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- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 53. |
- Jaramillo-Jimenez, A, et al.
(författare)
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Association Between Amygdala Volume and Trajectories of Neuropsychiatric Symptoms in Alzheimer's Disease and Dementia With Lewy Bodies
- 2021
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 12, s. 679984-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The amygdala is implicated in psychiatric illness. Even as the amygdala undergoes significant atrophy in mild dementia, amygdala volume is underexplored as a risk factor for neuropsychiatric symptoms (NPS).Objective: To analyze the association between baseline amygdala volume and the longitudinal trajectories of NPS and cognitive decline in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) over 5 years.Methods: Eighty-nine patients with mild dementia were included (AD = 55; DLB = 34). Amygdala volume was segmented from structural magnetic resonance images (sMRI) using a semi-automatic method (Freesurfer 6.0) and normalized by intracranial volumes. The intracranial volume-normalized amygdala was used as a predictor of the Neuropsychiatric Inventory (NPI) total score, ordinal NPI item scores (0 = absence of symptoms, 1–3 = mild symptoms, ≥4 = clinically relevant symptoms), and Mini-Mental State Examination (MMSE) as measured annually over 5 years using gamma, ordinal, and linear mixed-effects models, respectively. The models were adjusted for demographic variables, diagnosis, center of sMRI acquisition, and cognitive performance. Multiple testing-corrected p-values (q-values) are reported.Results: Larger intracranial volume-normalized amygdala was associated with less agitation/aggression (odds ratio (OR) = 0.62 [0.43, 0.90], p = 0.011, q = 0.038) and less MMSE decline per year (fixed effect = 0.70, [0.29, 1.03], p = 0.001, q = 0.010) but more depression (OR = 1.49 [1.09, 2.04], p = 0.013, q = 0.040).Conclusions: Greater amygdala volume in mild dementia is associated with lower odds of developing agitation/aggression, but higher odds of developing depression symptoms during the 5-year study period.
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- McGoohan, K, et al.
(författare)
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A Preliminary Investigation of the Views of People With Parkinson's (With and Without Psychosis) and Caregivers on Participating in Clinical Trials During the Covid-19 Pandemic: An Online Survey
- 2020
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Ingår i: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 11, s. 602480-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The coronavirus pandemic is having a profound impact on non-COVID-19 related research, including the delivery of clinical trials for patients with Parkinson's disease.Objectives: A preliminary investigation to explore the views of Parkinson's disease (PD) patients, with and without experience of psychosis symptoms, and carers on the resumption of clinical research and adaptations to trials in light of COVID-19.Methods: An anonymous self-administered online survey was completed by 30 PD patients and six family members/carers via the Parkinson's UK Research Support Network to explore current perceptions on taking part in PD research and how a planned clinical trial for psychosis in PD may be adapted so participants feel safe.Results: Ninety-one percent of respondents were enthusiastic about the continuation of non-COVID-19 related research as long as certain safety measures were in place. Ninety-four percent stated that they would be happy to complete assessments virtually. However, they noted that care should be taken to ensure that this does not exclude participants, particularly those with more advanced PD who may require assistance using portable electronic devices. Regular and supportive communication from the research team was also seen as important for maintaining the psychological well-being of participants while taking part in the trial.Conclusions: In the era of COVID-19 pandemic, standard approaches will have to be modified and rapid adoption of virtual assessments will be critical for the continuation of clinical research. It is important that alongside the traditional methods, new tools are developed, and older ones validated for virtual assessments, to allow safe and comprehensive assessments vital for ongoing research in people with Parkinson's.
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