Adult Changes in Thought Study: Dementia is an Individually Varying Convergent Syndrome with Prevalent Clinically Silent Diseases that may be Modified by Some Commonly Used Therapeutics

The Adult Changes in Thought (ACT) study is a longitudinal population-based prospective cohort study of brain aging and incident dementia in the Seattle metropolitan area. Observational studies using autopsies from ACT indicate that dementia is a convergent syndrome that commonly derives from Alzheimer’s disease (AD), microvascular brain injury (mVBI), and Lewy body disease (LBD), and that these diseases have prevalent subclinical forms that also are commonly co-morbid. The existence of subclinical diseases highlights potential opportunities to intervene before the development of clinically apparent impairments. Our observations suggest that some such interventions already may exist to suppress processes of AD (statin therapy) or mVBI (treatment of hypertension). Reduced burden of LBD is associated with cigarette smoking; although smoking is not recommended as an intervention, these exposure data may provide clues to alternative neuroprotective mechanisms. Self reported anti-oxidant supplementation was without apparent effect in this cohort on indices of AD, mVBI, or LBD. Continued observational studies of brain aging will provide further insight into the convergent complexity of the dementia syndrome and its subclinical forms as well as highlight potential interventions that will require validation in clinical trials.