Lacunes in — the Knowledge of — Vascular Dementia

A recent article on clinical-neuropathological correlations in multi-infarct dementia (MID) questions many assertions regarding the frequency and importance of MID [1]. Aiming to define neuropathological criteria for the diagnosis of MID, the authors searched for cases among the files of ten neuropathology departments in major medical centers involved in the CERAD program. After reviewing autopsies from patients with dementia, neuropathologists from four centers could not find even a single case in which cerebral infarction was “the only explanation of the clinical dementia.” The other six neuropathologists detected six valid cases … among 1929 patients with dementia! Even considering overly strict inclusion criteria and the biased interest of the ten centers in Alzheimer’s disease (AD), the quick conclusion is that “multi-infarct dementia unaccompanied by neuropathological evidence of Alzheimer’s disease is rare.” However, a second careful analysis of these unexpected numbers raises a number of questions regarding the concept of MID or vascular dementia (VD). At the pathological level the absence of commonly agreed upon diagnostic criteria is of concern. Lack of agreement may lead to a biased underestimation of the contribution of vascular lesions to cognitive impairment and dementia. The presence of senile plaques with or without neurofibrillary tangles in the brain of a patient with dementia and vascular lesions automatically excludes a diagnosis of VD in favor of AD. Paradoxically, when similar changes are present in a cognitively intact subject, establishing a diagnosis of AD may be too bold. This margin of uncertainty should be kept also for patients with vascular lesions, so that their relevance in the pathophysiology of cognitive decline and dementia can be investigated and clarified. Even when a case is labelled as mixed dementia, the responsibility for the clinical picture is heavily weighted towards the plausible degenerative rather than the vascular component. Observation, quantification and collection of neuropathological data may be laborious, but it is the interpretation and transformation of anatomical findings into clinical correlates that entails the highest difficulty and demands scientific rigor, inspiration, and open-mindedness. One of the most important sources of confusion and misunderstanding probably resides in the way clinical information is collected and classified.