Some things in life are less than fair. Not only do many women experience “Pregnancy brain” and “Mummy brain” when our ability to retain relevant information sometimes appears to go to mush, it also appears we can joyfully expect to experience “Menopause brain” when transitioning from being fertile to becoming infertile.

“Menopause brain” is nothing new, in fact 60% of women going through menopause will report memory problems, yet this has remained an area where fabulously little research has been undertaken to try and understand what is really going on with our brains at this time in our lives.

What has been reported, is that not only do many women experience significant changes with their memory, but because these changes occur typically in our late forties and early fifties, we become frightened that these changes could herald the first signs of cognitive impairment and Alzheimer’s disease. That fear of course then compounds the brain’s inability to think clearly and a vicious cycle can ensue.

So first things first: there are brain changes, which occur in the menopausal brain that can affect memory.
These changes reflect a physiological change and are not the first signs of neurodegenerative disease i.e. Alzheimer’s.

So what is going on here?

Back in 2009 a study on 2362 women aged between 42 and 52 looked at

• Verbal memory
• Working memory (short term)
• Speed of processing information

The women were tested at four different stages of transition through menopause i.e. pre- menopause (regular periods), early peri- menopause (some irregularity of periods), late peri-menopause (no period for 3 – 11 months) and post menopause.

As I mentioned earlier, up to 60% of women will report memory difficulties during menopause and this study confirmed that during the early and late peri menopause, women do not learn as well as when they are in the other stages.

The good news is that this effect appears to be temporary. Our ability to learn returns to pre menopausal levels once we become post menopausal.

Phew!

The other interesting note here is the role of hormones (or rather HRT) on our verbal memory and processing speed.

Taking HRT before menopause appears to help verbal memory and processing speed.
But taking HRT postmenopausally has no effect on these skills.

This suggests there is a critical window of opportunity for the benefit of oestrogen and progesterone supplementation here. However much depends on the individual and their relative risk factors for consideration of using HRT at all.

Another study in 2009 examined the relationship between peri menopausal memory complaints and performance in relation to other relevant factors such as hormone levels, mood state, and sleep quality. In this small study of 24 women, there was no association of memory complaint and performance on tests of retentive memory. What they did show was memory complaints were linked to poorer memory encoding (i.e. learning) and depressive symptoms.

Miriam Weber PhD a neuropsychologist at the University of Rochester Medical Centre has now published the findings of a new study in the journal Menopause. In this study 75 women aged 40 to 60 who were in early peri menopause underwent a series of cognitive tests to look at their

• Ability to learn and retain new information (encoding memory)
• Ability to mentally manipulate new information (using working or short term memory)
• Sustain attention over a period of time (paying attention)

They were also asked about any symptoms associated with menopause such as hot flushes, depression, and anxiety and sleep difficulty. Plus they underwent blood tests measuring oestrogen and FSH levels.

The study showed that those women who had noted memory problems were the ones who demonstrated difficulty with learning, retaining and manipulating new information.

The examples given of difficulty experienced included

“Calculating the tip after a meal at a restaurant, doing mental math, or adjusting a flight itinerary for a journey”

They were also noted to have difficulty staying on task i.e. paying attention.

Remembering specific items for example on a grocery list and recalling them when in a shop were not an issue.

The actual hormone levels were found to have no association with the memory complaints, though experiencing difficulty sleeping or anxiety and depression symptoms did.

What can we do to help?

The best thing to do if you are experiencing memory difficulty associated with the peri menopause would be to

1. Address any sleep problems. Talk to your GP. Follow good sleep hygiene practice.

2. Address anxiety or symptoms of depression. Talk to you GP about the different options you could choose to ameliorate these.

3. Find and use strategies to help you with encoding and retaining information. This could include simple tricks such as
• Repeating a new price of information out loud
• Saying it back to another person for confirmation
• Practice attention building skills such as meditation to help stay on task for longer.

And of course relax, it’s only your “Menopause brain” playing up and the good news is that by the time the post menopausal state is reached, your brain fog will have cleared and you can then enjoy the wisdom and serenity that being post menopausal will bring.

Refs:
1. Miriam T. Weber, Mark Mapstone. Memory complaints and memory performance in the menopausal transition. Menopause. 2009 Jul-Aug;16(4):694-700.

2. American Academy of Neurology (2009, May 25). Menopause Transition May Cause Trouble Learning. ScienceDaily. Retrieved March 18, 2012, from http://www.sciencedaily.com¬ /releases/2009/05/090525173427.htm

3. Miriam T. Weber, Mark Mapstone, Jennifer Staskiewicz, Pauline M. Maki. Reconciling subjective memory complaints with objective memory performance in the menopausal transition. Menopause, 2012; 1 DOI: 10.1097/gme.0b013e318241fd22

Physical exercise is a fantastic way to stimulate our brain function. It has been shown in numerous studies to boost our cognitive skills of memory and learning. Children who exercise are known to perform better academically. Older adults can also boost their memory and thinking skills by undertaking regular exercise of thirty minutes of aerobic activity (enough to get the heart rate up).

Whilst it is known that exercising leads to more oxygen and nutrients getting to the brain, how the brain uses fuel during the actual process of exercise, hasn’t been understood until fairly recently.

Our neurons don’t store fuel themselves and their primary energy source is glucose. Our brain uses 20% of all the energy we put into our body as fuel, despite only accounting for 2% of our actual body weight. Hence the need to supply our greedy brain with a regular amount of food.

Another discovery a few years back, was that our other brain cells or astrocytes, which act as support agents for our neurons, can store fuel in the form of glycogen. It is this glycogen that is important for the normal function of all of the cells in our brain.

In 2011 scientists from the University of Tsukuba in Japan undertook a study on astrocyte glycogen in rat brains. They suspected that this brain glycogen was used by the neurons as a fuel reserve during times when blood glucose levels were low i.e as in when exercising. In prolonged exercise, our muscular glycogen stores will typically get depleted, so the scientists looked at measuring muscle and brain glycogen in the rats after running them on treadmills at varying intervals of 30, 60 and 120 minutes and comparing levels to a non exercising group.

What they found was that after 30 and 60 minutes of running, the muscle and liver glycogen stores were depleted whilst the rat brain glycogen levels remained the same. But after 120 minutes running, the brain glycogen levels dropped in 5 different areas of brain, consistent with respective blood and brain glucose levels. In other words the glycogen stores from the astrocytes had been broken down and the energy released, and subsequently used by the energy hungry neurons.

In 2012 the same group of scientists did further studies,(again using rats)this time looking at the effect of exhaustive running on brain glycogen levels after a single running session and after 4 weeks of regular moderate intensity running.

After the single session of running on the treadmill, the rats were allowed to rest and feed prior to having their brain glycogen levels measured. What the scientists found was that the rats brains had over compensated with up to 60% more glycogen being stored in the astrocytes. This then dropped back to normal levels within 24 hours.
In the second case, after four weeks of exercise training this extra compensation level became the new “normal”, especially in those areas of the brain associated with learning and memory. The longer lasting super compensation of the cortex and hippocampus is thought to probably be a training adaptation to meet the increased energy demand of a brain in someone who exercises regularly.

So what does this imply for us as exercising humans?

Having a greater amount of fuel reserve in the astrocytes may explain why our thinking skills improve if we exercise regularly. Our brain then has a better and larger fuel supply to enable us to think and remember better.

So next time you have been for a bit of a burn, don’t forget to top up afterwards with a carbohydrate rich snack such as a banana to boost your brain glycogen levels.

Refs:
Matsui T, Soya S, Okamoto M, Ichitani Y, Kawanaka K, Soya H. Brain glycogen decreases during prolonged exercise. J Physiol. 2011 Jul 1;589 (Pt 13):3383-93. Epub 2011 Apr 26.

Matsui T, et al. Brain glycogen supercompensation following exhaustive exercise. J Physiol. 2012 Feb 1;590 (Pt 3):607-16. Epub 2011 Nov 7.

Physical exercise is known to be an essential lifestyle choice for anyone who wants to maintain their cognition. It boosts oxygen and nutrient supply to the brain as well as stimulating the release of neurochemicals, such as BDNF, (brain derived neurotrophic factor) which enhances the maintenance of existing neurons as well as stimulating the birth of new brain cells in a process called neurogenesis.

Previous studies have reported that people who exercise regularly, not necessarily with vigorous exercise but with a daily routine of 20-30 minutes of say walking, benefit the most in terms of maintaining memory and thinking skills.

Brain scan studies have shown exercise slows down brain shrinkage, which develops due to loss of neuronal connections. A U.S. study reported that walking for 6 -9 miles per week was associated with helping to maintain memory as well as reducing brain shrinkage. Other studies have shown that regular moderate exercise can reduce a person’s relative risk of dementia or Alzheimer’s disease and that certain forms of exercise such as ballroom dancing are particularly good because they produce cross-training for the brain.

One area of the brain that is associated with learning and memory is called the hippocampus. This brain area typically shows damage early in Alzheimer’s disease. Being able to maintain the size of one’s hippocampus is important as a means of reducing relative risk of cognitive decline.

One study reported in early 2011 showed that walking for 40 minutes three times a week produces an increase in hippocampal volume, significant enough not only to show up on brain scans but translating into one to two years of better cognition by preventing hippocampal volume loss.

In the study, 120 subjects in their mid sixties either walked for 40 minutes three times a week along with a warm up and cool down session while the control group did less aerobic stretching and toning exercises, yoga and resistance training with rubber bands.

After one year follow up brain scans showed that the control group had hippocampal volume loss of 1-2% while the walking group had increased in volume by 2%. Both groups showed improvements in spatial memory but this was more marked in the walking group. The walking group also had higher levels of BDNF the neurochemical associated with enhancing neuronal support and neurogenesis.

None of us can avoid the ageing process. Hippocampal loss is a common finding with ageing. However moderate exercise appears to be able to reverse this trend that could mean a lower risk of memory problems and Alzheimer’s disease in older age.

So what would you choose? A sedentary lifestyle associated with continuing brain shrinkage and hippocampal loss or a lifestyle, which incorporates daily regular exercise to ensure you keep your memory intact and sharper for longer?

I’ve already made my choice. What’s yours?

Ref:
Erickson, K.I., Voss, M.R., Prakash, R.S. et al
Exercise training increases size of hippocampus and improves memory PNAS 2011 108 (7) 3017-3022; published ahead of print January 31, 2011, doi:10.1073/pnas.1015950108

What is zinc?

Zinc is a mineral found in nearly every cell of our body and is involved in many different chemical reactions. One important role of zinc is in transport for the formation of some proteins.

You may have taken zinc as part of a multivitamin or used it when you have caught a cold. It boosts our immune system and is believed to shorten the length of the illness. And most kids will have had zinc applied to delicate skin to protect from sunburn.

Where do we get our zinc?

The best sources of zinc from our diet is found in seafood such as oysters and crabmeat, red meat, poultry, baked beans, pecans, milk and fortified foods such as breakfast cereals.

What is the role of zinc in the brain?

Scientists have been looking at the role of zinc in our brain. In 2009 a molecular sensor was devised to analyse how much zinc is found in different cells. For example, it was discovered that in the pancreas gland, insulin is packaged around zinc ions. In type two diabetes, this packaging process appears to be defective – this may give further clues as to the molecular changes involved relating to zinc and the development of type two diabetes. As type two diabetes is a risk factor for dementia, being able to reduce the risk at this level would be an important step forward.

Zinc as a regulator of brain cell communication

In the brain, communication between neurons relies on neurotransmitters, special brain chemicals that are packed into vesicles, which also contain zinc. Zinc gets into the brain via special ion channels and glutamate receptors.
It enters the neurons via protein gates called ZIP transporters. Researchers have found that removing these ZIP protein gates in certain areas of the brain such as the hippocampus can protect them from injury.

The hippocampus is the area of the brain where lots of zinc has been found in the neurons. It turns out that having the right amount of zinc at the level of the synapse is essential for normal neuronal communication and function. Too little or too much can lead to neuronal dysfunction or even cell death.

Zinc and Memory

Zinc has been shown to enhance neuronal communication. A team from the Duke University Medical Centre showed that increases in glutamate, the brain’s main excitatory neurotransmitter, enhances this zinc effect and this is thought to be important for memory function. Certain cells in the hippocampus with high levels of zinc were shown to be associated with a particular form of memory formation.

Zinc and Epilepsy

The hippocampus is an area of the brain susceptible to epileptic seizures. In epilepsy those neurons with high levels of zinc are thought to worsen the epilepsy through excessive enhancement of communication. During a seizure these hippocampal cells are then particularly susceptible to damage at a time when they may also be exposed to injury through loss of oxygen and glucose.

Research at the Baylor College of Medicine has shown that if two types of ZIP protein genes were removed, there was less damage to the hippocampal nerves following a seizure. This may help for the future management of epilepsy by leading to the development of drugs targeting removal of the ZIP proteins which will reduce zinc entry into the brain and help to protect the brain’s memory circuits. People who have epilepsy will often remark that their memory is affected in the post ictal or recovery state.

Dr. Jeffrey L. Noebels,Professor of neurology, neuroscience and molecular and human genetics at BCM Director of the Blue Bird Circle Developmental Neurogenetics Laboratory was quoted as saying “These findings pave the way for the development of a new type of neuroprotective medicine for conditions such as seizures, stroke, brain trauma and other neurodegenerative disorders. Many laboratories are looking for such drugs, and this provides an important clue.”

Refs:
Imperial College London (2009, August 31). Think Zinc: Molecular Sensor Could Reveal Zinc’s Role In Diseases.

Enhui Pan, Xiao-an Zhang, Zhen Huang, Artur Krezel, Min Zhao, Christine E. Tinberg, Stephen J. Lippard, James O. McNamara. Vesicular Zinc Promotes Presynaptic and Inhibits Postsynaptic Long-Term Potentiation of Mossy Fiber-CA3 Synapse. Neuron, 2011; 71 (6): 1116 DOI: 10.1016/j.neuron.2011.07.019

Jing Qian, Kaiping Xu, Jong Yoo, Tim T. Chen, Glen Andrews, and Jeffrey L. Noebels. Knockout of Zn Transporters Zip-1 and Zip-3 Attenuates Seizure-Induced CA1 Neurodegeneration The Journal of Neuroscience, 5 January 2011, 31(1):97-104; doi:10.1523/JNEUROSCI.5162-10.2011

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