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Dementia and Cancer

A Review of the Literature and Current Practice
Luke Solomons, Joyce Solomons, Margot Gosney
Aging Health. 2013;9(3):307-319.

Abstract and Introduction

Abstract

Age is a risk factor for dementia, and also for most cancers. Surprisingly, rates of cancer appear to be
lower in individuals with dementia and vice versa. Genetic mechanisms could underpin this inverse
relationship and are outlined, but underdiagnosis must also be taken into account. Individuals with
cancer and dementia pose unique challenges to healthcare professionals owing to the potential for
impaired decision-making capacity, poor communication and difficulties following medication regimes.
Mild cognitive impairment and 'chemo brain' should be differentiated from progressive
neurodegeneration.
Introduction

Dementia is a progressive neurodegenerative condition that increases with age. An aging population has
led to a rapid increase in the prevalence of dementia. [1] Age is a risk factor for most cancers and
estimates suggest that by 2030, 70% of all cancers will occur in elderly people. [2]
The increasing prevalence of these conditions has serious implications on healthcare provision and the
healthcare economy. Economic data on the cost of dementia are available from the UK, USA, western
Europe and developed countries, and less from developing ones we refer to economic data from the
UK in this review. According to the Global Burden of Disease estimates for the 2003 World Health
Report,[3] dementia contributed 11.2% of years lived with disability in people aged 60 years and older,
along with stroke (9.5%), musculoskeletal disorders (8.9%), cardiovascular disease (5.0%) and all forms
of cancer (2.4%).
Given that both cancer and dementia are seen as diseases of elderly people, the expectation is that
there will be a significant overlap of the two conditions. However, there appears to be a disconnect
between the prevalence rates of the two conditions occurring together. A small, but growing, body of
evidence appears to show lower rates of cancer in patients diagnosed with dementia, especially
Alzheimer's dementia, as compared with cognitively intact matched controls; [46] and a lower incidence of
Alzheimer's dementia in cancer survivors.[7] Genetic links between neurodegeneration and cell
proliferation have been suggested, but population-based studies also suggest that underdiagnosis might
be responsible for some of the mismatch.
The diagnosis and treatment of cancer is associated with high levels of psychological distress in patients
and their families.[8,9] Many survivors display important symptoms of psychological distress that are
related to the continuing effects of cancer and its treatment.[10] A diagnosis of cognitive impairment or
dementia is a well-established component of frailty scores, which are helpful in determining prognosis
and making treatment choices.[11] However, individuals with dementia who are diagnosed with cancer
pose unique challenges in clinical practice owing to impairments in understanding, communication,

capacity to consent and issues related to death and dying. Patients' relatives and carers are called on to
make surrogate decisions for them when they lack the capacity to do so, and this can be distressing for
both groups.
In the first part of this review, we look at current evidence in the area of overlap between cancer and
dementia. In the 'hands on' second section, the authors address common clinical considerations, such as
the differential diagnosis of dementia, assessment of decision-making capacity and the management of
pain and distress.

Epidemiology of Dementia & Cancer

The prevalence rates for dementia increase with age rates increase from 1.3% between the ages of 65
and 69 years to 32.5% in individuals over the age of 95 years in developed countries. [12] Rates in
developing countries seem to be lower there are several possible explanations, including the possibility
that early dementia is ignored, risk factors for dementia are lower and also, in very poor countries, fewer
individuals survive to 65 years. With increasing age, rates of dementia are higher in women compared
with men, but there do not appear to be racial differences in prevalence rates. Early-onset dementia
(onset before the age of 65 years) is rarer, accounting for 2.2% of people with dementia.
The prevalence rates of cancer increase with age as well 50% of all cancers occur in individuals over
the age of 70 years, but for some specific tumors the rates are higher, for example, in colorectal cancer,
where 65% of all tumors occur in individuals over the age of 70 years.

Costs of Cancer & Dementia Care

A report by the Alzheimer's Research Trust estimated that in 2008, the cost to the UK economy from
dementia was 19.7 billion, of which 6% was spent on healthcare, 46% on social care and 48% on
informal care. The same report estimated that cancer cost 12 billion, of which 33% was on healthcare,
5% on social care and 11% on informal care, and 51% of total costs was accounted for by productivity
losses.[13] The larger proportion of social care costs relative to healthcare costs incurred by dementia
serve to highlight the significant impact that dementia has on a person's quality of life (QoL) and
psychosocial environment. These need to be considered early in the process of management of the
small, but increasing, proportion of patients who have been diagnosed with cancer and dementia.
Given the inherent difficulties with measuring outcomes to evaluate the effectiveness of treatment plans,
health-related QoL measures can be used to record changes. There are several QoL instruments, such
as the QL-index and Euroqol,[14,15] that have been developed for patients with cancer that are used
extensively in clinical trials[16] these are mainly based on self-report scales and cognitive impairment
could impact on the individual's ability to complete these scales. Several QoL scales in dementia have
been developed for example, the DEMQOL, which has a linked 'proxy' version filled out by carers
(DEMQOL Proxy) that provides complimentary perspectives and information [17] and such measures
might be more appropriate for use in patients in the overlap group.

Cancer & Dementia: Diagnostic Uncertainties Leading to Underdiagnosis?

Population-based cohort studies report lower rates of dementia in cancer survivors. Studies on rates of
cancer in individuals with dementia have found that the converse is also true, with lower rates of cancer
in people with dementia.[47] There are several explanations put forward to explain this disconnect.

Underdiagnosis of cancer is one possible explanation one study reported that individuals with prevalent
Alzheimer's disease had a 69% lower risk of being admitted to hospital for cancer.[5] Individuals with
dementia tend to under-report symptoms, such as gastrointestinal discomfort, joint pain and vision
problems, which leads to delays in medical attention being sought. [18] Thus, they are diagnosed with more
advanced stages of cancer, often too late to be treated. One study on individuals with colon cancer found
that those with dementia were twice as likely to be diagnosed without tissue sampling and that they were
half as likely to receive surgical resection or adjuvant treatment. [19] A study on individuals with breast
cancer reached similar conclusions women with dementia were likely to have a more advanced stage
of cancer and less likely to have treatment.[20]
A Dutch study on elderly care physicians found that advanced dementia was the leading cause for
nonreferral of patients with suspected cancer.[21] A recent study found that approximately half of the
population of individuals with dementia were accidentally discovered to have cancer (48%) or had
unexpected unfolding of clinical signs (44%), whereas most cognitively intact patients (63%) voluntarily
sought medical evaluation.[22]

Cancer & Dementia: Possible Genetic Links

Overlapping biological pathways and genes could potentially explain the link between cancer and
dementia. The fundamental biological basis of cancer is uncontrolled cell proliferation and/or prolonged
cell survival, while dementia involves neuronal cell degeneration and death. Thus, it is not surprising that
various pathways and genes involved in cell-cycle regulation have been considered to link these two
major age-related diseases.
Tumor suppressor genes (TSGs) are a group of genes that play an integral role in cell-cycle regulation.
These genes act at different levels and are vital in preventing uncontrolled cell growth and inappropriate
cell survival, thus acting as potent barriers to cancers. TP53 is a vital TSG that is activated by various
stress inducers, such as hypoxia and DNA damage. p53 acts as a transcription factor for various
pathways resulting in inhibition of cell-cycle progression, promotion of senescence or apoptosis. TP53
mutations resulting in impaired function of the p53 protein are noted in more than half of all human
cancers.[23,24] In the tumors that retain wild-type p53, there is evidence that the activity of the p53 protein
could be attenuated by various mechanisms, including augmentation of p53-negative regulators, such as
Mdm2 and Mdm4.[25] Germline mutations of TP53 are known to cause LiFraumeni syndrome, a rare
familial predisposing cancer condition, with individuals prone to a significantly increased risk of various
cancers including breast cancers, sarcomas, leukemias and brain cancers. Inactivation of p53 as a major
cause of cancer is irrefutable. Interestingly, transgenic mouse models with gain-of-function TP53
mutations resulting in augmented p53 activity were found to exhibit features of aging and reduced
longevity ().[26]
Box 1. Some of the genes implicated in cancer and dementia.

Tumor suppressor genes

TP53

BRCA1

P16

Retinoblastoma family of genes

Peptidyl-propyl cis/trans isomerase (PPIase)

Pin1

DNA repair genes

DNA Pol-

miRNA genes

miR-29 family

Genes on chromosome 21

ERG

ETS2 APP

-amyloid accumulation induced in transgenic mice, which leads to progressive neuronal degeneration
and cell death, was correlated with increased activity of p53-mediated apoptosis. [27] Elevated levels of p53
have been noted in the CNS of patients diagnosed with neurodegenerative disorders [2831] and there have
been reports of elevated p53 levels in the brains of patients with Alzheimer's dementia. [3234] Presenelin 1
and 2 mutations, which cause familial dementia, are shown to act through p53-mediated apoptosis. [35,36]
This limited evidence suggests that p53 levels could have inverse effects in the pathogenesis of cancers
and dementia, but further research in this area is warranted. Other TSGs implicated in the causation of
human cancers and dementia include BRCA1, p16 and the Retinoblastoma family of genes.[3743]
The Pin1 gene encodes a peptidyl-propyl cis/trans isomerase (PPIase) that specifically binds to
phosphorylated ser/thr-pro motifs (pro-directed phosphorylation) and catalytically regulates the
postphosphorylated key proteins, including various cell-cycle regulatory mitotic factors, transcription
factors, apoptotic factors and the cytoskeletal tau protein. [44] Pin1 is reported to be overexpressed in
various common cancers, such as breast, prostate, brain, cervical, lung and colon cancers. [4548]
Dysregulation of the RbERF pathway in cancers is thought to cause overexpression of Pin1 in cancers.
[49,50]
The role of Pin1 in positive regulation of Cyclin D1 through C-jun interaction [46,47] and stabilization of
catenin- molecule by preventing APC-mediated suppression indicates that overexpression of Pin1 in
cancers could act by enhancing various oncogenic signals. [46] Furthermore, Pin1 is involved in regulating
p53 activity by interacting with phosphorylated p53 formed following DNA damage, thus promoting DNAbinding and transactivation of p53.[51]
Increased Pro-directed phosphorylation of tau and -amyloid protein is shown to be a precursor of tangle
formation and neurodegeneration in Alzheimer's dementia. [52] Pin1 appears to have a protective role in
age-related neurodegeneration by binding to the pro-directed phosphorylated tau protein, facilitating its
dephosphorylation, and thus restoring its stable form. [53,54] Pin1 could inhibit Cdc25c, which activates
mitotic cell-cycle kinases that induce apoptosis in neurons. [52] The protective nature of Pin1 is further
supported by depletion of Pin1 reported in Alzheimer's dementia. [53] Loss of Pin1 in mouse models has

been reported to cause age-dependent motor and behavioral phenotypes associated with tau
hyperphosphorylation, filament formation and neurodegeneration. [55]
Thus, Pin1 is a vital protein involved in the pathogenesis of both cancers and Alzheimer's dementia.
While overexpression of Pin1 is associated with various oncogenic pathways, depletion of Pin1 appears
to play a role in the causation of Alzheimer's dementia. Pin1 is, therefore, considered to be an important
genetic link that further supports the biological connection between cancers and dementia.
Germline mutations in certain DNA repair pathway genes are known to cause genetic conditions
characterized by a combination of cancer predisposition and neurodegenerative phenotypes. Examples
of such genetic conditions include xeroderma pigmentosa, a genetically heterogenous condition caused
by mutations in the nucleotide excision DNA repair pathway genes, and ataxia telangiectasia caused by
mutations in ATM, a gene that encodes a serine/threonine protein kinase involved in DNA repair or cellcycle arrest and apoptosis response to DNA damage.
Accumulation of DNA damage, genomic instability and the role of DNA repair pathway/genes in the
pathogenesis of cancers are well established. There is growing evidence to suggest a potential role of
DNA repair pathways/genes in neurodegenerative conditions including dementia. It has been proposed
that specific DNA repair pathways may be less accessible to postmitotic neurons in comparison with
mitotic cells, causing progressive accumulation of DNA damage, which could result in neuronal
degeneration and death.[56,57] Biochemical assays on isolated nuclei have shown a twofold increase in the
level of DNA strand breakage in patients with Alzheimer's dementia in comparison with controls. [58] DNA
polymerase-, an important enzyme in the DNA repair complex, has been implicated in the pathogenesis
of Alzheimer's dementia by loading in DNA replication forks in neurons with -amyloid accumulation.[59]
miRNAs are noncoding RNAs of 1825 nucleotides in length. They are known to regulate gene
expression, primarily through translational inhibition, by binding to imperfect complementary sequences
in the 3' untranslated region of mRNA. miRNAs bind to protein effector complexes, acting as a guide
strand to bring them to the target mRNA. This results in impairment of protein translation or mRNA
degradation. Recent studies have shown that miRNAs regulating cell proliferation, differentiation and
apoptosis could act through overlapping pathways linking cancer and dementia.
It has been found that onco-miRNAs and suppressor miRNAs could be representing two forms of the
same gene, functioning as an oncogene or TSG based on the tissue type and target site. [60] miRNAs
belonging to the miR-29 family are underexpressed in certain lung cancers, causing upregulation of
specific DNA methyltranferases and resulting in an aberrant DNA methylation pattern in these cancers. [60]
Furthermore, miRNAs from the same family have also been shown to regulate a specific antiapoptic
protein, MCL1.[61] These findings suggest that the miR-29 family could act as tumor suppressors through
the regulation of specific methyltranferases and MCL1.
Member miRNAs of the miR-29 family could have a potential role in the pathogenesis of Alzheimer's
dementia. Specific miRNAs from this family are shown to regulate BACE1, which is implicated in the
accumulation of -amyloid in patients with sporadic Alzheimer's dementia. The expression of specific
miRNAs from the miR-29 family are shown to be suppressed in patients with Alzheimer's dementia, thus
upregulating BACE1 activity, which could provide a potential explanation for the accumulation of amyloid and the pathogenesis of the disease. [62]
Finally, individuals with Down's syndrome (DS; trisomy 21) have a predisposition to developing certain
hematological malignancies and early-onset dementia. DS has, therefore, been a platform for studies to

investigate the possible candidate genes on chromosome 21 to explain the potential link between the
malignancies and dementia in these patients.
DS confers an approximately ten- to 50-fold increase in the risk of developing leukemias in children, the
most common types being acute myeloid leukemia and acute lymphoid leukemia. Several genes on
chromosome 21, including transcription factors, miRNAs, oncogenes and TSGs, have been implicated in
tumorigenesis. The oncogenic candidate genes on chromosome 21 include ERG, ETS2, DYRK1A,
TMPRSS2, TIFF1, SIM2, RUNX1, mir-125b2, -155 and let7c.[6372]
Linkage analyses have identified the APP gene on chromosome 21 as a candidate gene in familial
Alzheimer's dementia. APP, a precursor of -amyloid, has a tendency to form amyloid plaques, which are
linked to Alzheimer's dementia.[73] Interestingly, APP has been found to be the most overexpressed gene
in patients with acute myeloid leukemia with normal cytogenetics compared with controls. APP has been
hypothesized to cause leukemogenesis along with ERG and EST2. However, the exact molecular basis
is not clear.[74]
In summary, there are various overlapping biological pathways and genes that link cancer and dementia
these include TSG, DNA repair pathway genes, miRNAs and genes on chromosome 21. There are
potentially other genes in these pathways that could link these two common conditions of aging. The
limited evidence so far suggests links between cancer and neurodegeneration, and warrants further
research.

Cognitive Impairment That Is Not Dementia

Cognitive impairments in patients receiving treatment for cancer have been well documented, but the
phrase 'cognitive impairment' encompasses a variable cluster of symptoms. Studies in the early 2000s
reported prevalence rates of cognitive impairment following treatment for cancer of up to 75%; however,
there were several methodological criticisms of these studies. [75,76] A study looking at pretreatment
cognitive impairment in patients diagnosed with breast cancer found that up to a third of patients had
some cognitive impairment prior to treatment[77] the mean age of participants in the study was 50.4
years. The authors suggest that stress and depression could affect performance on neuropsychological
tests.
'Chemo brain' or 'chemo fog' are terms found in the literature and on numerous cancer support websites
that include a heterogenous cluster of cognitive symptoms in patients undergoing chemotherapy for
cancer.[201] These include a spectrum of impairments including verbal and visuospatial memory deficits,
language problems, frontal executive dysfunction, and disturbances of attention and concentration. Some
reviewers suggest that the phrase 'cognitive disorders related to cancer or therapy' should be used to
describe them.[78]
Chemo brain might be classified under the Diagnostic and Statistical Manual of Mental Disorders (4th
Edition) category of 'mild cognitive impairment either amnestic or nonamnestic' depending on the
cognitive domains involved. A recent meta-analysis of the literature on mild cognitive impairment reported
that the majority of individuals diagnosed with this condition did not progress to dementia over a 10-year
follow-up period.[79] This is in contrast with more severe cognitive impairment that falls into the dementia
spectrum, which is progressive, and hence it is important for the right diagnosis to be made.
Delirium is a syndrome of acutely altered mental status characterized by inattention and a fluctuating
course.[80,81] It is the most common complication in hospitalized older individuals [82] Increasing age is a risk

factor for delirium, with individuals over the age of 65 years being more prone to delirium. Some literature
on chemo brain suggests that the incidence increases with age, [83] but whether it is a potential marker for
future dementia (as is the case with delirium) is unclear.
The question about cancer treatment leading to dementia has been studied and the results in published
literature have been mixed the association has not been borne out by a large population-based study,[83]
while other studies seem to suggest that a group of women receiving chemotherapy were at a higher risk
of severe cognitive changes.[84,85] In a study comparing cognitive function in cancer patients with their
cancer-free twins, the authors reported an increased risk for long-term cognitive dysfunction in the
cancer group, and that the cancer group were twice as likely to be diagnosed with dementia, but the
odds ratio did not reach significance.[86]
There is increasing evidence that most types of treatment for cancer, including systemic therapy,
radiotherapy, immunotherapy and also adjuvant medication such as steroids, anticholinergic medication
and pain relief, have a negative impact on cognition. Some data on the effect of cancer therapies on the
symptom severity of an existing dementia are emerging, but the available evidence is anecdotal and in
the form of single-case reports. Given that age is an important risk factor for cognitive impairment, older
adults are much more likely to suffer cognitive impairments with treatment. Evidence from
histopathological studies seem to support this a study comparing the brains of individuals diagnosed
with vascular dementia (VaD) with Alzheimer's dementia also looked at the brains of patients given
radiation for brain tumors and found very low microvascular densities. [87]

Clinical Challenges
Screening & Diagnosing Dementia

Dementia is described in the Diagnostic and Statistical Manual of Mental Disorders (4th Edition) as a
disorder with memory impairment and at least one other symptom from another cognitive domain [81]
aphasia, apraxia, agnosia or disturbances in executive functioning accompanied by impairment in social
and occupational function. The course is characterized by gradual onset and continuing cognitive
decline.
The symptoms of dementia can be clustered under three domains: neuropsychological, neuropsychiatric
and executive function features ().
Box 2. Three domains/clusters of symptoms of dementia.

Neuropsychological:
o

Problems with memory

Problems with language

Neuropsychiatric:
o

Personality changes

Psychiatric symptoms (e.g., anxiety, depression, hallucinations and delusions)

Challenging behavior/restlessness/wandering

Impaired executive function:

o

Difficulty with basic activities of daily living (e.g., washing, dressing, feeding, grooming
and walking)

Given the spectrum of cognitive impairments associated with cancer, some experts point out that no
validated and practical tests are available for the assessment of cognitive function in cancer patients. [88]
Age and the effects of cancer treatment have been pointed out as possible causes of decreases in
cognitive function; in both instances, a strong possibility of a decrease in frontal lobe function exists. [89]
This uncertainty should not preclude screening for cognitive impairments as these scores can provide
useful baselines for future comparisons.
Older adults are more prone to delirium due to underlying physical illnesses, and the treatment of the
underlying delirium can lead to complete resolution of the cognitive impairments. Thus, a definitive
diagnosis of dementia in physically unwell patients with a single assessment poses challenges and
follow-up assessment should be arranged.
The Mini-Mental State Examination (MMSE) is the most widely used screening tool for dementia, [90] but
difficulties in detecting early stages of dementia and impairments in some cognitive domains have been
highlighted, including in patients with cancer.[77] In clinical practice, it might be used as a screen for all
individuals aged over 65 years, with scores under 27 triggering a referral for further screening, including
neuropsychological testing. The Montreal Cognitive Assessment is another bedside cognitive screening
tool. It encompasses more cognitive domains and appears to be more sensitive at detecting mild
cognitive impairment.[91] Routine screening of all patients with the Montreal Cognitive Assessment and
referral of those scoring <26 as a cutoff for more detailed neuropsychological testing or to liaison
psychiatry could increase the pick-up rates of cognitive impairment and result in earlier detection of
dementia.
Subtypes & Presentation of Dementia

The most common subtypes of dementia are Alzheimer's disease, VaD, mixed Alzheimer's and VaD,
dementia with Lewy bodies and frontotemporal dementia. Estimates of the proportion of each subtype
must be interpreted with caution since these are clinical diagnoses based on typical patterns of onset
and course.[92]
Patients with Alzheimer's and VaD present with prominent memory impairment, initially affecting their
recent memories. Patients with dementia with Lewy bodies present with prominent hallucinations, falls, a
fluctuant pattern of cognitive impairment and are very sensitive to neuroleptic medication. Patients with
frontotemporal dementia present with prominent language impairments (temporal variant) or personality
change and behavioral problems (behavioral variant).
The severity of dementia ranges from mild-to-moderate and -severe dementia ().
Box 3. Severity of dementia and relationship to clinical practice.

Mild

Cognitive impairments at this stage are often overlooked and attributed to the normal aging

process by family and professionals. Common features at this stage:

o

Forgetful about recent events, unable to give clear account of symptoms

Some impact on instrumental ADLs, including adherence to treatment regime and
taking medication reliably
Some loss of orientation to time, unable to record symptom diaries
Language difficulties can make communication of problems difficult/personality
change with frustration and irritability can be misdiagnosed as depression or
unwillingness to cooperate (in FTD)

Can still have capacity to make decisions about treatment and care

Moderate

Impairments become more obvious and impact on ADLs. Common features at this stage:
o

Very forgetful, unable to accurately describe symptoms including pain

Unable to carry out basic ADLs, needs medication supervision and an escort to clinic
Disorientation to time and place, getting lost in familiar places
Worsening language skills
Behavioral changes including wandering, agitation it can be hard to distinguish
whether these symptoms are due to physical health causes
Marked personality changes including aggression, inability to follow through with
conversations or consultations (in FTD)
Neuropsychiatric symptoms such as hallucinations, depression and anxiety

Severe

Marked impairment of cognition with almost complete dependence on family/carers. Common

features at this stage:
o

Unaware of surroundings/time or place

Marked impairment in receptive and expressive language skills
Motor systems affected
Difficulty eating, drinking and swallowing, higher risk of aspiration
Bowel and bladder affected, incontinence
Behavioral and psychological symptoms of dementia causing agitation and distress

Patients in the advanced stages of dementia are especially vulnerable to having untreated pain
and adequate analgesia needs to be considered in all cases

ADL: Activity of daily living; FTD: Frontotemporal dementia.

Capacity & Decision-making

The diagnosis and treatment of cancer is very stressful for patients and their families. [9] In patients with
dementia, this process might be further complicated by the fact that the patient might not be able to fully
understand the nature of the diagnosed cancer, the prognosis, and the risks and benefits associated with
treatment.
In most instances, individuals with mild dementia have decision-making capacity if the issues are
explained to them in simple language along with the various options available and they are supported by
the treating team and their families or carers.
Some carers and families are more prepared to make decisions on behalf of a loved one, while others
find the process very anxiety-provoking and guilt-inducing their wishes and strengths need to be
explored and considered by the treating team and have a significant impact on QoL outcomes. [9395]
In individuals with more advanced dementias, carers and families might be called on to make proxy
decisions legislation around this is better defined in some countries. With the increasing use of Last
Power of Attorney orders (these orders are called durable power of attorney in the USA), treating teams
should check whether an incapacitated person has nominated Last Power of Attorney for health and
welfare decisions and has also recorded advance directives on refusal of treatments. This should be
taken into consideration when making decisions in an individual's best interests.
Ethical considerations frequently arise in this subgroup offering an individual with dementia the chance
to understand their condition and options for treatment is to honor the individual's dignity. The process
might be time consuming and uncomfortable in a busy clinical environment, but could help with the
therapeutic process.
Each patient needs to be considered individually for a risk/benefit analysis. The individual's decisionmaking capacity, views of family/surrogates, as well personal views and experiences of physicians need
to be considered, and balanced against agism and generalization. In some cases, the risks outweigh the
benefits, for example, in patients with multiple comorbidities and high frailty where aggressive treatment
might cause more distress. However, in individuals with mild dementia and longer life expectancies, the
potential benefits could be significant and the person should not be denied them based on the 'dementia'
label. All discussions should consider maintenance of good QoL in the longer term as an outcome. [96]
Despite criticisms about the MMSE, there is some evidence to suggest that MMSE scores correlate with
clinical judgment on lack of capacity and could be employed as a baseline measure. [97] Structured
instruments for recording capacity assessments, such as the MacArthur Competence Assessment Tool
for Treatment, are available, but are time consuming and can be restrictive. Assessment of capacity is
generally considered a four-stage process, listed in , and the treating team should make every effort to
enhance decision-making capacity by ensuring sensory impairments are addressed and the process is
described in simple language without medical jargon.
Box 4. Assessment of capacity.

Always assume the patient has the capacity to make a decision

Four-step process: is the person able to:

o

Understand (in preferred language and with explanation) what the particular
investigation, treatment or arrangements involve?
Believe and retain the information relevant to the decision (e.g., common risks and
benefits) long enough to reach a decision?
Weigh the information and options in the balance to arrive at the decision?
Communicate the decision?

Decisions About Treatment

Patients with comorbid physical and mental illness have higher levels of morbidity and mortality, and the
group with cancer and dementia are no different.[98] As far back as 1968, studies reported a-third of
patients on mental health wards had significant physical comorbidities, [99] while a more recent study of
people with dementia found that 61% had significant physical illnesses. [100]
A study comparing survival outcomes for comorbid physical illness in people with dementia with
cognitively intact individuals found significantly increased survival in the cognitively intact group. Across
tumor types and stages, cognitively impaired patients had approximately one-third of the median survival
of the control group.[101] An explanation could be later presentation and diagnosis, and the clinical and
ethical dilemmas associated with decision-making capacity.
In a study on older women with breast cancer, conditions such as liver disease, chronic renal failure,
dementia and congestive heart failure produced the highest hazard ratios of all-cause mortality, and
patients with these conditions diagnosed at stage I have survival experiences similar to those of patients
with stage III and IV tumors who lack any coexisting disease.[102] Pre-existing dementia diagnoses were
associated with high mortality, mostly from noncancer causes. The effect of cancer stage at diagnosis on
mortality was significantly reduced in older patients with precancer diagnoses of dementia. [103]
Life expectancy in dementia has a bearing on clinical decision-making. [104] Recent studies have found that
survival times of patients with dementia are shorter than previously reported, with both clinicians and
family members overestimating life expectancy in the patient with dementia. [105] However, there are a
significant minority of patients with dementia (especially Alzheimer's dementia) who do not have
significant medical comorbidities and have good functional reserves and low risk scores. Such patients
should definitely be considered for curative treatments and not denied treatment because of their
dementia diagnosis.
Life expectancy varies with age at diagnosis of dementia from 3 to 10 years, [106] and also with the type of
dementia. A study found that patients with Alzheimer's dementia had better relative survival rates than
patients with VaD, with bronchopneumonia being the most common cause of death. They also found that
the prevalence of cancer in both of these groups was less than in the general population. [107]
Pain Assessment

Cancer pain is undertreated despite good evidence to support marked improvements in QoL with
adequate analgesia.[108] Individuals with dementia and cancer pose additional challenges when cognitive
impairment prevents the expression of pain symptoms. Individuals with dementia might express their

pain by grimacing, calling out, refusing to eat, clenching fists, fidgeting, pacing and rocking these are
symptoms that are considered in pain scales, such as the Abbey Pain scale [109] and Pain Assessment in
Advanced Dementia (PAINAD) scale.[110]
Families and carers who know the individual with dementia well can help medical staff to understand
these behaviors by filling out pain questionnaires and helping them alleviate pain better. A recent
randomized control trial found that a systematic approach to pain management significantly reduced the
behavioral and psychological symptoms of dementia in a population with advanced dementia in a nursing
home.[111]
Research

Dementia research lags behind research into other conditions, and a comparison with cancer in terms of
research funding is often made. The Alzheimer's Research Trust found that in the UK in 20072008,
590 million was spent on cancer research and 50 million spent on dementia research. [13]
Dementia research comes with inherent difficulties based on diminishing capacity and ethical dilemmas.
Dementia research registries and research networks such as the Dementia and Neurodegenerative
Diseases Research Network (DeNDRoN) in the UK have been effective in increasing understanding and
improving recruitment to research studies.[112]
Palliation

End-of-life and palliative care services are well developed for the treatment of people in the terminal
stages of cancer, and end-of-life care services for dementia are being set up along similar lines. With a
median survival time of 1.3 years, advanced dementia is associated with a life expectancy similar to that
of well-recognized terminal diseases, such as metastatic breast cancer. However, patients with dementia
pose unique challenges due to impairments in understanding and expression, and behavioral and
psychological symptoms of dementia. Several studies compare quality of end-of-life care in cancer and
dementia, but very little is known about care given to the small subset of patients who have both
conditions clinical anecdotes suggest that care is sometimes poor and involves much suffering.
There have been studies looking at carer and physician response to dementia and cancer both seen as
progressive, life-shortening illnesses.[113] General practitioners were more likely to discuss end-of-life care
arrangements for patients with cancer than with other conditions such as dementia. [114] Pain and physical
distress is well recognized and treated in patients with end-stage cancer, but people with advanced
dementia could also be suffering from behavioral and psychological symptoms of dementia or mental
distress. In individuals with terminal cancer, palliative radiotherapy and chemotherapy are often used to
improve QoL in the short term, although these treatments are associated with side effects that may
shorten life. A similar approach to mental distress in individuals with cancer and dementia should be
considered with antipsychotics being used to target psychosis, despite the known risks of cardiovascular
side effects.[115]
Future Directions

Some authors argue that a number of illnesses in the developed world, such as cancer and
neurodegenerative and cardiovascular conditions, have age as a major risk factor and are better
researched and managed together and it might be better to intervene and decelerate aging itself. [116,117]
Liaison psychiatry teams that bridge physical and mental healthcare can help with earlier diagnosis of
patients with cognitive impairments and work together with oncology teams in drawing up care plans.

Well-established liaison psychiatry services are well accepted and reported to improve outcomes for
patients and referrers,[118] and evidence for their benefits in patient care and cost savings is increasing. [119]
Psycho-oncology departments are relatively well established for younger patients with cancer and most
oncology services have multidisciplinary teams with psychologists, but very little support is available for
older patients with cognitive impairments. Given that cognitive impairments can preclude psychological
therapies, such as cognitivebehavior therapy, there is the need for more investment in specialist support
services for older adults given the growing number of patients over the age of 65 years attending clinics.
Joined up, multispecialty 'one stop' clinics involving oncologists, geriatricians, geneticists, psychiatrists
and allied health professionals are already being set up to help deal with the increasing number of
patients with cancer and dementia. Further research is required to expand on the tenuous links between
the two conditions that will help understand and improve management.

Conclusion & Future Perspective

With a global aging population, by 2030, 70% of all cancers will occur in elderly people, and 63 million
people worldwide will have dementia. The emerging evidence suggests that there is an inverse
relationship between cancer and neurodegeneration, although the exact mechanisms are still unclear.
Advances in the field of genetics will provide further clues toward the underpinnings of two conditions
seen at opposite ends of a spectrum cell proliferation and degeneration. A diagnosis of cancer in a
person suffering from dementia poses a number of unique clinical challenges that many oncology
departments are ill-equipped to deal with. People with dementia are diagnosed with cancer much later
than cognitively intact people and have much poorer outcomes this raises ethical challenges for
clinicians about treatment decisions. Future research on cognition and cancer will have to focus on the
growing population of older adults. Standardization of cognitive testing as part of physical health workups and frailty screens for older adults could increase recognition of cognitive impairment at an earlier
stage. Liaison psychiatry teams span acute oncology and mental health services and serve to integrate
treatment and care planning, thereby improving QoL for people with comorbid conditions.

Sidebar
Executive Summary

Research Evidence

Cancer and dementia share age as a risk factor, but current evidence suggests an inverse
relationship.

Both conditions have health economy costs, but a large proportion of dementia costs are
incurred for social care compared with medical care.

Genetic links are being explored, as are comorbidity registers, but little definitive evidence is
currently available.

Clinical Challenges

Cancer diagnosis and treatment is stressful and psychological input can help.

Cognitive impairment can increase challenges at all stages of cancer diagnosis and treatment.

Under-reporting of symptoms, communication difficulties and impaired decision-making capacity

can impinge on cancer care in individuals with dementia.

Unmet Needs

Existing psycho-oncology services are geared towards younger patients with very little support
for cognitive impairment.

Cognitive screening should be carried out on all older adults in cancer clinics to identify cognitive
impairments early.

Liaison psychiatry services for older adults require more investment.

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Papers of special note have been highlighted as: of interest

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