Health in Aging

Short-term declines in cognitive function can occur in elderly subjects after surgery, and persists in a small percentage.

Heart bypass surgery in particular is associated with cognitive decline - estimates of its prevalence range from 33% to 82%. This decline may persist in as many as 42% of patients. Age and level of education are both factors in determining the likelihood of long-term decline. The presence of a gene (apolipoprotein E4) carried by some 25% of the population may also increase the likelihood of decline after bypass surgery. There also seems to be a link between post-operative fever and cognitive decline. Long-term decline in cognitive function may be more a result of cardiovascular risk factors than the surgery itself.

High blood pressure in those over 60 seems to be associated with greater risk of cognitive decline.

High blood pressure and other circulatory problems, such as cardiovascular risk factors and diabetes, are linked to cognitive decline, perhaps through causing abnormalities in the white matter of elderly persons' brains.

Those with the gene ApoE4 also appear to have more difficulty recovering from traumatic brain injury.

Two drugs used for Alzheimer's have also been found to help those suffering from dementia following stroke.

A specific skills approach is having some success in helping those who suffer from attention problems following stroke.


See separate pages for



Heart health

Inflammation & infection

Sleep problems



Chung, C.-C., Pimentel, D., Jor’dan, A. J., Hao, Y., Milberg, W., & Novak, V. (2015). Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes. Neurology, 85(5), 450–458.

Growing research has implicated infections as a factor in age-related cognitive decline, but these have been cross-sectional (comparing different individuals, who will have a number of other, possibly confounding, attributes). Now a large longitudinal study provides more evidence that certain chronic viral infections could contribute to subtle cognitive deterioration in apparently healthy older adults.

The study involved 1,022 older adults (65+), who had annual evaluations for five years. It revealed an association between cognitive decline and exposure to several viruses: cytomegalovirus (CMV), herpes simplex (HSV 2), and the protozoa Toxoplasma gondii.

More specifically, the IgG levels for HSV-2 were significantly associated with baseline cognitive scores, while the IgG levels for HSV-2 (genital herpes), TOX (which has been much in the news in recent years for being harbored in domestic cats, and being implicated in various neurological disorders), and CMV (a common virus which unfortunately rarely causes symptoms), but not HSV-1 (the cold sore virus), were significantly associated with greater temporal cognitive decline that varied by type of infection.

More research is obviously needed to determine more precisely what the role of different infectious agents is in cognitive decline, but the findings do point to a need for a greater emphasis on preventing and treating infections. They also add to the growing evidence that age-related cognitive decline isn't 'normal', but something that occurs when other health-related factors come into play.

A large study, involving 3,690 older adults, has found that drugs with strong anticholinergic effects cause memory and cognitive impairment when taken continuously for a mere two months. Moreover, taking multiple drugs with weaker anticholinergic effects, such as many common over-the-counter digestive aids, affected cognition after 90 days’ continuous use. In both these cases, the risk of cognitive impairment doubled (approximately).

More positively, risk of Alzheimer’s did not seem to be affected (however, I do have to wonder how much weight we can put on that, given the apparent length of the study — although this is not a journal to which I have access, so I can’t be sure of that).

Although somewhat unexpected, previous research linking anticholinergics and cognitive impairment is consistent with this new finding.

Anticholinergic drugs block the neurotransmitter acetylcholine. Older adults commonly use over-the-counter drugs with anticholinergic effects as sleep aids and to relieve bladder leakage. Drugs with anticholinergic effects are also frequently prescribed for many chronic diseases including hypertension, cardiovascular disease and chronic obstructive pulmonary disease.

You can download a list detailing the ‘anticholinergic burden’ of medications at:

[3449] Cai X, Campbell N, Khan B, Callahan C, Boustani M. Long-term anticholinergic use and the aging brain. Alzheimer's & Dementia: The Journal of the Alzheimer's Association [Internet]. 2013 ;9(4):377 - 385. Available from:

Recent research has suggested that sleep problems might be a risk factor in developing Alzheimer’s, and in mild cognitive impairment. A new study adds to this gathering evidence by connecting reduced slow-wave sleep in older adults to brain atrophy and poorer learning.

The study involved 18 healthy young adults (mostly in their 20s) and 15 healthy older adults (mostly in their 70s). Participants learned 120 word- nonsense word pairs and were tested for recognition before going to bed. Their brain activity was recorded while they slept. Brain activity was also measured in the morning, when they were tested again on the word pairs.

As has been found previously, older adults showed markedly less slow-wave activity (both over the whole brain and specifically in the prefrontal cortex) than the younger adults. Again, as in previous studies, the biggest difference between young and older adults in terms of gray matter volume was found in the medial prefrontal cortex (mPFC). Moreover, significant differences were also found in the insula and posterior cingulate cortex. These regions, like the mPFC, have also been associated with the generation of slow waves.

When mPFC volume was taken into account, age no longer significantly predicted the extent of the decline in slow-wave activity — in other words, the decline in slow-wave activity appears to be due to the brain atrophy in the medial prefrontal cortex. Atrophy in other regions of the brain (precuneus, hippocampus, temporal lobe) was not associated with the decline in slow-wave activity when age was considered.

Older adults did significantly worse on the delayed recognition test than young adults. Performance on the immediate test did not predict performance on the delayed test. Moreover, the highest performers on the immediate test among the older adults performed at the same level as the lowest young adult performers — nevertheless, these older adults did worse the following day.

Slow-wave activity during sleep was significantly associated with performance on the next day’s test. Moreover, when slow-wave activity was taken into account, neither age nor mPFC atrophy significantly predicted test performance.

In other words, age relates to shrinkage of the prefrontal cortex, this shrinkage relates to a decline in slow-wave activity during sleep, and this decline in slow-wave sleep relates to poorer cognitive performance.

The findings confirm the importance of slow-wave brainwaves for memory consolidation.

All of this suggests that poorer sleep quality contributes significantly to age-related cognitive decline, and that efforts should be made to improve quality of sleep rather than just assuming lighter, more disturbed sleep is ‘natural’ in old age!

The issue of the effect of menopause on women’s cognition, and whether hormone therapy helps older women fight cognitive decline and dementia, has been a murky one. Increasing evidence suggests that the timing and type of therapy is critical. A new study makes clear that we also need to distinguish between women who experience early surgical menopause and those who experience natural menopause.

The study involved 1,837 women (aged 53-100), of whom 33% had undergone surgical menopause (removal of both ovaries before natural menopause). For these women, earlier age of the procedure was associated with a faster decline in semantic and episodic memory, as well as overall cognition. The results stayed the same after factors such as age, education and smoking were taken into consideration.

There was also a significant association between age at surgical menopause and the plaques characteristic of Alzheimer's disease. However, there was no significant association with Alzheimer’s itself.

On the positive side, hormone replacement therapy was found to help protect those who had surgical menopause, with duration of therapy linked to a significantly slower decline in overall cognition.

Also positively, age at natural menopause was not found to be associated with rate of cognitive decline.

Bove, R. et al. 2013. Early Surgical Menopause Is Associated with a Spectrum of Cognitive Decline. To be presented at the American Academy of Neurology's 65th Annual Meeting in San Diego, March 21, 2013.

A number of studies have come out in recent years linking age-related cognitive decline and dementia risk to inflammation and infection (put inflammation into the “Search this site” box at the top of the page and you’ll see what I mean). New research suggests one important mechanism.

In a mouse study, mice engineered to be deficient in receptors for the CCR2 gene — a crucial element in removing beta-amyloid and also important for neurogenesis — developed Alzheimer’s-like pathology more quickly. When these mice had CCR2 expression boosted, accumulation of beta-amyloid decreased and the mice’s memory improved.

In the human study, the expression levels of thousands of genes from 691 older adults (average age 73) in Italy (part of the long-running InCHIANTI study) were analyzed. Both cognitive performance and cognitive decline over 9 years (according to MMSE scores) were significantly associated with the expression of this same gene. That is, greater CCR2 activity was associated with lower cognitive scores and greater decline.

Expression of the CCR2 gene was also positively associated with the Alzheimer’s gene — meaning that those who carry the APOE4 variant are more likely to have higher CCR2 activity.

The finding adds yet more weight to the importance of preventing / treating inflammation and infection.

[2960] Harries LW, Bradley-Smith RM, Llewellyn DJ, Pilling LC, Fellows A, Henley W, Hernandez D, Guralnik JM, Bandinelli S, Singleton A, et al. Leukocyte CCR2 Expression Is Associated with Mini-Mental State Examination Score in Older Adults. Rejuvenation Research [Internet]. 2012 :120518094735004 - 120518094735004. Available from:

Naert, G. & Rivest S. 2012. Hematopoietic CC-chemokine receptor 2-(CCR2) competent cells are protective for the cognitive impairments and amyloid pathology in a transgenic mouse model of Alzheimer's disease. Molecular Medicine, 18(1), 297-313.

El Khoury J, et al. 2007. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nature Medicine, 13, 432–8.

Lesions of the brain microvessels include white-matter hyperintensities and the much less common silent infarcts leading to loss of white-matter tissue. White-matter hyperintensities are common in the elderly, and are generally regarded as ‘normal’ (although a recent study suggested we should be less blasé about them — that ‘normal’ age-related cognitive decline reflects the presence of these small lesions). However, the degree of white-matter lesions is related to the severity of decline (including increasing the risk of Alzheimer’s), and those with hypertension or diabetes are more likely to have a high number of them.

A new study has investigated the theory that migraines might also lead to a higher number of white-matter hyperintensities. The ten-year French population study involved 780 older adults (65+; mean age 69). A fifth of the participants (21%) reported a history of severe headaches, of which 71% had migraines.

Those with severe headaches were twice as likely to have a high quantity of white-matter hyperintensities as those without headaches. However, there was no difference in cognitive performance between the groups. Those who suffered from migraines with aura (2% of the total), also showed an increased number of silent cerebral infarcts — a finding consistent with other research showing that people suffering from migraine with aura have an increased risk of cerebral infarction (or strokes). But again, no cognitive decline was observed.

The researchers make much of their failure to find cognitive impairment, but I would note that, nevertheless, the increased number of brain lesions does suggest that, further down the track, there is likely to be an effect on cognitive performance. Still, headache sufferers can take comfort in the findings, which indicate the effect is not so great that it shows up in this decade-long study.

A six-year study involving over 1200 older women (70+) has found that low amounts of albumin in the urine, at levels not traditionally considered clinically significant, strongly predict faster cognitive decline in older women. Participants with a urinary albumin-to-creatinine ratio of >5 mcg/mg at the start of the study experienced cognitive decline at a rate 2 to 7 times faster in all cognitive measures than that attributed to aging alone over an average 6 years of follow-up. The ability most affected was verbal fluency. Albuminuria may be an early marker of diffuse vascular disease.

Data from 19,399 individuals participating in the Renal Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, of whom 1,184 (6.1%) developed cognitive impairment over an average follow-up of 3.8 years, has found that those with albuminuria were 1.31-1.57 times more likely to develop cognitive impairment compared to individuals without albuminuria. This association was strongest for individuals with normal kidney function. Conversely, low kidney function was associated with a higher risk for developing cognitive impairment only among individuals without albuminuria. Surprisingly, individuals with albuminuria and normal kidney function had a higher probability for developing cognitive impairment as compared to individuals with moderate reductions in kidney function in the absence of albuminuria.

Both albuminuria and low kidney function are characteristics of kidney disease.

Lin, J., Grodstein, F., Kang, J.H. & Curhan, G. 2010. A Prospective Study of Albuminuria and Cognitive Decline in Women. Presented at ASN Renal Week 2010 on November 20 in Denver, CO.

Tamura, M.K. et al. 2010. Albuminuria, Kidney Function and the Incidence of Cognitive Impairment in US Adults. Presented at ASN Renal Week 2010 on November 20 in Denver, CO.

More evidence that vascular disease plays a crucial role in age-related cognitive impairment and Alzheimer’s comes from data from participants in the Alzheimer's Disease Neuroimaging Initiative.

The study involved more than 800 older adults (55-90), including around 200 cognitively normal individuals, around 400 people with mild cognitive impairment, and 200 people with Alzheimer's disease. The first two groups were followed for 3 years, and the Alzheimer’s patients for two. The study found that the extent of white matter hyperintensities (areas of damaged brain tissue typically caused by cardiovascular disease) was an important predictor of cognitive decline.

Participants whose white matter hyperintensities were significantly above average at the beginning of the study lost more points each year in cognitive testing than those whose white matter hyperintensities were average at baseline. Those with mild cognitive impairment or Alzheimer's disease at baseline had additional declines on their cognitive testing each year, meaning that the presence of white matter hyperintensities and MCI or Alzheimer's disease together added up to even faster and steeper cognitive decline.

The crucial point is that this was happening in the absence of major cardiovascular events such as heart attacks, indicating that it’s not enough to just reduce your cardiovascular risk factors to a moderate level — every little bit of vascular damage counts.

Older news items (pre-2010) brought over from the old website

Common medications associated with cognitive decline in elderly

A study of over 500 relatively healthy men aged 65 years or older with high blood pressure has found that chronic use of medications with anticholinergic properties was associated with impairment in verbal memory and the ability to perform daily living tasks. The degree of impairment increased proportionally to the total amount of drug exposure. This effect was independent of age, education, morbidities, and severity of hypertension.

Han, L., Agostini, J.V. & Allore, H.G. 2008. Cumulative Anticholinergic Exposure Is Associated with Poor Memory and Executive Function in Older Men. Journal of the American Geriatrics Society, 56 (12), 2203-2210.

Using anti-cholinergic drugs may increase cognitive decline

The Religious Orders Study has thrown up more data, this time on the subject of anticholinergic medication. Over an eight year period, 679 of the 870 elderly participants took at least one medication with anticholinergic properties. The study found those people who took anticholinergic drugs saw their rate of cognitive function decline 1.5 times as fast as those people who did not take the drugs. Anticholinergic properties are found in many medicines, such as medicines for stomach cramps, ulcers, motion sickness, and urinary incontinence.

The research was presented at the American Academy of Neurology Annual Meeting in Chicago, April 12–19.

Injection of human umbilical cord blood helps aging brain

A rat study has found that a single intravenous injection of human umbilical cord blood mononuclear cells in aged rats significantly improved the microenvironment of the aged hippocampus and rejuvenated the aged neural stem/progenitor cells. The increase in neurogenesis seemed to be due to a decrease in inflammation. The results raise the possibility of cell therapy to rejuvenate the aged brain.

Bachstetter, A.D. et al. 2008. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain. BMC Neuroscience, 9, 22.

Relationship between statins and cognitive decline more complex than thought

Previous studies of a link between statins (which protect against cardiovascular disease) and cognitive decline have produced inconsistent results. A three year epidemiological study of older African Americans has now found cognitive decline in statin users was less than those who did not take statins, but those who continued to take statins from 2001 to 2004 had greater cognitive decline than those who were taking statins in 2001 but were no longer taking them in 2004. The finding that the benefit is stronger for those who had discontinued use than for continuous users points to a complex association between statins and cognitive decline.

Szwast, S.J. et al. 2007. Association of statin use with cognitive decline in elderly African Americans Neurology, 69, 1873-1880.

High-normal uric acid linked with mild cognitive impairment in the elderly

A study of 96 older adults has found that those with uric-acid levels at the high end of the normal range had the lowest scores on tests of mental processing speed, verbal memory and working memory. The correlation persisted even when controlled for age, sex, weight, race, education, diabetes, hypertension, smoking and alcohol abuse. Uric acid levels increase with age, and higher levels are linked with high blood pressure, atherosclerosis, Type 2 diabetes and the "metabolic syndrome" of abdominal obesity and insulin resistance — all known risk factors for dementia. Because uric acid levels are so easily tested, the finding may suggest a valuable biological marker for very early cognitive problems in old age.

Schretlen, D.J. et al. 2007. Serum Uric Acid and Cognitive Function in Community-Dwelling Older Adults. Neuropsychology, 21 (1)

Drug reverses aging effect on memory process

Rat studies suggest that a drug made to enhance memory triggers a natural mechanism in the brain that fully reverses age-related memory loss, even after the drug itself has left the body. In middle-aged rats given ampakines twice a day for four days, there was a significant increase in the production of brain-derived neurotrophic factor (BDNF), a protein known to play a key role in memory formation, and in long-term potentiation (LTP), the process by which the connection between the brain cells is enhanced and memory is encoded. Deficits in LTP occur with age. This restoration of LTP was found in the brains even after the ampakines had been cleared from the animals' bodies.

Rex, C.S. et al. 2006. Restoration of Long-Term Potentiation in Middle-Aged Hippocampus After Induction of Brain-Derived Neurotrophic Factor. Journal of Neurophysiology, 96, 677-685.

Nicotine patch may alleviate 'senior moments'

A small preliminary clinical trial has found that four weeks of nicotine skin patches helped decision-making and attention in people with age-associated memory impairment (the mildest form of cognitive impairment in seniors). Given the health risks of smoking, and health risks associated with nicotine patches, it is too early to recommend the use of nicotine to improve memory, however. Nicotine mimics the brain chemical acetylcholine, a nerve signal that plays a role in learning and memory.

White, H.K. & Levin, E.D. 2004. Psychopharmacology

Statins associated with rare cases of temporary amnesia

Two recent studies have documented cases of amnesia and other nervous-system side effects after taking statins, the cholesterol-lowering drugs being prescribed to millions of people at risk of heart disease. It is emphasized that this is a rare problem, but given the vast numbers of people taking statins, it might still add up to a significant number of problems.