Cognition at Each Stage of Lewy Body Disease with Co-occurring Alzheimer’s Disease Pathology1

Abstract

Background: Alzheimer’s disease neuropathologic change (ADNC) may contribute to dementia in patients with Lewy body disease (LBD) pathology. Objective: To examine how co-occurring ADNC impacts domain specific cognitive impairments at each pathologic stage (brainstem, limbic, cerebral cortical) of LBD. Methods: 2,433 participants with antemortem longitudinal neuropsychological assessment and postmortem neuropathological assessment from the National Alzheimer’s Coordinating Center’s Uniform Data Set were characterized based on the evaluation of ADNC and LBD. Longitudinal mixed-models were used to derive measures of cumulative cognitive deficit for each cognitive domain at each pathologic stage of LBD (brainstem, limbic, and cerebral cortical). Results: 111 participants with a pathologic diagnosis of LBD, 741 participants with combined LBD and ADNC, 1,357 participants with ADNC only, and 224 with no pathology (healthy controls) were included in the analyses. In the executive/visuospatial domain, combined LBD and ADNC showed worse deficits than LBD only when Lewy bodies were confined to the brainstem, but no difference when Lewy bodies extended to the limbic or cerebral cortical regions. The cerebral cortical LBD only group exhibited greater executive/visuospatial deficits than the ADNC only group. By contrast, the ADNC only group and the combined pathology group both demonstrated significantly greater cumulative memory deficits relative to Lewy body disease only, regardless of stage. Conclusion: The impact of co-occurring ADNC on antemortem cumulative cognitive deficits varies not only by domain but also on the pathological stage of Lewy bodies. Our findings stress the cognitive impact of different patterns of neuropathological progression in Lewy body diseases.

Differential Effects of Tau Stage, Lewy Body Pathology, and Substantia Nigra Degeneration on18F-FDG PET Patterns in Clinical Alzheimer Disease

“…S1) were comparable between pure-AD and AD-LB. Previous studies have similarly suggested that co-morbid LB pathology exacerbates AD-typical cognitive deficits but does not necessarily produce a mixed clinical phenotype (7,13,14), while others did observe more DLB symptomatology in AD-LB cases (8)(9)(10)(11)(12)39). These differences may be explained by different clinico-pathologic definitions of the AD-LB groups, as some autopsy studies define the different pathology groups based solely on neuropathologic criteria (8,39), while others also restrict their samples to a particular clinical phenotype as in our study (6,13,20,23).…”

“…Although AD and DLB have unique neuropathological profiles, up to 60% of clinical AD and DLB patients present with neuropathological findings of both diseases (5,6). Concomitant LB pathology in clinical AD has been associated with faster cognitive decline (7)(8)(9), younger age at death (8), and more DLB-like clinical features (9)(10)(11)(12), although this could not be confirmed by others (7,13,14). In the era of disease-modifying therapies, these patients may benefit less from amyloid-lowering therapies (15), whereas they may potentially show a better response to cholinesterase inhibitors (16).…”

Diagnosis and Treatment of Cognitive and Neuropsychiatric Symptoms in Parkinson Disease and Dementia With Lewy Bodies

“…Confrontation naming can be assessed using physical objects or line drawings of objects of varying frequency as visual stimuli, such as in the Boston Naming Test. Episodic memory loss and deficits in confrontation naming are linked to temporal lobe functioning, and in PDD/DLB is associated with underlying mixed AD tau pathology 61,62 . Thus, the presence of significant levels of AD neuropathology in Lewy body disorders may influence the clinical expression of dementia.…”

“…Episodic memory loss and deficits in confrontation naming are linked to temporal lobe functioning, and in PDD/DLB is associated with underlying mixed AD tau pathology. 61,62 Thus, the presence of significant levels of AD neuropathology in Lewy body disorders may influence the clinical expression of dementia.…”

The Effects of Dietary Interventions on Brain Aging and Neurological Diseases

“…Mixed dementia in which neuropathologies overlap is common, and different diseases may also have related characteristics. For instance, AD pathology is present in 10–59% of patients with LBD, with synergizing effects that may act on distinct cognitive domains [ 4 ]. Another example is found in PD and LBD, distinct disorders that both involve the aggregation of lewy bodies in the brain made up of α-synuclein [ 5 ].…”