Cognitive and Noncognitive Symptoms in Dementia Patients: Relationship to Cortisol and Dehydroepiandrosterone

1998 ◽  
Vol 10 (1) ◽  
pp. 85-96 ◽  
Author(s):  
Terry P. Miller ◽  
Joy Taylor ◽  
Stephanie Rogerson ◽  
Maritess Mauricio ◽  
Quinn Kennedy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Disease Assessment ◽  
Cognitive Measure ◽  
Dementia Patients ◽  
Basal Cortisol ◽  
Noncognitive Symptoms ◽  
Cortisol Levels ◽  
Clinical Measures

We investigated the relationship between basal cortisol and dehydroepiandrosterone (DHEA) levels and impairment in different cognitive and noncognitive measures and the possible interaction of DHEA with hypercortisolemia in dementia in 27 patients diagnosed with Alzheimer's disease (AD). There were 17 men and 10 women. Patients were mildly to moderately cognitively impaired at the time of the initial cortisol measures. Patients were administered the Alzheimer's Disease Assessment Scale (ADAS) and Folstein Mini-Mental State Examination (MMSE) at approximately 6-month intervals. Cortisol and DHEA were determined using conventional 125I radioimmunoassay procedures. Pearson product-moment correlations among cortisol and DHEA measures and both initial and longitudinal clinical measures were calculated. There was a relationship between baseline 8 a.m. cortisol levels and cognitive function at the initial testing as measured by the ADAS cognitive measure, with higher cortisol levels being associated with a greater level of impairment. We did not document a relationship between cortisol or DHEA levels and noncognitive measures. There was a significant correlation between both the initial MMSE and ADAS cognitive measures and initial DHEA level, with lower DHEA levels unexpectedly being associated with better performance on these measures. The initial DHEA levels did not predict decline in cognitive function over time. These findings bring into question the potential usefulness of DHEA as a therapeutic agent.

scholarly journals Saffron for mild cognitive impairment and dementia: a systematic review and meta-analysis of randomised clinical trials

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zahra Ayati ◽  
Guoyan Yang ◽  
Mohammad Hossein Ayati ◽  
Seyed Ahmad Emami ◽  
Dennis Chang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Function ◽  
Daily Living ◽  
Randomised Clinical Trials ◽  
Disease Assessment ◽  
Significant Difference

Abstract Background Saffron (stigma of Crocus sativus L.) from Iridaceae family is a well-known traditional herbal medicine that has been used for hundreds of years to treat several diseases such as depressive mood, cancer and cardiovascular disorders. Recently, anti-dementia property of saffron has been indicated. However, the effects of saffron for the management of dementia remain controversial. The aim of the present study is to explore the effectiveness and safety of saffron in treating mild cognitive impairment and dementia. Methods An electronic database search of some major English and Chinese databases was conducted until 31st May 2019 to identify relevant randomised clinical trials (RCT). The primary outcome was cognitive function and the secondary outcomes included daily living function, global clinical assessment, quality of life (QoL), psychiatric assessment and safety. Rev-Man 5.3 software was applied to perform the meta-analyses. Results A total of four RCTs were included in this review. The analysis revealed that saffron significantly improves cognitive function measured by the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinical Dementia Rating Scale-Sums of Boxes (CDR-SB), compared to placebo groups. In addition, there was no significant difference between saffron and conventional medicine, as measured by cognitive scales such as ADAS-cog and CDR-SB. Saffron improved daily living function, but the changes were not statistically significant. No serious adverse events were reported in the included studies. Conclusions Saffron may have the potential to improve cognitive function and activities of daily living in patients with Alzheimer’s disease and mild cognitive impairment (MCI). However, due to limited high-quality studies there is insufficient evidence to make any recommendations for clinical use. Further clinical trials on larger sample sizes are warranted to shed more light on its efficacy and safety.

scholarly journals Plasma Glutathione Levels Decreased with Cognitive Decline among People with Mild Cognitive Impairment (MCI): A Two-Year Prospective Study

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1839
Author(s):  
Chieh-Hsin Lin ◽  
Hsien-Yuan Lane
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Function ◽  
Prospective Study ◽  
Cognitive Decline ◽  
Cognitive Change ◽  
Disease Assessment ◽  
Healthy Individuals

Glutathione (GSH) is a major endogenous antioxidant. Several studies have shown GSH redox imbalance and altered GSH levels in Alzheimer’s disease (AD) patients. Early detection is crucial for the outcome of AD. However, whether GSH can serve as a biomarker during the very early-phase of AD, such as mild cognitive impairment (MCI), remains unknown. The current prospective study aimed to examine the longitudinal change in plasma GSH concentration and its influence on cognitive decline in MCI. Overall, 49 patients with MCI and 16 healthy individuals were recruited. Plasma GSH levels and cognitive function, measured by the Mini-Mental Status Examination (MMSE) and Alzheimer’s disease assessment scale-cognitive subscale (ADAS-cog), were monitored every 6 months. We employed multiple regressions to examine the role of GSH level in cognitive decline in the 2 years period. The MCI patients showed significant decline in plasma GSH levels and cognitive function from baseline to endpoint (month 24). In comparison, the healthy individuals’ GSH concentration and cognitive function did not change significantly. Further, both GSH level at baseline and GSH level change from baseline to endpoint significantly influenced cognitive decline among the MCI patients. To our knowledge, this is the first study to demonstrate that both plasma GSH levels and cognitive function declined 2 years later among the MCI patients in a prospective manner. If replicated by future studies, blood GSH concentration may be regarded as a biomarker for monitoring cognitive change in MCI.

scholarly journals The evaluation of cognitive function in the dementias: methodological and regulatory considerations

2003 ◽  
Vol 5 (1) ◽  
pp. 77-88
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Cognitive Skills ◽  
Lewy Bodies ◽  
Disease Assessment ◽  
Central Feature ◽  
Memory Problems ◽  
Automated Procedures

Impairment of cognitive function is the central feature of dementia. Although, clinically, the cognitive deficit most often manifests itself as memory problems, a number of other areas of cognition are affected, and memory is but one of the cognitive skills compromised in dementia. Dementia with Lewy bodies, for example, accounts for 15% to 25% of all dementias and does not have memory deficits as a core feature. Our cognitive facilities underlie our abilities to engage successfully in the activities of daily living (ADL) and it follows thai enhancement of cognitive function will facilitate performance of ADL The assessment and understanding of these impairments are crucial to any treatment of the disorder. Unfortunately, the principal instrument used to assess cognitive function in most of the major clinical trials of Alzheimer's disease in recent years, the Alzheimer's Disease Assessment Scale-Cognitive Subsection (ADAS-COG), primarily assesses aspects of memory, which has resulted in other important cognitive deficits in dementia being overlooked. Automated cognitive tests are now available that can identify an earlier onset of improvements in dementia in smaller samples than the ADAS, Regulatory authorities should encourage - or even require - the use of automated procedures alongside the ADAS in pivotal trials to help determine the relative utility of the instruments in the fairest way possible. Whatever the outcome, this will be of long-term benefit to patients, carers, drug developers, clinicians, and regulators in this important area.

scholarly journals Acupuncture and Related Therapies for the Cognitive Function of Alzheimer’s Disease: A Network Meta-Analysis

2021 ◽  
Author(s):  
Xue-Song Wang ◽  
Jia-Jia Li ◽  
Yue-Shen Wang ◽  
Chao-Chao Yu ◽  
Chuan He ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Meta Analysis ◽  
Chinese Herb ◽  
Indirect Evidence ◽  
Clinical Effectiveness ◽  
Disease Assessment ◽  
Memory Training ◽  
Better Than

Background: Acupuncture and acupuncture-related therapies are effective for Alzheimer's disease (AD), therefore, we aimed to compare and rank the interventions that mainly focus on acupuncture-related therapies in the treatment of patients with mild to moderate AD. Methods: We used network meta-analysis to evaluate the direct and indirect evidence shown in randomized controlled trials of AD. The data were analyzed using RavMan manager, Stata, and WinBUGS software after two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. Results: We analyzed a total of 36 eligible studies, including 2712 patients, involving 14 types of acupuncture-related therapies and comprehensive therapies. For Mini-Mental State Examination (MMSE), acupuncture (ACU) combined with cognitive and memory training (Training) was more effective than ACU, ACU+Chinese herb (CH), ACU+Donepezil (DON), CH, DON, DON+Nimodipine (NIM), Music therapy (Music), NIM, Placebo, and Training (P<0.05), while ACU+CH was batter than CH (P<0.05), and ACU+DON+NIM was better than DON+NIM (P<0.05). For Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-cog), ACU was more effective than DON and placebo (P<0.05). For Activities of Daily Living (ADL), ACU+DON was better than CH, DON, NIM, and Placebo (P<0.05). For the clinical effectiveness rate, ACU, ACU+CH, ACU+CH+DON, ACU+CH+DON+NIM, ACU+DON, CH, NIM were all more effective than DON+NIM (P<0.05), while ACU and ACU+CH were better than DON (P<0.05). The comprehensive ranking results show that ACU+training and ACU have the highest ranking probability. Conclusion: ACU+Training and ACU may be the best therapies to improve the cognitive function of patients with mild to moderate AD, while the combination of acupuncture-related therapies and other therapies has a higher overall benefit.  

scholarly journals Target Symptoms and Outcome Measures: Cognition

2007 ◽  
Vol 34 (S1) ◽  
pp. S42-S46 ◽  
Author(s):  
Andrew Kirk
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Dementia ◽  
Mental State ◽  
Assessment Tool ◽  
Lewy Bodies ◽  
Disease Assessment ◽  
Cognitive Measure ◽  
Trial Entry ◽  
Severe Impairment

The Cognitive section of the Alzheimer's Disease Assessment Scale (ADAS-Cog) remains the most widely used cognitive measure in dementia trials although it does not assess attention, executive function, or agnosia. Designed for use in Alzheimer's disease (AD), it may not be ideal in assessing patients with other diagnoses. The ADAS-Cog differentiates between AD patients, patients with Mild Cognitive Impairment, and normal controls. It has been used in trials of drugs for vascular and mixed dementia and dementia with Lewy bodies. It is not clear that the ADAS-Cog is adequate for assessing cognition in frontotemporal dementia. Well-validated aphasia batteries, such as the Western Aphasia Battery, can be used to assess language. Brief tests of frontal function such as the Frontal Assessment Battery or the Executive Interview might be useful additions in frontotemporal dementia trials. The most widely used assessment tool for patients with advanced dementia is the Severe Impairment Battery. The domains tested are analogous to those assessed by the ADAS-Cog. The Mini-Mental State Exam and the Modified Mini-Mental State Examination are useful in stratifying patients for trial entry. Cognitive measures better tailored to the diseases in question are needed for non-Alzheimer dementias.

scholarly journals The Effect of Hormone Replacement Therapy on Cognitive Function in Female Patients With Alzheimer's Disease: A Meta-Analysis

2020 ◽  
Vol 35 ◽  
pp. 153331752093858
Author(s):  
ChengCheng Zhou ◽  
Qingguang Wu ◽  
Zongwei Wang ◽  
Qi Wang ◽  
Youya Liang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hormone Replacement Therapy ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Replacement Therapy ◽  
Meta Analysis ◽  
Hormone Replacement ◽  
Disease Assessment ◽  
Female Patients

Previous studies have indicated that estrogen may delay disease progression and minimize the cognitive decline in patients with Alzheimer's disease (AD). However, the evidence for an estrogen deficiency in women with dementia and cognitive dysfunction is inconsistent. In the present review, a fixed effect meta-analysis revealed that the hormone replacement therapy (HRT) group exhibited significant improvements in Alzheimer Disease Assessment Scale-Cognitive subscale scores relative to those observed in the placebo group, suggesting that HRT is feasible for treating cognitive decline in patients with AD. However, no significant differences in Mini-Mental State Examination and Clinical Dementia Rating scale scores were observed between the 2 groups. The results of our systematic review indicate that HRT can improve cognitive function in female patients with AD. Due to limitations in sample size and the available literature, further multicenter trials with larger sample sizes are required to support these findings.

scholarly journals Genetic variants beyond amyloid and tau associated with cognitive decline

Neurology ◽  
2020 ◽  
Vol 95 (17) ◽  
pp. e2366-e2377 ◽  
Author(s):  
Hang-Rai Kim ◽  
Taeyeop Lee ◽  
Jung Kyoon Choi ◽  
Yong Jeong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Structural Equation ◽  
Equation Model ◽  
Disease Assessment ◽  
Glutathione Metabolism ◽  
Nucleotide Polymorphisms ◽  
Cognitive Subscale

ObjectiveTo identify single nucleotide polymorphisms (SNPs) associated with cognitive decline independent of β-amyloid (Aβ) and tau pathology in Alzheimer disease (AD).MethodsDiscovery and replication datasets consisting of 414 individuals (94 cognitively normal control [CN], 185 with mild cognitive impairment [MCI], and 135 with AD) and 72 individuals (22 CN, 39 with MCI, and 11 with AD), respectively, were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Genome-wide association analysis was conducted to identify SNPs associated with individual cognitive function (measured with the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale–Cognitive Subscale ) while controlling for the level of Aβ and tau (measured as CSF phosphorylated-tau/Aβ1-42). Gene ontology analysis was performed on SNP-associated genes.ResultsWe identified 1 significant (rs55906536, β = −1.91, standard error 0.34, p = 4.07 × 10−8) and 4 suggestive variants on chromosome 6 that were associated with poorer cognitive function. Congruent results were found in the replication data. A structural equation model showed that the identified SNP deteriorated cognitive function partially through cortical thinning of the brain in a region-specific manner. Furthermore, a bioinformatics analysis showed that the identified SNPs were associated with genes related to glutathione metabolism.ConclusionsIn this study, we identified SNPs related to cognitive decline in a manner that could not be explained by Aβ and tau levels. Our findings provide insight into the complexity of AD pathogenesis and support the growing literature on the role of glutathione in AD.

scholarly journals Case Report: Deep Brain Stimulation of the Nucleus Basalis of Meynert for Advanced Alzheimer's Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Wei Zhang ◽  
Wei Liu ◽  
Bhavana Patel ◽  
Yingchuan Chen ◽  
Kailiang Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Deep Brain Stimulation ◽  
Cognitive Function ◽  
Brain Stimulation ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert ◽  
Disease Assessment ◽  
Deep Brain ◽  
Stimulation Of

Patients with advanced Alzheimer's disease (AD) experience cognitive impairment and physical disabilities in daily life. Currently, there are no treatments available to slow down the course of the disease, and limited treatments exist only to treat symptoms. However, deep brain stimulation of the nucleus basalis of Meynert (NBM-DBS) has been reported to improve cognitive function in individuals with AD. Here, we report the effects of NBM-DBS on cognitive function in a subject with severe AD. An 80-year-old male with severe AD (Clinical Dementia Rating scale: 3.0 points) underwent surgery for bilateral NBM-DBS electrode placement. After 10 weeks of stimulation, Mini-Mental State Examination (MMSE) assessment improved from a score of 5 to 9 points, and assessment using the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-cog) showed a marked reduction in total score from 43 to 33 points, suggesting cognitive benefits from NBM-DBS. The patient's postoperative course was complicated by a subdural effusion that occurred several days after surgery, with complete recovery. Interestingly, the subject also displayed abnormal thermoregulation with stimulation initiation and stimulation parameter modifications. NBM-DBS may serve as a potential therapy for severe AD patients.Clinical Trial Registration: ChiCTR1900022324.

scholarly journals Diffusion MRI Indices and their Relation to Cognitive Impairment in Brain Aging: The updated multi-protocol approach in ADNI3

2018 ◽  
Author(s):  
Artemis Zavaliangos-Petropulu ◽  
Talia M. Nir ◽  
Sophia I. Thomopoulos ◽  
Robert I. Reid ◽  
Matt A. Bernstein ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
White Matter ◽  
Rating Scale ◽  
Brain Aging ◽  
Screening Tools ◽  
Disease Assessment ◽  
Clinical Impairment ◽  
Clinical Measures

AbstractBrain imaging with diffusion-weighted MRI (dMRI) is sensitive to microstructural white matter changes associated with brain aging and neurodegeneration. In its third phase, the Alzheimer’s Disease Neuroimaging Initiative (ADNI3) is collecting data across multiple sites and scanners using different dMRI acquisition protocols, to better understand disease effects. It is vital to understand when data can be pooled across scanners, and how the choice of dMRI protocol affects the sensitivity of extracted measures to differences in clinical impairment. Here, we analyzed ADNI3 data from 317 participants (mean age: 75.4±7.9 years; 143 men/174 women), who were each scanned at one of 47 sites with one of six dMRI protocols using scanners from three different manufacturers. We computed four standard diffusion tensor imaging (DTI) indices including fractional anisotropy (FADTI) and mean, radial, and axial diffusivity, and one FA index based on the tensor distribution function (FATDF), in 24 bilaterally averaged white matter regions of interest. We found that protocol differences significantly affected dMRI indices, in particular FADTI. We ranked the diffusion indices for their strength of association with four clinical assessments. In addition to diagnosis, we evaluated cognitive impairment as indexed by three commonly used screening tools for detecting dementia and Alzheimer’s disease: the Alzheimer’s Disease Assessment Scale (ADAS-cog), the Mini-Mental State Examination (MMSE), and the Clinical Dementia Rating scale sum-of-boxes (CDR-sob). Using a nested random-effects model to account for protocol and site, we found that across all dMRI indices and clinical measures, the hippocampal-cingulum and fornix (crus) / stria terminalis regions most consistently showed strong associations with clinical impairment. Overall, the greatest effect sizes were detected in the hippocampal-cingulum and uncinate fasciculus for associations between axial or mean diffusivity and CDR-sob. FATDF detected robust widespread associations with clinical measures, while FADTI was the weakest of the five indices for detecting associations. Ultimately, we were able to successfully pool dMRI data from multiple acquisition protocols from ADNI3 and detect consistent and robust associations with clinical impairment and age.

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