Frontal-Subcortical Dementias

Whereas Alzheimer’s disease (AD), the most common form of dementing illness, is typically characterized by initial deterioration within limbic and reticular structures (hippocampal/ entorhinal regions and basal forebrain cholinergic systems) with later involvement of the neocortex (particularly in temporal and parietal cortices), a second and diverse group of dementias do not initially present with a primary amnestic syndrome or initial pathology in regions affected in AD. Instead, these conditions are characterized by variable but primary changes in personality, working memory, attentional and executive function, and affective regulation and behavioral organization. These conditions constitute a large and heterogeneous group of conditions termed frontal-subcortical dementias (Bonelli & Cummings, 2008; Stewart, 2006; Bak, Crawford, Berrios, & Hodges, 2010). Unlike most typical presentations of AD, this group of dementias is typically characterized by primary deterioration in the prefrontal cortices, in various regions of the basal ganglia, within the white matter tracts connecting these regions, or in other associated subcortical systems in a functional partnership with prefrontal systems. As a result, these dementias can have very diverse etiologies, with clinical phenotypes mapping onto any number of etiologic substrates, making correlation of clinical syndrome and underlying etiology often difficult and challenging (Manes et al., 2010; Chow et al., 2008). Any disease process that affects the frontal lobes and/or their connections to subcortical structures, including basal ganglia, cerebellum, thalamus, or reticular activating systems, can generate a frontal system dementia phenotype. Additional complexities emerge from a host of low-grade encephalopathic conditions (see Chapter 19) that produce a subsyndromal presentation of confusional states that can closely mimic several behavioral and cognitive phenotypes of these frontal-subcortical dementias, with varying degrees of apathy versus behavioral and affective disinhibition along with cognitive disorganization, but shy of a full-blown delirium. These wide-rangingmild encephalopathic conditions can also mimic the neurocognitive phenotype of these frontal-subcortical dementias. Because of this enormous diversity of etiologies, the differential diagnosis of any condition presenting with the cognitive and behavioral phenotype of a frontal-subcortical dementia is particularly challenging to the clinician, even if one is confident that the etiology is neurodegenerative (Duff et al., 2010) and not due to a low-grade reversible encephalopathy. Thus, this group of frontalsubcortical dementias has highly diverse neuropathologies associated with a group of common clinical syndromes; diverse treatment implications, depending on neuropsychological phenotype and behavioral issues; as well as underlying etiology.