scholarly journals Empirically derived composite cognitive test scores to predict preclinical and clinical stages of Alzheimer’s disease

2021 ◽  
Vol 17 (S5) ◽  
Author(s):  
Rosita Shishegar ◽  
Tze Young Chai ◽  
Timothy Cox ◽  
Fiona Lamb ◽  
Joanne S. Robertson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Test Scores ◽  
Cognitive Test ◽  
Clinical Stages

scholarly journals SHORT-TERM PRACTICE EFFECTS AND AMYLOID DEPOSITION: PROVIDING INFORMATION ABOVE AND BEYOND BASELINE COGNITION

2017 ◽  
pp. 1-6
Author(s):  
K. Duff ◽  
D.B. Hammers ◽  
B.C.A. Dalley ◽  
K.R. Suhrie ◽  
T.J. Atkinson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Test Scores ◽  
Amyloid Deposition ◽  
Cognitive Testing ◽  
Practice Effects ◽  
Cognitive Test ◽  
Cognitive Tests ◽  
Short Term

Background: Practice effects, which are improvements in cognitive test scores due to repeated exposure to testing materials, may provide information about Alzheimer’s disease pathology, which could be useful for clinical trials enrichment. Objectives: The current study sought to add to the limited literature on short-term practice effects on cognitive tests and their relationship to amyloid deposition on neuroimaging. Participants: Twenty-seven, non-demented older adults (9 cognitively intact, 18 with mild cognitive impairment) received amyloid imaging with 18F-Flutemetamol, and two cognitive testing sessions across one week to determine practice effects. Results: A composite measure of 18F-Flutemetamol uptake correlated significantly with all seven cognitive tests scores on the baseline battery (r’s = -0.61 – 0.59, all p’s<0.05), with higher uptake indicating poorer cognition. Practice effects significantly added to the relationship (above and beyond the baseline associations) with 18F-Flutemetamol uptake on 4 of the 7 cognitive test scores (partial r’s = -0.45 – 0.44, p’s<0.05), with higher uptake indicating poorer practice effects. The odds ratio of being “amyloid positive” was 13.5 times higher in individuals with low practice effects compared to high practice effects. Conclusions: Short-term practice effects over one week may be predictive of progressive dementia and serve as an affordable screening tool to enrich samples for preventative clinical trials in Alzheimer’s disease.

scholarly journals Predicting Progression & Cognitive Decline in Amyloid-Positive Patients with Alzheimer's Disease

2021 ◽  
Author(s):  
Hákon Valur Dansson ◽  
Lena Stempfle ◽  
Hildur Egilsdóttir ◽  
Alexander Schliep ◽  
Erik Portelius ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Disease Progression ◽  
Test Scores ◽  
Amyloid Β ◽  
Cognitive Test ◽  
Progression Rate ◽  
Specific Level ◽  
Clinical Variables

Abstract BackgroundIn Alzheimer’s disease (AD), amyloid- β (Aβ) peptides aggregate in the brain forming amyloid plaques, which are a key pathological hallmark of the disease. However, plaques may also be present in cognitively unimpaired elderly individuals. Therefore, it is of great value to explain the variance in disease progression among patients with Aβ pathology. MethodsA cohort of n= 2293 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database was selected to study heterogeneity in disease progression for individuals with Aβ plaque pathology. The analysis used baseline clinical variables including demographics, genetic markers and neuropsychological data to predict how the cognitive ability and AD diagnosis of subjects progressed using statistical models and machine learning. Due to the limited prevalence of Aβ pathology, models fit only to Aβ-positive subjects were compared to models fit to an extended cohort including subjects without established Aβ pathology, adjusting for covariate differences between the cohorts. ResultsAβ pathology status was determined based the Aβ 42 /Aβ 40 ratio. The best predictive model of change in cognitive test scores for Aβ-positive subjects at the two-year follow-up achieved an R 2 score of 0.388 while the best model predicting adverse changes in diagnosis achieved a weighted F1 score of 0.791. Conforming to expectations, Aβ-positive subjects declined faster on average than those without Aβ pathology, but the specific level of Aβ plaques was not predictive of progression rate. For the four-year prediction task of cognitive score change, the best model achieved an R 2 score of 0.325 and it was found that fitting models to the extended cohort substantially improved performance. Moreover, using all clinical variables outperformed the best model based only on baseline cognitive test scores which achieved an R 2 score of 0.228. ConclusionOur analysis shows that levels of Aβ plaques are not strong predictors of the rate of cognitive decline in Aβ-positive subjects. Baseline assessments of cognitive function accounts for the majority of variance explained in the prediction of two-year decline but is insufficient for achieving optimal results in longer-term predictions. Predicting changes both in cognitive test scores and in diagnosis provides multiple perspectives of the progression of potential AD subjects.

scholarly journals Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer’s Disease in Patients with Mild Cognitive Impairment: A Pilot Study

2019 ◽  
Vol 20 (21) ◽  
pp. 5405 ◽  
Author(s):  
Zoya O. Serebrovska ◽  
Tetiana V. Serebrovska ◽  
Viktor A. Kholin ◽  
Lesya V. Tumanovska ◽  
Angela M. Shysh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Function ◽  
Pilot Study ◽  
Peripheral Blood ◽  
Test Scores ◽  
Cognitive Test ◽  
Circulating Biomarkers

Alzheimer’s disease (AD) affects not only the central nervous system, but also peripheral blood cells including neutrophils and platelets, which actively participate in pathogenesis of AD through a vicious cycle between platelets aggregation and production of excessive amyloid beta (Aβ). Platelets adhesion on amyloid plaques also increases the risk of cerebral microcirculation disorders. Moreover, activated platelets release soluble adhesion molecules that cause migration, adhesion/activation of neutrophils and formation of neutrophil extracellular traps (NETs), which may damage blood brain barrier and destroy brain parenchyma. The present study examined the effects of intermittent hypoxic-hyperoxic training (IHHT) on elderly patients with mild cognitive impairment (MCI), a precursor of AD. Twenty-one participants (age 51–74 years) were divided into three groups: Healthy Control (n = 7), MCI+Sham (n = 6), and MCI+IHHT (n = 8). IHHT was carried out five times per week for three weeks (total 15 sessions). Each IHHT session consisted of four cycles of 5-min hypoxia (12% FIO2) and 3-min hyperoxia (33% FIO2). Cognitive parameters, Aβ and amyloid precursor protein (APP) expression, microRNA 29, and long non-coding RNA in isolated platelets as well as NETs in peripheral blood were investigated. We found an initial decline in cognitive function indices in both MCI+Sham and MCI+IHHT groups and significant correlations between cognitive test scores and the levels of circulating biomarkers of AD. Whereas sham training led to no change in these parameters, IHHT resulted in the improvement in cognitive test scores, along with significant increase in APP ratio and decrease in Aβ expression and NETs formation one day after the end of three-week IHHT. Such effects on Aβ expression and NETs formation remained more pronounced one month after IHHT. In conclusion, our results from this pilot study suggested a potential utility of IHHT as a new non-pharmacological therapy to improve cognitive function in pre-AD patients and slow down the development of AD.

scholarly journals Predicting progression and cognitive decline in amyloid-positive patients with Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Hákon Valur Dansson ◽  
Lena Stempfle ◽  
Hildur Egilsdóttir ◽  
Alexander Schliep ◽  
Erik Portelius ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Disease Progression ◽  
Test Scores ◽  
Cognitive Test ◽  
Progression Rate ◽  
Multiple Perspectives ◽  
Specific Level ◽  
Clinical Variables

Abstract Background In Alzheimer’s disease, amyloid- β (A β) peptides aggregate in the lowering CSF amyloid levels - a key pathological hallmark of the disease. However, lowered CSF amyloid levels may also be present in cognitively unimpaired elderly individuals. Therefore, it is of great value to explain the variance in disease progression among patients with A β pathology. Methods A cohort of n=2293 participants, of whom n=749 were A β positive, was selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to study heterogeneity in disease progression for individuals with A β pathology. The analysis used baseline clinical variables including demographics, genetic markers, and neuropsychological data to predict how the cognitive ability and AD diagnosis of subjects progressed using statistical models and machine learning. Due to the relatively low prevalence of A β pathology, models fit only to A β-positive subjects were compared to models fit to an extended cohort including subjects without established A β pathology, adjusting for covariate differences between the cohorts. Results A β pathology status was determined based on the A β42/A β40 ratio. The best predictive model of change in cognitive test scores for A β-positive subjects at the 2-year follow-up achieved an R2 score of 0.388 while the best model predicting adverse changes in diagnosis achieved a weighted F1 score of 0.791. A β-positive subjects declined faster on average than those without A β pathology, but the specific level of CSF A β was not predictive of progression rate. When predicting cognitive score change 4 years after baseline, the best model achieved an R2 score of 0.325 and it was found that fitting models to the extended cohort improved performance. Moreover, using all clinical variables outperformed the best model based only on a suite of cognitive test scores which achieved an R2 score of 0.228. Conclusion Our analysis shows that CSF levels of A β are not strong predictors of the rate of cognitive decline in A β-positive subjects when adjusting for other variables. Baseline assessments of cognitive function accounts for the majority of variance explained in the prediction of 2-year decline but is insufficient for achieving optimal results in longer-term predictions. Predicting changes both in cognitive test scores and in diagnosis provides multiple perspectives of the progression of potential AD subjects.

scholarly journals Using a Digital Neuro Signature to measure longitudinal individual-level change in Alzheimer’s disease: the Altoida large cohort study

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Irene B. Meier ◽  
Max Buegler ◽  
Robbert Harms ◽  
Azizi Seixas ◽  
Arzu Çöltekin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Disease Risk ◽  
Intraindividual Variability ◽  
Cognitive Test ◽  
Individual Level ◽  
Level Change ◽  
Neuropsychological Assessments

AbstractConventional neuropsychological assessments for Alzheimer’s disease are burdensome and inaccurate at detecting mild cognitive impairment and predicting Alzheimer’s disease risk. Altoida’s Digital Neuro Signature (DNS), a longitudinal cognitive test consisting of two active digital biomarker metrics, alleviates these limitations. By comparison to conventional neuropsychological assessments, DNS results in faster evaluations (10 min vs 45–120 min), and generates higher test-retest in intraindividual assessment, as well as higher accuracy at detecting abnormal cognition. This study comparatively evaluates the performance of Altoida’s DNS and conventional neuropsychological assessments in intraindividual assessments of cognition and function by means of two semi-naturalistic observational experiments with 525 participants in laboratory and clinical settings. The results show that DNS is consistently more sensitive than conventional neuropsychological assessments at capturing longitudinal individual-level change, both with respect to intraindividual variability and dispersion (intraindividual variability across multiple tests), across three participant groups: healthy controls, mild cognitive impairment, and Alzheimer’s disease. Dispersion differences between DNS and conventional neuropsychological assessments were more pronounced with more advanced disease stages, and DNS-intraindividual variability was able to predict conversion from mild cognitive impairment to Alzheimer’s disease. These findings are instrumental for patient monitoring and management, remote clinical trial assessment, and timely interventions, and will hopefully contribute to a better understanding of Alzheimer’s disease.

Enhanced adrenal sensitivity to adrenocorticotrophic hormone (ACTH) is evidence of HPA axis hyperactivity in Alzheimer's disease

1996 ◽  
Vol 26 (1) ◽  
pp. 7-14 ◽  
Author(s):  
J. T. O'Brien ◽  
D. Ames ◽  
I. Schweitzer ◽  
M. Mastwyk ◽  
P. Colman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hpa Axis ◽  
Low Dose ◽  
Age At Onset ◽  
Neuronal Loss ◽  
Inverse Correlation ◽  
Cognitive Test ◽  
Cortisol Response ◽  
Adrenocorticotrophic Hormone

SynopsisAdrenal sensitivity was assessed in 16 non-depressed patients with NINCDS/ADRDA Alzheimer's disease (AD) and 18 control subjects by measuring cortisol response to low dose (0·05 μg/kg i.v.) exogenous adrenocorticotrophic hormone (ACTH). Controlling for sex and medication, both peak cortisol level (peak–baseline) and area under cortisol response curve (AUC above baseline) were significantly greater in AD subjects. This shows that HPA axis hyperactivity, as demonstrated by enhanced adrenal sensitivity to ACTH, occurs in AD. Similar findings have been reported to occur in depression. Among AD subjects, AUC cortisol response correlated with current age (r= 0·70,P= 0·001) and age at onset of dementia (r= 0·73,P= 0·001) and an inverse correlation was seen between cortisol AUC and cognitive test (CAMCOG) score (r= −0·51,P= 0·044). Our findings suggest that HPA axis hyperactivity in AD is associated with advancing age and cognitive dysfunction. Such changes may be cause, or consequence, of neuronal loss.

scholarly journals Callosal Atrophy Correlates with Temporal Lobe Volume and Mental Status in Alzheimer's Disease

2000 ◽  
Vol 27 (3) ◽  
pp. 204-209 ◽  
Author(s):  
Sandra E. Black ◽  
Scott D. Moffat ◽  
David C. Yu ◽  
Jayson Parker ◽  
Peter Stanchev ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Rating Scale ◽  
Anterior Commissure ◽  
Cognitive Status ◽  
Cognitive Test ◽  
Temporal Lobes ◽  
Cerebral Commissures ◽  
State Examination

Background:Recent studies have reported significant atrophy of the corpus callosum (CC) in Alzheimer's Disease (AD). However, it is currently unknown whether CC atrophy is associated with specific cortical volume changes in AD. Moreover, possible atrophy in extra-callosal commissures has not been examined to date. The purpose of the present study was to quantify atrophy in two cerebral commissures [the CC and the anterior commissure (AC)], to correlate this measure with cognitive status, and to relate commissural size to independent measures of temporal lobe volume in AD patients.Methods:A sample of AD patients and of age- and education-matched normal control subjects (NCs) underwent MRI and a cognitive test battery including the Dementia Rating Scale and Mini Mental State examination. Mid-sagittal regional areas within CC and AC were measured along with superior, middle and inferior temporal lobes volumes.Results:Alzheimer's Disease patients had significantly smaller callosa than did NCs. The callosal regions most affected in AD included the midbody, isthmus and genu. The isthmus and midbody areas of the CC were positively correlated with cognitive performance and with superior temporal lobe volume in AD patients. The mid-sagittal area of the AC and the superior temporal volumes did not differ between AD patients and NCs.Conclusion:The study demonstrated that the regional morphology of the CC correlates with current cognitive status and temporal lobe atrophy in AD. As well, the lack of difference for the AC suggests that commissural atrophy in AD is regionally specific.

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