scholarly journals CORRELATION BETWEEN COGNITION AND FUNCTION ACROSS THE SPECTRUM OF ALZHEIMER’S DISEASE

2016 ◽  
pp. 1-7
Author(s):  
H. Liu-Seifert ◽  
E. Siemers ◽  
K. Selzler ◽  
K. Sundell ◽  
P. Aisen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Mmse Score ◽  
Disease Stage ◽  
Two Phase ◽  
Identity Studies ◽  
Moderate Dementia ◽  
And Function ◽  
The Relationship

Background: Both cognitive and functional deterioration are characteristic of the clinical progression of Alzheimer’s disease (AD). Objectives: To systematically assess correlations between widely used measures of cognition and function across the spectrum of AD. Design: Spearman rank correlations were calculated for cognitive and functional measures across datasets from various AD patient populations. Setting: Post-hoc analysis from existing databases. Participants: Pooled data from placebo-treated patients with mild (MMSE score ≥20 and ≤26) and moderate (MMSE score ≥16 and ≤19) AD dementia from two Phase 3 solanezumab (EXPEDITION/2) and two semagecesatat (IDENTITY/2) studies and normal, late mild cognitive impairment (LMCI) and mild AD patients from the Alzheimer’s Disease Neuroimaging Initiative 2-Grand Opportunity (ADNI-2/GO). Intervention (if any): Placebo (EXPEDITION/2 and IDENTITY/2 subjects) Measurements: Cognitive and functional abilities were measured in all datasets. Data were collected at baseline and every three months for 18 months in EXPEDITION and IDENTITY studies; and at baseline, 6, 12, and 24 months in the ADNI dataset. Results: The relationship of cognition and function became stronger over time as AD patients progressed from preclinical to moderate dementia disease stages, with the magnitude of correlations dependent on disease stage and the complexity of functional task. The correlations were minimal in the normal control population, but became stronger with disease progression. Conclusions: This analysis found that measures of cognition and function become more strongly correlated with disease progression from preclinical to moderate dementia across multiple datasets. These findings improve the understanding of the relationship between cognitive and functional clinical measures during the course of AD progression and how cognition and function measures relate to each other in AD clinical trials.

Abstract T P160: Influence of Polyunsaturated Fatty Acids on Cognition in Elderly Alzheimer's Disease Patients

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Takashi Yamazaki ◽  
Ken Nagata ◽  
Daiki Takano ◽  
Tetsuya Maeda
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mmse Score ◽  
Characteristic Curve ◽  
Follow Up Study ◽  
Cognitive Stability ◽  
The Relationship

Background: Many genes and environmental factors linked to Alzheimer’s disease (AD) risk affect lipid metabolism or the cardiovascular system, strongly implicating cerebrovascular and metabolic dysfunction in AD pathogenesis. Although some PUFAs may improve cognitive function in aging individuals, it is still unclear how different PUFAs influence AD neuropathology and cognitive function. Objective: To examine the influence of polyunsaturated fatty acid (PUFA) metabolism on AD-associated cognitive decline, we investigated the relationship between serum PUFA profile and neuropsychological test performance. Methods: Cognitive functioning in patients with probable AD (n = 174, mean age 77.6 years) was examined using the Mini-Mental State Exam (MMSE) and clock drawing test (CDT). Serum samples were obtained for PUFA profile, including the eicosapentaenoic acid/arachidonic acid (EPA/AA) ratio, and measurement of brain natriuretic peptide (BNP) concentration. In the follow-up study, 47 subjects repeated MMSE and CDT after 1 year, According to the second MMSE score, the subjects were divided into the following 2 groups: those with unchanged or improved MMSE score and those with lower MMSE score. A receiver operating characteristic curve was used to evaluate the relationship between the EPA/AA ratio and 1-year cognitive stability. Results: In the cross-sectional study, total MMSE score correlated positively with the EPA/AA ratio and systolic blood pressure (SBP), and negatively with age and diastolic blood pressure (DBP) (p < 0.05). In the follow-up study, the MMSE score was lower than baseline in 20 subjects, whereas it was improved or unchanged in 29 patients. The EPA/AA ratio in the stable group was significantly greater than that in the deteriorating group, suggesting an association between higher EPA/AA ratio and cognitive stability over 1 year. The EPA/AA ratio predicted stability of cognitive performance with a sensitivity of 66% and specificity of 70% (odds ratio = 4.43) when the cut-off was 0.67. Conclusion: Our results suggest that serum EPA concentration strongly influences cognitive performances in AD patients. The EPA/AA ratio was a sensitive indicator of cognitive stability in this patient group.

Longitudinal changes in awareness over 36 months in patients with mild Alzheimer's disease

2014 ◽  
Vol 27 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Asmus Vogel ◽  
Frans Boch Waldorff ◽  
Gunhild Waldemar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Mmse Score ◽  
Neuropsychiatric Symptoms ◽  
Rapid Decline ◽  
Longitudinal Changes ◽  
Moderate Dementia ◽  
Over Time

ABSTRACTBackground:Longitudinal changes in awareness in dementia have been studied with short follow-up time and mostly in small patient groups (including patients with moderate dementia). We investigated awareness in patients with mild Alzheimer's disease (AD) over 36 months and studied if a decline in awareness was associated with decline in cognition and increase in neuropsychiatric symptoms.Methods:Awareness was measured on a categorical scale in 95 AD patients (age ≥50 years, Mini-Mental State Examination (MMSE) score ≥20). Awareness was rated at three time points (follow-up at 12 and 36 months) where MMSE, Neuropsychiatric Inventory (NPI-Q), and Cornell scale for Depression in Dementia also were applied.Results:At 12 months, 26% had lower awareness rating as compared to baseline and at 36 months lower awareness ratings were found in 39%. At both visits, 16% had higher awareness rating as compared to baseline. Patients with lower awareness at 36 months as compared to baseline had a more rapid increase in NPI-Q score (p = 0.002) over 36 months as compared to patients with stable or improved awareness over 36 months. A more rapid decline in MMSE score was observed for patients with lower awareness at 36 months (as compared to baseline) but only when compared to patients in whom awareness improved over time.Conclusions:The results show essentially no clear relationship between cognitive decline over three years and awareness. In some cases, awareness remained stable or even improved despite significant cognitive decline. In the subgroup where awareness declined over time, overall ratings of neuropsychiatric symptoms declined more rapidly than in the remaining patients.

scholarly journals Disease progression modeling of Alzheimer’s disease according to education level

2019 ◽  
Author(s):  
Ko Woon Kim ◽  
Sook Young Woo ◽  
Seonwoo Kim ◽  
Yeshin Kim ◽  
Hyemin Jang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Disease Progression ◽  
Education Level ◽  
Disease Stage ◽  
Mixed Effect ◽  
Progression Model ◽  
Education Group ◽  
Disease Progression Model

Abstract Background To develop a disease progression model of Alzheimer’s disease (AD) that shows cognitive decline from subjective cognitive impairments (SCI) to dementia and to investigate the effect of education level on the whole disease spectrum. Methods We enrolled 565 patients who were followed up more than three times and had a clinical dementia rating sum of boxes (CDR-SB) score. Three cohorts, SCI (n=85), amnestic mild cognitive impairment (AMCI, n=240), and AD dementia (ADD, n=240), were overlapped in two consecutive cohorts (SCI and AMCI, AMCI and ADD) to construct a model of disease course, and a model with multiple single-cohorts was estimated using a mixed-effect model. To examine the effect of education level on disease progression, the disease progression model was developed with data from lower (≤12) and higher (>12) education groups. Results Disease progression takes 277.0 months (23.1 years) to advance from 0 to 18 points using the CDR-SB score. Based on our predictive equation, it takes 101.9 months to progress from SCI to AMCI and 71.1 months to progress from AMCI to ADD. The rate of CDR-SB progression was different according to education level. The lower-education group showed faster CDR-SB progression from SCI to AMCI compared to the higher-education group, and this trend disappeared from AMCI to ADD. Conclusion In the present study, we developed a disease progression model of AD spectrum from preclinical to the end stage of the disease. Our findings suggest that the contribution of education to cognitive decline varies depending on disease stage.

Peptidylarginine Deiminase and Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Lai Wang ◽  
Hongyang Chen ◽  
Jing Tang ◽  
Zhengwei Guo ◽  
Yanming Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Targets ◽  
Therapeutic Potential ◽  
Peptidylarginine Deiminase ◽  
Post Translational Modification ◽  
Rodent Brain ◽  
The Central Nervous System ◽  
And Function ◽  
The Relationship

Peptidylarginine deiminases (PADs) are indispensable enzymes for post-translational modification of proteins, which can convert Arg residues on the surface of proteins to citrulline residues. The PAD family has five isozymes, PAD1, 2, 3, 4, and 6, which have been found in multiple tissues and organs. PAD2 and PAD4 were detected in cerebral cortex and hippocampus from human and rodent brain. In the central nervous system, abnormal expression and activation of PADs are involved in the pathological changes and pathogenesis of Alzheimer’s disease (AD). This article reviews the classification, distribution, and function of PADs, with an emphasis on the relationship between the abnormal activation of PADs and AD pathogenesis, diagnosis, and the therapeutic potential of PADs as drug targets for AD.

Impact of Rivastigmine on Costs and on Time Spent in Caregiving for Families of Patients With Alzheimer's Disease

2003 ◽  
Vol 15 (4) ◽  
pp. 385-398 ◽  
Author(s):  
Deborah Marin ◽  
Karine Amaya ◽  
Roman Casciano ◽  
Katherine L. Puder ◽  
Julian Casciano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Health Care ◽  
Disease Progression ◽  
Caregiver Burden ◽  
Health Care Professionals ◽  
Mmse Score ◽  
Global Functioning ◽  
Early Therapy ◽  
The Impact

Background: Alzheimer's disease (AD) places a significant burden on health care systems worldwide. As new treatments are developed, their cost-effectiveness is often assessed to help health care professionals make informed decisions. In addition to the more common practice of assessing direct medical costs, indirect costs, including time spent in caregiving, should be evaluated. Methods: This study examined the potential effects of the dual cholinesterase inhibitor rivastigmine (Exelon) on caregivers of patients with AD. Results from two 26-week, placebo-controlled trials have demonstrated the clinically relevant and statistically significant efficacy of rivastigmine (6–12 mg/day) compared to placebo, on cognition, activities of daily living, and global functioning. By delaying progression of AD, significant savings in caregiver burden are anticipated, as measured by time spent caregiving and its related costs. Data collected in a prospective, observational study of AD patients and their caregivers were used to establish the relationship between disease severity (based on Mini-Mental State Examination [MMSE] score) and time spent caregiving (according to the 5-item Caregivers Activity Survery score). A significant correlation was observed between the two scores (N = 43, r = −.56, p < .0001), demonstrating that more time for supervision from caregivers is required as the disease progresses. This finding was used to estimate the reduced caregiver burden resulting from the delay in disease progression that was demonstrated with use of rivastigmine. Results: Over a 2-year period, the reduction in time spent in caregiving reached 691 hours for caregivers of patients with mild AD (MMSE score 21–30), resulting in a total savings of approximately $11,253. Treatment of patients with moderately severe AD was also evaluated. The trend was similar but the impact was less, suggesting an economic benefit to early therapy. Conclusion: Early diagnosis and a pharmacologic intervention that allows the patients to remain at home longer by delaying disease progression would have a beneficial impact on patients, caregivers, and payers, and should therefore be encouraged through initiatives designed to identify and treat patients early in the course of disease.

A Mixed-Effects Model of Associations between Interleukin-6 and Hippocampal Volume

2021 ◽  
Author(s):  
Erin R Harrell ◽  
Chuong Bui ◽  
Sharlene D Newman ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Interleukin 6 ◽  
Mixed Models ◽  
Allostatic Load ◽  
Mmse Score ◽  
Hippocampal Volume ◽  
Within Subjects ◽  
Normative Aging ◽  
The Relationship

Abstract Previous studies report hippocampal volume loss can help predict conversion from normative aging to mild cognitive impairment (MCI) to dementia. Additionally, a growing literature indicates that stress-related allostatic load may increase disease vulnerability. The current study examined the relationship between stress related cytokines (i.e., interleukin-6 - IL-6), cognition as measured by Mini Mental Status scores (MMSE), and hippocampal volume. Mixed-models were employed to examine both within (across time) and between subjects effects of IL-6 and hippocampal volume on MMSE score among 566 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The within subjects analysis found left hippocampal volume significantly (p= .009) predicted MMSE score. Between subjects analysis found the effect of IL-6 on MMSE was moderated by right hippocampal volume (p = .001). These results replicate previous findings and also extend prior work demonstrating stress-related cytokines may play a role in Alzheimer’s disease (AD) progression.

scholarly journals Disease progression modeling in Alzheimer’s disease: insights from the shape of cognitive decline

2019 ◽  
Author(s):  
Lars Lau Raket ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Disease Progression ◽  
Latent Variables ◽  
Likelihood Estimation ◽  
Disease Stage ◽  
Cognitive Test ◽  
Nonlinear Mixed Effects Model ◽  
Cognitive Capability

AbstractBackgroundThe characterizing symptom of Alzheimer disease (AD) is cognitive deterioration. While much recent work has focused on defining AD as a biological construct, most patients are still diagnosed, staged, and treated based on their cognitive symptoms. But the cognitive capability of a patient at any time throughout this deterioration will not directly reflect the disease state, but rather the effect of the cognitive decline on the patient’s predisease cognitive capability. Patients with high predisease cognitive capabilities tend to score better on cognitive tests relative to patients with low predisease cognitive capabilities at the same disease stage. Thus, a single assessment with a cognitive test is not adequate for determining the stage of an AD patient.Methods and FindingsI developed a joint statistical model that explicitly modeled disease stage, baseline cognition, and the patients’ individual changes in cognitive ability as latent variables. The developed model takes the form of a nonlinear mixed-effects model. Maximum-likelihood estimation in this model induces a data-driven criterion for separating disease progression and baseline cognition. Applied to data from the Alzheimer’s Disease Neuroimaging Initiative, the model estimated a timeline of cognitive decline in AD that spans approximately 15 years from the earliest subjective cognitive deficits to severe AD dementia. It was demonstrated how direct modeling of latent factors that modify the observed data patterns provide a scaffold for understanding disease progression, biomarkers and treatment effects along the continuous time progression of disease.ConclusionsThe suggested framework enables direct interpretations of factors that modify cognitive decline. The results give new insights to the value of biomarkers for staging patients and suggest alternative explanations for previous findings related to accelerated cognitive decline among highly educated patients and patients on symptomatic treatments.

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