Nutrition and its role in Alzheimer’s Disease

By Shahnia Surendran

There are approximately 50 million people worldwide living with dementia, with an estimated 10 million new cases annually (World Health Organisation, 2019). As a result of the global population ageing phenomenon, the prevalence of dementia is estimated to double to over 100 million people by 2050 (Morris, 2009). Alzheimer’s disease (AD) is the most common form of dementia, representing the most critical stage of cognitive decline (Power et al., 2019), and is the fifth-leading cause of death among those aged over 64 (World Health Organisation, 2019).

The definite cause of Alzheimer’s disease is still unknown; it is often characterised by senile plaque and neurofibrillary tangles which are often associated with the aetiology of AD (Imahori, 2010). To this day, there has not yet been a cure identified for AD. Therefore, increased focus has been placed on palliative care and preventative approaches to control the progression and minimize the impact of neurological disease in order to foster and encourage healthy ageing (Power et al., 2019). 

There is much ambiguity underlying the exact mechanism by which these beta-amyloid peptides (in senile plaques) and neurofibrillary tangles cause such damage – although there are several theories, such as the amyloid hypothesis and the role of prion mechanisms. As a result, little is known regarding the modifiable risk factors influencing AD. However, there has been growing evidence regarding possible dietary risk factors that are involved in the development of AD and cognitive decline (Morris, 2009). 

These risk factors, which include low omega-3 intake and high homocysteine (Hcγ) levels, both posit a 22% population attributable risk (PAR) to AD (Beydoun et al., 2014). Homocysteine is made from dietary proteins and is normally converted to useful amino acids. However, if B vitamin intake or blood levels are low, homocysteine tends to rise, and this is associated with cognitive impairment.  According to Oulhaj et al., higher levels of plasma total homocysteine (tHcγ) have been linked to more rapid cognitive decline through increased brain atrophy and impaired synaptic function. Lowering of homocysteine status requires Vitamin B₆, B₁₂ and folate. Dietary sources of B vitamins include (but are not limited to) whole grains, meat, eggs and dairy products. B vitamins are vital during the assembly of phospholipids and encourage healthy membrane formation in neurons. Cognition is measured using the Cambridge Cognition Examination (CAMCOG), a standardised measure which assesses abstract thinking, attention, orientation, language, memory, praxis, perception and calculation (Figueiredo & Salter, 2009).

Following the findings of Oulhaj et al., the VITACOG study was carried out to test whether a B vitamin complex that acted to reduce homocysteine levels might improve cognition in individuals with mild cognitive impairment (MCI). The randomised controlled trial comprised of 266 people, aged over 70 with varying levels of MCI, and was carried out over the course of two years. Half the subject group was treated with a daily oral pill containing 0.5mg vitamin B12, 0.8 mg folic acid and 20mg B6 (TrioBe™) while the other half (control group) was given a daily placebo (de Jager et al., 2012). Baseline levels of plasma homocysteine, cobalamin (B12), folate and omega-3 (DHA and EPA) were recorded as well as MRIs of whole-brain volume, which were re-obtained at the study end (Smith et al., 2010).  

The results of the study indicated that treatment with B vitamins slowed decline in the CLOX (an executive clock-drawing task) by 30% (P=0.015) for all homocysteine levels (Smith et al., 2010). Those with high baseline homocysteine also demonstrated significant improvement in the linguistic and general cognition (MMSE) tasks. The imaging results from the MRIs illustrated that patients on B vitamin treatment showed grey matter loss seven times lower (Gwenaëlle Douaud et al., 2013). These studies suggested associations of homocysteine with omega-3 fatty acids (Smith et al., 2010) and consequently, the combined effects of different nutrients on cognition was an important factor to consider in preventing the decline from MCI to Alzheimer’s dementia.

Further objectives of the VITACOG trial then included analysing the effects of B vitamin intervention on cognition and brain atrophy according to tertiles of baseline total omega-3; which comprises of omega-3 fatty acids (FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are thought to protect against the onset of dementia (Beydoun et al., 2014). There were positive results seen on episodic memory (HVLT-DR) after 6 months of supplementation in patients with MCI (Yurko-Mauro et al., 2010). In other trials, omega-3 improved general cognitive performance (Chiu et al., 2008) and language (Sinn et al., 2011). In subjects with baseline omega-3 levels in the top tertile (>590 μM), B vitamins reduced brain atrophy rates by 40% (p=0.018) (Jernerén et al., 2015). 

In conclusion, B vitamins have been shown to impede cognitive decline and brain atrophy in subjects with MCI and elevated plasma total homocysteine. However, these favourable effects were most evident in those with optimal concentrations of baseline omega-3 fatty acids (Smith et al., 2010). These results highlight the importance of the symbiotic and multimodal effects of different nutrients (such as omega-3 fatty acids and homocysteine) on cognition in the elderly, which may be further harnessed in developing more comprehensive preventative nutritional approaches to ease the disease burden of AD.

References:

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