In 1991 I established a clinical research unit (UBC Alzheimer Clinical Trials Program) to conduct research on geriatric cognitive disorders, Alzheimer’s disease (AD) and other dementias. This unit has grown to its present size and has become a leading international centre for clinical cognitive research.
a) Epidemiological and Longitudinal Research Studies: I have been lead or co-lead Investigator on several large scale national epidemiological studies (the ACCORD and CIVIC studies), and been co-investigator on the Canadian Study of Health and Aging (CSHA) a study that has received international acclaim being the largest and perhaps most influential of its kind.
b) Experimental Therapeutics and Clinical Trials: I have been the Principal Investigator on a number international randomised clinical trials of experimental therapeutics for AD as well as its precursor state Mild Cognitive Impairment (MCI). I lead an investigator initiated study of the cholinesterase inhibitor (ChEI) in the treatment of moderate to severe AD, a trial that had a very large impact on the field of therapy opening this stage to ChEIs for the first time and establishing the methodology and outcomes needed to investigate this disease stage.
c) Research on Frontotemporal Dementia (FTD): In 2003 we began an investigation of FTD using a large data base in our research unit and identifying a new autosomal dominant form of FTD. This year we successfully identified the gene within this form of dementia (Progranulin-PGRN) as well as the consequence of this genetic abnormality in protein expression. This landmark genetic and proteinopathy discovery will not only explain 25% of the inherited FTDs but it invites an entirely new avenue of investigation in neurodegenerative disease (publication in Nature 2006 Baker et al, Science 2006 Neumann et al ). Rather than producing a toxic gain of function which has been the putative mechanism of injury in AD, ALS and PD this mutation leads to a loss of functional PGRN suggesting a haploinsufficiency mechanism. This research emerged from our well characterized clinical and curated tissue samples. Our CIHR funded research in this area is poised to continue to enjoy unprecedented scientific success and recognition.
d) Development of Biological Markers for Dementia: The core activities of the unit developing well characterized cohorts of patients, carefully followed longitudinally and put together with post mortem tissue findings and DNA banking enables the development of biomarkers to be evaluated from the MCI stage and across the dementias. Unique discoveries in this area have included the identification of p97 (mellanotransferrin) as an AD biomarker, with current focus on proteomic expression patterns.
Honours and Awards:
(a) Awards for Teaching
(b) Awards for Scholarship
(c) Other Awards and Distinctions
(a) Memberships on scholarly societies
(b) Memberships on other societies
(c ) Memberships on Scientific Committees and Boards
(d ) Editorships