| 1. |
- Jansen, Willemijn J, et al.
(author)
-
Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
-
In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
-
Journal article (peer-reviewed)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 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10 148 women [53.1%]) included, 10 139 (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.
|
|
| 3. |
- Sandberg, Jacob, et al.
(author)
-
Comparing recalled versus experienced symptoms of breathlessness ratings : An ecological assessment study using mobile phone technology
- 2022
-
In: Respirology (Carlton South. Print). - : John Wiley & Sons. - 1323-7799 .- 1440-1843. ; 27:10, s. 874-881
-
Journal article (peer-reviewed)abstract
- Background and objective: Recall of breathlessness is important for clinical care but might differ from the experienced (momentary) symptoms. This study aimed to characterize the relationship between momentary breathlessness ratings and the recall of the experience. It is hypothesized that recall is influenced by the peak (worst) and end (most recent) ratings of momentary breathlessness (peak-end rule). Methods: This study used mobile ecological momentary assessment (mEMA) for assessing breathlessness in daily life through an application installed on participants' mobile phones. Breathlessness ratings (0–10 numerical rating scale) were recorded throughout the day and recalled each night and at the end of the week. Analyses were performed using regular and mixed linear regression. Results: Eighty-four people participated. Their mean age was 64.4 years, 60% were female and 98% had modified Medical Research Council (mMRC) ≥ 1. The mean number of momentary ratings of breathlessness provided was 7.7 ratings/participant/day. Recalled breathlessness was associated with the mean, peak and end values of the day. The mean was most closely associated with the daily recall. Associations were strong for weekly values: peak breathlessness (beta = 0.95, r2 = 0.57); mean (beta = 0.91, r2 = 0.53); and end (beta = 0.67, r2 = 0.48); p < 0.001 for all. Multivariate analysis showed that peak breathlessness had the strongest influence on the breathlessness recalled at the end of the week. Conclusion: Over 1 week, recalled breathlessness is most strongly influenced by the peak breathlessness; over 1 day, it is mean breathlessness that participants most readily recalled. © 2022 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.
|
|
