Neurology Central

Ask the experts: should we screen for Alzheimer’s disease? (Part 2: The screening debate)


This week’s ‘Ask the experts’ column with Maria Carrillo (Alzheimer’s Association), Linda Nazarko (London North West Healthcare NHS Trust, UK), Gabriel Vargas (Amgen, CA, USA) & Henrik Zetterberg (University of Gothenburg, Sweden) focuses on the often controversial topic of screening for Alzheimer’s disease. Yesterday we introduced the topic and today we drill down deeper into the pros and cons of screening. You can find out more about the panelists at the bottom of this post.

Why is there such a strong debate as to whether we should screen individuals for Alzheimer’s?

Carrillo: The U.S Preventive Services Task Force’s (USPSTF) 2014 comprehensive review found that there is not enough available evidence about the benefit or harm of cognitive screening in older adults without cognitive symptoms to make a recommendation for or against it. The Alzheimer’s Association says that lack of recommendation points to the need for more, well-designed, long-term research to generate credible, high-quality evidence.

Much of the debate centers on whether there is enough evidence to support universal screening as beneficial. With early screening there is the potential for patient harm due to misdiagnosis, unnecessary tests and treatments, and the associated avoidable costs. On the other hand, there is the potential for positive outcome with early detection. The earlier one tries to diagnose an individual with Alzheimer’s, the more difficult it becomes to separate normal cognitive aging vs. changes due to Alzheimer’s.

Pertinent to this question is defining what population of people would be screened for AD or other dementias. It is also critical to define and clarify what is meant by ‘screening’ since its meaning may significantly differ from other terminology such as assessment, evaluation, detection or diagnosis.

While the USPSTF does not explicitly state the difference between one-time ‘screenings’ and regular assessments of cognitive status in their recommendations, most of the data reviewed involve cognitive assessments performed by providers in medical settings, which the Alzheimer’s Association supports, versus informal community screenings, which the Alzheimer’s Association does not support. The USPSTF recommendation statement specifically mentions cognitive assessment as part of the Medicare Annual Wellness Visit and acknowledges the Alzheimer’s Association published guidance on how to implement it – “Recommendations for operationalizing the detection of cognitive impairment during the Medicare Annual Wellness Visit in a primary care setting.”

More studies are needed to determine the optimal approach to detection of cognitive impairment with subsequent validation of the tools and approaches in clinical trials. This level of evidence will make it possible to examine and confirm whether early detection leads to better outcomes and reduced costs.

Vargas: In the last 10 years we have had a tremendous amount of data which suggests we can reasonably well determine who is going to develop AD by use of either PET imaging of amyloid or CSF biomarkers. These data have been obtained from efforts from many labs and in particular data gathered through a private public consortium known as the AD neuroimaging initiative. Additionally, the advent of direct to consumer genotyping companies such as 23andMe has allowed individuals to check their APOE4 genotype, which is the single highest risk factor for the development of late onset AD. Taken together, we are at a point in which individuals could check their risk status of developing AD. The problem is that once knowing that you may develop AD there are currently no disease-modifying treatments. For example the amyloid imaging agent Amyvid (florbetapir) has been FDA approved for estimating amyloid density in patients with cognitive impairment who are being evaluated for AD. Interestingly the Centres for Medicare & Medicaid Services (CMS) does not reimburse the cost of an Amyvid PET scan because it concluded there is not enough data to suggest that imaging is reasonable and necessary for the diagnosis or treatment of AD.

Do you think we should take on a population screening approach for AD?

Carrillo: The Alzheimer’s Association does not support community-based memory screening. Screening generally refers to a one-time action, involving a brief mental test that provides a score that may or may not accurately indicate the presence or absence of a disease or the need for further evaluation. These brief screens can often result in false positives or false negatives.

Nonetheless, it is important to provide individuals with ways to recognize memory problems that might be cause for concern but avoid assigning a score – a score that can run the risk of falsely alleviating concerns or falsely creating alarm that a disease is present.

An accurate diagnosis of AD requires a comprehensive diagnostic evaluation comprised of several components, including: a thorough review of a patient’s medical and family history; results from physical, neurological and laboratory tests; interviews with caregivers and family about changes in the individual’s cognitive and functional behavior; and results from a mental status test. A diagnostic evaluation based on this level of information provides the best possible assurance for an accurate diagnosis and appropriate follow up.

The Alzheimer’s Association supports efforts that increase early detection and diagnosis of AD and other dementias by trained professionals in a medical setting – such as through the Medicare Annual Wellness Visit. Cognitive assessments for older adults in a medical setting on a yearly basis provide a way for medical professionals to either detect current cognitive impairment or establish a baseline and track change over time. This may reveal cognitive decline that would not be detected by a one-time screen.

Zetterberg: No, not until we have effective, safe and affordable treatments.

Vargas: I think absolutely, once we have disease modifying medications. I don’t see much purpose if we can’t treat the disorder. I think once medications that have a real disease-modifying effect are available individuals should be screened using either PET or CSF for amyloid load much in the same way we now perform colonoscopies on subjects when they turn 50.

Nazarko: Yes, but I also think we need to promote health and wellbeing. We can reduce the risk of people developing dementia by encouraging people to maintain a healthy weight, a normal blood pressure and a healthy cholesterol. If we can reduce cardiovascular and metabolic risk factors we’ll have a healthier population. As people are living longer we need to enable them to live well and health promotion should begin in early adulthood.

How will patients benefit from an Alzheimer’s diagnosis?

Zetterberg: The medical evaluation of a patient with cognitive problems is important for many reasons. Secondary dementias (e.g., hypercalcemia, hypothyreosis, depression) may be identified and treated and when an accurate diagnosis of AD has been made, symptomatic treatment can be initiated. Getting a diagnosis per se could also be a relief for some patients in some situations (but this is individual).

Nazarko: It enables the person who is in the early stages to plan for the future, to work with their families and others to develop an advanced care plan and to have a voice in ongoing treatment and care. It can be empowering.

 Do people really want to know if they have Alzheimer’s?

Carrillo: Although there are limited studies examining the attitudes and opinions of people with memory complaints, evidence suggests that most individuals with mild dementia want to be told of their diagnosis. A recent 5-country survey (France, Germany, Poland, Spain and US) examining public attitudes about AD found that more than 80% of all adults would go to a doctor to determine if the cause was AD if they were experiencing memory or confusion symptoms. More than 65% of the US respondents said that even if they were asymptomatic they would be interested in getting a medical test that would determine if they have AD in the future should one become available. In a smaller study examining racial differences in the perceived benefits and barriers to dementia diagnosis, the majority of black and white adults agreed about the benefits of receiving a diagnosis.

Fear of causing emotional or psychological distress is one of the most common reasons healthcare providers and family members give for not sharing a dementia diagnosis with the affected individual. However, studies that have explored this issue have found that few patients become depressed or have other long-term emotional problems because of being informed of their diagnosis. In a study of individuals and their caregivers before and after a dementia diagnosis, no clinically significant changes in depressive symptoms were noted and anxiety either remained unchanged or decreased. Anecdotally, the Alzheimer’s Association has found that, for many individuals, receiving a clear reason for their changes in behavior and memory abilities actually provides some relief.

Nazarko: No one wants to know that they have a disease that cannot readily be treated, however I believe that clinicians have a duty to enable people to understand that their problems are as a result of a disease process and to enable that person to access support to manage the consequences, for example difficulty with managing day to day activities.

Coming up in the final installment…

Part 3: Current diagnostics & future biomarkers

What are the limitations associated with the current tests that are used to screen for Alzheimer’s?

Carrillo: The available published research on cognitive impairment screening tools is lacking in quality and quantity. More information is needed around the comparative validity of brief cognitive assessment tools especially in non-white ethnic group and races, persons for whom English is a second language and low-education populations. The Alzheimer’s Association strongly recommends that further research is needed to develop better and simpler diagnostic tools and validate emerging technologies that could assist in cognitive testing such as online or electronic applications.

In addition, the currently available cognitive assessment tools cannot provide insight on the underlying disease mechanisms. Several recent studies indicate that many people have brain pathology associated with more than one type of dementia. This ‘mixed dementia’ is particularly common in older age individuals and may obscure identifying a specific disease state.

As we go earlier in the disease process, it becomes more difficult to detect subtle cognitive changes. Tests are needed that have high sensitivity and specificity in indicating or predicting subtle cognitive impairment; especially tests that can differentiate early decline due to a disease state from normal aging. Current diagnosis of Alzheimer’s depends heavily on documenting mental decline but by the time cognitive symptoms are visible, significant damage to the brain has already occurred. For this reason, there is much emphasis on finding accurate ways to detect the disease before clinical symptoms are evident. One of the most promising paths to earlier and easier detection of Alzheimer’s and other dementias is through discovery and validation of biomarkers that would indicate the presence of disease in the absence of clinical symptoms.

If you missed the first instalment of this series, don’t forget to check it out:

Part 1: Introduction


Maria C. Carrillo, Chief Science Officer, Medical & Scientific Relations, Alzheimer’s Association (IL, USA)

Biography: Maria Carrillo, Ph.D., is Chief Science Officer, Medical and Scientific Relations, at the Alzheimer’s Association. Dr. Carrillo has a wide range of responsibilities, including oversight of the Association’s grant-making process and communication of scientific findings within and outside of the organization. Dr. Carrillo directly manages several Alzheimer’s Association initiatives, including the Research Roundtable, the World-Wide Alzheimer’s Disease Neuroimaging Initiative, and the Global Alzheimer’s Association Interactive Network. She is coauthor of the National Institute on Aging–Alzheimer’s Association revised criteria for the diagnosis of Alzheimer’s, and the Appropriate Use Criteria for Amyloid Imaging. She is on the Advisory Committee for the World Health Organization Dementia Setting Priorities & Portfolio Analysis.

Linda Nazarko, Consultant Nurse at London North West Healthcare NHS Trust (UK)

Biography: Linda Nazarko MSc, PgDip, Pg Cert, BSc (Hons), RN, NIP, OBE, FRCN is consultant nurse at London North West Healthcare NHS Trust (UK). She works as a clinician, educator and adviser with colleagues in the inpatient units and within intermediate care and community teams. Linda has clinical responsibility for two nurse led inpatient wards in a community hospital. She leads a team of nurses and therapists and admits patients directly from home and from A&E into the step-up unit and from acute hospitals into the step-down unit. Linda is also clinical lead for the IV service and for dementia. She has for the last year led a Commissioning for Quality and Innovation (CQUIN) on improving care for people with dementia within Ealing Community Services. Linda lectures and assesses at universities and speaks at conferences in the UK and Europe. Linda has specialized in care of older people for 30 years and has qualifications in gerontology, physical assessment, diagnostic reasoning, prescribing, continence, stoma care, research and management. She is the author of several books, reviews and contributes to major UK nursing journals.

Gabriel Vargas, Executive Medical Director and Head of the General Medicine, Bone & Neuroscience Therapeutic Area in Early Development, Amgen (CA, USA)

Biography: Gabriel Vargas, MD, PhD is a board certified psychiatrist and basic scientist. Gabriel obtained his undergraduate degree from the University of California at Berkeley (CA, USA) where he majored in anthropology & genetics. He received his MD and PhD degrees from the University of California at Irvine (CA, USA) and went on to complete a basic science research track residency in Psychiatry at the University of California at San Francisco (UCSF, CA, USA).

After both a clinical and research fellowship he was appointed an assistant professor in the Psychiatry Department at UCSF where he spent 3 years leading a research group studying G-protein coupled receptor (GPCR) signaling and trafficking. He also served as the Medical Director of the UCSF prodromal schizophrenia research program. He has published in the areas of GPCR signaling and membrane trafficking with a particular expertise in approaches using basic science to understand the molecular pathophysiology of genetic diseases. After leaving academia in 2006 he spent 5 years at Roche, the last three in Basel (Switzerland), as Head of the CNS Biomarker Group where he worked on biomarkers and diagnostics for Alzheimer’s disease, autism and schizophrenia.

He joined Amgen in 2011 and leads a group of physician-scientists doing early development work on migraine, Alzheimer’s disease and schizophrenia.

Henrik Zetterberg, University of Gothenburg (Sweden)

Biography: Henrik Zetterberg, MD, PhD, is Professor of Neurochemistry at the University of Gothenburg, Sweden, and at University College London, UK, as well as the Head of the Department of Psychiatry and Neurochemistry at the Sahlgrenska Academy at the University of Gothenburg, Sweden. With a background in molecular biology and medicine, Dr. Zetterberg has spent the past 10 years focusing on the development of biomarkers for Alzheimer’s disease and other brain disorders. His research involves evaluation of biomarkers in cell and animal models, as well as in longitudinal studies of patients and healthy individuals. He has published more than 500 scientific articles and has received the Erik K. Fernström prize for young scientists, the Inga Sandeborg prize for research on Alzheimer’s disease and the Parkinson Research Foundation Award.

The opinions expressed in this interview are those of the interviewees and do not necessarily reflect those of Neurology Central or Future Science Group.