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

Hwang, Jihye; Jeong, Jee Hyang; Yoon, Soo Jin; Park, Kyung Won; Kim, Eun-Joo; Yoon, Bora; Jang, Jae‐Won; Kim, Hee Jin; Hong, Jin Yong; Lee, Jongmin; Park, Hyuntae; Kang, Ju‐Hee; Choi, Yang Ho; Park, Gilsoon; Hong, Jae‐Keun; Byun, Min Soo; Yi, Dahyun; Kim, Yu Kyeong; Lee, Dong Hoon; Choi, Seong Hye

doi:10.3390/jcm8030341

Cited by 43 publications

(67 citation statements)

References 77 publications

(97 reference statements)

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“…The observation that approximately one-third of cognitively normal older adults have AD pathology in their brains has been approved by previous amyloid imaging [18][19][20] and neuropathological studies [21,22]. Similar distributions were found in studies of Asian populations [23][24][25]. Therefore, the cutoff values to define abnormal CSF core biomarkers were < 115.1 pg/ml (lower onethird) for Aβ 1-42 , > 40.05 pg/ml (upper one-third) for P-tau, and > 187.32 pg/ml (upper one-third) for T-tau, respectively Aggregated tau and neurodegeneration groups were merged to reduce the number of groups to be compared, which resulted in four different biomarker group combinations, including stage 0, stage 1, stage 2, and suspected non-AD pathology (SNAP).…”

Section: Discussionmentioning

confidence: 52%

Dynamic changes of CSF sTREM2 in preclinical Alzheimer’s disease: the CABLE study

Tan

et al. 2020

Mol Neurodegeneration

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Background: Loss of function of triggering receptor expressed on myeloid cell 2 (TREM2), a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer's disease (AD). Whether TREM2 levels are pathologically altered during the preclinical phase, and whether cerebrospinal fluid (CSF) soluble TREM2 protein (sTREM2) has a relationship with major pathological processes including Aβ and tau deposition are still unclear.Methods: According to the NIA-AA criteria, 659 cognitively normal participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) cohort were divided into four groups, stage 0 (normal Aβ 1-42 , T-tau and P-tau), stage 1 (low Aβ 1-42 , normal T-tau and P-tau), stage 2 (low Aβ 1-42 and high T-tau or P-tau), and suspected non-AD pathology (SNAP) (normal Aβ 1-42 and high T-tau or P-tau), to examine changes of CSF sTREM2 in the preclinical AD. Biomarker cut-off was based on the assumption that one-third of adults with normal cognition have AD pathology.Results: The level of CSF sTREM2 in the stage 1 decreased compared with the stage 0 (P < 0.001), and then increased in the stage 2 (P = 0.008). SNAP individuals also had significantly increased CSF sTREM2 (P < 0.001). Results of multiple linear regressions also showed positive correlations of CSF sTREM2 with Aβ 1-42 (β = 0.192, P < 0.001), T-tau (β = 0.215, P < 0.001) and P-tau (β = 0.123, P < 0.001).Conclusion: CSF sTREM2 levels are dynamic in preclinical AD. Aβ pathology is associated with a decrease in CSF sTREM2 in the absence of tau deposition and neurodegeneration. However, tau pathology and neurodegeneration are associated with an increase in CSF sTREM2.

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Section: Discussionmentioning

confidence: 52%

Dynamic changes of CSF sTREM2 in preclinical Alzheimer’s disease: the CABLE study

Tan

et al. 2020

Mol Neurodegeneration

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“…Rossetti et al [24] described the CERAD total score in AD patients, and the normal control for four years showed a significantly greater decrease in AD patients than in the normal group. Hwang et al [25] confirmed that the CERAD scores decreased as the disease progressed through three years of follow-up of participants in the cognitive normal, SCD, MCI, and ADD groups, and CSF Aβ42 levels in each group also decreased in correlation. In 2019, Meng et al [14] described that an increase in MDS-OAβ levels in AD patients correlated with episodic memory loss.…”

Section: Discussionmentioning

confidence: 88%

“…In 2019, Meng et al [14] described that an increase in MDS-OAβ levels in AD patients correlated with episodic memory loss. Other studies have reported that scores on language-related evaluative tasks such as word list memory and word list recall reflect AD-associated cognitive and memory function changes [25,26]. Furthermore, the decrease in the CERAD score in the order of normal individuals, MCI, and AD correlated with the atrophy of white matter lesions and gray matter in the brain [27], and scores for the word list recall and memory from the CERAD had a close relationship with atrophy in the medial temporal lobe [28].…”

Section: Discussionmentioning

confidence: 99%

Association of Plasma Oligomerized Beta Amyloid with Neurocognitive Battery Using Korean Version of Consortium to Establish a Registry for Alzheimer’s Disease in Health Screening Population

et al. 2020

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The increasing prevalence of Alzheimer’s disease (AD) has become a global phenomenon presenting serious social and health challenges. For detecting early molecular changes in the disease, several techniques to measure varied species of amyloid beta in the peripheral blood have been recently developed, but the efforts to associate them with cognitive assessments have yet to produce sufficient data. We prospectively collected participants from the consecutive population who visited our center for brain health screening. In total, 97 participants (F:M = 58:39) aged 69.4 ± 7.52 were assessed. Participants performed the Korean version of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD-K), the clinical dementia rating (CDR), plasma oligomeric amyloid-β (OAβ) level tests, routine blood tests, ApoE genotype, and brain MRI. Among total population, 55.7% had a CDR of 0, and 40.2% had a CDR of 0.5. The results showed that word memory and word recall, and the total scores of the CERAD-K were negatively correlated with the plasma OAβ level. With a cut-off value of 0.78 ng/mL for the OAβ level and a −1.5 standard deviation of age/sex/education adjusted norms for the CERAD-K; naming, word memory, word recall, word recognition, and total score were significantly correlated with the OAβ level. No correlation between the OAβ level and mini-mental status examination was found. Our results demonstrate that the level of plasma OAβ was well correlated with the measure of cognitive function through the CERAD-K in the field data collected from consecutive populations. Studies on longitudinal comparisons with large cohorts will further validate the diagnostic value of plasma OAβ as a useful biomarker for screening AD and predicting progression.

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“…The ADD patients met the criteria for dementia by the Diagnostic and Statistical Manual of Mental Disorders 4th Edition, Text Revision (DSM-IV-TR) [12] and were diagnosed with probable ADD according to the NIA-AA core clinical criteria [1]. The patients were recruited from 9 referral hospitals in South Korea (175 from Samsung Medical Center, 135 from Validation Cohort of Korean Brain Aging Study for the Early Diagnosis and Prediction of AD (KBASE-V) [13]). All participants underwent neurologic examination, neuropsychological test, and Apolipoprotein E (APOE) genotyping.…”

Section: Participantsmentioning

confidence: 99%

Clinical significance of focal ß-amyloid deposition measured by 18F-flutemetamol PET

et al. 2020

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Background: Although amyloid PET of typical Alzheimer's disease (AD) shows diffuse ß-amyloid (Aß) deposition, some patients show focal deposition. The clinical significance of this focal Aß is not well understood. We examined the clinical significance of focal Aß deposition in terms of cognition as well as Aß and tau cerebrospinal fluid (CSF) levels. We further evaluated the order of Aß accumulation by visual assessment. Methods: We included 310 subjects (125 cognitively unimpaired, 125 mild cognitive impairment, and 60 AD dementia) from 9 referral centers. All patients underwent neuropsychological tests and 18 F-flutemetamol (FMM) PET. Seventy-seven patients underwent CSF analysis. Each FMM scan was visually assessed in 10 regions (frontal, precuneus and posterior cingulate, lateral temporal, parietal, and striatum of each hemisphere) and was classified into three groups: No-FMM, Focal-FMM (FMM uptake in 1-9 regions), and Diffuse-FMM (FMM uptake in all 10 regions). Results: 53/310 (17.1%) subjects were classified as Focal-FMM. The cognitive level of the Focal-FMM group was better than that of Diffuse-FMM group and worse than that of No-FMM group. Among the Focal-FMM group, those who had FMM uptake to a larger extent or in the striatum had worse cognitive levels. Compared to the Diffuse-FMM group, the Focal-FMM group had a less AD-like CSF profile (increased Aß42 and decreased t-tau, t-tau/Aß42). Among the Focal-FMM group, Aß deposition was most frequently observed in the frontal (62.3%) and least frequently observed in the striatum (43.4%) and temporal (39.6%) regions. Conclusions: We suggest that focal Aß deposition is an intermediate stage between no Aß and diffuse Aß deposition. Furthermore, among patients with focal Aß deposition, those who have Aß to a larger extent and striatal involvement show clinical features close to diffuse Aß deposition. Further longitudinal studies are needed to evaluate the disease progression of patients with focal Aß deposition.

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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

Cited by 43 publications

References 77 publications

Dynamic changes of CSF sTREM2 in preclinical Alzheimer’s disease: the CABLE study

Dynamic changes of CSF sTREM2 in preclinical Alzheimer’s disease: the CABLE study

Association of Plasma Oligomerized Beta Amyloid with Neurocognitive Battery Using Korean Version of Consortium to Establish a Registry for Alzheimer’s Disease in Health Screening Population

Clinical significance of focal ß-amyloid deposition measured by 18F-flutemetamol PET

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