February
14, 2019| By Sabrina Link
For a long time, Alzheimer’s could
only be definitively diagnosed after a patient’s death based on
neuropathological findings in the brain. Positron emission
tomography (PET) scanning and spinal fluid technologies can improve on
purely clinical diagnosis, but their cost and a lack of any cure means they are
hardly used.
New blood tests potentially
represent a real step forward.1 They promise objective detection in
the living years before clinical symptoms arise. Their emergence coincides with
new Alzheimer’s diagnostic criteria from the National Institute on
Aging (NIA) and the Alzheimer’s Association (AA) that uses biomarkers
in place of cognitive signs and symptoms. This represents a shift from a
syndromal approach to a biological construct.2
Alzheimer’s is a degenerative brain
disease and the most common cause of dementia.3 Alzheimer’s causes
problems with memory, thinking and behaviour. Symptoms typically develop
gradually, worsening with time, eventually interfering with daily life to the
point where an individual needs extensive supervision and support.
People with Alzheimer’s live on
average eight years after symptoms become noticeable, but survival can range
from four to 20 years depending on age and co-morbidities.4
Available treatments only retard the worsening of symptoms but do not offer a
cure.
The overall severity of Alzheimer’s
(and other dementias) can be measurable using the Clinical Dementia
Rating (CDR) assessing not only cognitive ability but other important
areas of function: memory, orientation, judgement & problem solving,
community affairs, home & hobbies and personal care. Scoring
0.5 means questionable dementia while a score of 3 means severe.
The Mini Mental State
Examination (MMSE) is a commonly used measure of cognitive function alone.
A score of 25 or more out of 30 is considered normal. Scoring 24-21 implies
mild impairment, 20-10 moderate, and below 10 severe, although slightly
different thresholds are in circulation as well. On average, the MMSE score of
a person with Alzheimer’s will decline two to four points each year.5
The most important risk factors
remain age, family history and heredity, and they cannot be changed. But
evidence suggests other risk factors we can influence, for example eating a
healthy diet, staying socially active, avoiding tobacco and excess alcohol, and
exercising both the body and mind. Family status and poor sleep might have an
impact.6
Alzheimer’s is identified by two
abnormal structures that develop in the brain. Plaques – are the deposits of a
protein fragment called beta-amyloid that builds up in the spaces between nerve
cells, unnoticed for up to 30 years before clinical symptoms. Tangles -
are the twisted fibres of another protein called tau and build up inside cells.
Most aged brains have some plaques and tangles but the brains of people with
Alzheimer’s are present in greater number and develop in a predictable pattern.
According to the new NIA and AA
diagnostic criteria, Alzheimer’s can be diagnosed if there is evidence of significant
pathological changes in both amyloid and tau proteins even without clinical
symptoms. An individual with biomarker evidence of beta-amyloid deposition
alone, but has normal tau biomarkers would be categorised as “Alzheimers;
pathologic changes”, an early part of the ‘Alzheimer’s pathophysiologic
continuum’. Tests to detect these biomarkers include brain scans with
radioactive tracers or analysis of cerebro-spinal fluid taken via lumbar
puncture. Symptoms would still be used for the clinical staging of individuals
on the “Alzheimer’s continuum”. Having said this, the new definition is only
intended to be used for research, not routine clinical care so that for the
moment nothing changes for the daily practice.
Private long term care insurance
products often use a separate dementia trigger alongside a benefit trigger
focused on physical impairments like activities of daily living.
Although all kinds of dementia are
covered, not only Alzheimer’s, the new definition will not have an impact on
claims management for now. This might change once the relevant biomarkers can
be ascertained routinely. This underlines the importance of a severity
criterion in the definition of dementia in the contract wording. Benefits
should only be payable if symptoms of moderate or even severe cognitive decline
are present. Nonetheless, claims management could become more vulnerable to
early claims and even legal disputes. A respective exclusion clause might help
to a certain extent. On the other hand, using biomarkers could make the
assessment of Alzheimer’s more objective. Another question is whether the
underwriting process would have to be modified. Anti-selection might occur if
people undergo screening before applying for a policy. One might want to ask
the applicant whether a test has already been taken.
These issues will have to be
addressed even more so once diagnostic blood tests have become mature enough
for clinical routine. Three groups of scientists have recently developed and
validated blood tests to detect Alzheimer’s with relatively good statistical
outcomes. The blood tests detected abnormal beta-amyloid, or proteins from dead
nerve cells.
Although only one of these studies
suggested clinical utility might not be many years away, they have the
potential to increase the speed of screening for new drug trials. By replacing
expensive scanning and invasive investigations they could become invaluable in
accelerating the process of developing new therapeutic strategies for
Alzheimer’s.
In clinical practice the blood tests
could act as an initial screening funnel to identify people who should undergo
further diagnostics such as PET scanning or lumbar puncture. Understanding how
the tests work in the population as a whole is an important next step; abnormal
amyloid may be present in some individuals who do not have Alzheimer’s and be
absent in some people who have Alzheimer’s. However, once the tests reach
clinical maturity and become widely used they will be able to diagnose
Alzheimer’s disease years before outward signs of cognitive decline have begun
to show. This has implications for doctors attending to their patients, but
also for insurance companies covering dementia and especially Alzheimer’s
disease.
Endnotes
1.
Nakamura, A. et al., High
performance plasma amyloid-β biomarkers for Alzheimer’s disease. Nature 554,
249-254 (2018). Nabers, A. et al., Amyloid blood biomarker detects
Alzheimer’s disease. EMBO Molecular Medicine (2018). Preische, O. et al.,
Serum neurofilament dynamics predicts neurodegeneration and clinical progression
in presymptomatic Alzheimer’s disease, Nature Medicine (2019).
2.
Jack, C.R. et al (2018) NIA-AA
Research Framework; Towards a biological definition of Alzheimer’s disease.
Alzheimer’s & Dementia. 14. 535-562.
https://www.alzheimersanddementia.com/article/S1552-5260(18)30072-4/fulltext.
3.
Alzheimer’s Association. 2018
Alzheimer’s disease Facts and Figures. Alzheimer’s & Dementia
2018;14(3):367-429. https://www.alzheimersanddementia.com/article/S1552-5260(18)30041-4/abstract.
4.
Preische, O. et al., Serum
neurofilament dynamics predicts neurodegeneration and clinical progression in
presymptomatic Alzheimer’s disease, Nature Medicine (2019).
5.
Alzheimer’s Association, https://www.alz.org/alzheimers-dementia/diagnosis/medical_tests.
6.
Preventing Dementia through Mid-Life
Interventions. Risk Insights January 2019.
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