“That's when the relationship shifted”: Relational and communicative turning points in Alzheimer's disease and related dementias

Objectives: Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease characterized by progressive cognitive impairment and personality changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression of AD is still not clearly clarified. Methods: The protein and mRNA levels were measured by western blot and RNA extraction and quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR- 335-5p on the cognitive deficits in APP/PS1 transgenic mice. Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335- 5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3 and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved the cognitive abilities of APP/PS1 mice. Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression, indicating a novel approach for AD treatment.

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Assessing the Relationship between Health Utilities, Quality of Life, and Health Care Costs in Alzheimer's Disease: The CATIE-AD Study

Current Alzheimer Research ◽

10.2174/1567210197155522050 ◽

2010 ◽

Vol 999 (999) ◽

pp. 1-10

Author(s):

Edward Alan Miller ◽

Robert A. Rosenheck ◽

Lon S. Schneider

Keyword(s):

Quality Of Life ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Health Care ◽

Health Care Costs ◽

Health Utilities ◽

The Relationship ◽

Care Costs

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

Current Alzheimer Research ◽

10.2174/1567205014666171106150309 ◽

2018 ◽

Vol 15 (5) ◽

pp. 429-442 ◽

Cited By ~ 3

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.

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The Relationship Between Anxiety and Alzheimer’s Disease

Journal of Alzheimer s Disease Reports ◽

10.3233/adr-219003 ◽

2021 ◽

pp. 1-1

Author(s):

Mario F. Mendez

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

The Relationship

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RESTING HEART RATE MODERATES THE RELATIONSHIP BETWEEN NEUROPSYCHIATRIC SYMPTOMS, MCI, AND ALZHEIMER’S DISEASE

Innovation in Aging ◽

10.1093/geroni/igz038.2385 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S641-S641

Author(s):

Shanna L Burke

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Heart Rate ◽

Relative Risk ◽

Neuropsychiatric Symptoms ◽

Cognitive Status ◽

Resting Heart Rate ◽

Data Set ◽

Increased Risk ◽

The Relationship

Abstract Little is known about how resting heart rate moderates the relationship between neuropsychiatric symptoms and cognitive status. This study examined the relative risk of NPS on increasingly severe cognitive statuses and examined the extent to which resting heart rate moderates this relationship. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform Data Set was undertaken, using observations from participants with normal cognition at baseline (13,470). The relative risk of diagnosis with a more severe cognitive status at a future visit was examined using log-binomial regression for each neuropsychiatric symptom. The moderating effect of resting heart rate among those who are later diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) was assessed. Delusions, hallucinations, agitation, depression, anxiety, elation, apathy, disinhibition, irritability, motor disturbance, nighttime behaviors, and appetite disturbance were all significantly associated (p<.001) with an increased risk of AD, and a reduced risk of MCI. Resting heart rate increased the risk of AD but reduced the relative risk of MCI. Depression significantly interacted with resting heart rate to increase the relative risk of MCI (RR: 1.07 (95% CI: 1.00-1.01), p<.001), but not AD. Neuropsychiatric symptoms increase the relative risk of AD but not MCI, which may mean that the deleterious effect of NPS is delayed until later and more severe stages of the disease course. Resting heart rate increases the relative risk of MCI among those with depression. Practitioners considering early intervention in neuropsychiatric symptomology may consider the downstream benefits of treatment considering the long-term effects of NPS.

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