scholarly journals Identification of Cathepsin D as a Plasma Biomarker for Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 138
Author(s):  
Jae-Whan Kim ◽  
Soon-Young Jung ◽  
Youngbin Kim ◽  
Hansol Heo ◽  
Chang-Hyung Hong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cathepsin D ◽  
Rating Scale ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Clinical Dementia Rating ◽  
Multivariable Logistic Regression Model ◽  
Related Factors ◽  
Lysosomal Protease

Although Alzheimer’s disease (AD) is the most common neurodegenerative disease, there are still no drugs available to treat or prevent AD effectively. Here, we examined changes in levels of selected proteins implicated in the pathogenesis of AD using plasma samples of control subjects and patients with cognition impairment. To precisely categorize the disease, fifty-six participants were examined with clinical cognitive tests, amyloid positron emission tomography (PET) scan, and white matter hyperintensities scored by magnetic resonance imaging. Plasma cathepsin D levels of the subjects were examined by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Correlation of plasma cathepsin D levels with AD-related factors and clinical characteristics were examined by statistical analysis. By analyzing quantitative immunoblot and ELISA, we found that the plasma level of cathepsin D, a major lysosomal protease, was decreased in the group with amyloid plaque deposition at the brain compared to the control group. The level of plasma cathepsin D was negatively correlated with clinical dementia rating scale sum of boxes (CDR-SB) scores. In addition, our integrated multivariable logistic regression model suggests the high performance of plasma cathepsin D level for discriminating AD from non-AD. These results suggest that the plasma cathepsin D level could be developed as a diagnostic biomarker candidate for AD.

scholarly journals Efficacy and Limitations of rCBF-SPECT in the Diagnosis of Alzheimer’s Disease With Amyloid-PET

2019 ◽  
Vol 34 (5) ◽  
pp. 314-321
Author(s):  
Miwako Takahashi ◽  
Tomoko Tada ◽  
Tomomi Nakamura ◽  
Keitaro Koyama ◽  
Toshimitsu Momose
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Amyloid Pet ◽  
Clinical Dementia Rating ◽  
Positron Emission ◽  
Rcbf Spect

This study aimed to assess efficacy and limitations of regional cerebral blood flow imaging using single-photon emission computed tomography (rCBF-SPECT) in the diagnosis of Alzheimer’s disease (AD) with amyloid-positron emission tomography (amyloid-PET). Thirteen patients, who underwent both rCBF-SPECT and amyloid-PET after clinical diagnosis of AD or mild cognitive impairment, were retrospectively identified. The rCBF-SPECTs were classified into 4 grades, from typical AD pattern to no AD pattern of hypoperfusion; amyloid-beta (Aβ) positivity was assessed by amyloid-PET. Four patients were categorized into a typical AD pattern on rCBF-SPECT, and all were Aβ+. The other 9 patients did not exhibit a typical AD pattern; however, 4 were Aβ+. The Mini-Mental State Examination score and Clinical Dementia Rating scale were not significantly different between Aβ+ and Aβ– patients. A typical AD pattern on rCBF-SPECT can reflect Aβ+; however, if not, rCBF-SPECT has a limitation to predict amyloid pathology.

scholarly journals Predictors of rapid cognitive decline in Alzheimer's disease: results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing

2011 ◽  
Vol 24 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Alessandro Sona ◽  
Ping Zhang ◽  
David Ames ◽  
Ashley I. Bush ◽  
Nicola T. Lautenschlager ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Rating Scale ◽  
Cognitive Status ◽  
Imaging Biomarkers ◽  
Clinical Dementia Rating ◽  
Factors Associated ◽  
Biological Variables ◽  
Rapid Cognitive Decline

ABSTRACTBackground: The AIBL study, which commenced in November 2006, is a two-center prospective study of a cohort of 1112 volunteers aged 60+. The cohort includes 211 patients meeting NINCDS-ADRDA criteria for Alzheimer's disease (AD) (180 probable and 31 possible). We aimed to identify factors associated with rapid cognitive decline over 18 months in this cohort of AD patients.Methods: We defined rapid cognitive decline as a drop of 6 points or more on the Mini-Mental State Examination (MMSE) between baseline and 18-month follow-up. Analyses were also conducted with a threshold of 4, 5, 7 and 8 points, as well as with and without subjects who had died or were too severely affected to be interviewed at 18 months and after, both including and excluding subjects whose AD diagnosis was “possible” AD. We sought correlations between rapid cognitive decline and demographic, clinical and biological variables.Results: Of the 211 AD patients recruited at baseline, we had available data for 156 (73.9%) patients at 18 months. Fifty-one patients were considered rapid cognitive decliners (32.7%). A higher Clinical Dementia Rating scale (CDR) and higher CDR “sum of boxes” score at baseline were the major predictors of rapid cognitive decline in this population. Furthermore, using logistic regression model analysis, patients treated with a cholinesterase inhibitor (CheI) had a higher risk of being rapid cognitive decliners, as did males and those of younger age.Conclusions: Almost one third of patients satisfying established research criteria for AD experienced rapid cognitive decline. Worse baseline functional and cognitive status and treatment with a CheI were the major factors associated with rapid cognitive decline over 18 months in this population.

Associations of Blood Pressure with Functional and Cognitive Changes in Patients with Alzheimer's Disease

2016 ◽  
Vol 41 (5-6) ◽  
pp. 314-323 ◽  
Author(s):  
Fabricio Ferreira de Oliveira ◽  
Elizabeth Suchi Chen ◽  
Marilia Cardoso Smith ◽  
Paulo Henrique Ferreira Bertolucci
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Late Onset ◽  
Angiotensin Receptor Blockers ◽  
Channel Blockers ◽  
Clinical Dementia Rating ◽  
Cognitive Changes ◽  
Converting Enzyme Inhibitors

Background: Midlife hypertension followed by late life hypotension resulting from neurodegeneration increases amyloidogenesis and tauopathy. Methods: Consecutive outpatients with late-onset Alzheimer's disease (AD) at various stages and their respective caregivers were assessed for score variations in 1 year of tests assessing caregiver burden, functionality and cognition according to blood pressure (BP) variations and APOE haplotypes, while also taking into account differential effects of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, diuretics, or no antihypertensive medication on score changes. The diagnosis and treatment of arterial hypertension followed the JNC 7 report. Results: Variations in systolic BP (-11.76 ± 17.1 mm Hg), diastolic BP (-4.92 ± 10.3 mm Hg) and pulse pressure (-6.84 ± 12.6 mm Hg) were significant after 1 year (n = 191; ρ < 0.01). For APOE4+ carriers, rises in systolic or diastolic BP improved Clinical Dementia Rating Scale Sum of Boxes scores (ρ < 0.04), with marginally significant improvements in Mini-Mental State Examination scores resulting from risen systolic (ρ = 0.069) or diastolic BP (ρ = 0.079), and in basic independence only regarding risen diastolic BP (ρ = 0.055). APOE4- carriers resisted any functional or cognitive effects of BP variations. No differences were found regarding any antihypertensive class for variations in BP or any test scores, regardless of APOE haplotypes. Conclusions: Targeting mild BP elevations brings better functional and cognitive results for APOE4+ carriers with AD.

scholarly journals Effect of a Cognitive Training Program on the Platelet APP Ratio in Patients with Alzheimer’s Disease

2020 ◽  
Vol 21 (14) ◽  
pp. 5110
Author(s):  
Tiziana Casoli ◽  
Cinzia Giuli ◽  
Marta Balietti ◽  
Paolo Fabbietti ◽  
Fiorenzo Conti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Cognitive Training ◽  
Control Group ◽  
Word Fluency ◽  
Clinical Dementia Rating ◽  
Cognitive Improvement ◽  
App Ratio

In patients with Alzheimer’s disease (AD), synaptic plasticity seems to be involved in cognitive improvement induced by cognitive training. The platelet amyloid precursor protein (APP) ratio (APPr), i.e., the ratio between two APP isoforms, may be a useful peripheral biomarker to investigate synaptic plasticity pathways. This study evaluates the changes in neuropsychological/cognitive performance and APPr induced by cognitive training in AD patients participating in the “My Mind Project”. Neuropsychological/cognitive variables and APPr were evaluated in the trained group (n = 28) before a two-month experimental protocol, immediately after its termination at follow-up 1 (FU1), after 6 months at follow-up 2 (FU2), and after 24 months at follow-up 3 (FU3). The control group (n = 31) received general psychoeducational training for two months. Some memory and attention parameters were significantly improved in trained vs. control patients at FU1 and FU2 compared to baseline (Δ values). At FU3, APPr and Mini Mental State Examination (MMSE) scores decreased in trained patients. Δ APPr correlated significantly with the Δ scores of (i) MMSE at FU1, (ii) the prose memory test at FU2, and (iii) Instrumental Activities of Daily Living (IADL), the semantic word fluency test, Clinical Dementia Rating (CDR), and the attentive matrices test at FU3. Our data demonstrate that the platelet APPr correlates with key clinical variables, thereby proving that it may be a reliable biomarker of brain function in AD patients.

Serotonin 5-HT2A Receptor Binding in Platelets From Patients With Alzheimer's Disease or Vascular Dementia

2000 ◽  
Vol 12 (4) ◽  
pp. 537-545 ◽  
Author(s):  
Olav Spigset ◽  
Christer Wilhelmsson ◽  
Tom Mjörndal ◽  
Sture Eriksson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Receptor Binding ◽  
Rating Scale ◽  
Control Group ◽  
Receptor Status ◽  
Serotonin System ◽  
Significant Difference ◽  
Scale Scores

It is well known that abnormalities in the brain serotonin system exist in patients with dementia. The present study was performed in order to investigate whether a peripheral serotonin system marker, the platelet 5-HT2A receptor, is affected in dementia. Thirty-eight patients with Alzheimer's disease (AD), 13 patients with vascular dementia, and 40 healthy controls were included in the study. There were no significant differences in receptor density for 5-HT2A receptor binding between the groups. Affinity of the radioligand to the receptor was significantly lower in AD than in vascular dementia and in the controls (p = .006 and p = .003, respectively), whereas there was no significant difference between the vascular dementia group and the control group. In 12 patients, treatment with citalopram was started due to depression or agitation. This treatment significantly reduced the Behavioral Pathology in Alzheimer's Disease Rating Scale scores (p = .001), but did not affect the platelet 5-HT2A receptor status. There was no correlation between 5-HT2A receptor status before treatment and the therapeutic effect of citalopram. The study indicates that platelet 5-HT2A receptor status is of limited value as a peripheral marker in dementia.

Odor identification and cognitive abilities in Alzheimer’s disease

2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Mladenka Tkalčić ◽  
Nika Spasić ◽  
Matea Ivanković ◽  
Alessandra Pokrajac-Bulian ◽  
Daša Bosanac
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Abilities ◽  
Rating Scale ◽  
Cognitive Status ◽  
Odor Identification ◽  
Control Group ◽  
Elderly Persons ◽  
Neuropsychological Measures ◽  
Category Fluency

AbstractResearch results indicate systemic odor identification deficits in patients with Alzheimer’s disease (AD). The aims of this study were: 1) to compare the ability to identify different odors and to compare cognitive status among patients with AD, patients with vascular dementia (VaD) and a comparison group of elderly persons; 2) to test the efficiency of olfactory and neuropsychological measures to classify patients and 3) to relate the odor identification ability with cognitive functioning for each group, respectively. The participants were 15 patients with AD, 11 patients with VaD and 30 non-demented elderly persons, age range 58 to 90. To assess olfactory function, we used the Scandinavian Odor-Identification Test. To assess cognitive functions, we used the Dementia Rating Scale-2, the Clock Drawing Test, the Boston Naming Test and the Category Fluency Test. The ANOVA showed that patients with AD correctly identifed significantly fewer odors presented to them compared to patients with VaD and control group. Patients with AD achieved significantly lower scores on all neuropsychological measures compared to the control group and differ in the DRS-2 total score, initiation/perseveration, constructive and naming abilities comparing to patients with VaD. Discriminant analysis showed that category fluency and olfactory identification were the best predictors of AD. Significant correlations were found between the olfactory and initiation/perseveration, memory and animal naming abilities for patients with AD. Differences among patients with AD, VaD and elderly persons exist in their abilities to identify odors. The findings suggest that olfactory functional testing in combination with memory testing are important.

scholarly journals Education, leisure activities and cognitive and functional ability of Alzheimer's disease patients: A follow-up study

2013 ◽  
Vol 7 (2) ◽  
pp. 181-189 ◽  
Author(s):  
Margarida Sobral ◽  
Constança Paúl
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Functional Ability ◽  
Rating Scale ◽  
Leisure Activities ◽  
Functional Decline ◽  
Clinical Dementia Rating ◽  
High Participation ◽  
Relevant Variables

ABSTRACT Education and participation in leisure activities appear to be highly relevant variables in Alzheimer's disease (AD) and usually form the basis of the Cognitive Reserve construct. Objective: [A] To determine the association between education, cognitive and functional ability of AD patients; [B] To determine the association between participation in leisure activities and cognitive and functional ability of AD patients; [C] To evaluate the association of education and participation in leisure activities in the course of AD. Methods: Functional and neuropsychological abilities of 120 outpatients with probable AD were evaluated at baseline, at 36 and 54 months. Data collected at baseline included socio-demographics, clinical variables, education and frequency of participation in leisure activities throughout life. All participants and/or caregivers answered the questionnaire, "Participation in leisure activities throughout life" while patients completed the MMSE, the Clinical Dementia Rating scale, neuropsychological tests from the Lisbon Screening for Dementia Assessment, Barthel Index and Lawton and Brody's Index. Results: AD patients with higher levels of education achieved better results on cognitive tests. The participants with higher participation in leisure activities exhibited better results on cognitive and functional tests than those with lower participation. The disease progression was linear and progressed similarly regardless of the level of education of participants. However, the results suggest a slower disease progression in patients with a higher level of participation in leisure activities throughout their lives. Conclusion: AD patients with high education and high participation in leisure activities may benefit from a slower cognitive and functional decline after diagnosis of AD.

scholarly journals 97 Potentially Inappropriate Medications in Patients with Alzheimer’s Disease: Data from NILVAD

2019 ◽  
Vol 48 (Supplement_3) ◽  
pp. iii1-iii16
Author(s):  
Claire Murphy ◽  
Adam H Dyer ◽  
Brian Lawlor ◽  
Sean P Kennelly
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Drug Events ◽  
Rating Scale ◽  
Secondary Analysis ◽  
Median Number ◽  
Potentially Inappropriate Medications ◽  
Clinical Dementia Rating ◽  
Start Criteria ◽  
Inappropriate Medications

Abstract Background Prescription of Potentially Inappropriate Medications (PIMs) is common in older adults and is associated with adverse drug events, hospitalisation and mortality. Less well described are the patterns and predictors of PIM usage in patients with Alzheimer’s Disease (AD), a patient group who may be particularly vulnerable to polypharmacy and medication associated adverse events. Methods Secondary analysis of the NILVAD trial, an international phase three trial of Nilvadipine in mild/moderate AD. The v2 STOPP/START criteria were individually applied by a physician to each participant’s medication list and cross-reference with their medical history to identify PIM usage. Predictors of PIM usage were modelled using binary logistic regression. Results Five-hundred and ten patients with AD were included (mean age 72.8 +/-8.3 years; 62% female). The median number of prescribed medications was 5 (IQR 3-7). Over half (55.5%) were prescribed at least one PIM, whilst a minority of patients (14.8%) were prescribed three or more PIMs. The most frequent PIMs were benzodiazepines >4 weeks without indication (n = 55), long-term Proton-Pump Inhibitor (PPI) use without appropriate indication (n = 49), use of non-steroidal analgesics without use of PPI (n=19) and antimuscarinic use in dementia (n= 18). On multivariate analysis, significant predictors of PIM use were higher total number of medications (p=0.001; OR 1.52; 1.36-1.59) in addition to greater AD severity, as rated using the Clinical Dementia Rating Scale Sum-of-Boxes (CDR-sb) (p=0.024; OR 1.18; 1.02-1.35). Conclusion The majority of older patients with AD were prescribed at least one PIM. Usage of PIMs was associated with greater number of medications and increased dementia severity. Particularly concerning is the potentially inappropriate use of benzodiazepines and anti-muscarinic agents in this population, given recent evidence for the adverse cognitive profile associated with these medications. De-prescribing and medication review interventions aimed particularly at patients with AD are warranted.

scholarly journals Association between plasma exosome neurogranin and brain structure in patients with Alzheimer’s disease: a protocol study

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e036990 ◽  
Author(s):  
MengFei He ◽  
Li Sun ◽  
Wenhui Cao ◽  
Changhao Yin ◽  
Wenqiang Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Rating Scale ◽  
Early Stage ◽  
Verbal Learning ◽  
Blood Collection ◽  
Clinical Dementia Rating ◽  
Protocol Study ◽  
Medical University

IntroductionNeurogranin is known to be significantly elevated in patients with Alzheimer’s disease (AD) and may be an effective clinical predictor of cognitive decline and neurodegeneration. Amnestic mild cognitive impairment (aMCI) is an intermediate disease state between normal cognitive ageing and dementia, the latter of which can easily revert to AD. There remains significant uncertainty regarding the conversion of aMCI to AD, and therefore, elucidating such progression is paramount to the field of cognitive neuroscience. In this protocol study, we therefore aim to investigate the changes in plasma neurogranin in the early stage of AD and the mechanism thereof regarding the cognitive progression towards AD.Methods and analysisIn this study, patients with aMCI and AD patients (n=70 each) will be recruited at the memory clinic of the Department of Neurology of Hongqi Hospital affiliated with the Mudanjiang Medical University of China. Healthy older controls (n=70) will also be recruited from the community. All subjects will undergo neuroimaging and neuropsychological evaluations in addition to blood collection at the first year and the third year. We hope to identify a new biomarker of cognitive decline associated with AD and characterise its behaviour throughout the progression of aMCI to AD. This work will reveal novel targets for the therapeutic prevention, diagnosis and treatment of AD. The primary outcome measures will be (1) neuropsychological evaluation, including Mini-Mental State Examination, Montreal Cognitive Assessment, Clinical Dementia Rating scale, Shape Trail Test-A&B, Auditory Verbal Learning Test-HuaShan version; (2) microstructural alterations and hippocampal features from MRI scans; and (3) neurogranin levels in the neuronal-derived exosomes from peripheral blood samples.Ethics and disseminationThe ethics committee of the Hongqi Hospital affiliated with the Mudanjiang Medical University of China has approved this study protocol. The results will be published in peer-reviewed journals and presented at national or international scientific conferences.Trial registration numberChiCTR2000029055.

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