The importance of longitudinal cohort studies in understanding risk and protective factors for dementia

Abstract

As readers of this journal will be well aware, the last decade has witnessed a transformation in our understanding of the pathophysiology of dementias, perhaps most especially Alzheimer's disease (AD), as well as a much greater understanding of the undoubtedly complex and multifactorial etiology of the AD process. An increasing number of genetic risk and protective factors have been identified, as well as potentially modifiable risk factors, including vascular factors such as hypertension and exercise, education, lifestyle, and nutrition. In parallel, there has been considerable progress in developing and validating biomarkers for AD and other dementias. These have transformed the landscape for research, allowing in vivo patient stratification according to pathology, and now have fed through to inform our clinical diagnostic criteria. Particular examples include imaging biomarkers such as characteristic atrophy patterns on magnetic resonance imaging (MRI), hypoperfusion/hypometabolism on functional brain imaging, increased cortical amyloid uptake on positron emission tomography (PET), as well as CSF alterations in tau and β-amyloid. Several changes in blood have also been shown, including altered inflammatory markers, which may prove to be important biomarkers in the future.