Study uncovers link between Alzheimer's and Parkinson's

Scientists have discovered biological mechanisms that may link Parkinson's disease to Alzheimer's disease, according to a study published in the journal Acta Neuropathologica.

Researchers from the University of Florida say their findings could lead to targets for new treatment that combats both Alzheimer's and Parkinson's disease, as well as many other neurological disorders.

For their study, the researchers investigated a protein called tau. They explain that tau is a soluble protein in the brain that binds to microtubules - components that play an important part in cell processes - helping to support neuronal function.

The normal function of tau is supported by phosphorylation - a process that switches protein enzymes on and off and regulates their function and activity.

However, the researchers say that in some diseased brains, the tau protein can become abnormally phosphorylated and cause "clumps" or "tangles." These tangles, called tauopathies, are linked to cognitive impairment found in some neurodegenerative diseases, such as Alzheimer's, and are also linked to around 20% of Parkinson's cases.

LRRK2 'phosphorylates tau protein'

Parkinson's patients can develop tangles of the tau protein as a result of a mutated enzyme called LRRK2, the researchers say.

From conducting a series of mammalian studies, the researchers discovered that standard LRRK2 adds groups of phosphate to tau protein, while mutated LRRK2 adds significantly more phosphates to tau protein.

Using these findings, the research team were able to uncover two sites on the tau protein - T149 and T153 - where the mutated LRRK2 was able to add phosphate groups, which they linked to tangle formations.

The researchers then went on to test their findings on human brain tissue. From this, they discovered that the two sites previously identified on the tau protein that were targeted by LRRK2, were altered the same way in human tissue with LRRK2 mutation.

When testing this finding on human brain tissue that was affected by Alzheimer's disease, and other neurodegenerative diseases that form tangles, they found these alterations were the same.

Explaining their findings, the researchers say:

"Our data, in aggregate, demonstrate that LRRK2 directly phosphorylates tau at T149 and T153 in vitro and the ability of LRRK2 to phosphorylate tau at these sites may underlie its ability to promote tauopathy in our novel mouse model.

Our current in vivo studies are the first of their kind and provide compelling evidence that LRRK2 and tau interact in a disease-relevant manner."

Potential for therapeutic targets

The researchers add that their findings have the potential to provide new therapeutic targets for both Alzheimer's and Parkinson's disease.

"Until now, nobody has really understood what the overlap between Alzheimer's and Parkinson's disease was, or if it were important," says Jada Lewis, associate professor of neuroscience at the Centre for Translational Research in Neurodegenerative Disease at the University of Florida. "Our study ties these diseases together in a unique way."

The researchers conclude that their findings show that LRRK2 genetic studies in human tauopathies may be warranted.

Medical News Today recently reported on a study suggesting that exercise may ward off Alzheimer's and Parkinson's disease.

Written by Honor Whiteman

Copyright: Medical News Today 

Article c/o: http://www.medicalnewstoday.com/articles/267885.php

What is Dementia? What Causes Dementia? Symptoms of Dementia

Dementia is the progressive deterioration in cognitive function - the ability to process thought (intelligence). It is a set of signs and symptoms in which brain function, such as memory, language, problem solving and attention are affected.

The word "dementia" comes from the Latinde meaning "apart" and mens from the genitive mentis meaning "mind".

Progressive means the symptoms will gradually get worse. The deterioration is more than might be expected from normal aging and is due to damage or disease. Damage could be due to a stroke, while an example of a disease might be Alzheimer's.

Dementia is a set of signs and symptoms

Dementia is a non-specific syndrome in which affected areas of brain function may be affected, such as memory, language, problem solving and attention. Dementia, unlike Alzheimer's, is not a disease in itself. When dementia appears the higher mental functions of the patient are involved initially. Eventually, in the later stages, the person may not know what day of the week, month or year it is, he may not know where he is, and might not be able to identify the people around him. 

Dementia is significantly more common among elderly people. However, it can affect adults of any age.

What are the symptoms of dementia?

• Memory loss - the patient may forget his way back home from the shops. He may forget names and places. He may find it hard to remember what happened earlier on during the day.

• Moodiness - the patient may become more and more moody as parts of the brain that control emotion become damaged. Moods may also be affected by fear and anxiety - the patient is frightened about what is happening to him.


• Communicative difficulties - the affected person finds it harder to talk read and/or write.

As the dementia progresses, the patient's ability to carry out everyday tasks diminishes and he may not be able to look after himself.

Diseases and conditions that cause dementia

• Alzheimer's disease - This is by far the most common cause of dementia. The chemistry and structure of the brain of a person withAlzheimer's disease changes and his brain cells die prematurely.


• Stroke (Vascular problems) - this means problems with blood vessels (veins and arteries). Our brain needs a good supply of oxygen-rich blood. If this supply is undermined in any way our brain cells could die - causing symptoms of vascular dementia. Symptoms may appear suddenly, or gradually. A major stroke will cause symptoms to appear suddenly while a series of mini strokes will not.


• Dementia with Lewy bodies - spherical structures develop inside nerve cells. Brain cells are nerve cells; they form part of our nervous system. These spherical structures in the brain damage brain tissue. The patient's memory, concentration and ability to speak are affected. Dementia with Lewy bodies is sometimes mistaken for Parkinson's diseasebecause the symptoms are fairly similar.


• Fronto-temporal dementia - this includes Pick's disease. The front part of the brain is damaged. The patient's behavior and personality are affected first, later his memory changes.
• Other diseases - progressive supranuclear palsy, Korsakoff's syndrome, Binswanger's disease, HIV and AIDS, and Creutzfeldt-Jakob disease (CJD). Dementia is also more common among patients who suffer from Parkinson's disease, Huntington's disease, Motor Neurone disease and Multiple Sclerosis. People who suffer from AIDS sometimes go on to develop cognitive impairment.


• High glucose associated with dementia - a team from the University of Washington School of Medicine reported in NEJM (New England Journal of Medicine that people with high blood sugar (glucose) levels have a higher risk of dementia, even if they do not havediabetes.

There are two main categories of dementia

According to most experts, there are two main categories of dementia - cortical and subcortical dementias.
• Cortical Dementia - The cerebral cortex is affected. This is the outer layer of the brain. The cerebral cortex is vital for cognitive processes, such as language and memory. Alzheimer's disease is a form of cortical dementia, as is CJD (Creutzfeldt-Jakob disease).


• Subcortical Dementia - A part of the brain beneath the cortex (deeper inside) becomes affected or damaged. Language and memory are not usually affected. A patient with subcortical dementia will usually experience changes in his personality, his thinking may slow down, and his attention span may be shortened. Dementias which sometimes result from Parkinson's disease are subcortical dementias, as are those caused by AIDS and Huntington's disease.
A patient with multi-infarct dementia will have both the cortical and subcortical parts of the brain affected or damaged.

Diagnosis of dementia

Although there are some brief tests, a more reliable diagnosis needs to be carried out by a specialist, such as a geriatric internist, geriatric psychiatrist, neurologist, neuropsychologist or geropsychologist.

The following tests are commonly used:

• AMTS (Abbreviated Mental Test Score) A score lower than six out of ten suggests a need for further evaluation.
• MMSE (Mini Mental State Examination) A score lower than twenty-four out of thirty suggests a need for further evaluation)
• 3MS (Modified Mini-Mental State Examination)
• CASI (Cognitive Abilities Screening Instrument)
It is important that the patient's score is interpreted in context with his socio-economic, educational and cultural background. The tester must also factor in the patient's present physical and mental state - does the patient suffer from depression, is he in great pain? 

Poor physical performance in the very elderly - researchers from the University of California found that people aged at least 90 years who had poor physical performance tend to have a much higher risk of either having or soon developing dementia. They reported their findings in Archives of Neurology, October 2012 issue. They assessed a sample of over-90s for walking, standing up from a chair, standing and controlling balance, and gripping something.

What is the treatment for dementia?

In the majority of cases dementia is incurable. Researchers are making inroads into treatments that may slow down dementia's progress. Cholinestaerase inhibitors are frequently administered during the early stages. Cognitive and behavioral therapies may also be useful. Several studies have found that music therapy helps patients with dementia. It is important to remember that the patient's caregiver also needs training and emotional support. 

In the USA, Tacrine (Cognex), donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon) have been approved for the treatment of dementia caused by Alzheimer's disease - some physicians prescribe these drugs for vascular dementia as well. Selegiline, which is used for treating Parkinson's disease, has been found to slow down the progress of dementia. 

In Canada, a country where two languages are spoken, English and French, researchers found that bilingual people who develop dementia do so four years later than monolingual people who develop dementia. The four year difference prevails even after factoring for such variables as cultural differences, education, employment, gender and immigration.

Anti-psychotics - Researchers at Aston University and the University of East Anglia reported that health authorities around the world are becoming concerned about the over-prescribing of anti-psychotic medications for patients with dementia. UK health authorities reported in October 2012 that reducing the usage of anti-psychotics has been much more difficult than originally estimated. In the United Kingdom, up to 1,800 people with dementia die each year due to this type of medication.

Common drugs may treat dementia one day - drugs that are used to treat skin conditions, high blood pressure and diabetes could eventually be used one day for the treatment of Alzheimer's disease. Researchers from King's College London reported in the journal Nature Reviews Drug Discovery (issue October 2012):
• Calcium channel inhibitors, such as Nilvadipine, used for the treatment of hypertension, may considerably reduce the risk of dementia.
• Diabetes medications, exenatide and liraglutide, activate the brain and inhibit the formation of plaques.
• The psoriasis drug, acitretin may alter the way proteins connect to dementia structure, the researchers believe.
• There may also be benefits from minoclycline, a tetracycline antibiotic that is used for the treatment of acne.
Beta-blockers may reduce dementia risk - scientists from Pacific Health Research and Education Institute in Honolulu, found that in autopsies of elderly males, those who had been taking beta-blockers were less likely to have brain changes linked to Alzheimer's and other types of dementia. Beta-blockers are medications prescribed for hypertension and heart conditions.

Keeping brain active during old age

Retiring later lowers dementia risk - a study conducted at the Bordeaux School of Public Health involving 429,000 self-employed people living in France found that those who retired later had a lower risk of being diagnosed with dementia. Study leader, Carole Dufouil, said "Our data show strong evidence of a significant decrease in the risk of developing dementia associated with older age at retirement, in line with the 'use it or lose it' hypothesis. The patterns were even stronger when we focused on more recent birth cohorts."

The aging brain benefits from simple mental activities, such as playing games, doing puzzles, reading and writing, researchers from Rush University and Illinois Institute of Technology reported at the 98th scientific assembly and annual meeting of the Radiological Society of North America (RSNA) in Chicago, in November 2012.

Lead researcher, Konstantinos Arfanakis, said:



"Reading the newspaper, writing letters, visiting a library, attending a play or playing games, such as chess or checkers, are all simple activities that can contribute to a healthier brain."



The authors invited 152 people, average age 81 years, to report how often during the previous 12 months they had engaged in mental activities, such as playing cards, board games, writing letters, reading magazines and newspapers, doing puzzles, etc. They were all clinically evaluated - none of them had any signs of dementia or mild cognitive impairment.

Over a 12-month period, they underwent MRI brain scans that allowed the scientists to produce diffusion anisotropy maps.

They found that mental activity was closely linked with positive outcomes for brain health.

Arfanakis said "Several areas throughout the brain, including regions quite important to cognition, showed higher microstructural integrity with more frequent cognitive activity in late life."

Robot improves quality of life for people with dementia

Robot companions help dementia patients - Professor Glenda Cook, from Griffith University, Australia, and colleagues found that a fluffy robotic harp seal - PARO - helped mid-to-late stage dementia patients become less aggressive, anxious and lonely.



Professor Cook with PARO the baby seal
PARO is a baby harp seal robot that comes with artificial intelligence software and tactile sensors. The device can respond to touch or sound, shows emotions, including surprise, happiness and anger. It gradually learns and eventually responds to its own name and certain words if they are repeated often enough.

The researchers reported that PARO had a significantly positive effect on the quality of life of people with dementia. Unlike live animals, which have also been shown to help people with dementia, with PARO there is no risk of injury or infection.

Mediterranean diet lowers vascular dementia risk

People with risk factors for vascular dementia should consider following a Mediterranean dietwith added mixed nuts or extra olive oil. Researchers from the University of Navarra, Spain, reported in the Journal of Neurology Neurosurgery and Psychiatry (May 2013 issue) that such a diet considerably lowers the risk.

Virgin olive oil is the main source of fat in a Mediterranean diet. It also includes large quantities of fruits, vegetables, nuts, pulses, moderate amounts of fish, seafood and red wine, but limited quantities of red meat and dairy products.

In their study, involving 522 participants aged 55 to 80 years, who started off with no cardiovascular disease or cognitive impairment, they were randomly placed into one of three groups:
• The Mediterranean diet with added olive oil group
• The Mediterranean diet with added mixed nuts group
• The control group - they were advised on how to follow a low fat diet that is typically recommended for reducing the risk of stroke and heart attack
After a follow-up of 6.5 years, the researchers found that those in the two Mediterranean diets groups had much lower levels of mild cognitive impairment than in the control group. Mild Cognitive Impairment is often a precursor to dementia.

Omega-3 fatty acids do not reduce cognitive decline in older women, a study carried out at the University of Iowa and published in the journal Neurology found.

How common is dementia?

• United Kingdom - According to a report by the Alzheimer's Society (UK), approximately 700,000 people in the United Kingdom have dementia, out of a total population of about 61 million. Your chances of having dementia are 1 in 100 during your late 60s, this rises to 6 in 100 in your late 70s, and 20 in 100 in your late 80s. As people live longer experts predict dementia will rise significantly. According to predictions, there will be 940,000 people with dementia in the United Kingdom by 2021.
• Worldwide - According to a study published in The Lancet, approximately 24.3 million people had dementia worldwide in 2005, with 4.6 million new cases every year. The number of people with dementia will double every two decades and reach 81.1 million by 2040. The rate of increase is expected to be faster in developing countries which have rapidly-growing life expectancies. (Lancet. 2005 Dec 17;366(9503):2112-7)
Dementia care costing over $150 billion annually in America alone
A study conducted by the RAND Corporation reported in NEJM (New England Journal of Medicine) that caring for Americans with dementia is costing $157 billion annually, more than the treatments for cancer and heart disease. The bulk of the cost is not medications or other medical treatments, but the actual caring for patients either at home or in nursing homes, the authors explained.

Dementia prevalence is closely linked to age - the older people become, the higher their risk. By 2040, with longer lifespans, the financial toll of dementia could double.

Senior author, Michael Hurd, said "The economic burden of caring for people in the United States with dementia is large and growing larger. Our findings underscore the urgency of recent federal efforts to develop a coordinated plan to address the growing impact of dementia on American society."
Hot chocolate helps memory and blood flow to the brain
People who drink two cups of hot chocolate per day may be less likely to experience memory decline, especially when they are older, a team from Harvard Medical School reported in the journal Neurology.

The team was investigating the effect of cocoa consumption on thinking and memory performance, as well as neurovascular coupling, where blood flow in the brain changes in response to local brain activity.

Lead author Farzaneh A. Sorond, said "As different areas of the brain need more energy to complete their tasks, they also need greater blood flow. This relationship, called neurovascular coupling, may play an important role in diseases such as Alzheimer's."

Apparently, regularly drinking hot chocolate improves neurovascular coupling.



Risk factors for young-onset dementia

Young-onset dementia - dementia that is diagnosed before 65 years of age - is associated with nine risk factors, researchers reported in JAMA Internal Medicine.

Their study involved 488,484 Swedish males who had enlisted in mandatory military service between 1969 and 1979. They were followed up for up to 37 years.

The following are major risk factors for early-onset dementia:

• Alcohol abuse
• Depression
• Father having dementia
• High systolic blood pressure when enlisting
• Low cognitive function when joining up (to the military)
• Low height at enlistment
• Stroke
• Taking antipsychotics
• Taking illegal drugs

As most of the risk factors are "potentially modifiable" and began during adolescence, the authors believe they are excellent opportunities for early prevention.

Written by Christian Nordqvist
Copyright: Medical News Today 

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