Different apathy clinical profile and neural correlates in behavioral variant frontotemporal dementia and Alzheimer's disease

Abstract

Objectives: Apathy is one of the most common and disabling syndromes of dementia. Clinical apathy expression and neuroanatomical basis of apathy seem to differ between behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD), although evidence is scarce and poorly understood. Our main purposes were to compare the clinical apathy profile from patients with bvFTD and AD and analyze the relationship between apathy and brain metabolism measured using positron emission tomography imaging with 18 F fluorodeoxyglucose (FDG-PET). Methods: Forty-two bvFTD, 42 AD, and 30 healthy volunteers without cognitive or behavioral complaints were included. Apathy was defined using Robert's 2009 diagnostic criteria, and specific apathy characteristics were assessed with the Lille Apathy Rating Scale. All participants underwent FDG-PET brain scan to provide data for voxel-based morphometric analysis. Results: Multivariate analysis showed that subjects affected by bvFTD displayed greater impairment of emotional apathy and self-awareness in comparison with AD sample. Additionally, FDG-PET imaging analyses revealed that apathy was associated with different neuroanatomical substrates in each dementia group: left lateral prefrontal, medial frontal/anterior cingulate, lateral orbitofrontal and anterior insular cortices in bvFTD, and right anterior cingulate in AD. Conclusions: These results support that apathy is a complex syndrome, with different clinical expressions across different pathological conditions. Those differences in qualitative aspects of apathy seem to be associated with differences in the damage sites, as shown by our FDG-PET imaging analysis. Our findings provide a better knowledge about pathophysiology of apathy in dementia, which could have practical implications for therapeutic management.

A Novel Assessment and Profiling of Multidimensional Apathy in Alzheimer’s Disease

“…Additionally, deficits of emotional processing, social awareness [54] and emotional decision-making [55] have also been observed in AD, but may not be a defining deficit of the disease. More recent research using the LARS showed that people with AD showed less apathy in the "emotional" dimension and the "self-awareness" dimension when compared to people with behavioral variant frontotemporal dementia [56] and supports our findings of Emotional apathy as not a hallmark of AD. While the Dimensional Apathy framework attempts to incorporate observable behavioral and neuropsychological deficits, similar to Levy and Dubois [27,28], how apathy subtypes map on to cognitive functioning is yet to be determined.…”

Apathy in Alzheimer's disease

“…Another FDG-PET study analysing a subsample of the ADNI dataset ( N = 95 AD; 203 MCI and 104 controls) reported a cross-sectional and longitudinal association between posterior cingulate hypometabolism and higher apathy scores. There was no relation between apathy and hypometabolism in the inferior temporal lobe or ACC [ 33 ], as was reported in the previously mentioned studies [ 30 , 32• ]. This finding must be interpreted with caution, because the researchers did not differentiate between healthy controls, MCI, or mild AD in their analysis.…”

“…One recent investigation used positron emission tomography with 18F fluorodeoxyglucose (FDG-PET) to examine how brain metabolism is associated with apathy in AD cases [ 32 • ]. The researchers reported a relationship between apathy and right ACC hypometabolism in AD.…”

Functional Connectivity Alterations of the Temporal Lobe and Hippocampus in Semantic Dementia and Alzheimer’s Disease

“…6. The functional role of the involved regions suggests an association with a frequently observed clinical presentation of AD and SD characterized by apathy and agitation, associated with the right orbitofrontal cortex [72,73], and impairments in social behavior related to the right anterior temporal lobe [74]. According to Olson et al [75], social knowledge is part of semantic memory and involves memory about people including biographical information.…”