Women and Dementia in Europe: The way forward
Foreword by Vytenis Andriukaitis,
European Commissioner for Health and Food Safety
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As our population grows older and lives longer, dementia, in its many forms, is quickly becoming a public health challenge. In 2015, there were an estimated 9.6 million people living with dementia in the EU, or almost 1 in every 50 people.(1) It is important to note that the majority of those suffering from dementia are women. In the UK, for example, women make up 61% of dementia patients. In fact, dementia has become the leading cause of death for women in the UK (2) What makes this progressive disease particularly devastating is the way it affects not only the lives of the patients themselves, but everyone around them – carers, family members and society as a whole. Furthermore, it is women who bear most of the responsibility of: caring for dementia sufferers, be they family members or health care professionals. A recent study of family care patterns in five EU countries carried out by Alzheimer Europe found that 82.8% of carers were women. (3) This is why dementia is also an economic burden on women. We must address dementia through a multi-sectoral approach, in order to help the sufferers and their families cope both emotionally and financially. The European Commission remains committed to this goal, through leadership and financial support for national and international programmes, as well as research and development.(4) I hope that your position paper will accelerate the efforts to find better solutions for dementia, particularly for women suffering from this disease and those who might be struggling with caring for a sick relative. Sincerely,
Vytenis Andriukaitis, European Commissioner for Health and Food Safety |
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Women and Dementia in Europe: the way forward
Introduction
Dementia is the greatest global and societal challenge for health and social care in the 21st century. In 2018, 50 million people worldwide are living with dementia. With the ageing of the population, it is estimated that this number will more than triple by 2050 A, B, International Journal of Geriatric Psychiatry.
A https://onlinelibrary.wiley.com/doi/epdf/10.1002/gps.4997
B https://webgate.ec.europa.eu/chafea_pdb/health/projects/20102201/summary
The UN Convention on the Right of People with Disabilities (UNCRPD) is the first international legally binding instrument that sets minimum standards for rights for people with disabilities and the first human rights convention to which the EU has become a party. The EU as well as all EU Member States are thus committed to upholding and protecting the rights of persons with disabilities as enshrined in the Convention. The core elements of the Convention are reflected in the European Disability Strategy 2010-2020.
The Convention that has a broad definition of people with disabilities (“Persons with disabilities include those who have long-term physical, mental, intellectual or sensory impairments which in interaction with various barriers may hinder their full and effective participation in society on an equal basis with others”) obviously include people living with dementia.
The Convention also makes express references to women:
Preamble emphasizes ‘the need to incorporate a gender perspective in all efforts to promote the full enjoyment of human rights and fundamental freedoms by persons with disabilities” and article 6 Women with disabilities:
(1) States Parties recognize that women and girls with disabilities are subject to multiple discrimination, and in this regard shall take measures to ensure the full and equal enjoyment by them of all human rights and fundamental freedoms, and
(2) States Parties shall take all appropriate measures to ensure the full development, advancement and empowerment of women, or the purpose of guaranteeing them the exercise and enjoyment of the human rights and fundamental freedoms set out in the present Convention.”
The Convention has been ratified by the European Union with 152 million being affected by the disease. 1 According to Alzheimer’s Disease International (ADI), there will be one new case of dementia around the world every three seconds. Dementia is the most common neurological disorder in old age contributing to 11.9 years lived with disability in individuals aged 60 years and over. 2
Contrary to popular belief, dementia is not a natural or inevitable consequence of ageing. Dementia is a group of neurodegenerative syndromes that progressively lead to brain damage and gradual deterioration of an individual’s capacity to function autonomously. It is characterised by a decline in memory, language, problem solving or other cognitive skills that affects a person’s ability to perform everyday activities, compromising their ability to live independently. 3 Alzheimer’s disease (AD), a slow progressive brain disease, is the most common type of dementia, estimated to account for 60% to 80% of all dementia cases. 4
Most patients with AD (>95%) present with the sporadic form which is characterized by a late onset (80–90 years of age). It is believed to be caused by the failure to clear the amyloid-β peptide from the interstices of the brain. A small proportion of patients (<1%) have inherited mutations in genes that affect the synthesis of Aβ and develop the disease at a much younger age (mean age of – 45 yearsv, familial AD). Other dementias include vascular dementia, Lewy Body, fronto temporal dementia, alcohol associated dementia, Creutzfeldt-Jakob disease and Huntington’s disease. It is estimated that dementia will overtake cardiovascular diseases to become the leading cause of mortality world-wide in the near future. 6 It is the only condition in the top 10 causes of death without a treatment to prevent, cure or slow its progression. 7
For instance, figures from the Office for National Statistics in the UK show that dementia is the most common cause of death in England and Wales. The figures show that just over 60,000 people died due to dementia in 2015, which is slightly more than the number of deaths caused by coronary heart disease. 8, 9, 10
The personal, economic and social consequences of dementia are huge. The disease significantly compromises quality of life for the individuals affected, their carers and families. It is the greatest cause of disability and dependency in later life 11 and has a disproportionate impact on capacity for independent living compared to any other chronic disease. Symptoms of dementia and the additional risk of complications from comorbid conditions may compromise a person’s ability to maintain health and self-manage their care. In dementia patients with multiple conditions, dementia can often become the dominant clinical condition and this can lead to poor management of additional conditions and poorer outcomes.12
The prevalence of dementia in Europe
It is already clear that population growth and the ageing of the population have impacted on the numbers of Europeans living with dementia. The number of people with dementia is expected to continue rising in Europe to 13.4 million in 2030 and 18.7 million in 2050. 13 With 7.5 million dementia cases, Western Europe currently has the second highest proportion of people living with dementia over the total population (so called ‘prevalence’) by WHO GBD world region. 14 ADI estimates that this will double by 2050 to 14.32 million people with dementia living in Western Europe 15 (Table 1). Central Europe (1.07 million) and Eastern Europe (1.94 million) have comparatively lower numbers of people living with dementia, although ADI estimates a rise in both regions, albeit at a lower rate compared to Western Europe. It is expected that Western Europe will see a 92% increase in prevalence by 2050 compared to 78% for Central Europe and 26% for Eastern Europe.
Table 1.
Current + projected estimates of prevalence and frequency of dementia in Europe
Latest figures from OECD also recognise that much about dementia remains unknown despite the fact that its prevalence rises rapidly with age. The ‘Care Needed’ publication states that 2% of people between 65-69 live with dementia, while the figure rises to 90% for those aged over 90. As shown in Figure 1, the ageing of the population will exacerbate the situation.16
Figure 1. Dementia prevalence – People with dementia per 1000 population (all ages)
The current and projected prevalence rates of dementia are underestimated as AD and other dementias are substantially under-diagnosed in the EU. The European Brain Council ‘Value of Treatment’ 17 project highlights that approximately half of people living with dementia in Europe have never been diagnosed and for those who have been diagnosed it was most likely diagnosed at a moderate stage. 18, 19 A recent systematic review estimated the pooled rate of undetected dementia to be 61.7%. 20
Dementia risk is determined by a complex interaction of modifiable and non-modifiable factors. Non-modifiable factors include age, sex, learning disabilities and genetics.
Cardiovascular morbidities such as high blood pressure, hypercholesterolaemia, diabetes and obesity are major risk factors, as is stroke. Conversely, active engagement in mental, physical and social activities may delay the onset of the most common forms of dementia.
Dementia is clearly age related with incidence (number of new cases) doubling every 6.3 years. Dementia incidence peaks between age 80 and 89 years in Western and Central Europe and slightly earlier in Eastern Europe between ages 70 to 79 years (Figure 2). 21
Figure 2. Estimated annual numbers of incident cases of dementia by age group and GBD European Region
While ageing is the single, strongest risk factor for dementia 22, younger people can also be affected. ‘Young onset dementia’ (YOD) affects people of working age, usually between 30 and 65 years old. Population based studies on the epidemiology of YOD are limited and there is conflicting information about the prevalence of YOD. In the UK alone, over 42,000 people are living with YOD. 23 It takes on average 4.4 years for younger people to be diagnosed. 24 This is twice as long as older people, thus delaying access to treatment and support.
Younger people experience a variety of symptoms different from those which are typically linked to dementias in people over 65 years old. Changes in behaviour/mood/perception and balance are common, especially with frontotemporal dementia, posterior cortical atrophy, and Lewy Body dementia. Many younger people are misdiagnosed with depression, anxiety, stress, personality disorders, marital issues or menopause. In the absence of memory problems, these symptoms can be missed.
As an example, Young Dementia UK has recently published a Guide ‘Diagnosing dementia in younger people, a decision making guide for GPs’ 25 to educate them about some of the symptoms that a young patient may present with. This guide has been endorsed by the Royal College of General Practitioners.The low levels of awareness about the disease and the difficulties of diagnosing the condition at working-age mean popularly used statistics are likely to be inaccurate and do not reflect the true number of people who are affected.
However, studies indicate that AD is the most common form of dementia in younger people (around 4%-5% of people with AD are under 65). 26, 27 Harvey and colleagues 28 estimated that, in two London boroughs in the UK, AD was the most common single diagnosis of dementia in people younger than 65, followed by vascular disease, frontotemporal dementia and alcohol dementia. Most of the young onset AD cases are due to genetic defects; either familial AD mutations, or triplication of the APP gene in Down’s syndrome. Individuals affected by Down’s syndrome in fact invariably present AD neuropathology and are at markedly higher risk of YOD: 10-30% of people with Down’s syndrome aged 40-49 and 30-75% aged 60-69 are likely to develop dementia xxix which is due to Alzheimer pathology.30
YOD carries a higher mortality risk compared to late onset dementia. 31, 32 It is more prevalent than previously thought xxxiii and its prevalence is increasing.34 It is estimated that YOD may account for between 6 to 9% of all dementia cases.35
People with YOD face specific challenges: early symptoms of dementia are often dismissed and the diagnostic process is compounded by the idea that the person is likely to be ‘too young’ to develop dementia. The symptoms are similar to those of older people with dementia but the impact on their lives is much greater. These people are more likely to still be working when they are diagnosed, have significant financial commitments, children to care for and dependent parents.
Socio-economic impact of dementia in Europe
According to OECD, dementia is already the second largest cause of disability for the over 70s and costs societies more than half a trillion US dollar every year globally. Ageing populations will increase these costs. 36
The European Commission (Economic and Financial DG) projects an increase in the oldage dependency ratio (people aged 65 and above relative to those aged 15 to 64) in the EU during the period 2016-2070. This implies that the EU would go from having 3.3 working age people for every person aged over 65 years to only 2 working-age persons.
Most of this increase is driven by the very old-age dependency ratio (people aged 80 andabove relative to those aged 15-64), rising from 8.3% to 22.3% between 2016 and 2070. 37
The societal and economic impact of dementia in Europe is substantial including direct medical and social care costs as well as significant informal care contributions. 38
Direct healthcare costs such as doctor visits, hospital admissions and medication are putting European health systems under severe pressure and the indirect costs of caring for people with dementia place an unsustainable economic burden on families and carers. 39 Out of pocket costs for dementia care contribute significantly to the burden of the disease on the individual affected and their carers and families. In all European countries it is estimated that one half of the overall costs of dementia are indirect costs borne by carers and families.
The cost of dementia in Europe is becoming progressively onerous due to the increase in the proportion of the overall population with the disease. ADI estimates that Western Europe accounts for the greatest cost of dementia in Europe, explained by greater prevalence but also by the greater cost of care provision compared to other European regions (Table 2). 40 Wimo et al 41 estimated the per person cost of dementia in Europe to be € 22,000 per year. The overall cost of caring for dementia in Europe is likely to rise in future years due to a rapid increase in the per person cost of dementia in Eastern Europe.
Table 2. Estimated costs of dementia in Europe
The spiralling cost of care against a backdrop of fiscal challenges in Europe in the last decade is expected to put European economies under substantial pressure in the coming years. 42 Spending on prevention accounted for only 3% of all expenditure on health in 2010 in OECD EU countries. 43
Demographic ageing as well as recent changes in society (e.g. migration, declining fertility, higher levels of education, motherhood in older age, changing family structure, increased participation of women in the labour force, etc.) are draining the potential pool of carers which – given the important role played by carers in Europe – will put more and more pressure on them. 44 ,45
Adopting a public health approach to reduce the prevalence of dementia as advocated by the WHO, ADI and the Blackfriars Consensus 46 provides many opportunities to ‘invest to save’. WHO advocates sustained action and coordination across multiple levels and with all stakeholders at international, national, regional and local levels.
Women have greater frequency and prevalence of dementia in Europe
Table 3. The frequency of dementia in Europe (EU-28) according to sex
Austria 45,938 99,494
Belgium 62,972 128,309
Bulgaria 37,851 72,042
Croatia 20,394 46,682
Cyprus 4,333 6,917
Czechia 45,532 97,778
Denmark 29,715 55,847
Estonia 5,469 16,252
Finland 29,287 62,945
France 375,843 799,113
Germany 517,136 1,054,968
Greece 75,392 126,375
Hungary 43,636 105,291
Ireland 17,895 31,574
Italy 414,975 857,341
Latvia 8,902 26,812
Lithuania 12,567 34,768
Luxembourg 2,327 4,662
Malta 1,878 3,423
Netherlands 83,247 162,314
Poland 150,371 350,721
Portugal 62,260 120,266
Romania 90,484 179,820
Slovakia 17,834 40,774
Slovenia 9,324 22,711
Spain 280,149 538,197
Sweden 60,479 112,656
UK 360,581 677,210
Total 2,866,771 5,835,262
Women are at the epicentre of the Alzheimer’s crisis. In the EU, Alzheimer Europe estimates that close to 6 million women have dementia. The strikingly higher frequency of AD amongst women is observable in each EU28 country, as reported in Table 3. 46
This is a global trend: according to the Alzheimer’s Association’s report ‘Alzheimer’s Disease Facts and Figures’, almost two thirds of American seniors living with AD, are women. Among those aged 71 and older, 16% of women have AD and other dementias, compared with 11% of men. Life expectancy in the EU is on the rise, increasing by 3 months on average each year 47 and a greater degree of population ageing is expected for women.
The proportion of women aged over 75 is expected to double by 2060 (from 5.5% to more than 10% of the total population). (48) Given these trends and the strong impact of ageing on dementia risk, it is projected that the numbers of older women with dementia will increase substantially in the coming decades.
Whether women are universally at higher risk of AD is not fully elucidated. 49 However, several lines of research indicate that older women might be at higher risk than men, and this especially in Western Europe. According to ADI, the prevalence of dementia is related to age in all world regions. However, while in the United States prevalence did not seem to be affected by sex, a clear trend for higher prevalence in women is observed in Europe.
This trend reached significance in Western Europe. The higher prevalence of AD in women is consistently observed in older age brackets. Since prevalence data refer to the number of AD women patients over the total number of women of the same age, higher life expectancy in women is taken into account into this data and does not explain the sex effect observed. It has been suggested, however, that higher prevalence of dementia in older women as compared to older men might be due to the phenomenon of ‘selective survival’.
According to this hypothesis, generated in the US, men tend to die earlier in life of cardiovascular events, hence the ‘survivors’ have a healthier cardiovascular risk profile than women of the same age and are therefore protected from dementia at older ages.l If this was confirmed, it might indicate that older men and women present different comorbidities and risk factors for dementia, a crucial notion for effective preventative strategies. However, this hypothesis remains to be tested in European cohorts.
Sex, gender and risk of dementia
Evidence indicates that both sex and gender might modulate dementia risk across the life span. Biological as well as gendered experiences across the life course have been shown to modify brain health and dementia risk. The Women Brain Project and Alzheimer’s Disease Precision Medicine Initiative recent review of the scientific literature clearly demonstrates that sex and gender differences are indeed of very high relevance for diagnosis and treatment of AD. 51
For example, exposure to adversity and educational opportunities in early life and health behaviours throughout the life course are thought to be differentially influencing dementia risk for men and women. 52
Education and employment are important dementia risk factors that differ across genders. The crucial impact of education in AD has been recently highlighted by the study of Satizabal et al., reporting that high-school-level education significantly correlated with reduced incidence of dementia (including AD) over three decades in the Framingham heart study. 53 In AD studies, women show consistently lower education levels than men.
However, the specific interaction between sex, gender and education in dementia risk has not been properly studied. In terms of biological risk factors, several of them have been shown to affect men and women differently. While APOE4 is a prominent risk factor for both men and women, a recent study demonstrated that women with the APOE ε3/ε4 genotype have an increased risk at younger ages to develop AD than men. 54 Evidence suggests that vascular factors might differentially regulate risk of AD according to sex.
In population based studies conducted in Finland, history of late life vascular diseases significantly associated with Alzheimer’s dementia in women but not in men. 55 More recently, sex specific effects were reported between vascular risks factors and dementia onset, with overweight and physical activity being, respectively harmful and protective, specifically in women. A recent study in the population based Mayo Clinic Study of Ageing identified sex specific risk scores in the short term conversion (median 5 years) from normal cognition to mild cognitive impairment (MCI).
Smoking, midlife dyslipidaemia, diabetes and hypertension were specific predictors for MCI conversion in women. Obesity and marital status were specific to men, while stroke, atrial fibrillation, history of alcohol abuse, education and self reported memory concerns were confirmed AD predictors in both men and women. 56
A recent meta-analysis revealed that individuals with sleep problems have higher risk for AD dementia. 57 Epidemiologically, sex differences in sleep disorders have been reported with women 40% more likely to develop insomnia, as well as more prone to restless leg syndrome and obstructive sleep apnoea. 58 The specific interaction between sex and sleep in conferring risk to AD has to be yet characterised.
An emerging risk factor in dementia is depression. The greater the frequency and severity of depressive symptoms, the greater are the risks. 59 On average, women have higher rates of depression than men. Depression is also linked to cardiovascular disease, the latter a significant risk factor for stroke. 60 Late life depression has a strong correlation with the risk of developing AD.
61 Saczynski and colleagues found that the risk of developing dementia, including AD, nearly doubled in participants suffering from depression in the Framingham’s heart study.
Finally, there are women specific risk factors for dementia, like pregnancy induced hypertension, and pre-eclampsia. Pre-eclampsia 62 has been associated with higher risk for cardiovascular disease 63 and cognitive impairment later in life. 64 Hysterectomy and oestrogen loss after menopause may increase risk in women.
Cardiovascular morbidities such as high blood pressure, hypercholesterolaemia, diabetes and obesity are major risk factors, as is stroke. However, active engagement in mental, physical and social activities may delay the onset of the most common forms of dementia. 65
Dementia is experienced differently by men and women
Women are not only disproportionately affected by AD but they also experience the manifestation and progression of dementia differently. Sex-differences have been reported in rates of progression in MCI patients recruited in the ADNI study, with faster cognitive deterioration in women over a one-year period. 66
Women with mild cognitive impairment (MCI) experience memory declines twice as fast as in men. 67 The progression of dementia is different between men and women 68 and it may be faster in women and individuals with YOD. 69 However, clinical data are rarely stratified by sex and evidence supporting these reports is required. It has been reported that women experience more pronounced symptoms of dementia compared to men. 70 Women have a broader spectrum of dementia related behavioural symptoms with a predominance of depression and delusion 71, 72 while aggressive behaviour is more frequently observed in men. 73 Older research showed poorer cognitive profiles in women compared to men at the same stage of AD in several cognitive domains including language and semantic abilities, visuospatial abilities and episodic memory. These differences could be explained by other factors such as age, education or dementia severity. However, they need to be confirmed in recent studies.
Sex specific effects may be attributable to a reduction of oestrogen in postmenopausal women, greater cognitive reserve in men, and the influence of the APOE4 allele which increases risk disproportionately in women compared to men during younger age. 74
Recent papers suggest that women might be able to mask initial cognitive decline (at the MCI stage), as they are high performers in the neuropsychological test normally used to identify MCI even in the presence of neurodegeneration in their brains. Women show
better verbal memory than men in MCI despite similar levels of hippocampal atrophy. If this was confirmed, it might indicate that women are on average diagnosed later than men (as suggested by Pradier et al.75
Early diagnosis in women might therefore require sex specific diagnostic tests. Women also show more concern about a dementia diagnosis compared to men. In the U.S., 58% of women compared to 43% of men reported being fearful of developing dementia. 76 Studies report that this greater fear among women encompasses their loss of identity as primary family caregiver; a role that is reinforced by dominant society norms.77 Social care policies also reinforce this gendered perception of women’s role as the cornerstone of care giving in the community rather than recipients of care.
Research in Ireland found that female physicians were less likely to diagnose dementia compared to their male counterparts. 78 When women are diagnosed with dementia, they are less likely to access health and social care systems compared to men and they experience worse outcomes when they do. 79 Women face more economic and social disadvantage than men in later life. Women are more financially dependent on their male partners as a result of gender biased health and social care schemes in Europe. In particular, social insurance schemes which rely on a history of paid employment directly disadvantage women. 80 For example, the marriage bar introduced in The Netherlands and Ireland in the 1930’s effectively excluded women from paid employment and is now contributing to the economic marginalisation of women in later life. As a result, women are less likely to be able to afford and access appropriate dementia treatment and care in later life.