As we reach our forties and fifties, we start to notice a few changes with our brain. We forget things more easily, we experience more “tip of the tongue moments” and find it harder to stay focused or on task. We put it down to the fact that our speed of mental processing is slowing down. We may even have a couple of fleeting worrying thoughts that our brain might be showing the first signs of actual cognitive decline.

One of the biggest fears people express about ageing, is the loss of our mental faculties. That loss of that of course, has a significant impact on our ability to remain self-caring and independent.

Until now, the onset of actual cognitive decline has been thought to occur in our sixties. The clinical onset of Alzheimer’s disease typically occurs around age 65 or older, although it is well recognized that the actual condition slowly and silently develops over the preceding couple of decades. Brain scans can now show the pathological changes in younger brains, before the clinical signs of disease.
Those showing the greatest amount of pathological change in their brains are also known to be at greatest risk of developing clinical signs of dementia in later life.

Findings from a couple of studies (including a longitudinal study from Seattle, which has been following a group of 500 individuals since 1956) have suggested that cognitive decline did not start before the age of 60.
Those findings have now been challenged by a new study recently published in the British Medical Journal which has found that the age of onset of cognitive decline may be significantly earlier than previously thought: actually starting in our mid forties.

This study of 10308 men and women civil servants aged 45 to 70 years from London UK was set up to examine whether different age groups showed differing levels of cognitive decline over a ten-year period. The group underwent tests of memory, reasoning, vocabulary, phonemic and semantic fluency in three different assessments over the ten-year period.

The results of the study showed the following:

Between the age of 65 and 70, men on average showed a -9.6% decline in cognition,
women -7.4%. This was not unexpected.

However results of the younger age group age 45 to 49 also showed evidence of cognitive decline, albeit at a lower percentage; -3.5% cognitive decline for men and -3.6% for women.

The implications of this study suggest that we need to be taking a much closer note of how we are performing in midlife. Along with midlife obesity, high blood pressure and high cholesterol, our midlife cognitive function appears to be very important in determining how we will fare as we age.

If cognitive decline is picked up in our midlife, then at least that provides some valuable time to be putting into place specific strategies to to minimize any further decline and attempt to build cognitive reserve. What we don’t know (and requires further study) is whether midlife cognitive decline will lead to actual dementia – however it would seem prudent to do whatever we can, to keep our brains intact.

So what is the best thing we need to be doing in our midlife?

It’s all about maintain and improving brain function by adopting brain healthy lifestyles:

Eat healthily with a wide variety of green vegetables, fruit, lean proteins, seeds and nuts and keeping away from pies, pasties, cakes and biscuits, hot chips and fried foods.

Maintain a positive attitude to life. Being social engaged and active helps to keep stress levels down and stave off anxiety and depression.

Use your brain to learn new skills. Aim to include mental activities every day that are outside our usual habits. Card games, Sudoku, brain games, and apps are all useful.

Move your body. One of the biggest things we can do for our brain is to ensure we spend a minimum of thirty minutes every day doing some form of physical exercise – enough to get the heart rate up.

So next time you have a memory lapse, forget an appointment or lose your keys while it might simply a slower speed of processing, it could be an indication of a more serious reduction in your cognitive ability. So rather than ignoring it, be proactive and take the time every day to help restore your mental sharpness. Your brain may depend on it.

Ref:

Singh-Manoux,A.et al Timing of onset of cognitive decline: results from Whitehall 11 prospective cohort study. British Medical Journal 2012; 344 doi: 10.1136/bmj.d7622

Finding a reliable, affordable and relatively non–invasive way to accurately diagnose Alzheimer’s disease before the clinical symptoms develop is something many researchers have been investigating over the last few years.

PET scans (Positron Emission Tomography) have looked promising because they can show beta amyloid deposition in living brains. This has led to the hope that PET scans could be used as a predictive test, to determine who is at greater risk of developing cognitive impairment.

Professor Christopher Rowe from Austin Hospital, Victoria, Australia has led the way in this. Some of his latest research was presented earlier this year from a study on 366 subjects (average age 72 years). Of the group, 195 were healthy controls, 92 had mild cognitive impairment (MCI) and 79 had Alzheimer’s disease.

The group underwent PET scanning at the start of the study and again at 20 months and 36 months. In addition they also underwent 3D MRI scanning and had a full clinical and neuropsychological assessment at each visit.

The findings revealed that those of the healthy controls who were found to have amyloid deposition in their brains at the start of the study, and those with the greatest amount of beta amyloid plaques were the most likely to develop cognitive impairment.

Of those with MCI or Alzheimer’s disease, they were shown to have smaller volume hippocampi – the specialised area of the brain associated with learning and memory, and an area known to be affected early in Alzheimer’s disease.

On the PET scans, 98% of the subjects with Alzheimer’s’ disease were found to have a high level of beta amyloid in their brains, compared to 63% of those with MCI and 34% of the healthy controls.

Two years later it was possible to see from the follow-up scans, that healthy controls with beta amyloid deposition showed greater grey matter loss in the hippocampus and greater levels of mild memory decline.

Prof Rowe has stated he believes that the presence of beta amyloid in the brain signifies that person has a greater risk to future cognitive decline. He also said that carriers of the gene apoE4, a known risk factor for Alzheimer’s disease and vascular dementia, also showed a higher risk for cognitive decline on scans.

Because brain changes such as amyloid deposition occur at least 10 years prior to the onset of clinical symptoms, it is hoped that these imaging techniques will make it possible to identify the disease early enough for more effective treatments to be started.

In addition to PET scans, now a new form of MRI has also been shown to provide an early and reliable tool for predicting who is at greatest risk of cognitive decline.

Arterial spin labelling (ASL) is the technique which is being used to examine changes in brain function. The brain uses glucose primarily as its energy source. Changes in brain blood flow and the rate of consumption of glucose by the brain can be seen as changes in brain function using this technique.

MRI on its own provides a structural assessment to look at changes in the brain. In the diagram at the top of the page, the grey images on the left are from traditional MRI scans. Adding this new technique at the same time as a regular MRI allows a rapid assessment of brain function as well. This obviously saves the time and expense of otherwise having to wait for a PET scan, which is also very expensive.

In one recent study the investigators looked to see whether ASL-MRI or PET scans would be the better technique to use as a way to look for evidence of Alzheimer’s disease. In a group of 31 subjects (18 were healthy controls and 13 had Alzheimer’s disease) no demonstrable difference was noted in using either of the two tests.

In a second study in a similar size group, computer analysis of brain pattern blood flow and glucose metabolism again showed similar findings from both techniques.

The advantage of ASL-MRI however, is that it is non invasive, has no associated radiation exposure, and could be easily incorporated into existing MRI machines which are comparatively readily available. Further studies will continue to evaluate the usefulness of this as a potential screening and follow up investigative tool. It could be that ASL-MRI will provide the advantage, but PET may still be useful as an extra diagnostic tool where there is clinical uncertainty.

Refs:

1. Erik S. Musiek, Yufen Chen, Marc Korczykowski, Babak Saboury, Patricia M. Martinez, Janet S. Reddin, Abass Alavi, Daniel Y. Kimberg, David A. Wolk, Per Julin, Andrew B. Newberg, Steven E. Arnold, John A. Detre. Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer’s disease. Alzheimer’s and Dementia, 2011; DOI: 10.1016/j.jalz.2011.06.003

2. Y. Chen, D. A. Wolk, J. S. Reddin, M. Korczykowski, P. M. Martinez, E. S. Musiek, A. B. Newberg, P. Julin, S. E. Arnold, J. H. Greenberg, J. A. Detre. Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease. Neurology, 2011; DOI: 10.1212/WNL.0b013e31823a0ef7

3. Christopher C. Rowe, et al. Cognition and beta-amyloid in preclinical Alzheimer’s disease: Data from the AIBL study, Neuropsychologia, Volume 49, Issue 9, July 2011, Pages 2384-2390, ISSN 0028-3932, 10.1016/j.neuropsychologia.2011.04.012.

Credit for Image: Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association

A new study has found that the use of intranasal insulin produced an improvement in memory and cognitive function in a small group of people with either amnesic cognitive impairment or mild to moderate Alzheimer’s disease.

The role of insulin in Alzheimer’s has been extensively investigated. In the brain, abnormalities of insulin levels and activity have been known to be associated with the pathophysiology of Alzheimer’s. Type two diabetes (where a person has abnormal resistance to insulin) is a recognised risk factor for Alzheimer’s disease.

Having a normal blood sugar is important for our normal thinking skills and memory.
I’m sure many of us recognise how we don’t think so well either when we are really hungry when our blood sugar levels are really low, or conversely when we get that sugar high after eating a high sugar snack. The sugar fix is the signal for our body to release the hormone insulin which then restores our blood sugar to normal.

Using the insulin intranasally allowed the researchers to supply the brain with an extra shot of insulin, without producing any peripheral effect on blood sugar levels. This was important as the symptoms associated with having too low a blood sugar are not insignificant and include dizziness, confusion, heart palpitations, feeling anxious and altered vision.

In the study the intranasal insulin was administered over a 4 month period. One hundred and four subjects received either a 20 IU or 40IU dose of insulin or a placebo saline spray daily.
Those given the 20 IU insulin dose showed an improvement in memory that wasn’t apparent with the higher dose and both groups showed less decline in cognitive skills compared to the control group. There was also an improvement in functional ability for example in being able to handle money in those with Alzheimer’s who received the insulin spray.

This is a fabulous early study, which is now being followed up to involve a larger group of people over a longer period of time.

But the key for managing early Alzheimer’s disease, still remains in having an early diagnosis. This remains elusive for the present.

Intranasal treatments for delivery medication directly to the brain are not new. Earlier this year I blogged about how one research team have been investigating the use if intranasal Viagra as a means of preventing Alzheimer’s and stroke.

Ref:
Suzanne Craft; Laura D. Baker; Thomas J. Montine; Satoshi Minoshima; G. Stennis Watson; Amy Claxton; Matthew Arbuckle; Maureen Callaghan; Elaine Tsai; Stephen R. Plymate; Pattie S. Green; James Leverenz; Donna Cross; Brooke Gerton. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Archives of Neurology, 2011; DOI: 10.1001/archneurol.2011.233

What is stress?

It has been defined in a number of different ways but for the purpose of this article, is taken to be: a sense of irritation, tension, nervousness, anxiety, fear or difficulty sleeping, lasting over a month as a result of problems at home, at work or health worries.

Stress is a term often used in society, but do we really understand what stress actually is and why it matters to brain health?

Should we worry about stress as a risk factor for dementia and Alzheimer’s?

Severe chronic stress is bad for our health. This is the sort of stress that keeps you awake at night with worry. This is the sort of stress that is associated with excessive release of catecholamines, the substances associated with the “flight or fight” syndrome. Here cortisol, which in normal amounts causes no problem, exerts a toxic effect on our neurons.

Studies looking at dementia risk and stress.

A high level of cortisol in the brain, by accelerating the process of biochemical and behavioural pathology, has been linked to an increased risk of dementia.

The results of a population study on a group of 1400+ women in Sweden followed for over 35 years from 1968 was published in 2010. They were aged between 38 and 60 when first recruited to the study and answered questions including one asking about psychological stress in 1968, 1974, and 1980.

Of the group, 161 women developed dementia (mostly in the form of Alzheimer’s disease). Those who had reported having repeated periods of stress in middle age were shown to have a 65% increase in their risk of dementia. In those who reported stress in all three surveys had double the risk. In this study, the timing of the stress was relevant. In other words, exposure to repeated stress in middle age appears to elevate the risk

Should this be a surprise? Maybe not. It is already known that stress has a negative impact on our health, increasing our susceptibility to an impaired immune response and an increased risk of cardiovascular disease in the form of stroke, high blood pressure and heart attack.

Previous animal studies had also previously shown an association of stress and dementia risk.

But it also needs to be put into perspective. The vast majority of women participating in the study did not develop dementia. So while stress is significant and needs to be dealt with appropriately, it is important not to stress, that being stressed will lead you to developing dementia!

In another study, the physiological changes in neurons susceptible to the effect of stress were examined were examined.
Here, researchers using rats, showed how stress led to an increase in the formation of abnormal clumps of tau protein in neurons. This led to increased cell death, particularly in the area of the brain associated with learning and memory i.e. the hippocampus and prefrontal cortex.

This builds on previous findings that stress is associated with the build up of beta amyloid, another protein associated with the pathology of Alzheimer’s disease.

The next step will now be to examine to see whether these results implicating stress as a possible trigger of neurodegenerative disease can be replicated in humans. One of the researchers Osborne Almeida, has also questioned the relationship between stress and depression. Stress has been recognised as a major risk to a person’s propensity to develop major depression. Could beta amyloid and tau proteins, by being accelerated to form under the influence of stress, be implicated in the development of this disease as well?

Stress Management: The need to manage stress levels.

The bottom line is that the effect of stress on our health and well-being should not be underestimated.

• Be aware that stress is potentially harmful to your health.
• Make sure you know what you can do and how you can mitigate the effects of stress.

This could be in the form of physical exercise, talking to a trusted friend or family member, seeking medical advice, learning meditation, practicing yoga or tai chi, deep breathing or mindfulness training.

So don’t ignore symptoms of stress either personally or in someone else. Take the necessary steps to bring your stress under control and minimise any potential risk to the health of your body and brain.

Refs:

L. Johansson, X. Guo, M. Waern, S. Ostling, D. Gustafson, C. Bengtsson, I. Skoog. Midlife psychological stress and risk of dementia: a 35-year longitudinal population study. Brain, 2010; DOI: 10.1093/brain/awq116

Ioannis Sotiropoulos, Caterina Catania, Lucilia G. Pinto, Rui Silva, G. Elizabeth Pollerberg, Akihiko Takashima, Nuno Sousa, and Osborne F. X. Almeida. Stress Acts Cumulatively to Precipitate Alzheimer’s Disease-Like Tau Pathology and Cognitive Deficits. Journal of Neuroscience, May 25, 2011; 31(21):7840-7847 DOI: 10.1523/JNEUROSCI.0730-11.2011

Last week “The Shriver Report: A Women’s Nation Takes On Alzheimer’s.” was released and the message was stark.
Women are at the epicentre of the Alzheimer’s epidemic.

Maria Shriver, First Lady of California has been a major voice and campaigner promoting awareness of Alzheimer’s disease since her own father was diagnosed back in 2003. This report compiled with the Alzheimer’s Association reported the results of a poll of 3118 people.
The results indicted that 65% of Americans diagnosed with Alzheimer’s disease are women. One reason for this imbalance is thought to be because women on the whole tend to outlive men. However there may be other factors at play here as well.
Dr Roberta Brinton PhD, who specialises in studying the role of hormones and brain health in women, said she believed it is essential for all women between the age of 40 and 50 to maintain their brain health. This means trying to keep overall in good health, eating a balanced nutritious diet and exercising. Other risk factors need to be dealt with by women minimising their own risk of Type 2 diabetes, vascular disease and depression, which are all linked to a higher risk of Alzheimer’s disease.

The other major point raised by the report is that 60% of the caregivers for those living with the disease are also women.
Moreover these women themselves are at a higher risk. They have an x6-increased risk of developing Alzheimer’s because of the associated stresses from caring with someone with the disease.
The caregivers were also found to have an increased risk of heart disease, and hypertension and an overall increased mortality rate of 63%.

Of the 11 million caregivers in the States, two million are under the age of 18.
In this group, 250,000 of these minors are caregivers for a parent and 1.5 million of them are caregivers for a grandparent.

Shriver said that she wishes to support political candidates who will promote Alzheimer’s research and advocate for programs to help women. A major lifestyle issue is how to balance care-giving with jobs outside the home. She believes this balance is going to become increasingly important to find as more people (especially women) have to devote time to care-giving of a parent. Business and employers need to be mindful of the need to provide workplace flexibility to allow for “eldercare” she said. Women tend at present either to just swap to part-time work or leave the workplace altogether whereas men appear to find it easier to obtain work flexibility.

In California Maria Shriver has been instrumental in the setting up of an Intergenerational Playground where parents can take children as well as their parents.
As more people are diagnosed with Alzheimer’s, it is likely that more of these type of facilities will become available, in recognition of the many parents who find themselves as the “sandwich generation” looking after their children and their ageing parents.
The United States remains one of the few countries without a National Plan on how the country is going to tackle the expected Alzheimer’s epidemic.
Many Americans simply do not have long-term health care cover. It is estimated that it currently costs around $56,000 us per year to care for someone at home with Alzheimer’s disease. It has also been estimated that it will cost closer to US$20 trillion over the next 40 years.
Maria Shriver makes the point that it is going to cost the country that money anyway, so why not make it available for further research and facilities to care for those with the disease.