Relationships Between Cognition and Neuropathological Tau in Alzheimer’s Disease Assessed by 18F Flortaucipir PET

2021 ◽  
Vol 80 (3) ◽  
pp. 1091-1104
Author(s):  
Michael D. Devous Sr. ◽  
Adam S. Fleisher ◽  
Michael J. Pontecorvo ◽  
Ming Lu ◽  
Andrew Siderowf ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Pet Imaging ◽  
Disease Assessment ◽  
Digit Symbol Substitution Test ◽  
Cognitive Tests ◽  
Logical Memory ◽  
Domain Specific ◽  
The Relationship

Background: Tau neurofibrillary tangle burden increases with Alzheimer’s disease (AD) stage and correlates with degree of cognitive impairment. Tau PET imaging could facilitate understanding the relationship between tau pathology and cognitive impairment. Objective: Evaluate the relationship between 18F flortaucipir uptake patterns and cognition across multiple cognitive domains. Methods: We acquired flortaucipir PET scans in 84 amyloid-positive control, mild cognitive impairment (MCI), and AD subjects. Flortaucipir standardized uptake value ratio (SUVr) values were obtained from a neocortical volume of interest (VOI), a precuneus VOI, and VOIs defined by the correlation between flortaucipir SUVr images and domain-specific cognitive tests. Cognitive assessments included Mini-Mental State Exam (MMSE), Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog), and a neuropsychological test battery (i.e., Wechsler Memory Scale-Revised Logical Memory (WMS-R), Trail Making Test, Boston Naming Test, Digit Symbol Substitution Test, Animal List Generation, WMS-R Digit Span, American National Adult Reading Test, Clock Drawing Test, Judgment of Line Orientation, and WMS-R Logical Memory II (Delayed Recall)) and the Functional Activities Questionnaire (FAQ). Correlation analyses compared regional and voxel-wise VOIs to cognitive scores. Results: Subjects included 5 controls, 47 MCI, and 32 AD subjects. Significant correlations were seen between both flortaucipir and florbetapir SUVrs and MMSE, ADAS-Cog, and FAQ. Cognitive impairment was associated with increased flortaucipir uptake in regionally specific patterns consistent with the neuroanatomy underlying specific cognitive tests. Conclusion: Flortaucipir SUVr values demonstrated significant inverse correlations with cognitive scores in domain-specific patterns. Findings support the hypothesis that PET imaging of neuropathologic tau deposits may reflect underlying neurodegeneration in AD.

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

2018 ◽  
Vol 15 (5) ◽  
pp. 429-442 ◽  
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.

Deformation-based Statistical Shape Analysis of the Corpus Callosum in Mild Cognitive Impairment and Alzheimer’s Disease

2018 ◽  
Vol 15 (12) ◽  
pp. 1151-1160 ◽  
Author(s):  
Zihan Jiang ◽  
Huilin Yang ◽  
Xiaoying Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Corpus Callosum ◽  
Shape Analysis ◽  
Disease Assessment ◽  
Statistical Shape Analysis ◽  
Superior Part ◽  
Statistical Shape

Objective: In this study, we investigated the influence that the pathology of Alzheimer’s disease (AD) exerts upon the corpus callosum (CC) using a total of 325 mild cognitive impairment (MCI) subjects, 155 AD subjects, and 185 healthy control (HC) subjects. Method: Regionally-specific morphological CC abnormalities, as induced by AD, were quantified using a large deformation diffeomorphic metric curve mapping based statistical shape analysis pipeline. We also quantified the association between the CC shape phenotype and two cognitive measures; the Mini Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale-Cognitive Behavior Section (ADAS-cog). To identify AD-relevant areas, CC was sub-divided into three subregions; the genu, body, and splenium (gCC, bCC, and sCC). Results: We observed significant shape compressions in AD relative to that in HC, mainly concentrated on the superior part of CC, across all three sub-regions. The HC-vs-MCI shape abnormalities were also concentrated on the superior part, but mainly occurred on bCC and sCC. The significant MCI-vs-AD shape differences, however, were only detected in part of sCC. In the shape-cognition association, significant negative correlations to ADAS-cog were detected for shape deformations at regions belonging to gCC and sCC and significant positive correlations to MMSE at regions mainly belonging to sCC. Conclusion: Our results suggest that the callosal shape deformation patterns, especially those of sCC, linked tightly to the cognitive decline in AD, and are potentially a powerful biomarker for monitoring the progression of AD.

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.

Synaptic Loss is Associated With Cognitive Impairment in Early Alzheimer’s Disease: A PET Imaging Study With [11C]UCB-J

2021 ◽  
Vol 89 (9) ◽  
pp. S107-S108
Author(s):  
Ryan O'Dell ◽  
Adam P. Mecca ◽  
Emily S. Sharp ◽  
Emmie R. Banks ◽  
Hugh H. Bartlett ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Pet Imaging ◽  
Imaging Study ◽  
Synaptic Loss ◽  
Early Alzheimer’S Disease

scholarly journals Identification of and a Prediction Model for Cognitive Trajectories in Patients With Mild Cognitive Impairment Due to Alzheimer’s Disease

2020 ◽  
Author(s):  
Sang Won Seo ◽  
Seung Joo Kim ◽  
Sook-Young Woo ◽  
Young Ju Kim ◽  
Yeshin Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Prediction Model ◽  
Multinomial Logistic Regression ◽  
Standardized Uptake Value ◽  
Disease Assessment ◽  
Risk Scores ◽  
Clinical Biomarkers

Abstract Background: Few studies have investigated cognitive trajectories or developed a prediction model for amyloid beta-positive (Aβ+) mild cognitive impairment (MCI) patients. We aimed to identify distinct cognitive trajectories in Aβ+ MCI patients based on longitudinal Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-cog) 13 scores. Furthermore, we aimed to develop and visualize a prediction model to predict trajectory groups using the demographic, genetic, and clinical biomarkers of Aβ+ MCI patients.Methods: We performed a retrospective analysis of the data in 238 Aβ+ MCI patients from the Alzheimer’s Disease Neuroimaging Initiative who underwent at least three rounds of annual neuropsychological testing to identify cognitive trajectories. A group-based trajectory model (GBTM) was used to classify distinct groups based on ADAS-cog 13 scores. The prediction model was estimated using multinomial logistic regression and visualized using a bar-based method for risk prediction. Results: Three distinct classes, namely slow decliners (18.5%), intermediate decliners (42.9%), and fast decliners (38.7%), were suggested. Intermediate decliners were associated with higher age (≥70 years) (odds ratio [OR] 2.72, 95% confidence interval [CI] 1.78-6.28), higher AV45 standardized uptake value ratios (SUVRs)*10 (OR 1.69, 95% CI 1.22-2.34), and lower fluorodeoxyglucose (FDG) SUVR*10 (OR 0.65, 95% CI 0.46-0.93) than slow decliners. Fast decliners were associated with higher age (≥70 years) (OR 3.76, 95% CI 1.40-10.10), greater likelihood of being an apolipoprotein E 4 carrier (OR 4.2, 95% CI 1.53-11.58), higher AV45 positron emission tomography SUVR*10 (OR 2.14, 95% CI 1.50-3.05), and lower FDG SUVR*10 (OR 0.31, 95% CI 0.20-0.48) than slow decliners. The predicted probability of being classified to a trajectory group according to the risk scores of predictors was visualized.Conclusions: Our GBTM analysis yielded novel insights into the heterogeneous cognitive trajectories among Aβ+ MCI patients, which further facilitates the effective stratification of Aβ+ MCI patients in Aβ-targeted clinical trials.

The Role of Apolipoprotein E ε4 in Early and Late Mild Cognitive Impairment

2021 ◽  
Vol 84 (6) ◽  
pp. 472-480
Author(s):  
Yulin Luo ◽  
Li Tan ◽  
Joseph Therriault ◽  
Hua Zhang ◽  
Ying Gao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apolipoprotein E ◽  
Amyloid Β ◽  
Disease Assessment ◽  
Tau Pathology ◽  
Ε4 Allele ◽  
State Examination

<b><i>Background:</i></b> Apolipoprotein E (<i>APOE</i>) ε4 is highly associated with mild cognitive impairment (MCI). However, the specific influence of <i>APOE</i> ε4 status on tau pathology and cognitive decline in early MCI (EMCI) and late MCI (LMCI) is poorly understood. Our goal was to evaluate the association of <i>APOE</i> ε4 with cerebrospinal fluid (CSF) tau levels and cognition in EMCI and LMCI patients in the Alzheimer’s Disease Neuroimaging Initiative database, and whether this association was mediated by amyloid-β (Aβ). <b><i>Methods:</i></b> Participants were 269 cognitively normal (CN), 262 EMCI, and 344 LMCI patients. They underwent CSF Aβ42 and tau detection, <i>APOE</i> ε4 genotyping, Mini-Mental State Examination, (MMSE), and Alzheimer’s disease assessment scale (ADAS)-cog assessments. Linear regressions were used to examine the relation of <i>APOE</i> ε4 and CSF tau levels and cognitive scores in persons with and without Aβ deposition (Aβ+ and Aβ−). <b><i>Results:</i></b> The prevalence of <i>APOE</i> ε4 is higher in EMCI and LMCI than in CN (<i>p</i> &#x3c; 0.001 for both), and in LMCI than in EMCI (<i>p</i> = 0.001). <i>APOE</i> ε4 allele was significantly higher in Aβ+ subjects than in Aβ− subjects (<i>p</i> &#x3c; 0.001). Subjects who had a lower CSF Aβ42 level and were <i>APOE</i> ε4-positive experienced higher levels of CSF tau and cognitive scores in EMCI and/or LMCI. <b><i>Conclusions:</i></b> An <i>APOE</i> ε4 allele is associated with increased CSF tau and worse cognition in both EMCI and LMCI, and this association may be mediated by Aβ. We conclude that <i>APOE</i> ε4 may be an important mediator of tau pathology and cognition in the early stages of AD.

Diagnosing Alzheimer’s disease in clinical practice

2017 ◽  
Author(s):  
Gunhild Waldemar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Memory Impairment ◽  
Imaging Biomarkers ◽  
Cognitive Tests ◽  
Specific Diagnosis ◽  
Increased Risk ◽  
Patient Consent ◽  
Atypical Presentations

The diagnostic evaluation in a patient with cognitive impairment suspected of having Alzheimer’s disease (AD) should include investigations aimed at 1) confirming and characterizing the cognitive impairment using cognitive tests with particular attention to typical (episodic memory impairment) and atypical presentations of AD; 2) checking the diagnostic criteria for AD and considering biomarkers to document AD pathology; and 3) differential diagnosis: ruling out other conditions which could cause cognitive impairment. With the advent of CSF and imaging biomarkers for AD, it may be possible to establish an early specific diagnosis, or to confirm an increased risk of progressing to AD dementia, in patients with mild cognitive symptoms. In such cases pre-biomarker counselling and patient consent is essential.

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