New research from the US suggests that emotions triggered by events can endure longer than factual recollection in patients with severe amnesia; the researchers hope their findings will increase understanding of Alzheimer’s and related diseases and also bring comfort to caregivers and families in the knowledge that their loved ones may continue to feel the warmth of visits and conversations even if they can’t remember what happened.You can read about the research by scientists at the University of Iowa (UI) in Iowa City in the 12 April early online edition of the Proceedings of the National Academy of Sciences, PNAS.

Lead author Justin Feinstein, a student in the UI graduate programs of neuroscience and psychology, told the media that:

“A simple visit or phone call from family members might have a lingering positive influence on a patient’s happiness even though the patient may quickly forget the visit or phone call.”

However, he also described the downside:

“On the other hand, routine neglect from staff at nursing homes may leave the patient feeling sad, frustrated and lonely even though the patient can’t remember why,” said Feinstein.

Feinstein and colleagues studied five patients with a rare case of memory loss due to damage to their their hippocampus that caused new memories to disappear.The hippocampus is critical for transferring memories from short-term to long-term storage, and is one of the first regions of the brain to suffer damage in Alzheimer’s disease.The researchers showed the patients short extracts of sad and happy films; although they couldn’t remember details of the films, they retained the emotions elicited by what they had watched.Each patient watched 20 minutes of a sad film, underwent memory and mood tests, then on another day, they watched 20 minutes of a happy film and had the same tests.The researchers observed that the films induced the appropriate emotion in the patients, ranging from laughing out loud while watching the happy films to tears during the sad films.About 10 minutes after watching a film clip, Feinstein and colleagues tested the patients’ factual memories to see how much they could remember about it.

A person with a non-impaired memory would be expected to remember about 30 details from each film clip, but these patients’ memories were severely imparied: one patient couldn’t recall a single detail.Then they asked the patients another set of questions to gauge their emotional state.Feinstein said that they still felt the emotion, explaining that “sadness tended to last a bit longer than happiness, but both emotions lasted well beyond their memory of the films”.

“With healthy people, you see feelings decay as time goes on. In two patients, the feelings didn’t decay; in fact, their sadness lingered,” he added.

The researchers concluded that the findings suggest “both positive and negative emotional experiences can persist independent of explicit memory for the inducing event,” and provide “direct evidence that a feeling of emotion can endure beyond the conscious recollection for the events that initially triggered the emotion”.

These results appear to challenge the idea that wiping out a painful memory abolishes the associated emotional suffering, and stress the importance of attending to the needs of people with Alzheimer’s disease.According to a 2009 report from Alzheimer’s Disease International (ADI), 35 million people worldwide will have dementia this year, and the number is set to double every 20 years, reaching 115.4 million by 2050.The greatest risk factor for Alzheimer’s is age, and there is currently no cure, said Feinstein.

“What we’re about to face is an epidemic. We’re going to have more and more baby boomers getting older, and more and more people with Alzheimer’s disease. The burden of care for these individuals is enormous,” he added, urging that:

“… we need to start setting a scientifically-informed standard of care for patients with memory disorders. Here is clear evidence showing that the reasons for treating Alzheimer’s patients with respect and dignity go beyond simple human morals.”

The Fraternal Order of Eagles, the National Institutes of Health, the National Science Foundation and the Kiwanis International Foundation, funded the research.

“Sustained experience of emotion after loss of memory in patients with amnesia.”
Justin S. Feinstein, Melissa C. Duff and Daniel Tranel
PNAS, published ahead of print April 12, 2010.
DOI:10.1073/pnas.0914054107

Source: University of Iowa, ADI.

A new report reveals that the burden of dementia on the UK economy is twice that of cancer, yet dementia research receives one twenty sixth of the money that goes to studying cancer, agreeing with previous studies that concluded dementia research is severely underfunded.The UK’s leading research charity for dementia, the Alzheimer’s Research Trust, commissioned the University of Oxford to produce the report, “Dementia 2010″. The charity’s Chief Executive, Rebecca Wood, told the press that:

“The true impact of dementia has been ignored for too long. The UK’s dementia crisis is worse than we feared.”

“This report shows that dementia is the greatest medical challenge of the 21st century,” said Wood.

Following in the wake of the government’s National Dementia Strategy, the charity’s new major report reveals that dementia costs the UK economy £23 billion a year and affects 820,000 people in the UK, 15 per cent more than previously thought.The bulk of the £23 billion of annual cost is the £12.4 billion met by unpaid carers, followed by social care costs of £9 billion, health care costs of £1.2 billion, and productivity losses of £29 million, says the report.The huge burden of cost met by unpaid carers represents 1.5 billion hours provided by relatives and friends. The social care cost is the long term institutionalisation of an estimated 304,850 patients in care homes.Paul Burstow MP, Liberal Democrat Member of Parliament for Sutton and Cheam, writes in the foreword that:

“Dementia costs the UK twice as much as cancer, three times as much as heart disease and four times as much as stroke.”

Yet when it comes to funding research, it appears that dementia is the poor relation, writes Burstow, explaining that:

“For every one pound spent on dementia research twenty six pounds are spent on cancer research and fifteen pounds on research into heart disease.”

The report defines dementia, the most common form of which is Alzheimer’s disease, as a group of symptoms associated with “a progressive decline of brain functions, such as memory, understanding, judgement, language and thinking”.People with dementia are at higher risk of developing physical and health problems and rely increasingly on receiving care from other people, the health care and social services system.The report also confirms a “diagnosis gap” between the expected number of people with dementia and the number on GP registers. For example in England, less than one third of the expected number are on GP lists.It suggest this could be because of the low rate of diagnosis by GPs, caused by lack of training and confidence in diagnosing the condition, an issue that was highlighted in a recent National Audit Office report.In an attempt to explain why dementia research should be so poorly funded, the report highlights a number of problems that also affect stroke research, for example, it could be that:

“Both stroke and dementia are still largely perceived as untreatable diseases, which are difficult to research and occur mainly in the elderly population.”

Also, unlike cancer and heart disease:

“Stroke is mostly treated by generalist doctors while there is still no international consensus about which medical specialty should diagnose and treat dementia.”

The report proposes that this attitude could be preventing health professionals from applying for research funds.

Source: Alzheimer’s Research Trust.

A new study from a center for Alzheimer’s research in the US suggests that cognitive skills other than memory, for example visuospatial skills that help us work out how objects relate to each other in three dimensions as we look at them, start to decline years before patients receive a clinical diagnosis for Alzheimer’s.The study was the work of Dr David K Johnson, of the University of Kansas, Lawrence, and colleagues, and is published in the October issue of Archives of Neurology, one of the JAMA/Archives journals.

The authors wrote that more and more researchers are now looking at when healthy aging turns into the early stages of dementia.”As new interventions become available, it will become important to identify the disease as early as possible,” they explained.Loss of episodic memory, that part of memory that is like an autobiography, where one can explicity recount the times and places of particular events and the emotions we felt, is commonly linked to Alzheimer’s, but it is not the only part of cognition (thinking, learning and memory) that is affected by the disease.For the longitudinal study, Johnson and colleagues followed 444 people who did not have dementia when they enrolled between 1979 and 2006.

Upon enrolling, each participant underwent a clinical evaluation that also tested four cognitive factors: global cognition, verbal memory, visuospatial skill and working memory. They did the tests at least one more time before the end of the study in November 2007.

The average follow up was 5.9 years, during which 134 of the participants developed dementia, and 310 did not. 44 of those with dementia died and when their brains were examined post mortem they showed signs that confirmed a diagnosis of Alzheimer’s.Brains of people who die with Alzheimer’s disease contain abnormal amounts of amyloid plaques and neurofibrillary tangles that can be seen under a microscope.

When they modelled the results of the cognitive assessments in line with the timing of the clinical diagnoses for dementia, the researchers found that the results for visualspatial skills showed a sudden change to a steeper slope of decline (an “inflection point”), three years before clinical diagnosis.

After that followed decline in overall cognitive ability, which suddenly declined more steeply two years before diagnosis, with verbal and working memory doing the same one year before diagnosis.

When they looked at other subgroups of the dementia patients, the only subgroup to show a similar pattern of decline with the same inflection points was the subgroup of participants with Alzheimer’s disease whose diagnosis was confirmed by autopsy.

The authors concluded that:

“Research into early detection of cognitive disorders using only episodic memory tasks may not be sensitive to all of the early manifestations of disease.”

“In summary, converging longitudinal evidence suggests that after a sharp departure from the relatively flat course of normal aging there is a preclinical period in Alzheimer’s disease with insufficient cognitive decline to warrant clinical diagnosis using conventional criteria but that can be seen with longitudinal data from multiple domains of cognition and not just memory,” they added.

The study was supported by grants from the National Institute on Aging, part of the National Institutes of Health.

“Longitudinal Study of the Transition From Healthy Aging to Alzheimer Disease.”
David K. Johnson; Martha Storandt; John C. Morris; James E. Galvin.
Arch Neurol, Oct 2009; 66: 1254 – 1259.

Source: JAMA/Archives.

An international team of scientists working on the largest ever genome-wide study looking for genes linked to Alzheimer’s have discovered two new genes, CLU and PICALM, are related to the disease, a finding that is being described as a “leap forward” for dementia research, especially because the last time a gene was found to be linked to the common form of Alzheimer’s disease was in 1993.

The study, which was described by Welsh First Minister Rhodri Morgan as a “real feather in the cap of Welsh science”, was led by the University of Cardiff in Wales, UK, and involved 80 researchers from the UK, Ireland, France, Germany, Belgium, Greece and the US, was published in the online issue of Nature Genetics on 6 September.

Until this study only one gene, APOE4, had been linked to Alzheimer’s disease. Now, with the discovery of CLU and PICALM, scientists expect to pursue new avenues for developing treatments for the disease.

The only other genes that have been connected to Alzheimer’s disease are in extremely rare familial forms of the disease, which is inherited in fewer than 1 case in every 100.

Sir Leszek Borysiewicz, of the UK’s Medical Research Council (MRC) praised the discovery as:

“A huge step towards achieving an earlier diagnosis of Alzheimer’s.”

Rebecca Wood, Chief Executive of the Alzheimer’s Research Trust, which part-funded the study, said:

“These findings are a leap forward for dementia research.”

“At a time when we are yet to find ways of halting this devastating condition, this development is likely to spark off numerous new ideas, collaborations and more in the race for a cure,” she added.

Senior investigator professor Julie Williams, who is Chief Scientific Adviser to the Alzheimer’s Research Trust told the media that CLU and PICALM reveal new genetic pathways that lead to Alzheimer’s.

The CLU gene codes for a protein called clusterin which normally protects the brain in several ways. Variations in CLU could remove the protective benefit of clusterin, and this could be a potential route to Alzheimer’s, a disease whose features include the build up of amyloid protein plaques around brain cells.

Co-author Dr John C. Morris, of Washington University in St Louis, Missouri, US, said that previous research at the University’s Alzheimer’s Disease Research Center (ADRC), of which he is the director, suggests that in mice the CLU gene may be involved in the formation of amyloid deposits in the brain.

PICALM affects synapses, the connections between brain cells and plays a role in the transport of molecules into and within nerve cells, which helps to form memories and other important brain functions, said Williams.

“We know that the health of synapses is closely related to memory performance in Alzheimer’s disease, thus changes in genes which affect synapses are likely to have a direct effect on disease development,” she added.

For the study, Williams and colleagues conducted a genome-wide association (GWA) study that pooled DNA samples from more than 19,000 older European and US residents. 7,000 of the donors had Alzheimer’s, while the others had no clinical symptoms of the disease.

The samples came from brain and blood tissue made available and analyzed by dozens of laboratories in the UK, Ireland, Germany, Belgium, Greece and the US.

By looking at more than 600,000 common DNA markers, the investigators found the two new genes were linked to higher risk of Alzheimer’s; they also confirmed the importance of APOE4.

Co-author Dr Alison M. Goate, a professor of neurology at Washington University, said this study was the first to provide significant evidence of new genetic risk factors for the most common form of Alzheimer’s. In 1991, Goate led a team in England that that identified the first early-onset Alzheimer’s mutation in the APP gene on chromosome 21.

Goate said that the two new genes are significant but their effect appears to be much smaller than that of APOE.

“Using statistical methods, we’ve been able to estimate the amount of risk attributable to APOE at about 19 or 20 percent. The newly identified genes each come in under 10 percent, so it appears they have a much smaller effect,” said Goate.

However, the effect might be small but it is not insignificant, she added, explaining that while it isn’t yet clear how these new genes influence Alzheimer’s risk, levels of clusterin tend to rise when brain tissue is injured or becomes inflamed. Some researchers have found increased levels of clusterin in the brain and spinal fluid of patients with Alzheimer’s, said Goate.

The researchers also found 13 other genes that should be investigated further for possible links with Alzheimer’s risk, so there may be more discoveries yet to come.

In fact the Cardiff-led team shared their data with another French-led team who found convincing evidence that there may also be a third gene linked to Alzheimer’s that is called CRI. Their paper appears in the same issue of Nature Genetics.

The study was funded by the Wellcome Trust, Medical Research Council, Alzheimer’s Research Trust, the Welsh Assembly Government and other bodies.