"Experts"...again!

As mentioned in A slight hitch, Part 2., I attended a "robust" meeting with social services, representatives of the nursing home, mum's Community Psychiatric Nurse and mum's Memory Clinic consultant. Although the meeting didn't go quite as I'd hoped, the outcome was good as the standard of care at the nursing home has improved. She's moving to a better nursing home on Monday 15th March anyway as I'd had enough of the shenanigans with the management that runs the current nursing home.

After the meeting, I had a long chat with mum's Memory Clinic consultant. He explained that I couldn't give mum supplements based on weak evidence e.g. in-vitro studies, animal studies or epidemiological/observational human studies showing associations between "A" & "B". There had to be a sufficient number of large Randomised Controlled Trials (RCTs). Fair enough.

I recently e-mailed the consultant including a couple of links to RCTs showing the positive effect of Vitamin D3 on mood. He e-mailed back saying that the evidence was still weak and he linked me to The Cochrane Collaboration web-site and also to the book Evidence Based Medicine - How to Practice and Teach EBM. I bought the book and took a look at the web-site.

Due to a bug on Amazon, looking inside the above book showed me a completely different book which contained a very interesting piece of information.

The Flecainide Story
Pre-Ventricular Contractions (PVCs) are a fancy name for cardiac arrhythmias. PVCs often result in Ventricular Fibrillation (VF) & death during heart attacks. A crossover study done in the US in the 1980s showed that Flecainide drastically reduced PVCs compared to placebo. Flecainide was approved by the US Food & Drugs Administration (FDA) and prescribed to hundreds of thousands of American heart attack patients (though it never caught on in Europe or Australia).

Unfortunately a later study, the Cardiac Arrhythmia Suppression Trial (CAST) showed that, over an 18 month period, about 12% of patients taking Flecainide died compared to about 5% of patients taking placebo. Oh, whoops! It took quite a while for the bad news to be accepted (as nobody likes bad news especially when it adversely affects drug sales & profits) and for Flecainide to be taken off the market. In the meantime, tens of thousands of Americans died unnecessarily. This is what happens when "experts" focus on one outcome only and ignore the rather more important outcome of all-cause mortality.

Statins reduce cardiac deaths in men under 50 who have had one or more heart attacks. There's a statistically-insignificant reduction in all-cause mortality though as deaths from other causes increase. There's also no statistically-significant all-cause mortality benefit to men over 50 or all women who have had one or more heart attacks, or people who haven't had a heart attack. However, that hasn't stopped statins being prescribed to all and sundry, whether young or old, whether male or female and whether having had a heart attack or not.


The Cochrane Collaboration web-site was most interesting. During my long chat with mum's Memory Clinic consultant, he explained that mum was prescribed a cholinesterase inhibitor (Donepezil a.k.a. Aricept) as there was strong evidence for its benefit. I found Donepezil for dementia due to Alzheimer's disease which indeed confirmed the benefit to patients with Alzheimer's Disease (AD). The thing is, mum doesn't have AD. She has Dementia with Lewy Bodies (DLB). I then found Cholinesterase inhibitors for dementia with Lewy bodies, which concluded:-

"Patients with dementia with Lewy bodies who suffer from behavioural disturbance or psychiatric problems may benefit from rivastigmine if they tolerate it, but the evidence is weak." (emphasis added by me).

There is a condition called Parkinson's Disease Dementia (PDD) which is similar (but not identical) to DLB and I found Cholinesterase inhibitors for Parkinson's disease dementia which concluded:-

"Rivastigmine appears to improve cognition and activities of daily living in patients with PDD."

Rivastigmine is similar (but not identical) to Donepezil. There were no reviews showing the effect of Donepezil on DLB.

So "experts" can prescribe medications based on weak/no evidence but I can't give mum supplements based on weak evidence. I'm not going to e-mail the consultant pointing this out as he may withdraw Donepezil and it does actually have a slight benefit. I'm going to print the above studies and use them to try to persuade mum's new GP (when mum's moved to the new nursing home) to permit me to supply mum with supplements based on my evidence.

I also found Omega 3 fatty acid for the prevention of dementia which stated:-

"Background
Accruing evidence from observational and epidemiological studies suggests an inverse relationship between dietary intake of omega 3 polyunsaturated fatty acid (PUFA) and risk of dementia. Postulated mechanisms that might qualify omega 3 PUFA as an interventional target for the primary prevention of dementia include its anti-atherogenic, anti-inflammatory, anti-oxidant, anti-amyloid and neuroprotective properties.

Main results
There were no randomized trials found in the search that met the selection criteria. Results of two clinical trials are expected in 2008.

Authors' conclusions
There is a growing body of evidence from biological, observational and epidemiological studies that suggests a protective effect of omega 3 PUFA against dementia. However, until data from randomized trials become available for analysis, there is no good evidence to support the use of dietary or supplemental omega 3 PUFA for the prevention of cognitive impairment or dementia."

It's now 2010 and there are still no results from RCTs showing. So, omega-3 PUFAs will not be prescribed despite the evidence from biological, observational and epidemiological studies. Luckily, I keep mum's mini-fridge stocked with smoked salmon and I will request that the new nursing home gives mum a salmon meal twice a week.

Look after your brain.

"One in three people over 65 will die with dementia..." said Dr Susanne Sorensen, head of research at the Alzheimer's Society. I read this in a recent BBC News article Vitamin D 'is mental health aid' which referred to the study Serum 25-Hydroxyvitamin D Concentration and Cognitive Impairment.
The article contained the usual phrase "...more work was needed..."

The above article also led to Parkinson's linked to vitamin D which referred to the study Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease. "However, the Emory University researchers do not yet know if the vitamin deficiency is a cause or the result of having Parkinson's". "Further research is required...." yet again.

It's like someone standing by their broken-down car wondering whether it's the empty fuel tank that's made the car stop or whether it's the car stopping that's made the fuel tank empty. Does it matter? Just put some fuel in the tank and see what happens! See also Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer's disease.

Severe Mental Impairment blights the lives of many old people and their loved ones. My mum developed Parkinson's Disease a few years ago. I didn't know anything about the condition at the time, but it's caused by the formation of Lewy Bodies (blobs of abnormally-folded alpha-synuclein protein) in the substantia nigra part of the brain, which controls movement. This part of the brain has high levels of the Vitamin D receptor. I don't know why the brain contains Vitamin D receptors, but I think that they'd like to receive some Vitamin D!

As Lewy Bodies form in other parts of the brain, mental faculties decline. The hippocampus is involved with short-term memory. The neocortex is involved with concious thought.

Mum started showing obvious signs of mental impairment in mid-July 2007. She was assessed by a Community Psychiatric Nurse (CPN) in January 2008 when she scored 14/30 in a MMSE. She was unable to remember 3 words or follow 2 simple instructions in a row (e.g. fold this piece of paper in half and put it on the floor). I started her on 5,000iu/day of Vitamin D3, as it was having a positive effect on my mental function. She was prescribed Aricept, starting at 5mg/day for a month then increasing to 10mg/day. In May 2008 she was re-assessed and scored 26/30 in a MMSE. EDIT: In 2010, Mum's consultant told me that Aricept increases MMSE score by 3 points on average.

Unfortunately, Aricept has side-effects including severe diarrhoea and worsening of the symptoms of Parkinson's Disease, which she complained about, so her Aricept dose was reduced back down to 5mg/day.

Unsurprisingly, this resulted in a slight decline in mum's mental faculties. In November 2008, I increased her intake of smoked salmon to about 400g/week, as the consumption of long-chain omega-3 pufas have benefits. See
Low Plasma N-3 Fatty Acids and Dementia in Older Persons: The InCHIANTI Study.

After about four weeks, this had a noticeable (by myself and mum's friend) positive effect on her mental faculties so, inspired by Dr Art Ayers, I started her on Turmeric (curcumin) extract and Goldenseal (berberine) extract. See
Curcumin inhibits aggregation of alpha-synuclein
Neuroprotective effects of curcumin
Alpha-synuclein assembly as a therapeutic target of Parkinson's disease and related disorders
Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model
Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers
Research on the mechanism of neuronal apoptosis in Alzheimer's disease and the effects of tetrohydroberberine on the apoptosis... and
Berberine chloride can ameliorate the spatial memory impairment and increase the expression of interleukin-1beta and inducible nitric oxide synthase in the rat model of Alzheimer's disease.

On January 12th 2009, mum was re-assessed and still scored 26/30 in a MMSE. I thought that this was impressive considering that 1) she was taking half the dose of Aricept, compared to when she previously got that score, 2) she had no adverse effects from any of the supplements and 3) she was eight months older and degenerative brain diseases always worsen with increasing age.

I mentioned to the CPN who did the MMSE that I was starting mum on 15mg/week Vitamin K2 as there were benefits. See
Menaquinone-4 concentration is correlated with sphingolipid concentrations in rat brain ,
Vitamin K status influences brain sulfatide metabolism in young mice and rats ,
Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: potential role in disease pathogenesis and
The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease
New Vitamin K, an emerging nutrient in brain function
New The Science of Brain Health and Cognitive Decline | Eric Kandel
New Vitamin K2, Intelligence and the Aging Brain

I don't know anything about sphingolipids, but sulfatides are good and ceramides are bad.

Around the time that mum collapsed, I received a copy of a letter from the CPN to mum's GP which stated "I have informed him (i.e. me) that I am unaware of any robust evidence that these substances are of any benefit." However, there is no evidence that these substances are of any harm.

And finally......
What started the cascade of confusion and collapse leading to hospitalisation and discharge to a nursing home was a simple Urinary Tract Infection UTI) of e. coli. I don't know why UTIs cause so much confusion in elderly people, but elderly females are at a high risk of developing UTIs because a) elderly people don't drink enough so they don't pass enough urine, b) females have insufficient spacing between anus & urethra and c) elderly females who have any urinary/faecal leakage wear a Tena disposable "nappy/diaper", which increases the likelihood of faeces entering the urethra.

To reduce the risk of further UTIs, I have supplied the nursing home with a pot of D-mannose Plus, which contains D-mannose and cranberry extract, with instructions to add a heaped teaspoonful to a glass of juice once a week. See Intervening with urinary tract infections using anti-adhesives based on the crystal structure of the FimH-oligomannose-3 complex,
Natural approaches to prevention and treatment of infections of the lower urinary tract and
Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder.


EDIT: Thanks to Galina L for bringing the following study to my attention.
Magnesium supplementation in the treatment of dementia patients.
It's probably of no help to Lewy Body Dementia sufferers, as they already have high Mg levels in their CSF. See CSF Mg and Ca as diagnostic markers for dementia with Lewy bodies.

Continued on Look after your brain, Part 2.