Dataset Information

Misidentification Subtype of Alzheimer's Disease Psychosis Predicts a Faster Cognitive Decline.

ABSTRACT: The presence of psychosis is associated with a more rapid decline in Alzheimer's disease (AD), but the impact of paranoid (persecutory delusions) and misidentification (misperceptions and/or hallucinations) subtypes of psychosis on the speed of decline in AD is still unclear. We analyzed data on Alzheimer's Disease Neuroimaging Initiative 2 participants with late mild cognitive impairment or AD, and we described individual trajectories of Alzheimer's Disease Assessment Scale-Cognitive Subscale scores using a semimechanistic logistic model with a mixed effects-based approach, which accounted for dropout and adjusted for baseline Mini Mental State Examination scores. The covariate model included psychosis subtypes, age, gender, education, medications, and Apolipoprotein E epsilon 4 (Apo-e ?4 genotype). We found that the Alzheimer's Disease Assessment Scale-Cognitive Subscale rate of increase was doubled in misidentification (?_{r,misid_subtype} = 0.63, P = 0.031) and mixed (both subtypes; ?_{r,mixed_subtype} = 0.70, P = 0.003) when compared with nonpsychotic (or paranoid) patients, suggesting that the misidentification subtype may represent a distinct AD sub-phenotype associated with an accelerated pathological process.

SUBMITTER: D'Antonio F

PROVIDER: S-EPMC6533361 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Misidentification Subtype of Alzheimer's Disease Psychosis Predicts a Faster Cognitive Decline.

D'Antonio Fabrizia F Reeves Suzanne S Sheng Yucheng Y McLachlan Emma E de Lena Carlo C Howard Robert R Bertrand Julie J

CPT: pharmacometrics & systems pharmacology 20190315 5

The presence of psychosis is associated with a more rapid decline in Alzheimer's disease (AD), but the impact of paranoid (persecutory delusions) and misidentification (misperceptions and/or hallucinations) subtypes of psychosis on the speed of decline in AD is still unclear. We analyzed data on Alzheimer's Disease Neuroimaging Initiative 2 participants with late mild cognitive impairment or AD, and we described individual trajectories of Alzheimer's Disease Assessment Scale-Cognitive Subscale s ...[more]

PMID: 30779330

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Project description:For early detection of Alzheimer's disease, it is important to find biomarkers with predictive value for disease progression and clinical manifestations, such as cognitive decline. Individuals can now be profiled based on their biomarker status for Aβ42 (A) or tau (T) deposition and neurodegeneration (N). The aim of this study was to compare the cerebrospinal fluid (CSF) and imaging (PET/MR) biomarkers in each ATN category and to assess their ability to predict longitudinal cognitive decline. A subset of 282 patients, who had had at the same time PET investigations with amyloid-β and tau tracers, CSF sampling, and structural MRI (18% within 13 months), was selected from the ADNI dataset. The participants were grouped by clinical diagnosis at that time: cognitively normal, subjective memory concern, early or late mild cognitive impairment, or AD. Agreement between CSF (amyloid-β-1-42(A), phosphorylated-Tau181(T), total-Tau(N)), and imaging (amyloid-β PET (florbetaben and florbetapir)(A), tau PET (flortaucipir)(T), hippocampal volume (MRI)(N)) positivity in ATN was assessed with Cohen's Kappa. Linear mixed-effects models were used to predict decline in the episodic memory. There was moderate agreement between PET and CSF for A biomarkers (Kappa = 0.39-0.71), while only fair agreement for T biomarkers (Kappa ≤ 0.40, except AD) and discordance for N biomarkers across all groups (Kappa ≤ 0.14) was found. Baseline PET tau predicted longitudinal decline in episodic memory irrespective of CSF p-Tau181 positivity (p ≤ 0.02). Baseline PET tau and amyloid-β predicted decline in episodic memory (p ≤ 0.0001), but isolated PET amyloid-β did not. Isolated PET Tau positivity was only observed in 2 participants (0.71% of the sample). While results for amyloid-β were similar using CSF or imaging, CSF and imaging results for tau and neurodegeneration were not interchangeable. PET tau positivity was superior to CSF p-Tau181 and PET amyloid-β in predicting cognitive decline in the AD continuum within 3 years of follow-up.

Project description:BackgroundAlterations in circadian rhythms are present in the presymptomatic stage of Alzheimer's disease (AD), possibly contributing to its pathogenesis. However, it is unknown whether such alterations are associated with worse outcomes once individuals are diagnosed with symptomatic disease. We aimed to evaluate the association between the circadian rest-activity pattern and AD-related features in patients with mild-moderate AD.MethodsWe assessed the circadian rest-activity pattern of consecutive patients with mild-moderate AD through actigraphy for 14 days. Cerebrospinal fluid was obtained to determine the levels of important pathological markers including amyloid-beta protein (Aβ42), phosphorylated tau (P-tau), total tau (T-tau), and neurofilament light (NF-L). Neuropsychological evaluation was conducted at the beginning of the study and after 12 months of follow-up. Linear regression models were performed considering the global population and Aβ42+ patients only.ResultsThe cohort included 100 patients with mild-moderate AD. The median age [p25;p75] was 76.0 [73.0;80.0] years and 63.0% were female. Older age (effect size [SE] of 0.324 [0.096]; p = 0.001) and male sex (0.780 [0.193]; p = 0.001) were associated with increased fragmentation and decreased synchronization of the rhythm, respectively. After adjusting for age, sex, and season of the year, increased levels of T-tau (effect size [95% CI] of 0.343 [0.139 to 0.547]; p = 0.001) and NF-L (0.444 [0.212 to 0.676]; p = 0.001) were associated with a higher amplitude of the rest-activity rhythm. Increased fragmentation of the rhythm at baseline was associated with greater cognitive decline after one year of follow-up independent of age, sex, T-tau/Aβ42 ratio, educational level, and season of the year (- 0.715 [- 1.272 to - 0.157]; p = 0.013). Similar findings were obtained considering only the Aβ42+ patients.ConclusionsOur results suggest a potential role of the circadian rest-activity pattern in predicting the cognitive decline of patients with mild-moderate AD. Further studies are warranted to confirm these findings and to elucidate whether there is causality among the observed associations.

Dataset Information

Misidentification Subtype of Alzheimer's Disease Psychosis Predicts a Faster Cognitive Decline.

Publications

Misidentification Subtype of Alzheimer's Disease Psychosis Predicts a Faster Cognitive Decline.

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