Neurodegenerative pathologies associated with behavioral and psychological symptoms of dementia in a community-based autopsy cohort

Acta Neuropathologica Communications

Research

Jing Di¹  Ruth S. Nelson²  Justin M. Barber³  Yuriko Katsumata⁴  David W. Fardo⁴  Erin L. Abner⁵  Gregory A. Jicha⁶  Frederick A. Schmitt⁶  Linda J. Van Eldik⁷  Peter T. Nelson⁸  Donna M. Wilcock⁹ 

[1] Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY, USA;Emory University, Atlanta, GA, USA;Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA;Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA;Department of Biostatistics, University of Kentucky, Lexington, KY, USA;Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA;Department of Epidemiology and Environmental Health, University of Kentucky, Lexington, KY, USA;Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA;Department of Neurology, University of Kentucky, Lexington, KY, USA;Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA;Department of Neuroscience, University of Kentucky, Lexington, KY, USA;Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA;Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY, USA;University of Kentucky, Rm 575 Todd Building, 40536, Lexington, KY, USA;Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA;Department of Physiology, University of Kentucky, Lexington, KY, USA;

关键词: Synuclein;    Tau;    Psychiatric;    Psychosis;    Psychoses;    FTLD;    FTD;    Aphasia;    Tauopathy;    HS-aging;   

DOI  :  10.1186/s40478-023-01576-z

 received in 2023-04-25, accepted in 2023-04-30,  发布年份 2023

来源: Springer

【 摘 要 】

In addition to the memory disorders and global cognitive impairment that accompany neurodegenerative diseases, behavioral and psychological symptoms of dementia (BPSD) commonly impair quality of life and complicate clinical management. To investigate clinical-pathological correlations of BPSD, we analyzed data from autopsied participants from the community-based University of Kentucky Alzheimer’s Disease Research Center longitudinal cohort (n = 368 research volunteers met inclusion criteria, average age at death 85.4 years). Data assessing BPSD were obtained approximately annually, including parameters for agitation, anxiety, apathy, appetite problems, delusions, depression, disinhibition, hallucinations, motor disturbance, and irritability. Each BPSD was scored on a severity scale (0–3) via the Neuropsychiatric Inventory Questionnaire (NPI-Q). Further, Clinical Dementia Rating (CDR)-Global and -Language evaluations (also scored on 0–3 scales) were used to indicate the degree of global cognitive and language impairment. The NPI-Q and CDR ratings were correlated with neuropathology findings at autopsy: Alzheimer’s disease neuropathological changes (ADNC), neocortical and amygdala-only Lewy bodies (LBs), limbic predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC), primary age-related tauopathy (PART), hippocampal sclerosis, and cerebrovascular pathologies. Combinations of pathologies included the quadruple misfolding proteinopathy (QMP) phenotype with co-occurring ADNC, neocortical LBs, and LATE-NC. Statistical models were used to estimate the associations between BPSD subtypes and pathologic patterns. Individuals with severe ADNC (particularly those with Braak NFT stage VI) had more BPSD, and the QMP phenotype was associated with the highest mean number of BPSD symptoms: > 8 different BPSD subtypes per individual. Disinhibition and language problems were common in persons with severe ADNC but were not specific to any pathology. “Pure” LATE-NC was associated with global cognitive impairment, apathy, and motor disturbance, but again, these were not specific associations. In summary, Braak NFT stage VI ADNC was strongly associated with BPSD, but no tested BPSD subtype was a robust indicator of any particular “pure” or mixed pathological combination.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 1

Fig. 3

Fig. 2

Fig. 1

40517_2023_252_Article_IEq50.gif

40517_2023_252_Article_IEq45.gif

40517_2023_252_Article_IEq42.gif