Abstract
Dementia is a state of cognitive dysfunction which leads to functional decline. It
is a syndrome caused by several medical and neurological causes, but most cases of
dementia are due to “primary dementias.” Primary dementias are neurological diseases
whose manifestations are predominantly cognitive. Most primary dementias are caused
by neurodegenerative proteinopathies where an accumulation of misfolded proteins leads
to neuronal loss, neuroinflammation and glial reaction. Each proteinopathy is characterized
by the type of protein implicated in its pathophysiology. Neurodegenerative dementias
include the most prevalent cause of dementia—Alzheimer's disease—as well as Lewy body
dementia, Parkinson's disease dementia, frontotemporal dementias, and prion diseases.
Vascular dementia, especially small vessel disease, though not a neurodegenerative
condition, is often grouped together with primary dementias. Each type of proteinopathy,
characterized by the location and nature of misfolded protein accumulation, may correspond
to a particular clinical phenotype. The correspondence between pathologies and clinical
phenotypes is not exclusive, and there is a large degree of overlap. Although in the
research setting the clinicopathological construct is on the wane, in the clinic it
is the most practical way of approaching primary dementias. In this article, we introduce
the clinicopathological construct, the understanding of which will form the basis
of the other articles in this volume.
Keywords
primary dementia - clinicopathological - Alzheimer's disease - vascular dementia -
Lewy body disease - frontotemporal dementias - prion disease
