Journal of Alzheimer's Disease - Volume 90, issue 3

Authors: Shen, Jialun | Li, Meng | Long, Cheng | Yang, Li | Jiang, Jinxiang

Article Type: Research Article

Abstract: Background: Olfactory decline is an indicator of early-stage Alzheimer’s disease (AD). Although the anterior piriform cortex (aPC) is an important brain area involved in processing olfactory input, little is known about how its neuronal activity is affected in early-stage AD. Objective: To elucidate whether odor-induced electrophysiological responses are altered in the aPC of 3-5-month-old APP/PS1 mice. Methods: Using head-fixed multi-channel recording techniques in APP/PS1 AD mouse model to uncover potential aberrance of the aPC neuronal firing and local field potential (LFP) in response to vanillin. Results: We show that the firing rate of aPC …neurons evoked by vanillin is significantly reduced in conscious APP/PS1 mice. LFP analysis demonstrates reduced low- and high-gamma (γ low, γ high ) oscillations during both the baseline and odor stimulation periods in APP/PS1 mice. Moreover, according to spike-field coherence (SFC) analysis, APP/PS1 mice show decreased coherence between odor-evoked spikes and γ low rhythms, while the coherence with γ high rhythms and the Δ SFC of the oscillations is unaffected. Furthermore, APP/PS1 mice show reduced phase-locking strength in the baseline period, such that there is no difference between baseline and odor-stimulation conditions. This contrasts markedly with wild type mice, where phase-locking strength decreases on stimulation. Conclusion: The abnormalities in both the neuronal and oscillatory activities of the aPC may serve as electrophysiological indicators of underlying olfactory decline in early AD. Show more

Keywords: Alzheimer’s disease, anterior piriform cortex, APP/PS1, firing rate, head-fixed recording, olfaction, oscillations

DOI: 10.3233/JAD-220694

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 1277-1289, 2022

Authors: Ritchie, Marina | Witbracht, Megan | Nuño, Michelle M. | Hoang, Dan | Gillen, Daniel L. | Grill, Joshua D.

Article Type: Research Article

Abstract: Background: Clinical trials now test promising therapies in the preclinical stages of Alzheimer’s disease (AD). Participant willingness to enroll in different types of preclinical AD trials is understudied and whether the FDA approval of aducanumab affected these attitudes is unknown. Objective: To evaluate preferences toward three preclinical AD trial scenarios and whether the FDA approval of aducanumab changed willingness to participate among potential trial participants. Methods: Through an electronic survey, we asked enrollees in a recruitment registry age 50-79 to rate their willingness (using a 6-point Likert scale) to enroll in three hypothetical preclinical AD trial …scenarios: an in-clinic infused monoclonal antibody intervention, a home-infused monoclonal antibody intervention, and an oral BACE inhibitor intervention. We administered the survey before and after the FDA approval of aducanumab. We used a generalized estimating equation model to assess group differences in preference for the trial scenarios. We used a paired t-test to determine if willingness to participate (using total willingness across three scenarios as the outcome) changed after the FDA decision. Results: At baseline, the mean participant willingness was highest in the in-clinic infusion scenario. There was no significant change in willingness to participate, overall, after the FDA decision. Participants who were independently aware of the FDA’s decision (prior to the second survey) demonstrated reduced willingness to participate; participants unaware of the FDA decision demonstrated no change. Conclusion: Willingness to participate in preclinical AD trials may have been negatively affected by the FDA’s decision to approve aducanumab among those aware of the decision. Show more

Keywords: Aducanumab, Alzheimer’s disease, clinical trial, earned media, recruitment, secondary prevention

DOI: 10.3233/JAD-220801

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 1291-1300, 2022

Authors: Harrison, Krista L. | Garrett, Sarah B. | Halim, Madina | Bernstein Sideman, Alissa | Allison, Theresa A. | Dohan, Daniel | Naasan, Georges | Miller, Bruce L. | Smith, Alexander K. | Ritchie, Christine S.

Article Type: Research Article

Abstract: Background: In the United States, dementia specialty centers affiliated with centers of excellence for research hold promise as locations to develop innovative, holistic care in care systems otherwise siloed by discipline or payer. Objective: We conducted foundational research to inform development of patient-and family-centered palliative care interventions for dementia specialty centers. Methods: We interviewed persons living with dementia (PLWD), current, and former care partners (CP) recruited from a specialty dementia clinic and purposively selected for variation across disease syndrome and stage. A framework method of thematic analysis included coding, analytic matrices, and pattern mapping. …Results: 40 participants included 9 PLWD, 16 current CPs, and 15 former CPs of decedents; 48% impacted by Alzheimer’s disease dementia. While help from family, support groups and adult day centers, paid caregiving, and sensitive clinical care were invaluable to PLWD, CPs, or both, these supports were insufficient to navigate the extensive challenges. Disease-oriented sources of distress included symptoms, functional impairment and falls, uncertainty and loss, and inaccessible care. Social and relational challenges included constrained personal and professional opportunities. The obligation and toll of giving or receiving caregiving were challenging. Clinical care challenges for PLWD and/or CPs included care fragmentation, insufficient guidance to inform planning and need for expert interdisciplinary clinical care at home. Conclusion: Findings highlight the breadth and gravity of gaps, which surpass the disciplinary focus of either behavioral neurology or palliative care alone. Results can inform the development of novel interventions to add principles of geriatrics and neuropalliative care to dementia care. Show more

Keywords: Caregivers, dementia, geriatrics, hospice care, neuropalliative care, palliative care, quality of life

DOI: 10.3233/JAD-220536

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 1301-1320, 2022

Authors: Fonseka, Lochanie | Wang, David | Ryan, Brigid | Cheung, Gary | Ma’u, Etuini

Article Type: Research Article

Abstract: Background: There is limited epidemiological research on the incidence of young onset dementia (YOD). Estimates of YOD incidence in New Zealand are extrapolated from international studies that do not reflect New Zealand’s population and ethnic diversity. Objective: To determine the incidence of YOD in the geographical area served by the Waikato District Health Board Methods: All new inpatient and outpatient in the age range 30–64 years with a documented diagnosis of dementia at Waikato Hospital between 1 January 2014 –31 December 2016 were identified. Incidence rates were calculated by 5-year age-band, sex, and ethnicity. …Results: 64 incident cases of YOD were included. Incidence rates for all cause YOD were 13.3 (95% CI 10.3–17.0) and 22.7 (95% CI 17.5–29.1) per 100,000 person-years in the age range 30–64 years and 45–64 years respectively. The incidence rate in Māori (20.0, 95% CI 11.4–32.4) was higher compared to non-Māori (12.0, 95% CI 8.9–15.9), but this difference was not statistically significant (p  = 0.09). Conclusion: The incidence of YOD in this study is similar to global estimates. Incidence may be higher in Māori compared to non-Māori, highlighting the need for culturally appropriate approaches to dementia prevention, intervention, and care. Show more

Keywords: Epidemiology, incidence, New Zealand, young onset dementia

DOI: 10.3233/JAD-220802

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 1321-1327, 2022

Authors: Shi, Xiaolei | Zhou, Nan | Sun, Bin | Wu, Yongshun | Hu, Yachun | Ning, Yuping

Article Type: Research Article

Abstract: Background: Reduced signal on fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valid proxy for neurodegeneration in Alzheimer’s disease (AD). Perivascular space (PVS) is believed to be associated with AD pathology and cognitive decline. Objective: This study aimed to investigate the associations of PVS with FDG-PET and cognitive performance based on the burden of amyloid pathology. Methods: We used magnetic resonance imaging (MRI) data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). MRI-visible PVS in basal ganglia (BG) and centrum semi-oval (CSO) were visually classified as: none/mild, moderate or frequent/severe. The association of PVS with brain FDG-PET was explored …based on the burden of amyloid pathology, where a cerebrospinal fluid (CSF) t-tau/Aβ42 with the ratio≥0.27 was defined as high amyloid pathology. Moreover, the relationships between PVS and cognitive performance variables (ADNI-MEM and ADNI-EF) were studied. Results: For participants with higher tau/Aβ42 ratio, CSO-PVS severity was independently associated with lower FDG-PET. There were significant interaction effects between moderate or frequent/severe CSO-PVS and time on FDG decline in people with high amyloid pathology. The interaction between CSO-PVS and time (follow-up) was consistently associated with ADNI-MEM and ADNI-EF decline in individuals with high amyloid pathology. Conclusion: The study established the differential utility of PVS in BG and CSO for predicting brain metabolism. These findings suggest that CSO-PVS serves as a contributing factor to brain metabolism and cognitive decline associated with amyloid pathology. Show more

Keywords: Amyloid, basal ganglia, centrum semi-oval, metabolism, perivascular space

DOI: 10.3233/JAD-220426

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 1329-1337, 2022

Authors: Berger, Miles | Cooter, Mary | Roesler, Alexander S. | Chunga, Stacey | Park, John | Modliszewski, Jennifer L. | VanDusen, Keith W. | Thompson, J. Will | Moseley, Arthur | Devinney, Michael J. | Smani, Shayan | Hall, Ashley | Cai, Victor | Browndyke, Jeffrey N. | Lutz, Michael W. | Corcoran, David L.

Article Type: Correction

DOI: 10.3233/JAD-229018

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 1339-1340, 2022