scholarly journals Predicting Clinical Dementia Rating Using Blood RNA Levels

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 706
Author(s):  
Justin B. Miller ◽  
John S. K. Kauwe
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Operating Characteristic ◽  
Predictive Accuracy ◽  
Cognitive Status ◽  
Clinical Dementia Rating ◽  
Intracellular Channel ◽  
Rna Levels

The Clinical Dementia Rating (CDR) is commonly used to assess cognitive decline in Alzheimer’s disease patients and is included in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. We divided 741 ADNI participants with blood microarray data into three groups based on their most recent CDR assessment: cognitive normal (CDR = 0), mild cognitive impairment (CDR = 0.5), and probable Alzheimer’s disease (CDR ≥ 1.0). We then used machine learning to predict cognitive status using only blood RNA levels. Only one probe for chloride intracellular channel 1 (CLIC1) was significant after correction. However, by combining individually nonsignificant probes with p-values less than 0.1, we averaged 87.87% (s = 1.02) predictive accuracy for classifying the three groups, compared to a 55.46% baseline for this study due to unequal group sizes. The best model had an overall precision of 0.902, recall of 0.895, and a receiver operating characteristic (ROC) curve area of 0.904. Although we identified one significant probe in CLIC1, CLIC1 levels alone were not sufficient to predict dementia status and cannot be used alone in a clinical setting. Additional analyses combining individually suggestive, but nonsignificant, blood RNA levels were significantly predictive and may improve diagnostic accuracy for Alzheimer’s disease. Therefore, we propose that patient features that do not individually predict cognitive status might still contribute to overall cognitive decline through interactions that can be elucidated through machine learning.

scholarly journals Predicting Clinical Dementia Rating Using Blood RNA Levels

2019 ◽  
Author(s):  
Justin B. Miller ◽  
John S.K. Kauwe ◽  
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microarray Data ◽  
Predictive Accuracy ◽  
Cognitive Status ◽  
Clinical Dementia Rating ◽  
P Values ◽  
Intracellular Channel ◽  
Rna Levels

Structured AbstractINTRODUCTIONThe Clinical Dementia Rating (CDR) is commonly used to assess cognitive decline in Alzheimer’s disease patients.METHODSWe divided 741 participants with blood microarray data in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) into three groups based on their most recent CDR assessment: cognitive normal (CDR=0), mild dementia (CDR=0.5), and probable AD (CDR≥1.0). We then used machine learning to predict cognitive status using only blood RNA levels.RESULTSOne chloride intracellular channel 1 (CLIC1) probe was significant. By combining nonsignificant probes with p-values less than 0.1, we averaged 87.87 (s = 1.02)% predictive accuracy in classifying the three groups, compared to a 55.46% baseline for this study.DISCUSSIONWe identified one significant probe in CLIC1. However, CLIC1 levels alone were not sufficient to determine dementia status. We propose that combining individually suggestive, but nonsignificant, blood RNA levels can significantly improve diagnostic accuracy.

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.

Influence of Educational Attainment on Cognition-Based Intervention Programs for Persons with Mild Alzheimer’s Disease

2016 ◽  
Vol 22 (5) ◽  
pp. 577-582 ◽  
Author(s):  
Israel Contador ◽  
Bernardino Fernández-Calvo ◽  
Francisco Ramos ◽  
Javier Olazarán
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Effect Size ◽  
Study Groups ◽  
Total Sample ◽  
Cognitive Intervention ◽  
Potential Effect ◽  
Cognitive Status ◽  
Disease Assessment

AbstractObjectives: This research retrospectively analyzed the effect of education on cognitive interventions carried out in patients with mild Alzheimer’s disease (AD). Methods: The total sample consisted of 75 patients with mild AD receiving treatment with cholinesterase inhibitors. The participants were divided into two groups: cognitive intervention (IG; n=45) and waiting list (WLG; n=30). Patients in the IG received either the Big Brain Academy (n=15) or the Integrated Psychostimulation Program (n=30) during 12 weeks. The influence of education on intervention effect was analyzed comparing mean change scores of the two study groups in the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog), stratified by educational level. The potential effect of age, sex, cognitive status, and type of intervention was examined using post hoc stratification analyses. Results: Higher education was associated with faster cognitive decline in the WLG (effect size=0.51; p<.01). However, cognitive evolution was not influenced by education in the IG (effect size=0.12; p=.42). Conclusions: Our results suggest that cognitive intervention might delay accelerated cognitive decline in higher educated individuals with mild AD. (JINS, 2016, 23, 1–6)

scholarly journals Apathy in Alzheimer's disease: Contribution to a clinical view on progression of dementia

2010 ◽  
Vol 4 (3) ◽  
pp. 188-193 ◽  
Author(s):  
Florindo Stella ◽  
Larissa Pires de Andrade ◽  
Thays Martins Vital ◽  
Flávia Gomes de Melo Coelho ◽  
Carla Manuela Crispim Nascimento ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mini Mental State Examination ◽  
Cognitive Status ◽  
Clinical Dementia Rating ◽  
Global Deterioration Scale ◽  
Severe Dementia ◽  
Coefficient Corrélation ◽  
The Relationship ◽  
State Examination

Abstract In addition to cognitive impairment, apathy is increasingly recognized as an important neuropsychiatric syndrome in Alzheimer's disease (AD). Aims: To identify the relationship between dementia severity and apathy levels, and to discuss the association of this condition with other psychopathological manifestations in AD patients. Methods: This study involved 15 AD patients (mean age: 77 years; schooling: 4.9 years), with mild, moderate and severe dementia, living in Rio Claro SP, Brazil. Procedures included evaluation of cognitive status by the Mini-Mental State Examination, Clinical Dementia Rating, and Global Deterioration Scale. Apathy syndrome was assessed by the Apathy Evaluation Scale and Neuropsychiatric Inventory (NPI-apathy domain). Other psychopathological manifestations such as depression were also considered. Results: Patients with more severe dementia presented higher levels of apathy, reinforcing the hypothesis that apathy severity aggravates as the disease progresses. Using the Spearman coefficient correlation an association was identified between the MMSE and Apathy Evaluation Scale (r=0.63; p=0.01), and also between the MMSE and NPI-apathy domain (r=0.81; p=0.01). Associations were also found between the Global Deterioration Scale and Apathy Evaluation Scale (r=0.58; p=0.02), and between the Global Deterioration Scale and NPI-apathy domain (r=0.81; p=0.01). Conclusions: Apathy is a distinct syndrome among patients with AD and increases with global deterioration.

scholarly journals Gray matter volume and estimated brain age gap are not associated with sleep-disordered breathing in subjects from the ADNI cohort

2019 ◽  
Author(s):  
Bahram Mohajer ◽  
Nooshin Abbasi ◽  
Esmaeil Mohammadi ◽  
Habibolah Khazaie ◽  
Ricardo S. Osorio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Gray Matter ◽  
Sleep Disordered Breathing ◽  
Brain Aging ◽  
Gray Matter Volume ◽  
Cognitive Status ◽  
Matter Volume ◽  
Disordered Breathing

AbstractAlzheimer’s disease (AD) and sleep-disordered breathing (SDB) are prevalent conditions with rising burden. It is suggested that SDB may contribute to cognitive decline and advanced aging. Here, we assessed the link between self-reported SDB and gray matter volume in patients with AD, mild cognitive impairment (MCI) and healthy controls (HC). We further investigated whether SDB was associated with advanced brain aging. We included a total of 330 participants, divided based on self-reported history of SDB, and matched across diagnoses for age, sex and presence of the ApoE4 allele, from the Alzheimer’s Disease Neuroimaging Initiative. Gray-matter volume was measured using voxel-wise morphometry and differences reflecting SDB, cognitive status, and their interaction were evaluated. Further, using an age-prediction model fitted on gray-matter data of external datasets, we predicted study participants’ age from their structural scans. Cognitive decline (MCI/AD diagnosis) and advanced age were associated with lower gray matter volume in various regions, particularly in the bilateral temporal lobes. BrainAGE was well predicted from the morphological data in HC and, as expected, elevated in MCI and particularly in AD. However, there was neither a significant difference between regional gray matter volume in any diagnostic group related to the SDB status nor an SDB-by-cognitive status interaction. Also, we found neither a significant difference in BrainAGE gap (estimated - chronological age) related to SDB nor an SDB-by-cognitive status interaction. In summary, contrary to our expectations, we were not able to find a general nor a diagnostic specific effect on either gray-matter volumetric or brain aging.Statement of significanceDementia syndromes including Alzheimer’s disease (AD), are a major global concern, and unraveling modifiable predisposing risk factors is indispensable. Sleep-disordered breathing (SDB) and its most prevalent form, obstructive sleep apnea, are suggested as modifiable risk factors of AD, but their contribution to AD hallmarks, like brain atrophy and advanced brain aging, is not clear to this day. While self-reported SDB is suggested to propagate aging process and cognitive decline to AD in clinical studies, here, we demonstrated that, SDB might not necessarily associate to brain atrophy and the advanced brain aging assessed by morphological data, in AD progession. However, multimodal longitudinal studies with polysomnographic assessment of SDB are needed to confirm such fundings.

scholarly journals Benfotiamine and Cognitive Decline in Alzheimer’s Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial

2020 ◽  
Vol 78 (3) ◽  
pp. 989-1010
Author(s):  
Gary E. Gibson ◽  
José A. Luchsinger ◽  
Rosanna Cirio ◽  
Huanlian Chen ◽  
Jessica Franchino-Elder ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Placebo Group ◽  
Cognitive Decline ◽  
Controlled Trial ◽  
Amyloid Β ◽  
Cognitive Outcomes ◽  
Disease Assessment ◽  
Clinical Dementia Rating ◽  
Positron Emission

Background: In preclinical models, benfotiamine efficiently ameliorates the clinical and biological pathologies that define Alzheimer’s disease (AD) including impaired cognition, amyloid-β plaques, neurofibrillary tangles, diminished glucose metabolism, oxidative stress, increased advanced glycation end products (AGE), and inflammation. Objective: To collect preliminary data on feasibility, safety, and efficacy in individuals with amnestic mild cognitive impairment (aMCI) or mild dementia due to AD in a placebo-controlled trial of benfotiamine. Methods: A twelve-month treatment with benfotiamine tested whether clinical decline would be delayed in the benfotiamine group compared to the placebo group. The primary clinical outcome was the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Secondary outcomes were the clinical dementia rating (CDR) score and fluorodeoxyglucose (FDG) uptake, measured with brain positron emission tomography (PET). Blood AGE were examined as an exploratory outcome. Results: Participants were treated with benfotiamine (34) or placebo (36). Benfotiamine treatment was safe. The increase in ADAS-Cog was 43% lower in the benfotiamine group than in the placebo group, indicating less cognitive decline, and this effect was nearly statistically significant (p = 0.125). Worsening in CDR was 77% lower (p = 0.034) in the benfotiamine group compared to the placebo group, and this effect was stronger in the APOE ɛ4 non-carriers. Benfotiamine significantly reduced increases in AGE (p = 0.044), and this effect was stronger in the APOE ɛ4 non-carriers. Exploratory analysis derivation of an FDG PET pattern score showed a treatment effect at one year (p = 0.002). Conclusion: Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD.

Blink rate study in patients with Alzheimer's disease, Mild Cognitive Impairment and Subjective Cognitive Decline

2021 ◽  
Vol 19 ◽  
Author(s):  
Fabrizia D’Antonio ◽  
Maria Ilenia De Bartolo ◽  
Gina Ferrazzano ◽  
Micaela Sepe Monti ◽  
Letizia Imbriano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Cognitive Status ◽  
Subjective Cognitive Decline ◽  
Blink Rate ◽  
Compensatory Mechanisms ◽  
Rate Study

Background: Blink rate (BR) is considered a marker of dopaminergic activity in humans. BR is increased in patients with Mild Cognitive Impairment (MCI), but no study has yet investigated whether BR changes with the progression of cognitive decline from MCI to Alzheimer’s disease (AD) and whether BR abnormalities are present in subjects with Subjective Cognitive Decline (SCD). Objective: The aim of our study was to assess BR in patients with AD, MCI, and SCD and to correlate BR with demographic and clinical features of cognitive decline. Methods: We enrolled 22 subjects with SCD, 23 with MCI, and 18 with AD and a group of 20 age-matched healthy controls (HCs). Cognitive function was assessed by testing global cognitive status and frontal, attentional, memory, verbal, and visuospatial functions. BR was measured by counting the number of blinks per minute. Results: MCI subjects had an increased BR (p<0.001), whereas AD subjects had a lower BR than HCs (p<0.05). Conversely, SCD subjects had a BR similar to HCs. No significant correlations emerged between neuropsychological scores and BR in SCD, MCI, and AD subjects. Conclusion: Increased BR in MCI likely reflects early compensatory mechanisms occurring before AD, whereas decreased BR in AD suggests dopaminergic system involvement in this condition.

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.

scholarly journals Impact of coronary heart disease on cognitive decline in Alzheimer’s disease: a prospective longitudinal cohort study in primary care

2016 ◽  
Vol 67 (655) ◽  
pp. e111-e117 ◽  
Author(s):  
Markus Bleckwenn ◽  
Luca Kleineidam ◽  
Michael Wagner ◽  
Frank Jessen ◽  
Siegfried Weyerer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Coronary Heart Disease ◽  
Cohort Study ◽  
Heart Disease ◽  
Cognitive Decline ◽  
Late Onset ◽  
Cardiovascular Prevention ◽  
Clinical Dementia Rating ◽  
Prospective Longitudinal

BackgroundArteriosclerotic disorders increase the risk of dementia. As they have common causes and risk factors, coronary heart disease (CHD) could influence the course of dementia.AimTo determine whether CHD increases the speed of cognitive decline in Alzheimer’s disease, and to discuss the potential for secondary cardiovascular prevention to modify this decline.Design and settingProspective multicentre cohort study in general practices in six cities in Germany.MethodParticipants were patients with probable mild-to-moderate Alzheimer’s dementia or mixed dementia (n = 118; mean age 85.6 [±3.4] years, range 80–96 years). The authors assessed the presence of CHD according to the family physicians’ diagnosis. Cognitive performance was measured during home visits for up to 3 years in intervals of 6 months, using Mini Mental State Examination (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR-SoB). The authors also recorded whether patients died in the observation period.ResultsAt baseline, 65 patients (55%) had CHD and/or a heart condition following a myocardial infarction. The presence of CHD accelerated cognitive decline (MMSE, P<0.05) by about 66%, and reduced cognitive-functional ability (CDR-SoB, P<0.05) by about 83%, but had no impact on survival.ConclusionThe study shows that CHD has a significant influence on cognitive decline in older patients with late-onset dementia. The dementia process might therefore be positively influenced by cardiovascular prevention, and this possible effect should be further investigated.

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