A biomarker is “A specific physical trait used to measure or indicate the effects or progress of a disease or condition“. The role of a biomarker is to provide doctors with an accurate and a reliable tool to make a diagnosis of Alzheimer’s disease. With degenerative diseases such as Alzheimer’s a biomarker should ideally, many doctors believe, meet a number of criteria.
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I am proud to support Dementia Awareness Day on September 15th 2015 on behalf of many
I have devoted a large part of my life to raising awareness of dementia. I have done a huge amount of independent research for this, having written a large number of book chapters, reviews and original articles on dementia, especially frontotemporal dementia.
I have recently even launched a blog on quality-of-life and wellbeing in dementia.
You can go to this blog here. You can also join us on Twitter here.
This celebrates the work being done by colleagues of mine in the academic community on aspects of wellbeing in dementia, including assistive technology and telecare, cognitive neurorehabilitation, built environments, end-of-life decision-making in dementia, definitions of wellbeing, ambient technologies, optimal design of the home, person-centred care, the socio-economic argument, and UK policy.
I am very happy to be writing a book drawing on the work of about ten prominent labs in the UK on this subject. It is a pity that real individuals with dementia or immediates, as well as hard working NHS doctors and nurses and academic researchers, are not given an opportunity to talk about their experiences. This field is dominated by professional third sector officers and their bosses looking for marketing chances sadly, but who do not have a strong working background specifically in this field otherwise.
However, I feel it is an extremely important area, and I am very proud to support it. I am off to an international conference in India in December 2012 for the World Federation of Neurology to discuss the subject with colleagues who are also experts in the field.
Organisational dementia in the NHS?
The definition of ‘dementia’ in neurology has experienced a number of different iterations in recent years. This has been a direct result of physicians developing a growing awareness that Alzheimer’s Disease, although the most common form of dementia in the senile age group, is not the only form of dementia. In fact, there are about 200 different types of dementia at least. This means that dementia is not always typified by loss of memory, the so-called amnestic syndrome. However, in Alzheimer’s Disease, the most pervasive cognitive deficit is inability to learn new memories, whilst memory for previous events or people can be relatively well preserved consistent with that outstanding French physician from the Paris School, Ribot, in his famous 1881 treatise on memory. Frontal lobe dementia has been speculated to be the most common form of dementia in the pre-senile age-group, characterised instead by a profound change in behaviour and personality, rather a cognitive deficit of a strong amnestic flavour. The NHS is undergoing now, against the will of the medical Royal Colleges and the British Medical Association, a fundamental strategic change, and this tweet yesterday evening caught me eye. It seems to me that the term ‘organisational dementia‘ could be applied to this organisational change at a number of levels.
In organisational development, learning is a characteristic of an adaptive organization, i.e., an organisation that is able to sense changes in signals from its environment (both internal and external) and adapt accordingly. A central issue is how adaptable the culture of the NHS is in general – many would like to see the NHS to adopt a stronger innovation culture, and in fact the NHS Innovation and Change provides extremely useful guidance on how innovative change in the NHS can be implemented successfully. Helen Bevan from that unit points to Harold Sirkin and colleagues who have published a model in the Harvard Business Review. The reason Bevan likes this model is that it is based on evidence from more than 1,000 change initiatives globally. I view a failure to implement change in the NHS, for example as will be necessary following the implementation of the Health and Social Act, will be in part be due to a failure in organisational learning, what you could call an ‘organisational dementia’. Bevan, in her brief article, points to two critical factors where organisational change will be impossible to achieve, and this should very much be borne in mind as the Government, with the help of McKinseys, try to effect their change without stakeholder cooperation.
“There must be active, visible backing for the change from the most influential senior leaders. They say that if, as a senior leader, you feel you are talking up the change initiative at least three times as much as you need to, your organisation will feel you are backing the transformation. In addition, the change is unlikely to succeed if it is not enthusiastically supported by the people who will have to operate within the new structures and systems that it creates. Staff need to understand the reasons for the change and believe it is worthwhile. The final factor is effort. There is an NHS tendency to launch major improvement initiatives without taking account of the extra responsibilities for change projects on top of busy operational jobs. The authors assert that if anyone’s workload increases by more than ten per cent as a result of the initiative, it is likely to run into problems. Organisations need to calculate upfront how much extra time and effort will be required to execute the change and create the space for it to happen.”
A further interesting contribution to the ‘organisational learning’ research comes from Common (2004) who discusses the concept of organisational learning in a political environment to improve public policy-making. The author details the initial uncontroversial reception of organisational learning in the public sector and the development of the concept with the learning organisation. According to Common (2004), research in UK local government has centred around four powerful obstacles for organizational learning in the public sector: (1) overemphasis of the individual, (2) resistance to change and politics, (3) social learning is self-limiting, i.e. individualism, and (4) political “blame culture.” This could be responsible also for a type of organisational dementia in the NHS; resistance to change and ‘blame cultures’ are two particular potentially serious issues for the NHS.
So far, I have considered an ‘organisational dementia’ in the NHS where the dementia has an amnestic flavour. There could of course be relatively change in its capacity for learning or memory, but there could be a profound change in its behaviour and personality. As the NHS becomes increasingly privatised, where patient care is reconciled more-and-more with an obligation in law to maximise shareholder dividend, it may be that the personality of the NHS becomes unrecognisable in a few years’ time. This to me, and I suspect many others, would be very sad.
So, in conclusion, I have outlined how a label of ‘organisational dementia’ might be applied to the NHS using organisational learning defects as a basis of an argument, using Alzheimer’s disease as a corollary. I have also applied the term in the way akin to frontal dementia. Organisational learning is a very powerful notion in business management, and its critical application to the strategic change in the NHS has not gone unnoticed by me.
Lithium: a medication for Alzheimer's disease?
According to scientists Alzheimer’s disease, a condition which leads to the size of the brain decreasing faster than ageing, could be treated by lithium, a naturally occurring element that is extremely inexpensive and already in use for other psychiatric disorders.
Lithium has been in use to treat bipolar affective disorders and now, researchers at Sao Paulo University in Brazil, led by Dr Orestes Forlenza have discovered that the pills slowed down memory loss in the elderly, reducing their cognitive decline. They also noted that there was a decrease in build-up of tangles of damaging proteins called phospho- tau in people’s cerebrospinal fluid which characterized Alzheimer’s disease.
For the study the team examined 41 people over the age of 60 with mild cognitive impairment, out of whom 21 took low doses of lithium every day for a year. All went through tests of memory and attention and a sample of their brain fluid was analyzed for tau concentrations. Although all the participants showed a decline in memory function over the year, those taking lithium showed less of a decline than those taking the placebo. Those taking lithium also had less of a form of the tau protein, pTau – a hallmark of Alzheimer’s disease – in their cerebrospinal fluid. The findings are published today in the British Journal of Psychiatry. The researchers now want to see larger studies to investigate whether lithium could have potential as a preventative treatment for Alzheimer’s.
Professor Allan Young, a psychiatrist from Imperial College London, described the study as “encouraging” – and particularly presents a value therapeutic opportunity, because no pharmaceutical company has a patent on lithium, meaning it is very cheap to prescribe. He added, “This trial adds to the increasing evidence that lithium may have beneficial effects on the brain and begs to be replicated in further randomised trials.”
Brain size clue in Alzheimer's disease
The brains of people diagnosed with Alzheimer’s disease start shrinking up to a decade before symptoms appear, a new study finds.
Researchers from Rush University Medical Center in Chicago and Massachusetts General Hospital in Boston performed brain neuroimaging scans on older adults with no signs of memory loss.
Of the 33 people in the Mass General group, eight developed Alzheimer’s didease over the course of 11 years. In the Rush group, only seven of 32 people followed for an average of seven years developed the disease.
About 55 percent of those whose brains were in the upper tertile (third) of atrophy developed Alzheimer’s disease, while none of those whose brains in the bottom tertile (little or no atrophy) developed Alzheimer’s disease.
Among those with moderate amounts of atrophy, about 20 percent developed the disease.
They could differentiate those who would decline from those who would remain healthy, according to the senior study author Leyla deToledo-Morrell, director of the graduate program in neuroscience at Rush University Medical Center. Based on the atrophy measurements, they claimed that they could even determine how quickly they were going to develop Alzheimer’s disease.
Doctors have long known that Alzheimer’s is an insidious disease, and that changes in the brain begin long before the first symptoms become evident, said Dr. Jeffrey Burns, director of the Alzheimer and Memory Program at University of Kansas Medical Center. This suggests, along with other studies, that Alzheimer’s disease neuropathology is likely present years, if not decades, before the emergence of symptoms.
What’s probably happening is that biochemical changes in the brain that are only partially understood cause degeneration of brain cells. Over time, the cells begin to die off, leading to structural changes in the brain tissue, or atrophy. Specifically, people in the study who would later be diagnosed with Alzheimer’s disease were more likely to show cortical thinning, or shrinkage, in several brain regions, including the medial temporal lobe, temporal pole and the superior frontal gyrus, which prior research has implicated in the early stages of Alzheimer’s disease. The amount of atrophy was much, much, much less than in a person with Alzheimer’s disease, but because each one who developed Alzheimer’s disease showed it, the results are extremely significant.
Eventually, the hope is that one day there will be drugs to slow the progression of the disease – there are none currently available – and being able to diagnosis Alzheimer’s early would mean people could start treatment before they have experienced significant declines.
If doctors can identify people at risk of the disease, they would be at much greater benefit from receiving treatment, rather than people who have already developed Alzheimer’s, who already have a certain amount of cell death and you can’t really rescue those cells. Though the number of participants in the study was small and the findings need to be repeated in larger populations, it is arguably remarkable they saw changes this clear with this small number of cases.
A a second study from the same journal may have practical applications immediately. The study found that vascular disease risk factors, such as hypertension, diabetes, cardiovascular disease and high cholesterol, may raise the risk of Alzheimer’s disease. The good news is that treating those conditions lowered the risk of Alzheimer’s disease. Chinese researchers followed 837 people over age 55 with mild cognitive impairment, which is often a precursor to Alzheimer’s, for five years. During that time, 298 developed Alzheimer’s, while the others still had mild cognitive impairment but had not progressed to Alzheimer’s. People who were treated for all of their vascular disease risk factors were less likely to progress to Alzheimer’s disease than those who weren’t treated or who only had some of their risk factors treated, according to the study. This study appears to imply that vascular disease has a real effect on the manifestation of Alzheimer’s disease. The vascular disease is damaging the brain and is probably causing the individual to have lowered resistance to the pathological effects of Alzheimer’s disease. Cholesterol-lowering medications, blood pressure medications and lifestyle changes such as losing weight and exercising can all help lower vascular disease risk factors.
Cognitive reserve and Alzheimer's disease biomarkers are independent determinants of cognition
Cognitive reserve and Alzheimer’s disease biomarkers are independent determinants of cognition Brain (2011) awr049 first published online April 7, 2011 doi:10.1093/brain/awr049
The link to this article in Brain is here.
The objective of the study above was to investigate how a measure of educational and occupational attainment, a component of cognitive reserve, modifies the relationship between biomarkers of pathology and cognition in Alzheimer’s disease. The biomarkers evaluated quantified neurodegeneration via atrophy on magnetic resonance images, neuronal injury via cerebral spinal fluid t-tau, brain amyloid-? load via cerebral spinal fluid amyloid-?1–42 and vascular disease via white matter hyperintensities on T2/proton density magnetic resonance images. They included very large samples – 109 cognitively normal subjects, 192 amnestic patients with mild cognitive impairment and 98 patients with Alzheimer’s disease, from the Alzheimer’s Disease Neuroimaging Initiative study, who had undergone baseline lumbar puncture and magnetic resonance imaging. We combined patients with mild cognitive impairment and Alzheimer’s disease in a group labelled ‘cognitively impaired’ subjects.
Their main conclusions included: (i) that in cognitively normal subjects, the variability in cognitive performance is explained partly by the American National Adult Reading Test and not by biomarkers of Alzheimer’s disease pathology; (ii) in cognitively impaired subjects, the American National Adult Reading Test, biomarkers of neuronal pathology (structural magnetic resonance imaging and cerebral spinal fluid t-tau) and amyloid load (cerebral spinal fluid amyloid-?1–42) all independently explain variability in general cognitive performance; and (iii) that the association between cognition and the American National Adult Reading Test was found to be additive rather than to interact with biomarkers of Alzheimer’s disease pathology.
Regarding dementia – it's the tau, stupid!
Tau is implicated in a number of different forms of dementias.
A new study is looking at the earliest events associated with neurodegenerative diseases characterized by abnormal accumulation of tau protein. The research, published the prestigious journal Neuron, reveals how tau disrupts nerve-to-nerve communication at synapses and may help to guide development of therapeutic strategies that precede irreversible nerve damage.
Tau normally contributes to the supportive framework of proteins in the cell. It is meant to form the structural skeleton of the cell. It is well established that abnormal tau sometimes clumps into neuron-damaging filament deposits and that aggregates of tau with multiple phosphate groups attached are the defining feature of neurodegenerative disorders called “tauopathies”, which include Alzheimer’s disease and other dementias. Dr. Ashe and colleagues investigated how tau induces early memory deficits and disrupts communication between nerves, before actual obvious neuron damage. The researchers found that early accumulation of hyperphosphorylated tau in dendrites and dendritic spines disrupted communication coming in from other nerve cells.
Whether it’s the tau or the amyloid (a different protein) that is causing all the problems will be a focus of much research into Alzheimer’s disease and its treatment, as usual, in 2011.
A new way of diagnosing the earliest stages of Alzheimer's Disease?
Alzheimer’s disease is the most common form of dementia in the UK, characterized by profound memory problems in affected individuals. Currently there is no single test or cure for dementia, a condition that affects over 800,000 people in the UK. The prospect of disease modification has intensified the need to diagnose very early Alzheimer’s Disease with high accuracy. The ultimate goal is possibly to identify and treat asymptomatic individuals with early stages of Alzheimer’s Disease, or those at high risk of developing the disease. By definition, such individuals will be asymptomatic, and disease biomarkers or high-risk traits will be require identification. For pre-symptomatic treatment trials, demonstration of disease modification will ultimately require evidence of delay to symptom-onset or conversion to Alzheimer’s Disease.
In a paper reported recently, UK experts say they may have found a way to check for Alzheimer’s years before symptoms appear. A lumbar puncture test (a test to get spinal fluid from an individual via his back) combined with a brain scan can identify patients with early tell-tale signs of dementia, they believe. Ultimately, doctors could use this to select patients to try out drugs that may slow or halt the disease. Although there are many candidate drugs and vaccines in the pipeline, it is hard for doctors to test how well these work because dementia is usually diagnosed only once the disease is moreadvanced. Researchers at the Institute of Neurology, University College of London, working with the National Hospital for Neurosurgery and Neurosurgery, Queen Square, London, believe they can now detect the most common form of dementia – Alzheimer’s disease – at its earliest stage, many years before symptoms appear.
Their approach checks for two things – shrinkage of the brain and lower than normal levels of a protein, called amyloid, in the cerebrospinal fluid (CSF) that bathes the brain and spinal cord. Experts already know that in Alzheimer’s there is loss of brain volume and an unusual build up of amyloid in the brain, meaning on the whole less amyloid in the CSF. There is, however, rather conflicting evidence for a relationship between measures of amyloid burden and brain volume in healthy controls, The research team reasoned that looking for these changes might offer a way of detecting the condition long before than is currently possible. To confirm this, they recruited 105 healthy volunteers to underwent a series of checks. All subjects were drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a multi-centre publicly/privately-funded longitudinal study investigating adult subjects with Alzheimer’s Disease, ‘mild cognitive impairment’ of the memory variety, and normal cognition. Participants undergo baseline and periodic clinical and neuropsychometric assessments and serial MRI.
The volunteers had lumbar puncture tests to check their spinal cerebrospinal fluid (CSF) for levels of amyloid and MRI brain scans to calculate brain shrinkage. The results, published in Annals of Neurology (reference provided below), revealed that the brains of those normal individuals with low CSF levels of amyloid (38% of the group), shrank twice as quickly as the other group. They were also five times more likely to possess the APOE4 cholesterol risk gene and had higher levels of another culprit Alzheimer’s protein, tau. Crucially, the results may allow doctors to pursue avenues to test which drugs might be beneficial in delaying or preventing dementia.
Potential limitations of the study include the relatively high percentage of amyloid-positive normal controls, which may or may not reflect the true population prevalence of individuals with significant amyloid pathology in this age range. There are also a number of issues relating to the reproducibility, reliability, and reporting of biomarker levels in spinal fluid, which need to be standardized to allow for cross-study comparisons.
Notwithstanding that, the scope for further research is enormous. Whether excess rates of brain atrophy in apparently cognitively normal aged patients with CSF profiles suggestive of AD inevitably lead to cognitive impairment, and if so over what time frame, needs to be established. If this proves to be the case, the results we present have significant implications for very early intervention, demonstrating that biomarkers may be used not only to identify Alzheimer’s Disease pathology in asymptomatic individuals, but also to demonstrate and quantify pr-esymptomatic clinical dementia. This suggests that disease-modifying trials in asymptomatic individuals with the aim of preventing progression to cognitive impairment and dementia may be feasible one day.
Reference:
Increased brain atrophy rates in cognitively normal older adults with low cerebrospinal fluid A?1-42. Jonathan M. Schott MD, Jonathan W. Bartlett PhD, Nick C. Fox MD, Josephine Barnes, for the Alzheimer’s Disease Neuroimaging Initiative Investigators Article first published online: 22 DEC 2010 DOI: 10.1002/ana.22315
You can view this paper here.
(c) Dr Shibley Rahman 2010
Poor standards in reporting of slow protein clearance in Alzheimer's disease on the BBC website
Kwasi G. Mawuenyega, Wendy Sigurdson, Vitaliy Ovod, Ling Munsell, Tom Kasten, John C. Morris, Kevin E. Yarasheski and Randall J. Bateman. Decreased Clearance of CNS ?-Amyloid in Alzheimer’s Disease. Science DOI: 10.1126/science.1197623 Published Online 9 December 2010
http://www.sciencemag.org/content/early/2010/12/08/science.1197623
The reporting of this on the BBC News health website was for me inadequate by academic professional standards.
http://www.bbc.co.uk/news/health-11962174
“Plaques” of a protein called amyloid build up in the brains of patients in Alzheimer’s disease (AD). Actually, Alzheimer’s disease is characterized by increased amounts of soluble and insoluble b(=beta) amyloid (Ab) – this predominantly is in the form of Ab42 in amyloid plaques and Ab40 in amyloid angiopathy (amyloid build-up in the blood vessels inter alia).
The amyloid hypothesis proposes that AD is caused by an imbalance between Ab amyloid production and clearance, resulting in increased amounts of Ab amyloid in various forms in the Central Nervous System. High levels of this type of amyloid then initiate a powerful chain-reaction of events culminating in damage and death to brain cells, manifesting sadly as progressive clinical dementia of the Alzheimer type. In rare cases of AD, straightforward inherited alterations increase the production of Ab. However, Ab dysregulation in the far-more common late-onset non-family history types of AD is less well understood. Impaired clearance of Ab may also cause late onset AD and this is what this paper from the prestigious journal Science is about. Limitations of this study stated in the paper include the relatively small numbers of participants (twelve in each group) and the inability to prove causality of impaired Ab clearance for AD, and these seem entirely reasonable.
Research participants were enrolled from the “Washington University Alzheimer ’s Disease Research Center”. The inclusion criteria were age >60 years, cognitively normal (Clinical Dementia Rating or CDR 0), very mild AD (CDR 0.5) or mild AD (CDR 1). The study included the typical exclusion criteria. 25 participants were clinically evaluated and rated as either very mild to mild dementia of the Alzheimer type (n=12, average age 77), or as cognitively normal (n=12 average age 71). After baseline blood and spinal fluid samples were collected, a shot of radioactively-labelled material was infused at 2 mg/kg over 10 minutes, followed by 2 mg/kg/hr for the remaining 8 hours and 50 minutes. During and after infusion, spinal fluid and blood samples were collected for a total of 36 hours and frozen at -70°C.
The first major criticism of this study must be that an approximate screening test for Alzheimer’s Disease was administered (the Clinical Dementia Rating scale); of course, there is no definitive diagnosis of patients until death, but with such small numbers taking part in this study, this is a concern, as some of the patients with a proposed diagnosis of Alzheimer’s disease could turn out to have a totally different type of dementia, such as dementia with Lewy Bodies or frontotemporal dementia, or not even dementia at all (such as geriatric depression).
To determine the balance of Ab production to clearance rates in AD versus controls, they measured the ratios of production to clearance (fig. S2). The ratio of Ab42 production to clearance rates were balanced for cognitively normal participants (0.95), however, due to decreased clearance in the AD participants, there was an imbalance in the A42 production to clearance ratio (1.35). Similarly, they observed an imbalance in AD Ab 40 production to clearance ratio (1.37), compared with cognitively normal participants (0.99). They found that late onset AD was associated with a 30% impairment in the clearance of both Ab 42 and Ab40, indicating that Ab clearance mechanisms may be critically important in the development of AD.
This is the most significant problem with this study, because it does matter whether these differences were statistically significant. I would find it hard to convince myself that they are using ‘parametric tests’ (assuming that all samples were as equally widespread in variation, in other words) simply eyeballing the data. It is, of course, a moot point whether these biomarkers in the spinal fluid reflect very accurately what is happening in the brain at all, but I have written about the possible usefulness of these ‘biomarkers’ elsewhere on this blog, and there is much excitement over their use currently in the research community.
The data supplied in their ‘supporting materials’ are as follows.
Dr Shibley Rahman is an international academic expert in frontotemporal dementia
The clinical iceberg of dementia and nursing
“Clinical Iceberg” is a term used to describe the large amount of illnesses that go unreported. For example, medical statistics are created based on information from the doctors, these statistics go on to make government policies on healthcare. According to Last (1963) as much as 94% of illness is not reported to doctors. It is the vast amount of unreported illnesses that are known as the ‘Clinical Iceberg’. Almost a million people in England will have dementia within a generation and the bill for dealing with the disease will rise to £35bn a year.
[Picture from the US: Acute Care Geriatric Nurse Network: link here.The Acute Care Geriatric Nurse Network (ACGNN) was established in British Columbia in 2003 by a collaborative of Clinical Nurse Specialists in gerontology, geriatric medicine, geriatric psychiatry and geriatric rehabilitation and orthopaedics. The purpose of the collaborative and the ACGNN is to enhance nurses’ ability to provide evidence based care to acutely ill older adults.]
Almost two-thirds of people living with dementia have Alzheimer’s disease. Andrew Ketteringham, head of external affairs at the Alzheimer’s Society, said: ‘The projected growth in people with dementia is huge. Our own research has shown that by 2025 more than a million people in the UK will have the disease, so it will touch the lives of every one of us because every family in the country will have someone with dementia. The society predicted last year that 1,735,087 people in the UK would have dementia by 2051. Numbers are increasing sharply, mainly because of the UK’s ageing population. But mounting evidence also suggests that lifestyle-related conditions, such as obesity and physical inactivity, increase someone’s chances of developing dementia. Martin Knapp, a professor of social policy at the London School of Economics, and Dr Paul McCrone, a health economist at King’s College London. Sir Derek Wanless, chaired its steering group for a paper on this from the King’s Fund.
Now the King’s Fund have reported that people with dementia in general (including to Alzheimer’s disease) are having NHS-funded care withdrawn in the later stages of their illness. It says relatives have to pick up the bill for additional nursing support. Barbara Pointon, from Dementia UK and the Alzheimer’s Society, today described: “What’s happening with NHS continuing health care is it’s getting more and more difficult to get in the first place, and when people with dementia move into the advanced stage and need more care, it’s being taken away from them.” This finding is important because the King’s Fund is calling for a shake-up of the system that differentiates between health care, which the NHS pays for, and social care, which local authorities and individuals have to fund.
Biomarkers in dementia
The National Institute of Aging has initiated the Alzheimer’s Disease Neuroimaging Initiative, a large observational study of patients with Alzheimer’s Disease (AD), patients with mild cognitive impairment and cognitively normal volunteers to assess longitudinal changes in AD. Because cognitive measures do not easily correlate disease-modifying effects of treatment, current trials of investigational compounds require large sample sizes and long treatment duration. Therefore the use of biomarkers in such trials can help in the understanding of disease progression and drug effect.
Biomarkers allow new therapies to be developed more quickly and can be directly associated with a drug treatment as companion diagnostic. Since a clinical diagnosis of Alzheimer disease is inaccurate even among experienced investigators in about 10% to 15% of cases, biomarkers might improve the accuracy of diagnosis. Indeed it is mandatory in a diagnosis to exclude other forms of dementia as fronto-temporal lobe degeneration (FTLD), dementia with Lewy bodies (DLB) and vascular dementia (VaD). In addition biomarkers might also serve as indirect measures of AD severity and could help to follow the evolution of the disease during a drug treatment. There are two directions in developing biomarkers of AD: (i) neuroimaging techniques which provide both structural and metabolic information about the brain, (ii) and cerebrospinal fluid (CSF) biomarkers which correlate the intensity of the disease. Cerebrospinal fluid (CSF) collection is a test to look at the fluid that surrounds the brain and spinal cord, and is performed through a ‘lumbar puncture’. The CSF acts as a cushion, protecting the brain and spine from injury. The fluid is normally clear.
According to a recent review, the identification and validation of biomarkers for diagnosing Alzheimer’s disease and other forms of dementia are increasingly important. To date, biochemical measurements of ?-amyloid(1-42), total tau and phospho-tau-181 in cerebrospinal fluid (CSF) is the most advanced and accepted method to diagnose probable AD with high specificity and sensitivity. Specificity means that a test can pick up an abormality in that particular condition, rather than other conditions; sensitivity means that it’s very adept at doing so. Biomarkers should be totally reliable, obtaining the sample should be simple, should have few side effects, and should be cheap.
However, it is a great challenge to search for novel biomarkers in CSF and blood by using modern mega-sophisticated biochemical methods, such as microarrays and mass spectrometry, and to optimize the handling of samples (e.g. collection, transport, processing, and storage), as well as the interpretation using biological metrics.
It seems likely that only a combined analysis of several biomarkers will define a patient-specific signature to diagnose AD in the future.
