ANALYSIS OF THE RELATIONSHIP OF COGNITIVE IMPAIRMENT AND FUNCTIONAL IMPAIRMENT IN MILD ALZHEIMER’S DISEASE IN EXPEDITION 3

2018 ◽  
pp. 1-4
Author(s):  
H. Liu-Seifert ◽  
E. Siemers ◽  
K. Sundell ◽  
M. Mynderse ◽  
J. Cummings ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Functional Impairment ◽  
Functional Decline ◽  
Clinical Trial Data ◽  
Cognitive Outcomes ◽  
Functional Measures ◽  
Functional Scores ◽  
The Relationship

BACKGROUND: Clinical progression of Alzheimer’s disease is characterized by impairment in cognition and function. OBJECTIVE: To assess the relationship between cognitive and functional impairment in mild Alzheimer’s disease. DESIGN: Spearman’s rank correlations between cognitive and functional measures were calculated. Autoregressive cross-lagged panel analyses were used to determine the temporal relationship between cognitive and functional decline. SETTING: Post-hoc analysis of clinical trial data. PARTICIPANTS: Placebo-treated patients with mild Alzheimer’s disease from the Phase 3 solanezumab study EXPEDITION 3. INTERVENTION: Placebo MEASUREMENTS: Cognitive and functional measures were assessed at baseline and at six post-baseline time points through Week 80. RESULTS: Correlation between cognitive and functional measures was 0.41 at baseline and 0.65 at Week 80. Autoregressive cross-lagged panel analysis demonstrated that cognitive impairment preceded and predicted subsequent functional decline, but functional scores did not predict cognitive outcomes. CONCLUSIONS: This study supports the hypothesis that functional impairment predictably follows cognitive decline in mild Alzheimer’s disease dementia.

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials

2018 ◽  
Vol 15 (5) ◽  
pp. 429-442 ◽  
Author(s):  
Nishant Verma ◽  
S. Natasha Beretvas ◽  
Belen Pascual ◽  
Joseph C. Masdeu ◽  
Mia K. Markey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Latent Variable ◽  
Brain Regions ◽  
Disease Assessment ◽  
Latent Variable Analysis ◽  
The Relationship ◽  
Selection Of

Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.

scholarly journals Impaired spike-gamma coupling of area CA3 fast-spiking interneurons as the earliest functional impairment in the AppNL-G-F mouse model of Alzheimer’s disease

2021 ◽  
Author(s):  
Luis Enrique Arroyo-García ◽  
Arturo G. Isla ◽  
Yuniesky Andrade-Talavera ◽  
Hugo Balleza-Tapia ◽  
Raúl Loera-Valencia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Functional Impairment ◽  
Amyloid Β ◽  
Gamma Oscillations ◽  
Gamma Oscillation ◽  
Gamma Rhythm ◽  
Fast Spiking

AbstractIn Alzheimer’s disease (AD) the accumulation of amyloid-β (Aβ) correlates with degradation of cognition-relevant gamma oscillations. The gamma rhythm relies on proper neuronal spike-gamma coupling, specifically of fast-spiking interneurons (FSN). Here we tested the hypothesis that decrease in gamma power and FSN synchrony precede amyloid plaque deposition and cognitive impairment in AppNL-G-F knock-in mice (AppNL-G-F). The aim of the study was to evaluate the amyloidogenic pathology progression in the novel AppNL-G-F mouse model using in vitro electrophysiological network analysis. Using patch clamp of FSNs and pyramidal cells (PCs) with simultaneous gamma oscillation recordings, we compared the activity of the hippocampal network of wild-type mice (WT) and the AppNL-G-F mice at four disease stages (1, 2, 4, and 6 months of age). We found a severe degradation of gamma oscillation power that is independent of, and precedes Aβ plaque formation, and the cognitive impairment reported previously in this animal model. The degradation correlates with increased Aβ1-42 concentration in the brain. Analysis on the cellular level showed an impaired spike-gamma coupling of FSN from 2 months of age that correlates with the degradation of gamma oscillations. From 6 months of age PC firing becomes desynchronized also, correlating with reports in the literature of robust Aβ plaque pathology and cognitive impairment in the AppNL-G-F mice. This study provides evidence that impaired FSN spike-gamma coupling is one of the earliest functional impairment caused by the amyloidogenic pathology progression likely is the main cause for the degradation of gamma oscillations and consequent cognitive impairment. Our data suggests that therapeutic approaches should be aimed at restoring normal FSN spike-gamma coupling and not just removal of Aβ.

scholarly journals Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer’s Disease

2015 ◽  
Vol 47 (1) ◽  
pp. 205-214 ◽  
Author(s):  
Hong Liu-Seifert ◽  
Eric Siemers ◽  
Karen Price ◽  
Baoguang Han ◽  
Katherine J. Selzler ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Functional Impairment

scholarly journals Assessment of balance in mild and moderate stages of Alzheimer's disease: implications on falls and functional capacity

2011 ◽  
Vol 69 (2a) ◽  
pp. 202-207 ◽  
Author(s):  
Eliane Mayumi Kato-Narita ◽  
Ricardo Nitrini ◽  
Marcia Radanovic
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Functional Capacity ◽  
Functional Decline ◽  
Berg Balance Scale ◽  
Control Group ◽  
Disability Assessment ◽  
Balance Impairment ◽  
Balance Scale

OBJECTIVE: To analyze the correlation between balance, falls and loss of functional capacity in mild and moderate Alzheimer's disease(AD). METHOD: 40 subjects without cognitive impairment (control group) and 48 AD patients (25 mild, 23 moderate) were evaluated with the Berg Balance Scale (BBS) and the Disability Assessment for Dementia (DAD). Subjects answered a questionnaire about falls occurrence in the last twelve months. RESULTS: Moderate AD patients showed poorer balance (p=0.001) and functional capacity (p <0.0001) and it was observed a correlation between falls and balance (r= -0.613; p=0.045). CONCLUSION: There is a decline of balance related to AD which is a factor associated to the occurrence of falls, albeit not the most relevant one. The loss of functional capacity is associated with the disease's progress but not to a higher occurrence of falls. The balance impairment did not correlate with functional decline in AD patients.

scholarly journals VEGF Family Gene Expression as Prognostic Biomarkers for Alzheimer’s Disease and Primary Liver Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Kai Xu ◽  
Chuan-ling Wu ◽  
Zhi-xin Wang ◽  
Hai-jiu Wang ◽  
Feng-jiao Yin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Liver Cancer ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Biomarkers ◽  
Vegf Expression ◽  
Immune Infiltration ◽  
Cancer Tissues ◽  
The Relationship

Background. To analyze the expression of vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and cognitive impairment, explore the relationship between the expression of VEGF family genes and prognosis of patients with HCC, and evaluate the predictive ability of VEGF in cognitive impairment using computerized methods. Methods. VEGF expression in liver cancer tissues and normal tissues was analyzed using bioinformatics methods. The Kaplan-Meier survival analysis method was also used to analyze the relationship between VEGF expression and the prognosis of patients with HCC. Furthermore, immune infiltration assessment and gene set enrichment analysis were performed. Meanwhile, the differential expression of VEGF family genes between patients with Alzheimer’s disease (AD) and healthy controls was also checked. Results. Based on The Cancer Genome Atlas (TCGA) database, the VEGF family genes (VEFGA, VEGFB, VEGFC, and VEGFD) were highly expressed in cancer tissues and were significantly associated with poor prognosis in HCC. In HCC, the VEGF family genes showed significant heterogeneity in their functional and immune infiltration characteristics. Finally, VEGF family genes were identified as prognostic biomarkers in AD and risk prediction markers in HCC. Conclusions. VEGF is highly expressed in patients with HCC and lowly expressed in patients with AD. VEGF has opposite opposing roles in the treatment of tumors and cognitive impairment.

J'accuse! depression as a likely culprit in cases of AD

2016 ◽  
Vol 28 (9) ◽  
pp. 1407-1408 ◽  
Author(s):  
David C. Steffens
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
The Relationship

Clinicians have long appreciated the links between depression, cognitive impairment, and development of Alzheimer's disease (AD) and other dementias. More recently, investigators in the fields of epidemiology, genetics, neuroimaging, and neuropathology have sought to quantify the risk and to understand the underlying neurobiology of the relationship between depression and AD.

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