The severity of neuropsychiatric symptoms is higher in early-onset than late-onset Alzheimer’s Disease.

Dec 6, 2021

Contributor: Neus Falgàs,Isabel E Allen,Salvatore Spina,Harli Grant,Stefanie D Piña Escudero,Jennifer Merrilees,Rosalie Gearhart,Howard J Rosen,Joel H Kramer,William W Seeley,Thomas C Neylan,Bruce L Miller,Gil D Rabinovici,Lea T Grinberg,Christine M Walsh

The severity of neuropsychiatric symptoms is higher in early-onset than late-onset Alzheimer’s Disease.

The faster rates of cognitive decline and predominance of atypical forms in early-onset Alzheimer’s Disease (EOAD) suggest that neuropsychiatric symptoms could be different in EOAD compared to late-onset AD (LOAD), however, prior studies based on non-biomarker diagnosed cohorts show discordant results. Our goal was to determine the profile of neuropsychiatric symptoms in EOAD and LOAD, in a cohort with biomarker/postmortem-confirmed diagnoses. Additionally, we explored the contribution of co-pathologies.
We evaluated 219 participants (135 EOAD, 84 LOAD) meeting NIA-AA criteria for AD (115 amyloid-PET/CSF biomarkers, 104 postmortem diagnosis) at UCSF. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was assessed at baseline and during follow-up. NPI-Q mean comparisons and regression models adjusting by cognitive (MMSE) and functional status (CDR SoB) were performed to determine the effect of EOAD/LOAD and amnestic/non-amnestic diagnosis on NPI-Q. Regression models assessing the effect of co-pathologies on NPI-Q were performed.
At baseline, the NPI-Q scores were higher in EOAD compared to LOAD (p<0.05). Longitudinally, regression models showed a significant effect of diagnosis, where EOAD had higher NPI-Q total, anxiety, motor disturbances and nighttime behaviors scores (p<0.05). No differences between amnestics/non-amnestics were found. Argyrophilic grain disease (AGD) co-pathology predicted higher severity of NPI-Q scores in LOAD.
Anxiety, nighttime behaviors and motor disturbances are more severe in EOAD than LOAD across the disease course. The differential patterns of neuropsychiatric symptoms observed between EOAD/LOAD could suggest a pattern of selective vulnerability extending to the brain’s subcortical structures. Further, co-pathologies such as AGD in LOAD may also play a role in increasing neuropsychiatric symptoms.

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About The Expert

Neus Falgàs

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Global Brain Health Institute, University of California, San Francisco, CA, USA.

Alzheimer’s disease and other cognitive disorders Unit, Hospital Clínic de Barcelona. Barcelona, Catalonia, Spain.

Isabel E Allen

Department of Epidemiology and Biostatistics, University of California, San Francisco.

Salvatore Spina

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Harli Grant

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Stefanie D Piña Escudero

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Global Brain Health Institute, University of California, San Francisco, CA, USA.

Jennifer Merrilees

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Rosalie Gearhart

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Howard J Rosen

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Global Brain Health Institute, University of California, San Francisco, CA, USA.

Joel H Kramer

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Global Brain Health Institute, University of California, San Francisco, CA, USA.

William W Seeley

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Thomas C Neylan

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Department of Psychiatry, University of California, San Francisco, CA, USA.

Bruce L Miller

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Gil D Rabinovici

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Global Brain Health Institute, University of California, San Francisco, CA, USA.

Lea T Grinberg

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Global Brain Health Institute, University of California, San Francisco, CA, USA.

Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil.

Department of Pathology, University of California, San Francisco, CA, USA.

Christine M Walsh

Department of Neurology, Weill Institute for Neurosciences, University of California, Memory & Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

References

PubMed