middle-aged

Is there really a level at which alcohol benefits cognition?

  • A very large study of adults aged 40-73 found evidence that alcohol's suggested benefit for cognition applies to a much lower level of alcohol consumption than previously claimed — only one drink a day.
  • Another longitudinal study that also removed the bias that's thought to come from including non-drinkers in the analysis, found no evidence for any cognitive benefits at any level of alcohol consumption.

Large study shows level of beneficial alcohol consumption much lower than thought

A UK study using data from 13,342 middle-aged and older adults (40-73) has found that having up to one standard unit of alcohol a day improved reaction time, but more than that amount harmed cognitive performance. The effect was more pronounced in older adults.

While several studies have suggested a U-shaped relationship between alcohol and cognition, with light to moderate consumption being beneficial to older adults, this has been quite controversial, with little consensus on how much is too much.

This study uses data from the over half a million people who participated in the UK Biobank prospective cohort study. Of these, 20,346 undertook a repeat assessment 5 years after the initial assessment. The study excluded any who disclosed a history of neurological disorder, and then included only those who consumed alcohol at least once a week. Weekly drinkers had lower levels of socioeconomic deprivation, were more likely to hold a university degree, and to be male.

Cognitive performance was assessed very simply, using a 'stop-go' reaction time task. RT decreased as alcohol consumption increased up to 10g/day, and then increased after that point. This harmful effect became stronger as people got older.

This level of 10 g/day is markedly lower than that suggested by other studies, which have variously argued for: up to 40g for women and 80g for men; up to 34g for middle-aged adults; no more than 16g.

The study omitted people who didn't drink at all, because of the 'sick quitter' effect — it's been argued that the apparent connection between moderate alcohol consumption and better health and cognition is due to bias in the control group, with many people abstaining or quitting due to health issues, and this has been supported by some recent studies. For example, a 2016 review and meta-analysis found no significant difference in mortality for low-volume drinkers once abstainer biases were adjusted for.

The main takeaway from this study — which seems quite robust given the scale of the study — is that the level of 'positive' alcohol consumption is much lower than previously claimed.

The study is open access, and can be read in its entirety at https://academic.oup.com/jpubhealth/article/40/2/304/4793394

Study shows no benefits from alcohol consumption once abstainer bias accounted for

Another longitudinal study, using a subset of participants in the Swedish Twin Registry, found no evidence for any cognitive benefits at any level of alcohol consumption.

Participants were those 486 individuals who had been surveyed on their alcohol intake in their midlife (in 1967), and also taken part in cognitive assessments 25 years later. Cognitive tests occurred at 2-year intervals for the next 10 years.

The study found a significant negative dose-response association between alcohol intake in midlife and performance on the MMSE and tests of episodic memory. There was no significant association with semantic memory and spatial ability.

As with the other study, in order to remove abstainer bias, non-drinkers were excluded from the analysis. There were 181 non-drinkers, and this group were more likely to be women, to have less education, lower socioeconomic status, higher BMI, and were more likely to have diabetes and hypertension. They did indeed perform worse on all cognitive tests, but as you can see, most of the characteristics of this group do lend themselves to such a result.

Midlife alcohol consumption was used because it was assumed that this would give a better reflection of lifetime habits than that reported in old age. As it happened, there were no heavy drinkers in the cohort — the highest consumption was 15 units/week. In this study, 1 unit corresponded to 12g.

The study is open access, and can be read in its entirety at https://www.frontiersin.org/articles/10.3389/fnagi.2018.00081/full

Reference: 

Giovanni Piumatti, Simon C Moore, Damon M Berridge, Chinmoy Sarkar, John Gallacher, The relationship between alcohol use and long-term cognitive decline in middle and late life: a longitudinal analysis using UK Biobank, Journal of Public Health, Volume 40, Issue 2, June 2018, Pages 304–311, https://doi.org/10.1093/pubmed/fdx186

Hassing, L. B. (2018). Light Alcohol Consumption Does Not Protect Cognitive Function: A Longitudinal Prospective Study. Frontiers in Aging Neuroscience, 10. https://doi.org/10.3389/fnagi.2018.00081

 

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Diet quality in midlife not associated with dementia risk

  • A large, long-running study found that self-reported diet during midlife was not linked to later dementia risk.

A long-running study involving 8225 adults found that self-reported diet during midlife (mean age 50) was not significantly associated with subsequent risk for dementia.

Dietary intake was assessed in 1991-1993, 1997-1999, and 2002-2004, with follow-up for incident dementia until March 31, 2017. Diet quality was assessed using the Alternate Healthy Eating Index (AHEI), an 11-component diet quality score (score range, 0-110), with higher scores indicating a healthier diet.

There were 344 cases of incident dementia developed in the study period. 69.1% of participants were male.

https://www.eurekalert.org/pub_releases/2019-03/jn-wdq030719.php

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Smoking, hypertension, diabetes & obesity each linked to poor brain health

  • A large study has found that smoking, high blood pressure, diabetes, and obesity are each linked to more brain atrophy, and damage to white matter.
  • The more of these you have, the greater the shrinkage and damage.

Brain scans of 9,772 people aged 44 to 79, who were enrolled in the UK Biobank study, have revealed that smoking, high blood pressure, high pulse pressure, diabetes, and high BMI — but not high cholesterol — were all linked to greater brain shrinkage, less grey matter and less healthy white matter.

Smoking, high blood pressure, and diabetes were the most important factors, but there was also a compound effect, with the number of vascular risk factors being associated with greater damage to the brain. On average, those with the highest vascular risk had nearly 3% less volume of grey matter, and one-and-a-half times the damage to their white matter, compared to people who had the lowest risk.

The brain regions affected were mainly those involved in ‘higher-order’ thinking, and those known to be affected early in the development of dementia.

The associations were as strong for middle-aged adults as for older ones, suggesting the importance of tackling these factors early.

While the effect size was small, the findings emphasize how vulnerable the brain is to vascular factors even in relatively healthy adults. This also suggests the potential of lifestyle changes for fighting cognitive decline.

Although this study didn't itself examine cognitive performance in its participants, other studies have shown links between cognitive impairment and vascular risk factors, particularly diabetes, obesity, hypertension, and smoking.

https://www.eurekalert.org/pub_releases/2019-03/esoc-shb030719.php

Cognitive decline in type 2 diabetes linked to white matter hyperintensities

While type 2 diabetes has been associated with cognitive problems, the mechanism has been unclear. Now a study involving 93 people with type 2 diabetes has found that greater white matter hyperintensities (indicative of cerebral small vessel disease) were associated with decreased processing speed (but not with memory or executive function).

https://www.eurekalert.org/pub_releases/2018-09/w-rem091818.php

Reference: 

Cox, Simon R. et al. 2019. Associations between vascular risk factors and brain MRI indices in UK Biobank. European Heart Journal. doi:10.1093/eurheartj/ehz100

[4395] Mankovsky, B., Zherdova N., van den Berg E., Biessels G.-J., & de Bresser J.
(2018).  Cognitive functioning and structural brain abnormalities in people with Type 2 diabetes mellitus.
Diabetic Medicine. 35(12), 1663 - 1670.

 

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Daily crosswords linked to sharper brain in later life

  • A very large online study has found that doing word puzzles regularly protects against age-related cognitive decline.

Data from more than 17,000 healthy people aged 50 and over has revealed that the more regularly participants engaged with word puzzles, the better they performed on tasks assessing attention, reasoning and memory.

Study participants took part in online cognitive tests, as well as being asked how frequently they did word puzzles such as crosswords. There was a direct relationship between the frequency of word puzzle use and the speed and accuracy of performance on nine cognitive tasks.

The effect was considerable. For example, on test measures of grammatical reasoning speed and short-term memory accuracy, performing word puzzles was associated with brain function equivalent to ten years younger than participants’ chronological age.

The next question is whether you can improve brain function by engaging in puzzles.

The study used participants in the PROTECT online platform, run by the University of Exeter and Kings College London. Currently, more than 22,000 healthy people aged between 50 and 96 are registered in the study. PROTECT is a 10 year study with participants being followed up annually to enable a better understanding of cognitive trajectories in this age range.

https://www.eurekalert.org/pub_releases/2017-07/uoe-dcl071417.php

Reference: 

The Relationship Between the Frequency of Word Puzzle Use and Cognitive Function in a Large Sample of Adults Aged 50 to 96 Years, was presented at the Alzheimer's Association International Conference (AAIC) 2017 on July 17.

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Rapid blood pressure drops in middle age linked to dementia in old age

  • A large study indicates that an inclination to dizziness on standing up is associated with a greater risk of developing cognitive impairment and dementia decades later.

Data from over 11,500 participants in the Atherosclerosis Risk in Communities (ARIC) cohort has found evidence that orthostatic hypotension in middle age may increase the risk of cognitive impairment and dementia 20 years later.

Orthostatic hypotension is the name for the experience of dizziness or light-headedness on standing up. Previous research has suggested an association between orthostatic hypotension and cognitive decline in older adults.

In this study, participants aged 45-64 were tested for orthostatic hypotension in 1987. Those with it (703, around 6%) were 40% more likely to develop dementia in the next 20 years. They also had some 15% more cognitive decline.

Orthostatic hypotension was defined as a drop of 20 mmHg or more in systolic blood pressure or 10 mmHg or more in diastolic blood pressure, when the individual stood up after 20 minutes lying down.

More work is needed to understand the reason for the association.

https://www.eurekalert.org/pub_releases/2017-03/jhub-rbp030817.php

Rawlings, Andreea. 2017. Orthostatic Hypotension is Associated with 20-year Cognitive Decline and Incident Dementia: The Atherosclerosis Risk in Communities (ARIC) Study. Presented March 10 at the American Heart Association's EPI|LIFESTYLE 2017 Scientific Sessions in Portland, Oregon.

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Higher coffee consumption linked to lower dementia risk in women

  • A large study adds to evidence that caffeine helps older women fight cognitive impairment and dementia.
  • This is supported by two animal studies showing precisely how caffeine is valuable for keeping the brain healthy.

Data from the Women's Health Initiative Memory Study, involving 6,467 postmenopausal women (65+) who reported some level of caffeine consumption, has found that those who consumed above average amounts of coffee had a lower risk of developing dementia.

Caffeine intake was estimated from a questionnaire. The median intake was 172 mg per day (an 8-ounce cup of brewed coffee contains 95mg of caffeine, 8-ounces of brewed black tea contains 47mg, so slightly less than 2 cups of coffee or less than 4 cups of tea). The women were cognitively assessed annually.

Over ten years, 388 were diagnosed with probable dementia (209) or MCI (179). Those who consumed above the median amount of caffeine had a 36% reduction in risk. The average intake in this group was 261 mg (3 cups of coffee), while the average intake for those below the median was 64 mg per day (less than one cup).

Risk factors such as hormone therapy, age, race, education, body mass index, sleep quality, depression, hypertension, prior cardiovascular disease, diabetes, smoking, and alcohol consumption, were taken into account.

The findings are consistent with other research finding a benefit for older women. It should not be assumed that the findings apply to men. It also appears that there may be a difference depending on education level. This sample had a high proportion of college-educated women.

It should also be noted that there was no clear dose-response effect — we could put more weight on the results if there was a clear relationship between amount of caffeine and benefit. Part of the problem here, however, is that it’s difficult to accurately assess the amount of caffeine, given that it’s based on self-report intake of coffee and tea, and the amount of caffeine in different beverages varies significantly.

Moreover, we do have a couple of mechanisms for caffeine to help fight age-related cognitive decline.

A recent study using rats modified to have impaired receptors for the adenosine A2A produced rats showing typical characteristics of an aging brain. In humans, too, age-related cognitive decline has been associated with over-activation of these receptors and dysfunction in glucocorticoid receptors.

The rat study shows that over-activation of the adenosine A2A receptors reduces the levels of glucocorticoid receptors in the hippocampus, which in turn impairs synaptic plasticity and cognition. In other words, it is the over-activation of the adenosine receptors that triggers a process that ends with cognitive impairment.

The point of all this is that caffeine inhibits the adenosine A2A receptors, and when the rats were given a caffeine analogue, their memory deficits returned to normal.

Another more recent study has found that caffeine increases the production of an enzyme that helps prevent tau tangles.

Building on previous research finding that an enzyme called NMNAT2 not only protects neurons from stress, but also helps prevent misfolded tau proteins (linked to Alzheimer’s, and other neurodegenerative disorders), the study identified 24 compounds (out of 1,280 tested) as having potential to increase the production of NMNAT2. One of the most effective of these was caffeine.

When caffeine was given to mice modified to produce lower levels of NMNAT2, the mice began to produce the same levels of the enzyme as normal mice.

https://www.eurekalert.org/pub_releases/2016-10/oupu-fwc100316.php

https://www.eurekalert.org/pub_releases/2016-08/ind-cai083016.php

https://www.eurekalert.org/pub_releases/2017-03/iu-cbe030717.php

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