Vascular Risk Factors Promote Conversion from Mild Cognitive

Impairment to Alzheimer disease

Jackson Wang, PGY-3

Clinical Vignette

• A 75 y.o woman with PMH HTN, DM presents to your K6 clinic with increasing forgetfulness for the past few months. She has been noticing difficulty remembering certain important appointments and dates. She had difficulty recalling what she had for dinner last night and also recent scores of her favorite baseball game. Patient lives independently and is able to perform all her IADL and ADL. – On exam, she scored normal on GDS, no neurological deficit except

some decreased proprioception in the lower extremities. She did well on MMSE except for short term recall.

What is your diagnosis?

MCI vs. Dementia

• Similarities and Differences?– Age • Usually affects population 65 years or older

– Functional status and executive function

• Course of progression around 10% per year• 8th leading cause of death in US (cannot be

prevented?) • Financial burden

QUOTE

• “Only effective treatment -- or prevention -- can reduce health care costs by preventing millions of boomers from living an average of 10 years with dementia and tripling costs from up to $200 billion to as much as $600 billion a year.” – Dr. George Bartzokis is a professor of psychiatry at the UCLA Semel Institute for Neuroscience

and Human Behavior and a member of the UCLA Brain Research Institute and the UCLA Laboratory of Neuro Imaging

Goals for the Study

• Primary Endpoint– Investigate the effect of VRF and their treatment

on the conversion of MCI to AD

Methods and Design• Observation study conducted between Jan

2004 to Dec 2009 involving 10 local communities within the city of Chongqing, China

• Inclusion/exclusion criteria

26841 eligible

18683 screened

837 with MCI enrolled

638 completed, 352 in MCI vs. 268 in AD

3496 N/A, 4302

declined

17846 excluded

NOVRF

VRF

NO TX

FEW TX

ALLTX

MMSE/AD= I + (B)VRF(T)+ C

Function of Time x VRF

MMSE

TIME

VRF

NO VRF

Discussion• Primary endpoint reached– VRF associated with increased risk of incident for

AD – Treatment group showed reduced risk

• Mechanisms– Unclear • Possible CV related? • Metabolism of B-amyloid ?

Uncertainties • Confounders?– Age and Time

• Power of the study • Treatment targets? Severity of VRF?• Long term f/u ?• Unexplained pathophysiology (increase in VRF

increased risk of MCI, therefore affecting AD, or MCI ->AD or perhaps lower the threshold)?

Questions for the Audience

• What are some possible confounders in this observational study?

• Assuming these results are valid, what do you interpret them to mean, and will that change the way you practice?

THANK YOU

• Special thanks to Dr. Acharya, Dr. Desai, and Dr. Nelson, Ingeborg and Hong.