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food for the brain

Championing optimum nutrition for the mind


The process of memory decline and brain shrinkage associated with Alzheimer’s Disease is thought to occur over a 30 to 40 year period, hence the need for screening from age 50. Both high homocysteine (Hcy) levels, and low folic and B12 levels in blood correlate with increasing risk for AD. This article reviews the research evidence that support this position and discusses the follow on research questions: at what point in the process is cognitive decline reversible; and what dose of nutrients confers protection?

Alzheimer’s Disease

Alzheimer’s Disease (AD) is characterised by a progressive loss of cognitive functions including memory, language, judgment, praxis and orientation and is diagnosed on the basis of shrinking in the thickness of the medial temporal lobe, which is considered to be the primary pathology that generates the associated symptoms. [1] The detectable, preclinical phase of AD presents as mild cognitive impairment (MCI).[2] Episodic memory impairment is the most common initial symptom of MCI.[3] Poor performance in verbal or visuospatial memory recall, processing speed, attention and executive function tasks requiring planning or judgement & semantic fluency are common predictors of Alzheimer’s risk.[4] These are included in Food for the Brain’s Cognitive Function Test, which has been validated against existing best tests for these functions [18].

The process of memory decline and brain shrinkage associated with AD is thought to occur over a 30 to 40 year period, hence identifying the need for screening from age 50.[1]

Figure 1 below shows the spread of Alzheimer’s neurodegeneration over 50 years.

 

disease

Figure 1: Spread of Alzheimer’s neuro-degeneration over 50 years (used with permission of AD Smith, adapted from PNAS, 2002 paper)

High homocysteine, and low folic acid and B12 status as markers

Both high homocysteine (Hcy) levels, and low folic and B12 levels in blood correlate with increasing risk for AD according to a systematic review.[5] Another review[6], in 2008, concludes that: ‘Of seventy-seven cross-sectional studies on more than 34,000 subjects and 33 prospective studies on more than 12,000 subjects have shown associations between cognitive deficit or dementia and homocysteine and/or B vitamins’.

Hcy levels also predict and correlate with rate of cognitive decline[7], as does B12 status[8]. There is, therefore, ample evidence to propose that lowering homocysteine by giving appropriate supplemental levels of homocysteine lowering nutrients, including B6, B12 and folic acid, would reduce risk. The main research questions are then: at what point in the process is cognitive decline reversible; and what dose of nutrients confers protection?

Homocysteine-lowering B vitamin treatment

Does lowering Hcy by supplementing B vitamins arrest cognitive decline?
Four studies have been published in this regard.

  • In older adults (>50 years) with raised Hcy (>13mmol/l), but not diagnosed with MCI, supplementing folic acid (0.8mg/d) versus placebo for three years resulted in a highly significant improvement in the memory, information processing speed and sensorimotor speed group than in the placebo group.[9]
  • Professor David Smith and his group at the Optima Project at the University of Oxford, investigated the effects of giving B vitamins versus placebo in a Randomised Control Trial (RCT), to those with MCI, measuring brain shrinkage with an MRI scan, as well as cognitive function[10]. In this study the level of Hcy, above 9.5 mmol/l, correlated with accelerated brain shrinkage and cognitive decline. Those given folic acid (0.8mg/d), vitamin B12 (0.5 mg/d) and B6 (20mg/d) had a significant reduction in the rate of brain shrinkage as shown in Figure 2 below.

HCY

Figure 2: Brain scan images showing a reduction in the rate of brain shrinkage in the active treatment group (used with permission of AD Smith, PLos ONE 2010)

The rate of atrophy in participants with homocysteine >13 mmol/L was 53% lower in the active treatment group as shown in Figure 3 below.

 

Figure3

Figure 3: The active treatment group showed a 53% lower atrophy rate (used with permission of AD Smith, PLos ONE 2010)

A greater rate of atrophy was associated with a lower final cognitive test scores. Also, the cortical regions of the brain that were relatively protected by the B vitamins are similar to those described as declining in those who develop AD.[11]

  • Dr Celeste de Jager, part of the Optima Project, evaluated changes in cognition in those with MCI in the previous study, either given B vitamins or placebo. The B vitamins slowed cognitive and clinical decline in people with MCI, in particular in those with elevated homocysteine.[12]
  • A further study headed by Professor David Smith found those people with raised homocysteine given B vitamins, compared to placebos, had an eight-fold reduction in shrinkage of the medial temporal lobe, which is the specific area of the brain that shrinks in Alzheimer’s.[13]

    Douaud et al, PNAS 2013

    Figure 4: The active treatment group with raised baseline homocysteine showed more than an eight-fold reduction in Alzheimer's related areas of the brain (used with permission from G.Douaud, PNAS. Yellow denotes area of significant atrophy in 2 years)

  • Dr Paul Aisen and colleagues at the University of California, gave homocysteine-lowering B vitamins to those already diagnosed as suffering from mild to moderate Alzheimer’s.[14] Patients were not selected on the basis of Hcy values (average Hcy was 9.1mmol/l at baseline), and brain scans were not conducted. The patients received folic acid (5mg/d), B12 (1mg/d), and B6 (25mg/d) over a period of 18 months. No overall difference occurred in the rate of cognitive decline in those on the supplements versus placebo. However, when the patients were divided into those with high and low cognitive test scores at the start, those who had milder Alzheimer’s did significantly respond; those taking the B vitamins only slightly worsened over 15 months, while those on the placebo showed a steady decline. The average drop in homocysteine over the 18 months was from 9.1 to 6.8µmol/l.
  • Dr Kwok at the Chinese University in Hong Kong gave homocysteine lowering B vitamins (folic acid 5mg, B12 1mg) to those with mild to moderate AD or vascular dementia and reported no further decline of cognitive function, but only in those with raised homocysteine (>13µmol/l).[15]