1-3 The impetus to distinguish between the two types of dementia, Alzheimer’s disease (AD) and the entity initially termed multi-infarct dementia (MID) and later on vascular dementia (VD), had both scientific and pragmatic underpinning (the change from MID to VD was necessary, since the term MID did not cover the full range of cerebrovascular pathology). Reasoning for differentiation between AD and VD The scientific reasoning for the distinction between AD and VD was based on evidence collected Inhibitors,research,lifescience,medical during the 1970s

and 1980s, leading investigators to conclude that a vascular pathology was not the main underlying pathology for most demented individuals. First, many demented individuals had diffuse amyloid deposits or plaques and neurofibrillary tangles as the predominant postmortem pathology, with no or minimal vascular pathology or infarcts.1 Second, in some of these demented individuals with predominantly plaques and tangles, the counts of the cholinergic cells in the nucleus basalis of Meynert were diminished, as was the Inhibitors,research,lifescience,medical activity of the neurotransmitter acetylcholine in the cortex.4-8 Taken together, these findings convinced researchers that AD was a unique and discrete disease entity with well-defined

histology (GS-1101 solubility dmso presence of plaques and tangles) and neurochemistry (cholinergic Inhibitors,research,lifescience,medical deficiency), thus leading a sustainable hypothesis regarding its pathophysiology.9 On the other hand, as VD was conceptualized as a “matter of strokes large and small,”10 the Hachinski Ischemic Score was developed in order to differentiate it from AD. The scale is based on presence of risk factors for VD, such as hypertension, history of strokes, and evidence of associated atherosclerosis, and on the clinical characteristics of strokes (abrupt, onset, stepwise deterioration, fluctuating Inhibitors,research,lifescience,medical course, focal neurological signs, and symptoms). Additional support Inhibitors,research,lifescience,medical for a vascular origin of dementia according to the Hachinski Ischemic Score were the presence of nocturnal confusion, relative preservation of personality, depression, somatic complaints, and emotional incontinence.

The items making up the scale reflect the conceptualization of vascular risk factors as exclusively associated with brain infarcts, which, in turn, are responsible for the clinical manifestations of MID (and later VD). The pragmatic reasoning for the distinction between AD and VD was aminophylline the assumption in the late 1970s and early 1980s that specific treatments for AD exist, This assumption was based on the apparent finding that increasing cholinergic activity by pharmacological manipulations could improve symptoms in demented individuals.11-13 In order to increase the likelihood of demonstrating an effect for drugs enhancing cholinergic activities, it was believed to be essential to identify patients affected by a cholinergic deficit, ic, AD patients, and distinguish them from VD patients, who were not expected to benefit from cholinergic enhancement.