Unifying concept for Alzheimer's disease, vascular dementia and normal pressure hydrocephalus – a hypothesis

Abstract

The three common forms of dementias in the elderly include Alzheimer's disease (AD), vascular dementia (VD) and normal pressure hydrocephalus (NPH). These disorders are distinguished by their specific pathological features. However, overlapping clinical and imaging features in a given case are not too uncommon. Based on alterations in CSF dynamics study, a unifying concept in the pathogenesis of AD and NPH has been proposed recently which may have therapeutic implications. Altered CSF dynamics by affecting the absorptive process may lead to hydrocephalic change. This may also affect clearance of amyloid protein leading to increased amyloid deposition in brain parenchyma resulting in AD pathology. Hence it is likely that a subgroup of patients may have an AD-NPH syndrome who may be benefitted by CSF drainage procedure. The present author attempts to extend this concept to hypothesise a unifying concept to explain the pathophysiology of all the three disorders which may explain overlapping features observed clinically and in neuroimaging studies. It is surmised that altered CSF dynamics and hypoperfusion from vascular disease may be interlinked. The defective clearance of amyloid may also lead to amyloid angiopathy perpetuating hypoperfusion. Hypoperfusion may also affect formation as well as absorption of CSF altering clearance of amyloid and promoting vascular and parenchymal deposition. Thus the pathologies of AD, VaD and NPH get interrelated.