Can we influence the onset or progression of neurodegenerative diseases like Alzheimer’s Disease?

It seems that there is an overlap among the neurodegenerative disorders, Alzheimer’s, Lewy body dementia, vascular dementia, and Parkinson’s disease.

Only 1% of Alzheimer’s is caused by those with ‘deterministic genes’, in other words those that inevitably lead to the disease and in these patients the disease begins early.

The majority of the population normally inherits one or two ApoE3 genes. But in the remaining 99% who develop Alzheimer’s, two thirds have at least one ApoE 4 gene instead of an ApoE3 or ApoE2 gene variety. (it is possible to inherit two ApoE 4 genes, two genes confer up to 16 times the risk)

There are some genes that amplify the risk of ApoE4, and others reduce the risk. Having the ApoE4 gene does not mean you will develop Alzheimer’s but the 25% of the population that carry the gene make up two thirds of all cases. So, is it worth being tested for the condition, it is easy to do with a blood test? It is if there are steps you can take to prevent or delay the condition. Let’s explore this further.

Alzheimer’s is twice as common in women, Parkinson’s is twice as common in men (as is Lewy body dementia).

A trial called the Chicago health and Aging project divided a study group into those with Apo E and those without (ApoE4/ApoE4 people were excluded).

They then looked at the two groups separately and considered which of five healthy behaviours people undertook (not smoking, good quality sleep, exercise, nutrition among others).

All four groups, healthy, unhealthy, ApoE4, non ApoE4 were tested for cognitive function before and during the test period and matched to give similar groups.

What they found was that cognitive function (general memory testing with spatial testing etc) fell faster in the healthy ApoE4 group than the normal group but they fell only at the same rate as in the non ApoE4 group with unhealthy habits.

In summary, healthy behaviours slowed the progression in both the ApoE4 and non ApoE4 groups.

What lifestyle changes can we undertake to reduce risk?

1. Do not smoke! It increases relative risk by 60%. Absolute risk is the actual increase in risk, relative risk is a comparison between, in this case, smokers and non-smokers. In the UK 1.3% of the population has Alzheimer’s so a 60% increased risk increases risk to 2.08%. But the risk in over 65s is 7% so a 60% increase gives a 11% risk.
2. Drink alcohol, not at all or in moderation, less than 7 drinks a week. Frequent drinkers with ApoE4 have a 260% higher risk than lifelong teetotallers of the disease.
3. If I have not lost you with step 2, adequate sleep is very important, aim for at least 7 hours a night. It is during deep sleep that the brain undergoes a deep clean, removing all the debris built up during the day. Look at sleep hygiene. If you still struggle, consider drugs like Trazadone and Pregabalin which do not impact sleep quality in the way sleeping pills do. If you compare those who get less than 5 hours of sleep to those who get more than 7 hours there is a 160% increase in all cause dementia in the poor sleepers.
4. Avoid head injury. Avoid activities where head injury is likely, rugby, football, boxing. The risk appears to rise by about 80% in those with repeated head injury.
5. Keep your blood pressure well controlled, ideally at 120/80 average. In one trial, 10000 patients were treated for 3.5 years and divided in to two groups, BP target 140 systolic and 120 systolic. After that trial period there was a 16% lower incidence of Alzheimer’s in the low blood pressure group after a five year follow up. You might consider what impact this might have over 20 or 30 years.
6. Metabolic syndrome. A British trial followed a group of patients. 17% developed diabetes and this group had a 58% higher risk of dementia. Another study compared 70-year-olds who had had diabetes for 10 years or more with non-diabetics and found the risk to be 132% higher in the diabetic group. Those with ApoE4 and diabetes had a fivefold higher risk.
7. Obesity in the absence of Diabetes is an independent risk factor, increasing risk by about 46%.
8. Nutrition. Several diets have suggested a benefit. The MIND diet and the Mediterranean diet are the two most quoted. There is evidence that an increase in nuts and olive oil may also have benefit. MIND has nuts berries and olive oil but also red meat.
9. Supplements. We think those with ApoE4 benefit from Omega 3. Based on this I take 3g of Omega 3 daily (there is a tiny risk of developing atrial fibrillation with high dose). Low vitamin D levels are associated with ill health and poor cognition, but we do not know if this is caused by the deficiency. I think everyone should take vitamin D (under 5s, pregnant women and over 65s should already be taking it), 2000iu may be necessary. Vitamin B12, folate and B6 reduce the level of Homocysteine. We aim for less than 9 on homocysteine levels. Homocysteine levels are high in those with diminished cognition, but we do not know for sure if this causes the problem. Homocysteine is also linked with heart disease.
10. Exercise has been discussed before. It increases growth factors that brain neurones love, like BDNF and IGF1, it regulates cytokines which cause inflammation, improves cerebral blood flow, and reduces beta amyloid which is found in patients with AD. The types of exercise thought to be most effective have been outlined in another blog; level 2 exercise, strength training and high intensity exercise with coordinated movements, dancing, shadow boxing. Interestingly this also slows the progression of Parkinson’s disease.
11. Sauna. A Finnish study compared a weekly sauna to 4-7 saunas a week and found a 50% reduction in relative risk of Alzheimer’s. This is difficult to achieve but there is some evidence a very hot bath or shower might replicate these benefits.
12. Oral hygiene. Periodontal disease results in gum inflammation. This inflammation has been linked with cardiovascular disease and with neurodegenerative diseases like Alzheimer’s. Two minutes, twice a day with an electric toothbrush is recommended to reduce this risk.
13. Lipid lowering. Lowering lipids with statins appears to reduce risk by about 38%.

Hearing loss has a significant association with Alzheimer’s disease increasing risk by 90%. We do not know if this is causal, i.e.: the hearing loss causes AD or the reverse situation is the case, a trial is underway to look at this.

This blog is based on information from Peter Attia’s podcast, AMA 46 available to subscribers to The Drive podcast.

Dr Allan Fox, Private GP Healthcare in Canterbury.