Neuropathology of the dementias other than Alzheimer’s

Dementia is due to lesions destroying a large amount of circuits anatomically connected with, or func- tionally related to, the associative areas of the cortex and the limbic structures. Dementia is not only the clinical hallmark of neurodegenerative diseases, most often pro- teinopathies, primarily involving the cerebral cortex, but also a symptom frequently associated to movement disor- ders, or secondary to systemic or neurological, non- degenerative diseases. In the elderly, it is often the conse- quence of the cumulative effect of different diseases. Dementia is the comprehensive symptom of the dementias. As a symptom, dementia is due to lesions involving cortical and subcortical circuits that are related to the associative cortex and to the limbic structures. A critical amount of cir- cuits have to be interrupted to generate dementia. In most Alzheimer patients, dementia can be recognised as soon as neurodegeneration, moved from the mesial temporal struc- tures, has reached the temporal and frontal associative areas (1). Nevertheless, Alzheimer changes, such as α-protein deposits and neurofibrillary tangles, are often observed in the associative areas of the cortex of elderly people still cognitively normal. A relationship between amount of cere- bral lesions and dementia has been roughly calculated in patients with multiple infarct encephalopathy. In this dis- ease, dementia should appear as soon as the total volume of vascular lesions localised in both hemispheric grey struc- tures and white matter reaches the value of 150 ml. A small- er value is found in patients with both vascular and neu- rodegenerative lesions (2). Dementias can be classified according to clinical and neuropathological criteria (3). The temporal relationship of cognitive to motor symptoms, which are variably asso- ciated in these diseases following selective vulnerability of diverse nerve cell populations, may serve to separate primary dementias from associated dementias. The for- mer include such diseases as Alzheimer's disease (AD), frontotemporal degenerations (FTD) and diffuse (cortical) Lewy-body disease (LBD), in which the cognitive decline anticipates the onset of motor symptoms. The opposite sequence occurs in such diseases as Huntington's disease (HD), Parkinson's disease (PD), multiple system atrophy (MSA), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), in which dementia is associated to movement disorders. The temporal profile of symptoms depends on the progression of neurodegenerative changes that follows the most vulnerable anatomical links. In pri- mary dementias, degeneration moves from the mesial tem- poral structures and the frontotemporal cortex, reaching