Women and Dementia

AProf Cassandra SzoekeGAICD, PhD, FRACP, MBBS, BSc(Hons)

Director of the Women’s Healthy Ageing Project

Disclosures• on the Board of Executive Directors for the Western

Health Service, Victoria

• may accrue revenue from patent; pharmacogenomic diagnostic assay for seizure prediction,

• has been a paid clinical consultant and speaker for the Australian Commonwealth, Pfizer, Sanofi, other relationships subject to confidentiality clauses

• has been a chief investigator on investigator driven research projects receiving funds from Bayer, Merck, Piramal and GE Healthcare.

• Twice as likely as men the same age to develop dementia (Association, 2014).

• Women have more severe disease and rapid decline (Holland, Desikan et al, 2013) than age matched men

Ageing Australia - Women

• The majority of people aged over 85 - almost 70% - are women (Department of Health and Ageing, 2000).

• Women over 80 – 4 times more likely to get AD

Many many women are living with dementia

Women with dementia have more morbidity and more severe disease

Social Engagement Caring

Executive function and time minding grandchildren

COMMERCIAL IN CONFIDENCE – CONTAINS PILOT AND UNPUBLISHED DATA

p< 0.01

Unpaid Care

• 63 % are women. – Studies have consistently shown that women

make up 60 percent to 70 percent of Alzheimer’s caregivers.

• 10 million women in USA are currently providing unpaid care to someone with Alzheimer’s or another dementia.

Intense Care for someone with Dementia• on-duty care 24-hours a day.

• for more than five years.

• Female caregivers receive less caregiving support

• Even advanced Alzheimer’s disease received less support from family and friends than men caring for wives in similar situations.

Effect of Care on women• Isolation linked to depression more often

• ¾ express concern about the ability to maintain their own health since becoming a caregiver

• 62% of women find caregiving to be emotionally stressful.

• 50% responsibilities are physically stressful.– twice the rate as male Alzheimer’s caregivers.

Other employment effects on working women caregivers

• 18 percent have taken a leave of absence from work

• 10 percent have lost job benefits

• 17 percent felt they had been penalized at work because of their caregiving duties

Many many women are living with dementia

Women with dementia have more morbidity and more severe disease

More women are carers of people with dementia

GAPS IN RESEARCH• women are often excluded from medical

research (D. et al, Rogers-Clark et al)

• Current evidence based guidelines – rely on research that either excludes women, or

assumes that men and women are the same.

• Policy on the national priority areas ignores evidence about differences between men and women and the need for services that cater for their differing needs (Care. 1999).

An example• More women than men dying of heart disease

• 1985 Report encourage more inclusion of women in studies.

• 1991 women still seriously underrepresented

• 1993, the FDA new guideline

• 2000 NIH reports improvement

• 2003-2004 First recorded reduction in women dying from heart disease 1 in 4 from 1 in 3.

Awareness

• 2002 34% awareness

• 2002 NIH The Heart Truth Campaign®

• 2009 increased awareness to 69% in 2009.

Cardiovascular Disease• heart disease

– risk factors

– symptoms

– approaches to prevention

– management

“are entirely different”

• http://www.health.harvard.edu/topics/womens-health

Australia

• TODAY

• More women than men have CVRF– 90% of Australian women over 50 have at

least one vascular risk factor• (smoking, high blood pressure, high cholesterol,

diabetes, weight, depression and family history)

Un-recognized• 97% of Australian’s unaware that

vascular disease is the leading cause of death for women

• Only 71% womens health physicians and obstetric gynaecologists responding correctly to all 13 questions that assessed knowledge about cardiac risk factors.

3% awareness

• VASCULAR risk factors (VRF)

• Increased risk for Dementia due to Alzheimer’s Disease (AD) in later life

• Vascular is different in women

• Dementia?

Differences• differences in brain structure

• different forms of behavioral changes associated with the disease

– Ott BR, Tate CA, Gordon NM, Heindel WC. Gender differences in the behavioral manifestations of Alzheimer’s disease. J Am Geriatr Soc 1996;44(5):583–587.

• structural changes in the brain that differ between men and women.

– Radiological Society of North America. Researchers Discover Gender-based Differences in Alzheimer’s Disease. Oak Brook, Ill.; 2012. Available at http://www2.rsna.org/timssnet/media/ pressreleases/pr_target.cfm?id=634.

Differences

• different hormonal physiology, and sex-specific hormones are known to have effects on the brain.

• differences in the molecular characteristics of cells in women and men, including genetic differences.

Differences

• the higher risk associated with APOE-ε4 is more pronounced in women

– Ungar L, Altmann A, Greicius MD. Apolipoprotein E, gender, and Alzheimer’s disease: An overlooked, but potent and promising interaction. Brain Imaging Behav 2013. Epub ahead of print.

• specific brain regions changed at different rates in women versus men

– Skup M, Zhu H, Wang Y, Giovanello KS, Lin JA, Shen D, et al. Sex differences in grey matter atrophy patterns among AD and aMCI patients: Results from ADNI. Neuroimage 2011;56(3):890-906.

• more research is needed to define biological differences

Cognition and Ageing – Women• CSF Ab42 reduction correlating with memory in

female healthy elderly but not in males

• Amyloid load on Pib scans relating to cognition in women but not men Pike et al, 2011, Neuropsychologica

No relationship between vascular risk and amyloid

Midlife PROCAM, E4 and Late-life FBB SUVR• Interaction of Midlife

PROCAM tertile x APOE ε4 status significantly associated with late-life FBB SUVR (p=0.04).

• ie. the association of high vascular risk tertile with A was greatest in ε4+

• age and years of education.

SU

VR

PROCAM Tertile

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But will such risk factor modification have an effect on disease?

Many many women are living with dementia

Women with dementia have more morbidity and more severe disease

Women are different biologically and socially and this affects disease risk, disease and treatment

To understand Chronic Disease we need Long research follow-up

Example of therapeutic window

Chronic Disease • “diseases of long duration and generally slow progression”1

• Diseases with a long prodrome – importance of the timing and duration of required intervention/prevention

– crucial in determining disease outcome.

• Without longitudinal studies of appropriate duration– the optimal timing and duration of intervention cannot be determined

– may result in negative trials for otherwise appropriate therapies

1 World Health Organisation International

Year 0 Year 10 Year 20 Year 30

Is there evidence that the timing of intervention is important?

Shepardson, Shankar, Selkoe (2011), Arch Neurology, 68 (10), 1239-44

WHAP

Have we made mistakes examining only over 65’s before

TIMING OF THERAPY

• >200 research publications– oestrogen has a favourable effect on brain tissue,

physiology and cognition in later life.

• Large Women’s Health Initiative memory study (WHIMS) – oestrogen supplementation did not improve

cognition when initiated in women >65 years (Resnick, Maki et al 2005).

National Position Statement

How long before revision?

Many many women are living with dementia

Women with dementia have more morbidity and more severe disease

Women are different biologically and socially and this affects disease risk, disease and treatment

Timing is CRUCIAL – we need longitudinal studies from midlife

Summary• More women than men have dementia

• Women with dementia have more severe disease

• Women are more likely to be carers and take on a greater burden

• Vascular disease is very different in men and women, only focused research identified different requirements for prevention, risk reduction, early identification and management

• We need more studies in women (particularly with vascular measures

Summary• In dementia timing of intervention is important

• We have made mistakes on this before by only examining populations for intervention over 65

• Such mistakes take decades to rectify

• Current Australian dementia studies recruit over 60 years of age – this precludes truly “early” detection

• Risk factors can have different effects on disease over the lifespan

• Modification could halve the cases of dementia

WHAPA/Prof Cassandra SzoekeProf Lorraine DennersteinProf Philippe LehertResearch TeamRafael SmithJacqui GiummarraMorgan Radler

PUBLIC HEALTH BIOINFORMATICSProf John HopperProf Danny LiewDr Mark TaceyDr Chuhui Chan

Participants and their families

National Health and Medical Research Council (NHMRC), Ramaciotti Foundation, Bayer Healthcare, Piramal Life-Science, Brain Foundation, 

Alzheimer’s Association of Australia, Australian Menopausal Society, Brain Foundation, Shepherd Foundation, Scobie and Claire McKinnon Foundation, Alzheimer’s Association,

Collier Trust Fund, J.O. & J.R. Wicking Trust, Mason Foundation.

ENDOCRINOLOGICAL Prof Henry BurgerProf Elizabeth FarrellDr Charlene ChuaDavid ThawleyDr Jo Ryan

NEURO PSYCHIATRICProf David AmesKatherine CampbellDr Jo RobertsonKatherine Burns

MUSCULOSKELETAL AND BONE HEALTHProf John WarkProf Flavia CicuttiniAlexander Blizzard

CARDIOVASCULAR HEALTHProf Helena TeedeArti AppannahKaren ChenDr Paul Yates

NEUROIMAGING

PETProf Christopher RoweA/Prof Victor VillemagneLana PejoskaNarelle LangdonRobyn VeljanovskiDr Fiona LambDenise El-SheikhDr Kevin Ong

MRIProf Patricia DesmondDr Chris StewardMary Barnes

BiomarkersProf Colin MastersDr Alan RembachBrett Trounsen

CSZOEKE@UNIMELB.EDU.AU