Neuropsychiatric Features of Frontal Lobe Dysfunction in Autopsy-Confirmed Patients with Lewy Bodies and “Pure” Alzheimer Disease

Abstract

Objective To compare patients with autopsy-confirmed Alzheimer’s disease (AD, #14) and Dementia with Lewy bodies (DLB) on the frequency of behaviors related to frontal systems dysfunction and the association of these behaviors with dementia severity. Design Cross-sectional survey of longitudinal cohort. Setting University Alzheimer’s disease research center. Participants Volunteer sample of 19 DLB and 38 AD participants with autopsy-confirmed diagnoses, similar in age (DLB: 77.3, AD: 77.5), education (15.2, 14.7), and Mini-Mental State Examination (MMSE) score (20.6, 20.5), with impairment ranging from mild deficits to moderate dementia. Measurements The Frontal Systems Behavior Scale (FrSBe)-Family Rating Form assessing patient apathy, disinhibition, and executive dysfunction by a knowledgeable informant. Results A two-way analysis of variance with the FrSBe total as the dependent variable revealed a significant MMSE by diagnosis interaction (F(1,53)=9.34, p=.004). Mean FrSBe total for AD patients showed significant impairment across the range of dementia severity, while it was relatively preserved for DLB patients in early stage of disease. The interaction term showed the same pattern for the executive dysfunction (F(1,53)=7.62, p=.008), disinhibition (F(1,53)=4.90, p=.031), and apathy (F(1,53)=9.77, p=.003) subscales. Conclusions While frontal behavioral symptoms in AD patients were present regardless of stage of dementia, DLB patients showed significant frontal dysfunction only in later stages. Results suggest that frontal subcortical circuits associated with behaviors assessed by the FrSBe are affected early in AD but not until later stages in DLB. Assessing specific behaviors related to frontal systems, coupled with stage of cognitive decline, may aid in clinical differentiation of AD and DLB.

Update on Dementia with Lewy Bodies

“…Patients with DLB generally have early, prominent deficits on tests of executive functions (e.g., judgment, organization, planning) relative to patients with AD [15, 16], although, this is not always the case [17]. Recent work suggests that frontal subcortical circuits associated with executive dysfunction, disinhibition, and apathy are actually affected early in AD but not until later stages in DLB [17].…”

“…Recent work suggests that frontal subcortical circuits associated with executive dysfunction, disinhibition, and apathy are actually affected early in AD but not until later stages in DLB [17]. Simple attention can be normal in both DLB and AD (as assessed by digit span tasks); however, group differences (DLB > AD) more often emerge on complex attentional tasks, such as those requiring mental control, visual search and set shifting, and visual selective attention [18].…”

Neuropsychiatric Symptoms in Alzheimer Disease, Vascular Dementia, and Mixed Dementia

“…Frontal lobe injury in particular is associated with personality changes and the development of NPS [14,15], including disinhibition and apathy [16]. Apathy has been related to anterior cingulate atrophy [17,18].…”

Accounting for functional loss in Alzheimer's disease and dementia with Lewy bodies: Beyond cognition

“…Several studies suggest that psychosis and depression are more common in DLB than in AD [24, 25]. Apathy and disinhibition, both thought to be mediated by frontal systems, may present at a milder level of dementia in AD than in DLB [26]. …”