Download pptx - 2.17 MBAD - Epidemiology and Burden

Epidemiology and Burden
Alzheimer Disease (AD)
Causes and Underlying biology of AD
What causes Alzheimer’s disease?
• The etiology of AD is not fully understood1
• Genetic factors directly linked to early-onset AD (familial cases account for 1–5% of
cases)1
• Mutations in APP, PSEN1 and PSEN2 genes
• Genetics of sporadic AD2
• ApoE 4 – increased risk of AD (3–13 times3)
• ApoE 2 – moderately decreased risk of AD in some studies
• Environmental factors1
• Occupational exposures
• Pre-existing medical conditions
• Lifestyle factors
ApoE=apolipoprotein E; APP=amyloid precursor protein; PSEN=presenilin gene
1. Jiang et al. Curr Alzheimer Res 2013;10(8):852–867;
2. Bendlin et al. Mauritas 2010;65(2):131–137; 3. Sando et al. BMC Neurol 2008;8:9
Pre-existing medical conditions related to Alzheimer’s disease
Reviewed in: Jiang et al. Curr Alzheimer Res 2013;10(8):852–867
Modifiable lifestyle factors related to Alzheimer’s disease
Reviewed in: Jiang et al. Curr Alzheimer Res 2013;10(8):852–867
Accumulation of Alzheimer’s disease risk factors over time
Protective factors
Physical
activity
Education
Medications
Genetics
Diet and nutrition
Alcohol in
Mental and social
moderation
activity
Coffee
Adult life
ApoE, other
genes
Cognitive reservea
Old
Dementia
Transition
Middle age
0
20
age
60
Neuronal damage
75
Vascular insults
Hypercholesterolemia
Inflammation
Obesity
Hypertension
Risk factors
Smoking
Unhealthy
diet
Diabetes
Alcohol
misuse
Depression
aResilience
to neuropathological damage
Jiang et al. Curr Alzheimer Res 2013;10(8):852–867; Bendlin et al. Maturitas
2010;65(2):131–137; Winblad et al. Lancet Neurol 2016;15:455–532
Putative risk and protective factors for late-onset dementia and Alzheimer’s disease
Risk factors
Older age
Genetic
• Familial aggregation (two or more
family members with the disease)
• ApoE ε4 allele
• Other susceptibility genes (e.g.,
CR1, PICALM, CLU, TREM2,
TOMM40)
Vascular and metabolic
• Atherosclerosis
• Cerebral macrovascular and
microvascular lesions
• Cardiovascular diseases
• Diabetes mellitus and
pre-diabetes
• Midlife hypertension
• Midlife overweight and obesity
• Midlife high serum cholesterol
Protective factors
Lifestyle
• Sedentary lifestyle
• Smoking
• Heavy alcohol consumption
Diet and nutrition
• Saturated fats
• Hyperhomocysteinemia
• Deficiencies in vitamin B6, B12,
and folate
Other
• Depression
• Traumatic brain injury
• Occupational exposure
(e.g., heavy metals, extremelylow-frequency electromagnetic
fields)
• Infectious agents (e.g., herpes
simplex virus type I,
Chlamydophila pneumoniae,
spirochetes)
Genetic
• Some genes proposed (e.g.,
APP, ApoE ε2 allele)
Psychosocial factors
• High education and
socioeconomic status
• High work complexity
• Rich social network and social
engagement
• Mentally stimulating activity
Lifestyle
• Physical activity
• Light-to-moderate alcohol
intake
ApoE=apolipoprotein E; APP=amyloid precursor protein; CR1=complement component receptor 1; PICALM=phosphatidylinositol-binding clathrin assembly
protein; CLU=clusterin; TREM2=triggering receptor expressed on myeloid cells 2; TOMM40=translocase of outer mitochondrial membrane 40 homologue
Winblad et al. Lancet Neurol 2016;15:455–532
Diet and nutrition
• Mediterranean diet
• Polyunsaturated fatty acid
and fish-related fats
• Vitamin B6, vitamin B12, and
folate
• Antioxidant vitamins
(A, C, E)
• Vitamin D
Drugs
• Antihypertensive drugs
• Statins
• Hormone replacement
therapy
• Non-steroidal antiinflammatory drugs
Burden of AD
Projected increase in the prevalence of Alzheimer’s disease
Projected number of people aged ≥65 (total and by age group) in the US population with Alzheimer’s disease, 2010 to 2050 1,2
Alzheimer’s Association. Alzheimers Dement 2016;12:459–509;
Adapted from: Hebert et al. Neurology 2013;80:1778–1783
Domains of Alzheimer’s disease
Caregiver burden
Cognitive
function
Global
function
Activities of
daily living (ADLs)
Behavior
Alzheimer’s disease has a large impact on society
• AD was the 6th leading cause of death in the US, in 20141
• 5th leading cause of death for those aged ≥65 years (2013)2
• Between 2000 and 2014, deaths resulting from heart disease, and cerebrovascular disease all
decreased, whereas deaths from AD increased1-3
• In 2016, an estimated one-third of people in the US aged ≥65 years will have AD when they die2,4
• By 80 years of age, nursing home admission is expected for 75% of people with AD, compared with
only 4% of the general population2,5
• In 2016, total payments for all Americans ≥65 years of age with AD and other dementias have been
estimated at $236 billion2
• In 2015, >15 million family members and other unpaid caregivers provided an estimated 18.1
billion hours of care to people with AD and other dementias
– a contribution valued at >$221 billion2
1. Kochanek et al. National Vital Statistics Reports 2016;63(9):1–122;
2. Alzheimer’s Association. Alzheimers Dement 2016;12:459–509;
3. Miniño et al. National Vital Statistics Reports 2002;50(15):1–120;
4. Weuve et al. Alzheimers Dement 2014;10:e40–e46;
5. Arrighi et al. Alzheimer Dis Assoc Disord 2010;24:90–95
Alzheimer’s disease has a large impact on caregivers
Georges et al. Int J Geriatr Psychiatry 2008;23(5):546–551
Caregiver burden
With advancing disease, patients with dementia become
increasingly dependent on others – both physically and
mentally.1 Consequently, the pressure on caregivers increases,
in terms of time and money.1 There is also a substantial
negative impact on the health of individuals who share a
household with an AD patient.2
• In the US, more than 15 million people – mainly family
members or friends – provide unpaid care for people with AD
and other dementias.3 In 2015, this unpaid care amounted to
an estimated 18.1 billion hours, valued at $221.3 billion.3
• Some of the most problematic symptoms reported by
caregivers of patients with dementia are difficulties with
ADLs, such as going to the lavatory or washing, and
behavioral issues, such as agitation or aggression.1 Even in
mild AD, behavioral symptoms increase caregiver burden.4
1. Georges et al. Int J Geriatr Psychiatry 2008;23(5):546–551; 2. Suehs et al. J Am Geriatr Soc 2014;62(3):435–441;
3. Alzheimer’s Association. Alzheimers Dement 2016;12(4):459–509; 4. Kamiya et al. Geriatr Gerontol Int 2014;14(Suppl 2):45–55
Caregiver burden
With advancing disease, patients with dementia become
increasingly dependent on others – both physically and
mentally.1 Consequently, the pressure on caregivers increases,
in terms of time and money.1 There is also a substantial
negative impact on the health of individuals who share a
household with an AD patient.2
• The majority of patients with dementia are cared for at home,
by a partner or other family member.1
• In the US, more than 15 million people – mainly family
members or friends – provide unpaid care for people with AD
and other dementias.3 In 2015, this unpaid care amounted to
an estimated 18.1 billion hours, valued at $221.3 billion.3
• Some of the most problematic symptoms reported by
caregivers of patients with dementia are difficulties with
ADLs, such as going to the lavatory or washing, and
behavioral issues, such as agitation or aggression.1 Even in
mild AD, behavioral symptoms increase caregiver burden.4
• Often, the caregiver is elderly, and their ability to cope may
be limited by their own personal health issues.1
1. Georges et al. Int J Geriatr Psychiatry 2008;23(5):546–551; 2. Suehs et al. J Am Geriatr Soc 2014;62(3):435–441;
3. Alzheimer’s Association. Alzheimers Dement 2016;12(4):459–509; 4. Kamiya et al. Geriatr Gerontol Int 2014;14(Suppl 2):45–55
Caregiver burden
With advancing disease, patients with dementia become
increasingly dependent on others – both physically and
mentally.1 Consequently, the pressure on caregivers increases,
in terms of time and money.1 There is also a substantial
negative impact on the health of individuals who share a
household with an AD patient.2
• The financial impact of caring for someone with dementia
includes medical fees, care costs, and lost earnings.1
• In the US, more than 15 million people – mainly family
members or friends – provide unpaid care for people with AD
and other dementias.3 In 2015, this unpaid care amounted to
an estimated 18.1 billion hours, valued at $221.3 billion.3
• Some of the most problematic symptoms reported by
caregivers of patients with dementia are difficulties with
ADLs, such as going to the lavatory or washing, and
behavioral issues, such as agitation or aggression.1 Even in
mild AD, behavioral symptoms increase caregiver burden.4
1. Georges et al. Int J Geriatr Psychiatry 2008;23(5):546–551; 2. Suehs et al. J Am Geriatr Soc 2014;62(3):435–441;
3. Alzheimer’s Association. Alzheimers Dement 2016;12(4):459–509; 4. Kamiya et al. Geriatr Gerontol Int 2014;14(Suppl 2):45–55
Caregiver burden
With advancing disease, patients with dementia become
increasingly dependent on others – both physically and
mentally.1 Consequently, the pressure on caregivers increases,
in terms of time and money.1 There is also a substantial
negative impact on the health of individuals who share a
household with an AD patient.2
• Among individuals who share a household with an AD patient
there is an increased prevalence of rheumatoid arthritis,
mood disorders, anxiety disorders, insomnia, substance
abuse or dependence, and cardiovascular disease.2
• In the US, more than 15 million people – mainly family
members or friends – provide unpaid care for people with AD
and other dementias.3 In 2015, this unpaid care amounted to
an estimated 18.1 billion hours, valued at $221.3 billion.3
• Some of the most problematic symptoms reported by
caregivers of patients with dementia are difficulties with
ADLs, such as going to the lavatory or washing, and
behavioral issues, such as agitation or aggression.1 Even in
mild AD, behavioral symptoms increase caregiver burden.4
• In 2015, the physical and emotional impact of dementia
caregiving resulted in approximately
$10.2 billion in US health care costs.3
1. Georges et al. Int J Geriatr Psychiatry 2008;23(5):546–551; 2. Suehs et al. J Am Geriatr Soc 2014;62(3):435–441;
3. Alzheimer’s Association. Alzheimers Dement 2016;12(4):459–509; 4. Kamiya et al. Geriatr Gerontol Int 2014;14(Suppl 2):45–55
Caregiver burden
With advancing disease, patients with dementia become
increasingly dependent on others – both physically and
mentally.1 Consequently, the pressure on caregivers increases,
in terms of time and money.1 There is also a substantial
negative impact on the health of individuals who share a
household with an AD patient.2
• In the US, more than 15 million people – mainly family
members or friends – provide unpaid care for people with AD
and other dementias.3 In 2015, this unpaid care amounted to
an estimated 18.1 billion hours, valued at $221.3 billion.3
• Some of the most problematic symptoms reported by
caregivers of patients with dementia are difficulties with
ADLs, such as going to the lavatory or washing, and
behavioral issues, such as agitation or aggression.1 Even in
mild AD, behavioral symptoms increase caregiver burden.4
• The time spent caring for a patient with dementia increases
with progressing disease severity.1 However, the burden on
caregivers is substantial even in milder stages of dementia.1
• Approximately one third of caregivers spend 14 hours or
more every day looking after a person with dementia.1 Some
people are unable to work due to their caregiving
responsibilities.1
1. Georges et al. Int J Geriatr Psychiatry 2008;23(5):546–551; 2. Suehs et al. J Am Geriatr Soc 2014;62(3):435–441;
3. Alzheimer’s Association. Alzheimers Dement 2016;12(4):459–509; 4. Kamiya et al. Geriatr Gerontol Int 2014;14(Suppl 2):45–55
Conclusion
• AD is a complex neurodegenerative disease with multifactorial etiology involving multiple
neurotransmitter systems
• Due to the aging population, there is a growing number of people who are living with dementia
and AD
• Numerous putative risk and protective factors have been proposed – genetic and environmental
factors all play their part
• Age is the most important risk factor for AD; the prevalence of AD is estimated to double with
every 5-year increment in age, after 65 years
• AD has a large impact on society – in terms of impaired abilities and quality of life, healthcare
costs, caregiver burden, lost earnings, and premature deaths