scholarly journals Clinical and Biomarker Characteristics According to Clinical Spectrum of Alzheimer’s Disease (AD) in the Validation Cohort of Korean Brain Aging Study for the Early Diagnosis and Prediction of AD

2019 ◽  
Vol 8 (3) ◽  
pp. 341 ◽  
Author(s):  
Jihye Hwang ◽  
Jee Jeong ◽  
Soo Yoon ◽  
Kyung Park ◽  
Eun-Joo Kim ◽  
...  

We aimed to present the study design of an independent validation cohort from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (AD) (KBASE-V) and to investigate the baseline characteristics of the participants according to the AD clinical spectrum. We recruited 71 cognitively normal (CN) participants, 96 with subjective cognitive decline (SCD), 72 with mild cognitive impairment (MCI), and 56 with AD dementia (ADD). The participants are followed for three years. The Consortium to Establish a Registry for AD scores was significantly different between all of the groups. The logical memory delayed recall scores were significantly different between all groups, except between the MCI and ADD groups. The Mini-Mental State Examination score, hippocampal volume, and cerebrospinal fluid (CSF) amyloid-β42 level were significant difference among the SCD, MCI, and ADD groups. The frequencies of participants with amyloid pathology according to PET or CSF studies were 8.9%, 25.6%, 48.3%, and 90.0% in the CN, SCD, MCI, and ADD groups, respectively. According to ATN classification, A+/T+/N+ or A+/T+/N− was observed in 0%, 15.5%, 31.0%, and 78.3% in the CN, SCD, MCI, and ADD groups, respectively. The KBASE-V showed a clear difference according to the AD clinical spectrum in neuropsychological tests and AD biomarkers.

2019 ◽  
Vol 75 (7) ◽  
pp. 1382-1392 ◽  
Author(s):  
Marie Caillaud ◽  
Carol Hudon ◽  
Benjamin Boller ◽  
Simona Brambati ◽  
Simon Duchesne ◽  
...  

Abstract Objective The concepts of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) have been proposed to identify individuals in the early stages of Alzheimer’s disease (AD), or other neurodegenerative diseases. One approach to validate these concepts is to investigate the relationship between pathological brain markers and cognition in those individuals. Method We included 126 participants from the Consortium for the Early Identification of Alzheimer’s disease-Quebec (CIMA-Q) cohort (67 SCD, 29 MCI, and 30 cognitively healthy controls [CH]). All participants underwent a complete cognitive assessment and structural magnetic resonance imaging. Group comparisons were done using cognitive data, and then correlated with hippocampal volumes and white matter hyperintensities (WMHs). Results Significant differences were found between participants with MCI and CH on episodic and executive tasks, but no differences were found when comparing SCD and CH. Scores on episodic memory tests correlated with hippocampal volumes in both MCI and SCD, whereas performance on executive tests correlated with WMH in all of our groups. Discussion As expected, the SCD group was shown to be cognitively healthy on tasks where MCI participants showed impairment. However, SCD’s hippocampal volume related to episodic memory performances, and WMH to executive functions. Thus, SCD represents a valid research concept and should be used, alongside MCI, to better understand the preclinical/prodromal phase of AD.


2020 ◽  
Vol 78 (1) ◽  
pp. 439-452
Author(s):  
Dongxue Li ◽  
Yuancheng Liu ◽  
Xianchun Zeng ◽  
Zhenliang Xiong ◽  
Yuanrong Yao ◽  
...  

Background: Advanced Alzheimer’s disease (AD) has no effective treatment, and identifying early diagnosis markers can provide a time window for treatment. Objective: To quantify the changes in cerebral blood flow (CBF) and iron deposition during progression of AD. Methods: 94 subjects underwent brain imaging on a 3.0-T MRI scanner with techniques of three-dimensional arterial spin labeling (3D-ASL) and quantitative susceptibility mapping (QSM). The subjects included 22 patients with probable AD, 22 patients with mild cognitive impairment (MCI), 25 patients with subjective cognitive decline (SCD), and 25 normal controls (NC). The CBF and QSM values were obtained using a standardized brain region method based on the Brainnetome Atlas. The differences in CBF and QSM values were analyzed between and within groups using variance analysis and correlation analysis. Results: CBF and QSM identified several abnormal brain regions of interest (ROIs) at different stages of AD (p < 0.05). Regionally, the CBF values in several ROIs of the AD and MCI subjects were lower than for NC subjects (p < 0.001). Higher QSM values were observed in the globus pallidus. The CBF and QSM values in multiple ROI were negatively correlated, while the putamen was the common ROI of the three study groups (p < 0.05). The CBF and QSM values in hippocampus were cross-correlated with scale scores during the progression of AD (p < 0.05). Conclusion: Iron deposition in the basal ganglia and reduction in blood perfusion in multiple regions existed during the progression of AD. The QSM values in putamen can be used as an imaging biomarker for early diagnosis of AD.


2020 ◽  
Author(s):  
D. Puttaert ◽  
N. Coquelet ◽  
V. Wens ◽  
P. Peigneux ◽  
P. Fery ◽  
...  

AbstractHuman brain activity is intrinsically organized into resting-state networks (RSNs) that transiently activate or deactivate at the sub-second timescale. Few neuroimaging studies have addressed how Alzheimer’s disease (AD) affects these fast temporal brain dynamics, and how they relate to the cognitive, structural and metabolic abnormalities characterizing AD.We aimed at closing this gap by investigating both brain structure and function using magnetoencephalography (MEG) and hybrid positron emission tomography-magnetic resonance (PET/MR) in 10 healthy elders, 10 patients with Subjective Cognitive Decline (SCD), 10 patients with amnestic Mild Cognitive Impairment (aMCI) and 10 patients with typical Alzheimer’s disease with dementia (AD). The fast activation/deactivation state dynamics of RSNs were assessed using hidden Markov modeling (HMM) of power envelope fluctuations at rest measured with MEG. HMM patterns were related to participants’ cognitive test scores, whole hippocampal grey matter volume and regional brain glucose metabolism.The posterior default-mode network (DMN) was less often activated and for shorter durations in AD patients than matched healthy elders. No significant difference was found in patients with SCD or aMCI. The time spent by participants in the activated posterior DMN state did not correlate significantly with cognitive scores. However, it correlated positively with the whole hippocampal volume and regional glucose consumption in the right temporo-parietal junctions and dorsolateral prefrontal cortex, and negatively with glucose consumption in the cerebellum.In AD patients, alterations of posterior DMN power activation dynamics at rest correlate with structural and neurometabolic abnormalities. These findings represent an additional electrophysiological correlate of AD-related synaptic and neural dysfunction.


2021 ◽  
Author(s):  
Willem S. Eikelboom ◽  
Esther van den Berg ◽  
Ellen Singleton ◽  
Sara J. Baart ◽  
Michiel Coesmans ◽  
...  

ABSTRACTObjectiveTo investigate the prevalence and trajectories of neuropsychiatric symptoms (NPS) in relation to cognitive functioning in a cohort of amyloid-β positive individuals across the Alzheimer’s disease (AD) clinical spectrum.MethodsWe included 1,524 amyloid-β positive individuals from the Amsterdam Dementia Cohort with subjective cognitive decline (SCD, n=113), mild cognitive impairment (MCI, n=321), or dementia (n=1,090). We measured NPS with the neuropsychiatric inventory (NPI), examining total scores and the presence of specific NPI-items. Cognition was assessed across five cognitive domains and with the MMSE. We examined trajectories including model based trends for NPS and cognitive functioning over time. We used linear mixed models to relate baseline NPI scores to cognitive functioning at baseline (whole-sample) and longitudinal time-points (subsample n=520, Mean=1.8 [SD=0.7] years follow-up).ResultsNPS were prevalent across all clinical AD stages (NPI total score ≥1 81.4% in SCD, 81.2% in MCI, 88.7% in dementia). Cognitive functioning showed an uniform gradual decline; while in contrast, large intra-individual heterogeneity of NPS was observed over time across all groups. At baseline, we found associations between NPS and cognition in dementia that were most pronounced for NPI total scores and MMSE (range β:-0.18–0.11, FDR-adjusted p<0.05), while there were no cross-sectional relationships in SCD and MCI (β:-0.32– 0.36, FDR-adjusted p>0.05). There were no associations between baseline NPS and cognitive functioning over time in any clinical stage (β:-0.13–0.44, FDR-adjusted p>0.05).ConclusionNPS and cognitive symptoms are both prevalent across the AD continuum, but show a different evolution during the course of the disease.


2011 ◽  
Vol 7 ◽  
pp. S174-S174
Author(s):  
Adriana Servello ◽  
Alessandra Barbara Fioretti ◽  
Letizia Lambusier ◽  
Alberto Eibenstein ◽  
Marco Fusetti ◽  
...  

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Jessica Z. K. Caldwell ◽  
Jeffrey L. Cummings ◽  
Sarah J. Banks ◽  
Sebastian Palmqvist ◽  
Oskar Hansson

Abstract Background We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes. Methods We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer’s disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes. Results Amyloid-positive (Aβ/P-tau+) CN women (women with preclinical AD) showed memory equivalent to amyloid-negative (Aβ/P-tau−) CN women. In contrast, Aβ/P-tau+ CN men (men with preclinical AD) showed poorer memory than Aβ/P-tau− CN men. Symptomatic groups showed no sex differences in effect of AD proteinopathy on memory. There was no interactive effect of sex, diagnosis, and Aβ/P-tau on other measures of cognition or on hippocampal volume. Conclusions CN women show relatively preserved verbal memory, but not general cognitive reserve or preserved hippocampal volume in the presence of Aβ/P-tau+. Results have implications for diagnosing AD in women, and for clinical trials.


2020 ◽  
pp. 1-11
Author(s):  
Qiang Wang ◽  
Ben Chen ◽  
Xiaomei Zhong ◽  
Huarong Zhou ◽  
Min Zhang ◽  
...  

Background: Odor identification dysfunction occurs early in Alzheimer’s disease (AD) and is considered a preclinical symptom along with subjective cognitive decline (SCD). Nevertheless, whether subjects with SCD are co-symptomatic with odor identification dysfunction remains unclear. Objective: To compare the degree of odor identification dysfunction and assess the relation between odor identification and cognitive performance in the AD spectrum (including SCD, mild cognitive impairment (MCI), and AD). Methods: Patients (84 SCD, 129 MCI, 52 AD) and 35 controls underwent the Sniffin’ Sticks Screen 16 test and comprehensive neuropsychological examination. Results: Odor identification scores were progressively lower moving from normal older adult to SCD, MCI, and AD. Additionally,the proportion of odor identification dysfunction were increasingly higher in the AD spectrum (p for trend <0.001), but no significant difference was found in the proportion of subjective olfactory dysfunction. No significant correlation was found between odor identification and cognition in the normal older adults and SCD subjects, but odor identification correlated with global cognition in the MCI (r = 0.199, p = 0.033) and in the AD (r = 0.300, p = 0.036) patients. Multiple linear regression showed that odor identification dysfunction was most strongly associated with memory among different cognitive subdomains and was most strongly associated with immediate verbal recall among different memory subdomains. Conclusion: Odor identification dysfunction is already present with SCD and deepens with disease severity in the AD spectrum, and it may contribute to predicting cognitive decline and identifying SCD subjects who are at risk of developing AD.


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