Interest in disorders of later life have grown in proportion with the increase of this population group in many societies. We are accustomed to see age as a confounder, so attempts to pinpoint group difference while adjusting for age effects often result in the removal of differences that may be crucial to understanding the aging process. In addition, age reflects between-subject variation (particularly in cross-sectional studies), as well as within-subject changes over time in repeat measures designs. Both are relevant clinically, as the importance of education or IQ for dementia diagnosis and the gradual development of vascular and cognitive risks in mid-life for accelerated ageing demonstrate. I will try to illustrate these issues with studies from UK Biobank and the EU Lifebrain Consortium, covering concepts such as brain-, cognitive age and -reserve, and the role of the natural history and life-time course of depression in its relation to biomarkers and putative aetiologies.