Progress Report on Alzheimer’s Disease

Taking the Next Steps

NIA NIH

Alzheimer’s Disease (AD)

• Age-related• Irreversible brain disorder• Occurs gradually• Results: memory loss• behavior/personality changes• decline in thinking abilities

• Course of disease varies from person to person• Rate of decline varies• Ave. after Dx: 8-10 years• Advances from mild forgetfulness to severe loss

of mental fx

• Symptoms appear after 60• EARLY LATE

– loss of recent memory faulty judgement &personality changes

– easily confused forget simple tasks

• FINALLY:– become completely dependent on others for

everyday care– become debilitated, likely to develop other

illnesses/infections– Usually die of pneumonia

• “Although the risk of developing AD increases wih age, AD and dementia symptoms are not a part of normal aging”. (p.2)

IMPACT OF AD

• Most common cause of dementia among those 65& older

• Up to 4 million currently have AD• Prevalence doubles every 5 years beyond age

65• Numbers are bound to increase as the

population ages

• A Question: Are there differences in AD risk, incidence & prevalence among various racial/ethnic groups?

• Why? #s of over-65 non-Caucasians is growing rapidly--increase from 16 to 34% by 2050

• African Americans & Hispanic Americans may have higher overall risk of AD

Impact of AD

• Heavy economic burden on society--annual cost of care:– mild AD:$18,408– moderate AD: $30,96– severe AD: $36,132

– Tremendous caregiver burden

• Impact of delaying AD onset: an enormous public health impact

• Fed AD research areas:– causes/risk factors– diagnosis– treatment/caregiving

General AD Progress

• Destruction of cells in hippocampus--failure of short term memory and easy tasks become more difficult

• Attack on cells in cerebral cortex--loss of language skills & judgement-making abilities

• As more & more of the brain becomes involved (atrophies):– Personality changes– Emotional outbursts– Wandering– Agitation– Finally--bedridden, incontinent, helpless &

unresponsive to outside world

Main AD Features: Plaques & Tangles

• Amyloid Plaques– Insoluble deposits of beta-amyloid– portions of neurons– non-nerve cells such as microglia

– Are they a cause, or an effect of AD?

Neurofibrillary tangles

• Primary component: tau proteins, which normally stabilize a cell’s internal support structure by binding and stabilizing microtubules

Types of AD

• Familial AD (FAD)--early onset--only 5-10% of cases

• Sporadic AD--late onset

Brain changes with normal aging

• Some neurons in some regions die--most important to learning don’t

• Some neurons shrink & function less well• Tangles & plaques develop in some regions• Inflammation increases• Oxidative stress increases

• Free radicals--product of normal metabolism• --may be helpful to cells in fighting

infection• --highly reactive• Production of too many is oxidative

stress

Exploration of rel. of AD with other “diseases of aging”

• Possible link between brain infarcts & AD• Blood cholesterol and rate of plaque deposition.• Parallels between AD & other progressive

neurodegenerative disorders--all involve deposits of abnormal proteins in the brain

Can AD be treated?

• FDA has approved 3 meds– 1993: Cognex– 1996: Aricept– 2000: Exelon– Slows symptom advance, but will not stop or reverse

AD– Act by inhibiting acetylcholinesterase (enzyme that

breaks down a key neurontransmitter)

AD Research areas/goals

• Understanding etiology of AD

• Improving early Dx

• Developing drug Tx’s

• Improving support for caregivers