Associations of Anxiety with Amyloid, Tau, and Neurodegeneration in Older Adults without Dementia: A Longitudinal Study

2021 ◽  
pp. 1-11
Author(s):  
Wen-Jie Cai ◽  
Yan Tian ◽  
Ya-Hui Ma ◽  
Qiang Dong ◽  
Lan Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Regression Model ◽  
Proportional Hazards Model ◽  
Amyloid Β ◽  
Multiple Linear Regression Model ◽  
Cox Proportional Hazards Model ◽  
Clinical Progression ◽  
Preclinical Phase ◽  
Increased Risk

Background: The pathophysiological process of amyloid-β, tau deposition, and neurodegeneration of Alzheimer’s disease (AD) begin in a preclinical phase, while anxiety is associated with an increased risk of AD in preclinical phase. Objective: To examine the relationships between anxiety and amyloid-β, tau deposition, and neurodegeneration. To test the hypothesis that anxiety could predict clinical progression in the elderly without dementia. Methods: 1,400 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were included in the study and were studied over a median period of 3 years. In multivariable models, the cross-sectional and longitudinal associations between anxiety and amyloid-β PET, tau PET, and FDG PET SUVRs in participants without dementia were explored using Spearman rank correlation, logistic regression model, multiple linear regression model, Kaplan-Meier survival curves, and Cox proportional hazards model. The association between baseline anxiety and clinical progression was also explored. Results: There was a positive correlation between anxiety and amyloid-β deposition (r = 0.11, p = 0.0017) and a negative correlation between anxiety and neurodegeneration (r = –0.13, p = 0.00022). MCI participants with anxiety showed a faster clinical progression of dementia (HR = 1.56, p = 0.04). Non-anxious participants with more amyloid-β deposition or more severe neurodegeneration displayed accelerated development into anxiety (HR = 2.352, p <  0.0001; HR = 2.254, p <  0.0001). Conclusion: Anxiety was associated with amyloid-β deposition and neurodegeneration in non-dementia elderly. Anxiety in MCI predicted conversion to dementia. Anxiety may play a selective role and prediction of disease progression in the early phase of AD.

Effect of antipsychotics on mortality in elderly patients with dementia: a 1-year prospective study in a nursing home

2005 ◽  
Vol 17 (3) ◽  
pp. 429-441 ◽  
Author(s):  
Guk-Hee Suh ◽  
Ajit Shah
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mortality Rate ◽  
Behavioral Problems ◽  
Rating Scale ◽  
Proportional Hazards Model ◽  
Mortality Rates ◽  
Cox Proportional Hazards Model ◽  
Korean Version ◽  
Increased Risk

Background and objectives: The use of risperidone or olanzapine to treat behavioral problems associated with dementia is no longer recommended in the U.K. because of the increased risk of cerebrovascular adverse effects (CVAEs) and/or mortality. To evaluate the risks and benefits of antipsychotics, we measured the rate of mortality in patients with dementia, Alzheimer's disease (AD) and vascular/mixed dementia and compared mortality rates between those who had received antipsychotics and those who had not received antipsychotics.Methods: A total of 273 subjects were assessed at baseline, 6 months and 12 months using a 1-year prospective follow-up design. Mortality rates between groups were compared using a Kaplan–Meier curve and log-rank statistics. Relative risks (RRs) were examined by the Cox proportional-hazards model.Results: The overall 1-year mortality rate in dementia was 23.8%. The mortality rate in those who had not received antipsychotics (26.8%) was higher than that in those who had received antipsychotics (20.6%). RR and 95% confidence interval (CI) of mortality, when we compared those who had not received antipsychotics with those who had received antipsychotics, was 1.277 (95% CI 1.134–1.437) after controlling for age, severity of dementia, medical comorbidities, cognitive impairment (measured by the Korean version of the Mini-mental State Examination (MMSE)) and behavioral and psychological symptoms of dementia (BPSD), measured by the Behavioral Pathology in Alzheimer's Disease Rating Scale, Korean version (BEHAVE-AD-K). When those who had not received antipsychotics were compared with those who had received both risperidone and haloperidol, RR (95% CI) was 1.225 (1.101–1.364).Conclusion: This study does not support reports that antipsychotics increase mortality in dementia.

scholarly journals Changes in Metabolic Syndrome Status and Risk of Dementia

2020 ◽  
Vol 9 (1) ◽  
pp. 122 ◽  
Author(s):  
Ji Eun Lee ◽  
Dong Wook Shin ◽  
Kyungdo Han ◽  
Dahye Kim ◽  
Jung Eun Yoo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Metabolic Syndrome ◽  
Vascular Dementia ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Screening Program ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model

This study investigated the effects of changes in metabolic syndrome (MS) status and each component on subsequent dementia occurrence. The study population was participants of a biennial National Health Screening Program in 2009–2010 and 2011–2012 in Korea. Participants were divided into four groups according to change in MS status during the two-year interval screening: sustained normal, worsened (normal to MS), improved (MS to normal), and sustained MS group. Risk of dementia among the groups was estimated from the second screening date to 31 December 2016 using a Cox proportional hazards model. A total of 4,106,590 participants were included. The mean follow-up was 4.9 years. Compared to the sustained normal group, adjusted hazard ratios (aHR) (95% confidence interval) were 1.11 (1.08–1.13) for total dementia, 1.08 (1.05–1.11) for Alzheimer’s disease, and 1.20 (1.13–1.28) for vascular dementia in the worsened group; 1.12 (1.10–1.15), 1.10 (1.07–1.13), and 1.19 (1.12–1.27) for the improved group; and 1.18 (1.16–1.20), 1.13 (1.11–1.15), and 1.38 (1.32–1.44) for the sustained MS group. Normalization of MS lowered the risk of all dementia types; total dementia (aHR 1.18 versus 1.12), Alzheimer’s disease (1.13 versus 1.10), and vascular dementia (1.38 versus 1.19). Among MS components, fasting glucose and blood pressure showed more impact. In conclusion, changes in MS status were associated with the risk of dementia. Strategies to improve MS, especially hyperglycemia and blood pressure, may help to prevent dementia.

scholarly journals CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts

2018 ◽  
Vol 14 (11) ◽  
pp. 1470-1481 ◽  
Author(s):  
Oskar Hansson ◽  
John Seibyl ◽  
Erik Stomrud ◽  
Henrik Zetterberg ◽  
John Q. Trojanowski ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Csf Biomarkers ◽  
Clinical Progression

scholarly journals Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer’s disease

2019 ◽  
Vol 11 (507) ◽  
pp. eaav6221 ◽  
Author(s):  
Michael Ewers ◽  
Nicolai Franzmeier ◽  
Marc Suárez-Calvet ◽  
Estrella Morenas-Rodriguez ◽  
Miguel Angel Araque Caballero ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Elderly Subjects ◽  
Amyloid Β Peptide ◽  
Loss Of Function ◽  
Clinical Progression ◽  
Cognitively Normal ◽  
Soluble Trem2

Loss of function of TREM2, a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer’s disease (AD). We therefore examined whether soluble TREM2 (sTREM2) concentrations in cerebrospinal fluid (CSF) were associated with reduced rates of cognitive decline and clinical progression in subjects with AD or mild cognitive impairment (MCI). We measured sTREM2 in CSF samples from 385 elderly subjects, including cognitively normal controls, individuals with MCI, and subjects with AD dementia (follow-up period: mean, 4 years; range 1.5 to 11.5 years). In subjects with AD defined by evidence of CSF Aβ1–42 (amyloid β-peptide 1 to 42; A+) and CSF p-tau181 (tau phosphorylated on amino acid residue 181; T+), higher sTREM2 concentrations in CSF at baseline were associated with attenuated decline in memory and cognition. When analyzed in clinical subgroups, an association between higher CSF sTREM2 concentrations and subsequent reduced memory decline was consistently observed in individuals with MCI or AD dementia, who were positive for CSF Aβ1–42 and CSF p-tau181 (A+T+). Regarding clinical progression, a higher ratio of CSF sTREM2 to CSF p-tau181 concentrations predicted slower conversion from cognitively normal to symptomatic stages or from MCI to AD dementia in the subjects who were positive for CSF Aβ1–42 and CSF p-tau181. These results suggest that sTREM2 is associated with attenuated cognitive and clinical decline, a finding with important implications for future clinical trials targeting the innate immune response in AD.

Survival in Subcortical Vascular Dementia: Predictors and Comparison to Probable Alzheimer's Disease in a Tertiary Memory Clinic Population

2015 ◽  
Vol 40 (3-4) ◽  
pp. 210-221 ◽  
Author(s):  
Jong Hun Kim ◽  
Seok Min Go ◽  
Sang Won Seo ◽  
Suk Hui Kim ◽  
Juhee Chin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family History ◽  
Vascular Dementia ◽  
Proportional Hazards Model ◽  
Late Onset ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Subcortical Vascular Dementia ◽  
History Of

Background: Subcortical vascular dementia (SVaD) is one of the most common dementias, after Alzheimer's disease (AD) dementia. Few survival analyses in SVaD patients have been reported. Methods: The dates and causes of death of 146 SVaD and 725 AD patients were included. We used the Cox proportional hazards model to compare survival between SVaD and AD patients and to explore possible factors related to survival of SVaD patients. Results: The median survival time after the onset of SVaD (109 months) was shorter than that recorded for AD (152 months). The most common cause of death in SVaD was stroke (47.1%). Factors associated with shorter survival in SVaD were late onset, male sex, worse baseline cognition, absence of hypertension and a family history of stroke. Conclusions: Stroke prevention may be important in SVaD treatment because 47.1% of SVaD patients died of stroke. A family history of stroke and absence of hypertension were associated with a shorter survival in SVaD, suggesting the existence of genetic or unknown risk factors.

scholarly journals The Associations of Cerebrospinal Fluid ApoE and Biomarkers of Alzheimer’s Disease: Exploring Interactions With Sex

2021 ◽  
Vol 15 ◽  
Author(s):  
Ying Liu ◽  
Jing-Hui Song ◽  
Wei Xu ◽  
Xiao-He Hou ◽  
Jie-Qiong Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Multiple Linear Regression Model ◽  
Linear Mixed Effects ◽  
Longitudinal Changes ◽  
Apoe Isoforms ◽  
T Tau ◽  
Normal Cognition

BackgroundSex-related difference in Alzheimer’s disease (AD) has been proposed, and apolipoprotein E (ApoE) isoforms have been suggested to be involved in the pathogenesis of AD.ObjectiveWe aimed to explore whether cerebrospinal fluid (CSF) ApoE is associated with AD biomarkers and whether the associations are different (between sexes).MethodsData of 309 participants [92 with normal cognition, 148 with mild cognitive impairment (MCI), and 69 with AD dementia] from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were cross-sectionally evaluated with the multiple linear regression model and longitudinally with the multivariate linear mixed-effects model for the associations of CSF ApoE with AD biomarkers. Sex–ApoE interaction was used to estimate whether sex moderates the associations of CSF ApoE and AD biomarkers.ResultsSignificant interactions between CSF ApoE and sex on AD biomarkers were observed [amyloid-β (Aβ): p = 0.0169 and phosphorylated-tau (p-tau): p = 0.0453]. In women, baseline CSF ApoE levels were significantly associated with baseline Aβ (p = 0.0135) and total-tau (t-tau) (p &lt; 0.0001) as well as longitudinal changes of the biomarkers (Aβ: p = 0.0104; t-tau: p = 0.0110). In men, baseline CSF ApoE levels were only correlated with baseline p-tau (p &lt; 0.0001) and t-tau (p &lt; 0.0001) and did not aggravate AD biomarkers longitudinally.ConclusionThe associations between CSF ApoE and AD biomarkers were sex-specific. Elevated CSF ApoE was associated with longitudinal changes of AD biomarkers in women, which indicates that CSF ApoE might be involved in the pathogenesis of AD pathology in a sex-specific way.

scholarly journals Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence?

2016 ◽  
Vol 213 (8) ◽  
pp. 1375-1385 ◽  
Author(s):  
Molly Stanley ◽  
Shannon L. Macauley ◽  
David M. Holtzman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Insulin Signaling ◽  
Amyloid Β ◽  
Tau Phosphorylation ◽  
Intranasal Insulin ◽  
Increased Risk ◽  
High Insulin ◽  
Neuronal Insulin Resistance

Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD.

IC-P-086: Amyloid-β and Hyperphosphorylated TAU Synergy Drives Clinical Progression to Alzheimer’s Disease

2016 ◽  
Vol 12 ◽  
pp. P66-P67
Author(s):  
Tharick A. Pascoal ◽  
Sulantha S. Mathotaarachchi ◽  
Monica Shin ◽  
Andrea Lessa Benedet ◽  
Min Su Kang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Hyperphosphorylated Tau ◽  
Clinical Progression

scholarly journals Cerebral hypoperfusion is a late pathological event in the course of Alzheimer's disease

2021 ◽  
Author(s):  
Khazar Ahmadi ◽  
Joana B. Pereira ◽  
David Berron ◽  
Jacob Vogel ◽  
Silvia Ingala ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Amyloid Β ◽  
Cognitive Status ◽  
Cerebral Hypoperfusion ◽  
Synaptic Dysfunction ◽  
Early Event ◽  
Preclinical Phase ◽  
Disease Progression Modeling

Although several studies have shown decreased cerebral blood flow (CBF) in Alzheimer's disease (AD), the role of hypoperfusion in the disease pathogenesis remains unclear. Combining arterial spin labeling MRI, positron emission tomography, and biomarkers of cerebrospinal fluid, we investigated the associations between CBF and the key mechanisms in AD including amyloid-β (Aβ) and tau pathology, synaptic dysfunction and axonal degeneration. Further, we applied a disease progression modeling to characterize the temporal sequence of different AD biomarkers. Lower perfusion was observed in the temporo-occipito-parietal regions in the Aβ-positive cognitively impaired compared to both the Aβ-positive and Aβ-negative cognitively unimpaired individuals. In participants along the AD spectrum (those with Aβ pathology regardless of their cognitive status), CBF was inversely associated with tau and synaptic dysfunction, but not Aβ in similar cortical regions. Moreover, the disease progression modeling revealed that CBF disruption followed the abnormality of biomarkers of Aβ, tau and brain atrophy. These findings indicate that tau tangles and synaptic degeneration are more closely connected with CBF changes rather than Aβ pathology. This supports the notion that hypoperfusion is not an early event associated with the build-up of Aβ during the preclinical phase of AD.

scholarly journals Endosomal structure and APP biology are not altered in preclinical cellular models of Down syndrome

2021 ◽  
Author(s):  
Claudia Cannavo ◽  
Karen Cleverley ◽  
Cheryl Maduro ◽  
Paige Mumford ◽  
Dale Moulding ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Cell Biology ◽  
Amyloid Β ◽  
Chromosome 21 ◽  
App Processing ◽  
Cellular Models ◽  
Increased Risk ◽  
Primary Mouse

Individuals who have Down syndrome (trisomy 21) are at greatly increased risk of developing Alzheimer’s disease – dementia. Alzheimer’s disease is characterised by the accumulation in the brain of amyloid-β plaques that are a product of amyloid precursor protein, encoded by the APP gene on chromosome 21. In Down syndrome the first site of amyloid-β accumulation is within endosomes and changes to endosome biology occur early in disease. Here we determine if primary mouse embryonic fibroblasts isolated from two mouse models of Down syndrome can be used to study endosome and APP cell biology. We report that in these cellular models of Down syndrome endosome number, size and APP processing are not altered, likely because APP is not dosage sensitive in these models, despite three copies of App .

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