-term treatment regimen. It was also confirmed that CaE functions as an antioxidant in vitro, scavenging free radicals, reducing lipid peroxidation and protecting against DNA damage. The data indicate that CaE can impact the amyloid cascade altering amyloid beta pathology in the brains of PSAPP mice and modulating components of the oxidative stress response that has been implicated in the neurodegenerative changes that occur with Alzheimer's disease. Copyright 2008 John Wiley & Sons, Ltd.

Full study here http://www3.intersci...541810/PDFSTART

edit: Seems tham already posted this abstract. However, I linked the full study if anyone's interested.

Edited by Lufega, 15 May 2010 - 04:45 PM.

[tham]

This Ayurvedic memory formula uses, together with
Withania somniferam Acorus calamus and Tinospora
cordifolia (as also used in the Mentat formula),
Clitoria ternatea, the Butterfly pea.

http://www.ayurvedic...a2a60c126d6d3c3


Clitoria ternatea, the butterfly pea.

Local Malaysian flower. Called "bunga telang" by the Malays,
and widely used as a food colorant by them, especially in
their traditional glutinous rice cakes, and rice itself.


http://www.malaysiab...lower-food-dye/

http://www.cookingmomster.com/?p=1606

http://en.wikipedia....itoria_ternatea



Cognitive enhancement, anxiolytic, antidepressant, anticonvulsant,
antibacterial, antiinflammatory, antidiabetic properties.

Ayurvedic medicine uses mainly the roots. One of the herbs
used in their revered Shankhpushpi formula.


http://www.ncbi.nlm....t_uids=18926895

http://www.ncbi.nlm....t_uids=12895670

http://www.jcimjourn...ID=jcim20091101

http://www.ansijourn...?...&linkid=pdf



The blue flowers are a source of delphinidin, which has activity
against aggressive androgen-independent prostate (PC-3) and
liver cancer as given in Scott's prostate cancer thread.

http://www.ncbi.nlm....t_uids=14568080


The roots have antidementia properties. I'm wondering
if the flowers show this activity too.

http://www.ncbi.nlm....t_uids=16161034

http://www.ncbi.nlm....t_uids=12490229

[tham]

The roots also have marked cathartic, diurectic
and natriuretic properites, which are undesirable.

http://resources.met...mp;size=largest


http://www.sandmount...terfly_pea.html

http://www.herbalist...sid=xaupeplryaj


This study shows that delphinidin, cyanidin and malvidin
crosses the blood-brain barrier with memory enhancing effects.

http://www.ars.usda....q_no_115=172468

[tham]

Another memory study on the butterfly pea's roots.

http://www.ncbi.nlm....t_uids=11881569



Centella asiatica, pennywort. Native also in Malaysia, where
the Malays call "pegaga" and use it as both food and medicine.

Sri Lankan name, Gotu kola.


http://www.ncbi.nlm....les/PMC1513148/





http://www.authorsde...le.asp?id=20467

http://www.rcentre.u...ews.php?cod=118

http://www.borneofoc...alth/pegaga.htm

http://www.thehealth...lems-00949.html

http://adikbongsu.wo...nnywort-leaves/

http://www.anyvitami...u-kola-info.htm

http://www.globinmed...t.aspx?mgid=267

http://www.vitaminst...-gotu-kola.html

[tham]

Purple sweet potatoes.

http://www.hawaiipri...weetpotato.html


http://www.ncbi.nlm....t_uids=19863544

http://www.ncbi.nlm....t_uids=18316211

http://www.hindawi.c...009/564737.html



Purple mulberries, Morus atropurpurea.

http://www.jnutbio.c...0075-8/abstract



Blueberries, bilberries.

http://www.ncbi.nlm....t_uids=18457678

http://www.ncbi.nlm....t_uids=20047325

http://www.ncbi.nlm....t_uids=16053243

http://www.ncbi.nlm....t_uids=16098760

[chrwe]

The clinical studies for Alzheimer immunisation are now in phase II and the results seem promising. They are even searching for volunteers in the general public, which in my experience means that phase III is approaching. The vaccine focuses on Amyloid-ß 40 und 42

links are in German, so I am not posting them

Edited by chrwe, 22 May 2010 - 04:34 AM.

[tunt01]

http://www.scienceda...00525103935.htm

deficient GGA3 leads to higher BACE1 and alzheimer's.

[chrwe]

Does anyone know if there is any natural way to increase GGA3 in your body?

[Sillewater]

J

Neuroendocrinol. 2010 Apr 9. [Epub ahead of print]
Adult-onset hypothyroidism induces the amyloidogenic pathway of APP processing in the rat hippocampus.
Ghenimi Rahab N, Alfos S, Redonnet A, Higueret P, Pallet V, Enderlin V.

Université de Bordeaux, Unité de Nutrition et Neurosciences, Avenue des Facultés, 33405 Talence cedex, France Phone : (33) 5 40 00 87 22 Fax : (33) 5 40 00 27 76.
Abstract
Abstract Thyroid dysfunction and dementia are conditions that become more prevalent with advancing age. Localized hypothyroidism of the central nervous system has been sugested in some patients with Alzheimer's disease (AD). We investigated the consequence of adult-onset hypothyroidism on beta-amyloid precursor protein (APP) degrading pathways in rats treated with propylthiouracyl (PTU) during a period of 5 weeks. We evaluated the amount of T3 nuclear receptors (TRalpha1 and TRbeta) and the expression of some APP processing indicators i.e. APP, ADAM 10, BACE and PS1. The activity of secretases and Abeta peptides has been also quantified. Our study showed that hypoactivity of the thyroid signaling pathway in the hippocampus induced an increase in the APP770-751/APP695 ratio accompanied by a modification in the amyloidogenic pathway for APP processing, leading to an increased amount of Abeta peptides. In this area of the brain, modification in the non-amyloidogenic pathway of APP processing characterized by alpha-secretase activity was only about 10% in hypothyroid rats as compared to control rats. We suggest here that hypothyroidism, which becomes more prevalent with advancing age, increased the vulnerability to the formation of amyloid deposits.

Effect of hypothyroidism on amyloidogenic signaling of APP degrading process

Effects on BACE mRNA and protein levels and on β-secretase activity (Figure 2)
Concerning BACE, the mRNA level increased significantly (+39%, p < 0.05) in the neocortex
of hypothyroid rats. No difference in protein expression was observed in the two areas studied
in hypothyroid rats compared to the controls. Hypothyroidism was accompanied by a
significant increase in β-secretase activity in the neocortex and hippocampus (respectively
+21%, p < 0.01 and +20%, p < 0.01).

I don't know what increases GGA3 but according to this new study hypothyroidism increases BACE.

[MoodyBlue]

J

Neuroendocrinol. 2010 Apr 9. [Epub ahead of print]
Adult-onset hypothyroidism induces the amyloidogenic pathway of APP processing in the rat hippocampus.
Ghenimi Rahab N, Alfos S, Redonnet A, Higueret P, Pallet V, Enderlin V.

Université de Bordeaux, Unité de Nutrition et Neurosciences, Avenue des Facultés, 33405 Talence cedex, France Phone : (33) 5 40 00 87 22 Fax : (33) 5 40 00 27 76.
Abstract
Abstract Thyroid dysfunction and dementia are conditions that become more prevalent with advancing age. Localized hypothyroidism of the central nervous system has been sugested in some patients with Alzheimer's disease (AD). We investigated the consequence of adult-onset hypothyroidism on beta-amyloid precursor protein (APP) degrading pathways in rats treated with propylthiouracyl (PTU) during a period of 5 weeks. We evaluated the amount of T3 nuclear receptors (TRalpha1 and TRbeta) and the expression of some APP processing indicators i.e. APP, ADAM 10, BACE and PS1. The activity of secretases and Abeta peptides has been also quantified. Our study showed that hypoactivity of the thyroid signaling pathway in the hippocampus induced an increase in the APP770-751/APP695 ratio accompanied by a modification in the amyloidogenic pathway for APP processing, leading to an increased amount of Abeta peptides. In this area of the brain, modification in the non-amyloidogenic pathway of APP processing characterized by alpha-secretase activity was only about 10% in hypothyroid rats as compared to control rats. We suggest here that hypothyroidism, which becomes more prevalent with advancing age, increased the vulnerability to the formation of amyloid deposits.

Effect of hypothyroidism on amyloidogenic signaling of APP degrading process

Effects on BACE mRNA and protein levels and on β-secretase activity (Figure 2)
Concerning BACE, the mRNA level increased significantly (+39%, p < 0.05) in the neocortex
of hypothyroid rats. No difference in protein expression was observed in the two areas studied
in hypothyroid rats compared to the controls. Hypothyroidism was accompanied by a
significant increase in β-secretase activity in the neocortex and hippocampus (respectively
+21%, p < 0.01 and +20%, p < 0.01).

I don't know what increases GGA3 but according to this new study hypothyroidism increases BACE.

A possible way to undo hypothyroidism is to use Gugulipid and Ashwaganda. I found another source on the subject of hypothyroid treatment: http://www.ei-resour...roid-treatment/. To make sure you are getting enough iodine, I suggest not using kelp or any iodine supplement which has potassium iodide because too much of it can congest the thyroid. Iosol is probably a very good form with the worries of congesting the thyroid. See here: http://www.wellnessr...osol_iodine.php. Another form which is more expensive is nascent iodine.

[Sillewater]

Sci Signal. 2009 May 5;2(69):pe29.
Nitric oxide links mitochondrial fission to Alzheimer's disease.
Westermann B.

Institut für Zellbiologie and Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, 95440 Bayreuth, Germany. benedikt.westermann@uni-bayreuth.de
Abstract
Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced neuronal injury in the pathogenesis of Alzheimer's disease. Neurotoxic Abeta peptide, thought to be a key mediator of Alzheimer's disease, may be imported into human brain mitochondria, where it inhibits key enzymes of respiratory metabolism. Nitric oxide (NO) produced in response to Abeta induces S-nitrosylation of the mitochondrial division protein, dynamin-related protein 1 (Drp-1), which leads to excessive mitochondrial fission, synaptic loss, and neuronal damage. Furthermore, brains of patients with Alzheimer's disease contain high amounts of S-nitrosylated Drp-1. Abeta-dependent mitochondrial fragmentation likely enhances the decline in bioenergetic capacity of damaged mitochondria and therefore contributes to neuronal injury and pathogenesis of Alzheimer's disease.

PMID: 19417214 [PubMed - indexed for MEDLINE]

Haven't encountered this idea before.

Antioxid Redox Signal. 2009 Nov;11(11):2717-39.
Nitric oxide in cell survival: a janus molecule.
Calabrese V, Cornelius C, Rizzarelli E, Owen JB, Dinkova-Kostova AT, Butterfield DA.

Department of Chemistry, Biochemistry and Molecular Biology Section, Faculty of Medicine, University of Catania , Catania, Italy. calabres@unict.it
Abstract
Nitric oxide (NO), plays multiple roles in the nervous system. In addition to regulating proliferation, survival and differentiation of neurons, NO is involved in synaptic activity, neural plasticity, and memory function. Nitric oxide promotes survival and differentiation of neural cells and exerts long-lasting effects through regulation of transcription factors and modulation of gene expression. Signaling by reactive nitrogen species is carried out mainly by targeted modifications of critical cysteine residues in proteins, including S-nitrosylation and S-oxidation, as well as by lipid nitration. NO and other reactive nitrogen species are also involved in neuroinflammation and neurodegeneration, such as in Alzheimer disease, amyotrophic lateral sclerosis, Parkinson disease, multiple sclerosis, Friedreich ataxia, and Huntington disease. Susceptibility to NO and peroxynitrite exposure may depend on factors such as the intracellular reduced glutathione and cellular stress resistance signaling pathways. Thus, neurons, in contrast to astrocytes, appear particularly vulnerable to the effects of nitrosative stress. This article reviews the current understanding of the cytotoxic versus cytoprotective effects of NO in the central nervous system, highlighting the Janus-faced properties of this small molecule. The significance of NO in redox signaling and modulation of the adaptive cellular stress responses and its exciting future perspectives also are discussed.

PMID: 19558211 [PubMed - indexed for MEDLINE]

Edited by Sillewater, 18 June 2010 - 08:09 AM.

[babcock]

From an exciting article on Science Daily today about a new way of detecting Alzheimer's early.

The nerve cell-damaging plaque that builds up in the brain with Alzheimer's disease also builds up in the retinas of the eyes -- and it shows up there earlier, leading to the prospect that noninvasive optical imaging of the eyes could lead to earlier diagnosis, intervention and monitoring of the disease, according to new research.

Among the new findings:

1. In lab tests, plaques in the retinas of mice genetically modified to model Alzheimer's disease could be detected at a very early, pre-symptomatic stage -- before the plaque appeared in the brain.
2. A high-resolution, noninvasive optical imaging approach was developed to monitor individual beta-amyloid plaques in the retinas of live mice. The system is based on a harmless specific marker and the adaptation of an existing optical system used to examine rodent eyes.
3. The research team used a fluorescent compound called curcumin to label and detect retinal plaques. This is believed to be the first use of curcumin as an imaging agent to detect Alzheimer's disease-related plaques in the retinas of live animals. Curcumin, a natural component of the spice turmeric, binds to beta-amyloid plaques and makes them visible when viewed microscopically. In the Cedars-Sinai research, curcumin injected into the bloodstream of live mice crossed the blood-retinal barrier and specifically bound to the retinal plaques, allowing them to be viewed in high resolution with a noninvasive procedure.
4. Observations from multiple genetically engineered mouse models of Alzheimer's disease demonstrated a correlation between retinal plaques and brain plaques as disease progressed.
5. In the laboratory mice, a unique immune system-based therapy that reduces the amount of plaques in the brain also reduced plaque load in the retina to the same extent, suggesting that the retina could faithfully represent the brain in assessing response to therapy.
6. Beta-amyloid plaques were identified in retinal samples from human patients who had died from Alzheimer's disease, and their features correlated with the diagnosed stage of the disease. Importantly, plaques were clearly detected not only in patients who definitely had the disease, but also in the retinas of some people who were suspected of having early-stage Alzheimer's disease based on clinical diagnosis and microscopic examination of brain tissue after death.

Very exciting news! I think i would be the first in line to get this non-invasive test.

[chrwe]

We`ll all queue up for the non-invasive tests as soon as they are available to the general public I believe

It is very promising that Alzheimer is targeted by so many companies and approaches, one of them is bound to work in the near future

Since some 60+% of all dementia is related to Alzheimer and it is such a dreadful, debilitating disease (basically, to my mind, it is death of the person before the body expires), that is very promising indeed

Eating a lot of curcumin seems to be beneficial in several anti-aging strategies. Seems the "spice up your life" movement has merits.

The vaccine testing seems to be getting on as well:

http://www.physorg.c...s191238912.html

http://www.firmenpre...lease19558.html

[tham]

Coptis chinensis, Chinese goldthread.

Chinese name "Huang Lian".

http://www.ncbi.nlm....l=pubmed_docsum

http://www.ncbi.nlm....l=pubmed_docsum

http://www.brighthub...8.aspx#comments

http://www.kalyx.com...6020.0/file.htm


Anticancer properties, mainly due to its berberine content.

http://www.sciencedi...98e48c65bda43d9

[Dmitri]

" Remember this: Before the age of processed foods (from the
1950's on), Alzheimer's was an extremely rare condition. It
was so rare that doctors traveled long distances just to study
the brains of people who died with the condition. A century ago,
Alzheimer's disease was an oddity; today it's the norm. And
our processed food diets are largely to blame. "


http://www.naturalne...anti-aging.html

Would this not be tied to life expectancy as well? Decades ago people did not live as long as they do now, which could partially explain why we're seeing it more often since it's a disease of aging? A century ago the average life expectancy for males was 48.4 yrs and 51.8 for females (using 1910 figures).

[tham]

Classic 1,000-year old Chinese formula with immune-boosting (upregulation of interferon gamma, IL-12 and IL-18), "chi"
(or "qi") boosting and adaptogenic properties, as posted earlier in Denise's melanoma thread under "Regimens".

Also popular and extensively studied in Japan.

Chinese name - Shi Quan Da Bu Tang
("Ten Herbs Great Tonic Formula")

Japanese - Juzen-Taiho-To , Juzentaihoto


http://www.ncbi.nlm....t_uids=20675883

"Yokukansan" (Chinese Yi Gan San), another formula, has been mentioned
in an earlier post in this thread.


http://www.ncbi.nlm....t_uids=18509234



Note that rehmannia and poria cocos,
both used in the Rehamannia Six and
Eight formulas, are two of the principal
herbs.


http://www.massageto...le.php?id=31937

http://www.helpofchi...QuanDaBuWan.htm

http://www.mtspring..../03-941132.html

http://www.chinesehe...u-wan-p-51.html

Edited by tham, 18 August 2010 - 10:33 AM.