Serum levels of vitamin B12 are not accurate for brain health and cognition

Numerous times over the past couple decades I’ve regrettably had to contradict a colleague when a patient has been told that their serum levels of vitamin B12 are adequate and supplementation is not warranted. A study just published in the journal Neurology offering yet more evidence that serum vitamin B12 levels within the typical normal range can mislead about serious consequences of B12 deficiency in the brain. The authors’ intent was to…

“…investigate the interrelations of serum vitamin B12 markers with brain volumes, cerebral infarcts, and performance in different cognitive domains in a biracial population sample cross-sectionally.”

They examined serum markers of vitamin B12 in relation to neuropsychological tests of 5 cognitive domains and brain MRI studies obtained on average 4.6 years later among 121 older community dwelling adults. The data paint an important picture:

Concentrations of all vitamin B12–related markers, but not serum vitamin B12 itself, were associated with global cognitive function and with total brain volume. Methylmalonate levels were associated with poorer episodic memory and perceptual speed, and cystathionine and 2-methylcitrate with poorer episodic and semantic memory. Homocysteine concentrations were associated with decreased total brain volume. The homocysteine-global cognition effect was modified and no longer statistically significant with adjustment for white matter volume or cerebral infarcts. The methylmalonate-global cognition effect was modified and no longer significant with adjustment for total brain volume.”

In other words, the decrease in total brain volume due to vitamin B12 insufficiency appeared to the mediating the impact on function of the markers besides homocysteine (also associated with brains infarcts)—and serum B12 did not correlate with the MRI or cognitive testing results. For lay readers, your brain can be shrinking with concomitant loss of cognitive function due to B12 insufficiency and the blood test for B12 can still appear normal. The authors’ conclusion needs to become common knowledge among all practitioners:

Methylmalonate, a specific marker of B12 deficiency, may affect cognition by reducing total brain volume whereas the effect of homocysteine (nonspecific to vitamin B12 deficiency) on cognitive performance may be mediated through increased white matter hyperintensity and cerebral infarcts. Vitamin B12 status may affect the brain through multiple mechanisms.”

Note: methylmalonate (methylmalonic acid) in urine or serum, while not perfect, are practicable. This study also adds more evidence to the importance of homocysteine and brain health.

Is moderate wine consumption good for women?

More data on the effect of alcohol on health is offered by a study recently published in the journal Acta Neurologica Scandinavica in which the authors specifically investigate its influence on the risk of dementia.

“The impact of moderate alcohol consumption on cognitive function and dementia is unclear. We examined the relationship between consumption of different alcoholic beverages and cognitive function in a large population-based study.”

Their study subjects were 5033 Norwegian men and women whose alcohol consumption was correlated with cardiovascular risk factors and cognitive function at baseline and after 7 years. What did the data show?

Moderate wine consumption was independently associated with better performance on all cognitive tests in both men and women.

Moreover…

“There was no consistent association between consumption of beer and spirits and cognitive test results. Alcohol abstention was associated with lower cognitive performance in women[!].

There are a lot of good reasons to not drink alcohol; but for those whom it is not contraindicated, their conclusion is interesting:

“Light-to-moderate wine consumption was associated with better performance on cognitive tests after 7 years follow up.”

The common danger of delirium and dementia after surgery, and pre-existing neurodegeneration

British Journal of SurgeryPerhaps you saw the recent New York Times article about the devastating experience of delirium in the hospitalized elderly. This is an important topic because it is associated with persistent diminished cognitive function, dementia and earlier death; and it is surprisingly common. As a number of studies point out, it is evidence of pre-existing neurodegeneration that puts brains ‘on the edge’. In a recent study published in the British Journal of Surgery the authors…

“…evaluated the incidence of postoperative delirium (POD) in elderly patients undergoing general surgery, the risk factors associated with POD, and its impact on hospital stay and mortality.”

Their data showed a huge difference between the study subjects with post-operative delirium and those without. The average length of hospital stay was 21 days with POD versus 8 days without. Moreover the mortality rate was 19% versus 8.4% respectively. Their conclusion is very important for both doctors and patients to bear in mind:

The incidence of POD is high in elderly patients for both emergency and elective surgery, leading to an increase in hospital stay and perioperative mortality. To minimize POD, associated risk factors of co-morbidity, cognitive impairment, psychopathology and abnormal glycaemic control must be identified and treated.

Note the comment on glycemic control—this will be expanded in a subsequent post.

British Journal of AnaesthesiaAlthough the danger is more marked in the elderly because there has been more time for neurodegeneration, it is not limited to the geriatric population. A recent paper in the British Journal of Anaesthesia warns that postoperative cognitive dysfunction (POCD, impaired cognition long after the surgery) must not be overlooked:

Postoperative delirium and cognitive dysfunction (POCD)…although not limited to geriatric patients, the incidence and impact of both are more profound in geriatric patients. Delirium has been shown to be associated with longer and more costly hospital course and higher likelihood of death within 6 months or postoperative institutionalization. POCD has been associated with increased mortality, risk of leaving the labour market prematurely, and dependency on social transfer payments.”

Practitioners take note:

“Delirium as a behavioural manifestation of cortical dysfunction is associated with characteristic signs. The EEG may show diffuse slowing of background activity. A wide variety of disturbances in neurotransmitter systems has been described. Serum anticholingeric activity has been associated with delirium and may be especially important, and also other mediators such as melatonin, norepinephrine, and lymphokinespostoperative chemokines have been found to be more elevated in patients who became delirious than in matched controls.”

Regarding postoperative cognitive dysfunction:

Increased inflammatory activity may play a role in early POCD. Elevated C-reactive protein is associated with impaired mental status in elderly hip fracture patients.”

How could we argue with what the authors assert in their conclusion:

Good basic care demands identification of at-risk patients, awareness of common perioperative aggravating factors, simple prevention interventions, recognition of the disease states, and basic treatments for patients with severe hyperactive manifestations.”

American Journal of Geriatric PsychiatryIt’s not just our British colleagues who are diligently investigating this devastating phenomenon. A fascinating study published recently in the American Journal of Geriatric Psychiatry reveals evidence that pre-existing white matter lesions are a risk factor for postoperative delirium:

“Delirium is a common and critical clinical syndrome in older persons. The authors examined whether any abnormalities in the white matter (WM) assessed by diffusion tensor imaging (DTI) predisposes patients to develop delirium…”

Their data clearly showed that damage to the white matter by accelerated neurodegeneration is an important risk factor:

“The abnormalities in the deep WMs and thalamus that were mainly accelerated by aging may account for the vulnerability to postoperative delirium…”

In other words, these are brains already ‘on the edge’ and predisposed to delirium and postoperative cognitive dysfunction from neurodegeneration that has been occurring for years. Now is the time, before more damage is done, to understand what you personally need to prevent unnecessary loss of brain function with age. Another paper published around the same time in the same journal focuses on the critical point of brain reserve. The authors provide…

“…a review of original articles on cognitive and brain reserve across many conditions affecting the central nervous system, with a focus on delirium…Reserve may be a potentially modifiable characteristic. Studying the role of reserve in delirium can advance prevention strategies for delirium and may advance knowledge of reserve and its role in aging and neuropsychiatric disease generally.”

I don’t think I can overemphasize this point. It is the brains that are low on reserve due to pre-existing neurodegeneration that are prone to delirium and postoperative cognitive dysfunction with all their depredations when challenged. How is your brain reserve? How easily do you experience cognitive (memory, focus, attention) or emotional (rage, irritability, depression, etc) dysfunction when stressed? There are objective, evidence-based ways to find out the contributing underlying causes and treat them from a functional perspective if we don’t wait too long.

Acute or critical care hospitilization damages cognitive function in older adults

JAMA 022410This is something to take to heart if you or someone you know require hospital care for an acute or critical illness. This paper just published in The Journal of the American Medical Association presents a study that set out to…

“To determine whether decline in cognitive function was greater among older individuals who experienced acute care or critical illness hospitalizations relative to those not hospitalized and to determine whether the risk for incident dementia differed by these exposures.”

If you have experience with this their conclusion will not surprise you:

“Among a cohort of older adults without dementia at baseline, those who experienced acute care hospitalization and critical illness hospitalization had a greater likelihood of cognitive decline compared with those who had no hospitalization. Noncritical illness hospitalization was significantly associated with the development of dementia.”

Note the last sentence: even noncritical illness hospitalization was associated with dementia. You too may have been distressed to see older folks decline in cognitive function following hospitalization due to depletion of critical internal resources that were already suboptimal, oxidative stress, etc.—and nothing was done to help it (even though functional medicine resources are available). Considering the central role of the brain in regulating all bodily functions, this must be kept  in mind when evaluating subsequent health complaints of any kind.

Ecstasy (MDMA) damages cognitive performance

Journal of PsychopharmacologyIt’s a ‘no-brainer, of course, that ‘ecstasy’ (MDMA) would ‘burn’ the brain. This paper published in the Journal of Psychopharmacology describes research that documents what you might expect:

“…on immediate word recall and delayed word recall, both groups of MDMA users recalled significantly less words than controls. Animal research has shown that MDMA can lead to serotonergic neurodegeneration, particularly in the hippocampus and frontal cortex…these data are consistent with other findings of memory decrements in recreational MDMA users, possibly caused by serotonergic neurotoxicity.”

Lying obliquely is a clinical sign of cognitive impairment

Have you ever had a doctor straighten you while you were lying on his or her treatment table even though you felt like your position was already straight? Did the objectively straight position feel funny at first? This study just published in the British Medical Journal examined the correlation between “failure to spontaneously orient the body along the longitudinal axis” and cognitive impairment. They found that “Angular deviation of at least 7° predicted cognitive impairment according to the three different tests…” and concluded “The oblique sign was clearly present in patients with cognitive impairment but who had not reached dementia…” Remember (while you still can) the importance of having an active and informed brain preservation strategy. BMJ

Medium Chain Fatty Acids Improve Cognitive Function

You may remember that we use Medium Chain Triglycerides (MCT) in their pure form to make medical foods such as Clearvite® and Ultrameal® more complete. This form of fat is especially easy for the body to burn for energy, supports metabolism and stabilizes blood sugar. Two very interesting papers in the journals Diabetes and Neurobiology of Aging document that MCT oils also oppose neurodegeneration related to glucose dysregulation and improve cognition:

  1. Cognitive function improves in Type 1 Diabetes
  2. Memory improves with Alzheimer’s

MCT’s are abundant in coconut butter, and easily added to shakes in the form of MCT Oil which is liquid at room temperature.