The Challenge of Dementia: Prospects for Prevention A 100 year - - PowerPoint PPT Presentation

The Challenge of Dementia: Prospects for Prevention

A 100 year journey from discovery to prevention trials?

Alzheimer and Auguste D

Neurofibrillary Tangle Amyloid Plaque Brain atrophy

Dementia is not the same as Alzheimer’s disease

Dementia and Alzheimer’s disease

• Dementia: impairment of cognitive

functions

– Usually progressive – Sufficient to interfere with daily life

• Alzheimer’s disease is the most common

cause but many others – including treatable and preventable causes

Causes of Dementia

• Neurodegenerative

– Alzheimer’s Disease (AD) – Parkinson’s Dementia & Dementia with Lewy Bodies (DLB) – Frontotemporal lobar degeneration (FTLD) – Huntington’s disease

• Vascular (VaD)
• Other causes

– Brain tumours, infections (HIV, syphilis), vitamin and hormone deficiencies, Creutzfeldt Jakob disease (CJD),

Causes of dementia

Alzheimer’s disease 50-60% Vascular dementia 15% Dementia with Lewy bodies 15% Frontotemporal Dementia 5% Other ~2%

HIV, Head injury, Prion diseases/CJD, Corticobasal degeneration, PSP, Huntington’s, alcohol-related dementia, tumours, infections, vitamin & hormone deficiencies, …

Dementia Research Group

40-65 0.1% (1 in 1,000) 65-70 2.0% (1 in 50) 70-80 4.0% (1 in 25) 80 Plus 20.0% (1 in 5)

Age (Years) Prevalence

Source: Alzheimer's Society Prevalence doubles with every 5 years of age over 65

Dementia: a demographic time bomb with aging populations

Those born in 2013 can expect to live to

• ver 90y

Office of National Statistics & Christensen et al (2009) Lancet

Dementia is common and getting more common

• 800,000 people with dementia in UK
• 160,000 new cases per year - one

every ~3 minutes

• ~40% of the population have a family

member or close friend with dementia

Matthews F et al. (2005) The Incidence of Dementia PLoS Medicine, 2, e193 Alzheimer’s Research Trust / YouGov, 2008

Dementia

4% of 70-74y 8% of 75-79y 16% of 80-84y olds

2014

• £23 billion cost to UK
• ¼ of hospital beds
• ¾ of those in residential care
• ½ of us will care for someone …

Risk Factors – those we cannot do much about

• Age
• Family history (RR ~ 2)
• Genetic risk

– Rare familial cases – Genetic risk modifiers

• Female > male

“Choose your parents carefully and die young”

• Selkoe

AD: Genetics and Risk

• Risk related to family history depends on

detail: numbers affected, age at onset …

• APOE – is the major genetic risk factor

– ~1/5 of the population have an E4 allele – ~2/3 of AD patients have an E4 allele

• Familial AD accounts for only 1% but has

given great insights into the disease

– Three different genes – each is rare – Onset may be as early as 30 yrs

Risks we can do something about?

• Smoking
• Diabetes
• Raised blood pressure
• Raised cholesterol
• Head injury
• Exercise
• Depression
• Education – use it or lose it?

Prevalence is increasing but is there evidence that it is not increasing as fast as expected in developed economies?

Changes in UK age-specific prevalence 1990-2010

A range of proposed interventions…

Can walking keep your mind young?

But when do we need to act to prevent, delay or reduce the risk of diseases that cause dementia: e.g. Alzheimer’s disease and vascular dementia?

When do we need to treat ?

• When does the disease start to

cause irreversible losses?

• When most to save?
• When we (individuals or society)

would want disease modification?

• Failure of trials to date in AD?

Too little … too late?

Brain imaging – MRI – allows us to “see” the brain in life

Healthy control Alzheimer’s

Benefits of earlier intervention

Fewer neurons lost = more to save

In moderate AD some parts of the brain

have already lost 1/3 of their volume

Time 0 18months 36months H Serial MRI of an individual with initially mild AD

Scan 1

Scan 2 – 1 year later

In “mild” AD the hippocampus is

• n average already ~20% smaller than

controls

Seab ’88, De Leon ’89, Scheltens ’92, Soininen ’94, Jack ’99, Du ’01, Killiany ’02

How and when does Alzheimer’s disease begin?

• Recognition of a preclinical period to AD
• Isolated memory or other deficits

– 5-10% progression to AD per year

• Could we see changes with imaging?
• Would that offer an opportunity for

treatments to prevent symptoms?

• How could we study people before

symptoms?

Rarely Alzheimer’s is inherited - usually young onset

?

Allows us to study “at-risk” subjects

93 94 95 96 4/97 11/97

AD: At risk subject - serial scans registered to 1993 baseline

93 11/97

Red = loss

65 70 75 80 85 90 500 1000 1500 2000 2500

Time since first scan (days)

Symptoms Normal range: 95%CI

Brain Volume as percentage

• f TIV

Could we image amyloid plaques?

[11C] PIB, Flutemetamol, Florbetapir, Florbetaben

And now – tau – the tangles that Alzheimer saw

Remains well Subsequently converted to AD

Amyloid increases some years before AD symptoms – perhaps more than 10y before

Brooks, Archer, Okello

So if we can detect and track presymptomatic changes …

• Could we trial treatments at this

stage?

• What would their chances of success

be? A window of opportunity to delay onset

• f Alzheimer’s disease

100 years on from Alzheimer and Auguste D

• We can now see what Alzheimer could

not – changes in the brain in life

• We know there is a long pre-clinical

period – perhaps 10-15 years

• We can see and track changes before

symptoms And finally we are starting trials to slow or delay the onset of disease

• I would like to acknowledge the

tremendous and selfless contributions

• f patients and at risk subjects and

their families in taking part in research And thank you for listening