Cerebrospinal fluid Aβ42 is the best predictor of clinical progression in patients with subjective complaints

Harten, Argonde C. van; Visser, Pieter Jelle; Pijnenburg, Yolande A.L.; Teunissen, Charlotte E.; Blankenstein, Marinus A.; Scheltens, Philip; Flier, Wiesje M. van der

doi:10.1016/j.jalz.2012.08.004

Cited by 178 publications

(138 citation statements)

References 41 publications

Supporting

Mentioning

122

Contrasting

Unclassified

Order By: Relevance

“…We found that lower plasma Abeta42/Abeta40 ratio is associated with an increased risk of developing MCI or dementia. It was also found that low CSF Abeta42 concentrations increase the risk of cognitive decline6 and clinical disease progression 42. Although the HR for clinical progression of the plasma Abeta42/Abeta40 ratio is lower compared to CSF, the finding of the present study shows clinical validity of the plasma measure.…”

Section: Discussionsupporting

confidence: 52%

Plasma Amyloid as Prescreener for the Earliest Alzheimer Pathological Changes

Verberk

Slot

Verfaillie

et al. 2018

Annals of Neurology

Self Cite

243

237

View full text Add to dashboard Cite

ObjectiveWe investigated the association of plasma amyloid beta (Abeta)40, Abeta42, and total tau (tTau) with the presence of Alzheimer pathological changes in cognitively normal individuals with subjective cognitive decline (SCD).MethodsWe included 248 subjects with SCD (61 ± 9 years, 42% female, Mini‐Mental State Examination = 28 ± 2) from the SCIENCe project and Amsterdam Dementia Cohort. Subjects were dichotomized as amyloid abnormal by cerebrospinal fluid (CSF) and positron emission tomography (PET). Baseline plasma Abeta40, Abeta42, and tTau were measured using Simoa technology. Associations between plasma levels and amyloid status were assessed using logistic regression analyses and receiver operating characteristic analyses. Association of plasma levels with risk of clinical progression to mild cognitive impairment (MCI) or dementia was assessed using Cox proportional hazard models.ResultsFifty‐seven (23%) subjects were CSF‐amyloid abnormal. Plasma Abeta42/Abeta40 ratio and plasma Abeta42 alone, but not tTau, identified abnormal CSF‐amyloid status (plasma ratio: area under the curve [AUC] = 77%, 95% confidence interval [CI] = 69–84%; plasma Abeta42: AUC = 66%, 95% CI: 58–74%). Combining plasma ratio with age and apolipoprotein E resulted in AUC = 83% (95% CI = 77–89%). The Youden cutoff of the plasma ratio gave a sensitivity of 76% and specificity of 75%, and applying this as a prescreener would reduce the number of lumbar punctures by 51%. Using PET as outcome, a comparable reduction in number of PET scans would be achieved when applying the plasma ratio as prescreener. In addition, low plasma ratio was associated with clinical progression to MCI or dementia (hazard ratio = 2.0, 95% CI = 1.4–2.3).InterpretationPlasma Abeta42/Abeta40 ratio has potential as a prescreener to identify Alzheimer pathological changes in cognitively normal individuals with SCD. Ann Neurol 2018;84:656–666

show abstract

Section: Discussionsupporting

confidence: 52%

Plasma Amyloid as Prescreener for the Earliest Alzheimer Pathological Changes

Verberk

Slot

Verfaillie

et al. 2018

Annals of Neurology

Self Cite

243

237

View full text Add to dashboard Cite

show abstract

“…Some individuals with SMI may already have AD-related pathology [2] . However, a considerable proportion of SMI subjects exhibit 'worried well' conditions, such as anxiety, depression, and non-AD-related pathology, and do not progress to neurodegenerative disease [6] . Therefore, predicting whether an SMI subject will progress to mild cognitive impairment (MCI) or AD is important, but the predictors related to SMI progression are not well clarified.…”

Section: Introductionmentioning

confidence: 99%

Predictors of Clinical Progression of Subjective Memory Impairment in Elderly Subjects: Data from the Clinical Research Centers for Dementia of South Korea (CREDOS)

Hong

Yoon

Shim

et al. 2015

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

Background/Aims: The aims of this study were to determine baseline factors related to the progression of subjective memory impairment (SMI) in elderly subjects and to develop a new modeling scale to predict progression. Methods: Elderly subjects with SMI were recruited from the nationwide Clinical Research Centers for Dementia of South Korea (CREDOS) multicenter cohort and divided into two groups: (1) progressed to mild cognitive impairment or Alzheimer's disease or (2) stable without progression. Baseline clinical characteristics were compared between the groups, and the most relevant predictors of progression were assessed. A new modeling scale combining the predictors was developed. Results: In total, 129 subjects with SMI were analyzed. The follow-up duration was 0.5-4.7 years, and the median time to event was 3.64 years. The progressing group (n = 29) differed from the stable group (n = 100) in terms of baseline age, apolipoprotein E4 (APOE4) status, and some cognitive domains. Older age, a lower Mini-Mental State Examination recall score, APOE4 carrier, and a lower verbal delayed recall score were the most relevant predictors of progression, and a new modeling scale with these 4 predictors provided a better explanation of progression. Conclusion: SMI subjects with a higher risk of progression can be identified using a new modeling scale and might need further evaluations and more frequent follow-up.

show abstract

“…[1][2][3][4][5] Although prior studies use incident dementia as an endpoint, there is a need to consider the effect of SMC on the occurrence of MCI as well. 6 Little is known about risk factors associated with the occurrence of SMCs other than depression or poor psychological well-being.…”

Section: Introductionmentioning

confidence: 99%

“…9 Finally, while Alzheimer disease (AD)-type neuropathologic changes occur years before clinical symptoms are detectable, only a few studies link SMC to neuropathology 10,11 or to biomarkers. 2 We hypothesized that baseline cognitively intact subjects who declared an SMC would be at a higher risk of a cognitive impairment and may harbor AD-type brain pathology even in the absence of observable impairment. We analyzed data from a longitudinal cohort study (Biologically Resilient Adults in Neurological Studies [BRAiNS]).…”

mentioning

confidence: 99%

“…16,17 Briefly, brain regions sampled include middle frontal gyrus (Brodmann area 9), superior and middle temporal gyri (areas 21 and 22), inferior parietal lobule (areas 39 and 40), occipital lobe including primary visual area (areas 17 and 18), amygdala, entorhinal cortex, and hippocampal CA1 and subiculum. Then mean neuritic plaques (NPs) (number/2.35 mm 2 ) and neurofibrillary tangles (NFTs) (number/0.586 mm 2 ) were generated per brain region based on the 5 most involved fields (subjectively determined). We averaged counts into 2 brain regions for data analysis: the medial temporal lobe (MTL) and neocortex.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Self-reported memory complaints: Implications from a longitudinal cohort with autopsies

Jenkins

Schmitt

Bayer³

et al. 2015

Neurology

View full text Add to dashboard Cite

Objective: We assessed salience of subjective memory complaints (SMCs) by older individuals as a predictor of subsequent cognitive impairment while accounting for risk factors and eventual neuropathologies.Methods: Subjects (n 5 531) enrolled while cognitively intact at the University of Kentucky were asked annually if they perceived changes in memory since their last visit. A multistate model estimated when transition to impairment occurred while adjusting for intervening death. Risk factors affecting the timing and probability of an impairment were identified. The association between SMCs and Alzheimer-type neuropathology was assessed from autopsies (n 5 243).Results: SMCs were reported by more than half (55.7%) of the cohort, and were associated with increased risk of impairment (unadjusted odds ratio 5 2.8, p , 0.0001). Mild cognitive impairment (dementia) occurred 9.2 (12.1) years after SMC. Multistate modeling showed that SMC reporters with an APOE e4 allele had double the odds of impairment (adjusted odds ratio 5 2.2, p 5 0.036). SMC smokers took less time to transition to mild cognitive impairment, while SMC hormone-replaced women took longer to transition directly to dementia. Among participants (n 5 176) who died without a diagnosed clinical impairment, SMCs were associated with elevated neuritic amyloid plaques in the neocortex and medial temporal lobe.Conclusion: SMC reporters are at a higher risk of future cognitive impairment and have higher levels of Alzheimer-type brain pathology even when impairment does not occur. As potential harbingers of future cognitive decline, physicians should query and monitor SMCs from their older patients. Neurology ® 2014;83:1359-1365 GLOSSARY AD 5 Alzheimer disease; BRAiNS 5 Biologically Resilient Adults in Neurological Studies; CERAD 5 Consortium to Establish a Registry for Alzheimer's Disease; HRT 5 hormone replacement therapy; MCI 5 mild cognitive impairment; MTL 5 medial temporal lobe; NFT 5 neurofibrillary tangle; NP 5 neuritic plaque; NSI 5 no serious impairment; OR 5 odds ratio; SMC 5 subjective memory complaint.Subjective memory complaints (SMCs) may signal increased risk of progression into clinically recognized states of impairment, namely, mild cognitive impairment (MCI) and dementia. [1][2][3][4][5] Although prior studies use incident dementia as an endpoint, there is a need to consider the effect of SMC on the occurrence of MCI as well. 6 Little is known about risk factors associated with the occurrence of SMCs other than depression or poor psychological well-being.7 SMCs may reflect aspects of metamemory, as older adults monitor their own forgetting.8 Persons with SMC may show MRI-based hippocampal atrophy, a finding also seen in MCI.9 Finally, while Alzheimer disease (AD)-type neuropathologic changes occur years before clinical symptoms are detectable, only a few studies link SMC to neuropathology 10,11 or to biomarkers. 2We hypothesized that baseline cognitively intact subjects who declared an SMC would be at a higher risk of a cognitive impa...

show abstract

Cerebrospinal fluid Aβ42 is the best predictor of clinical progression in patients with subjective complaints

Cited by 178 publications

References 41 publications

Plasma Amyloid as Prescreener for the Earliest Alzheimer Pathological Changes

Plasma Amyloid as Prescreener for the Earliest Alzheimer Pathological Changes

Predictors of Clinical Progression of Subjective Memory Impairment in Elderly Subjects: Data from the Clinical Research Centers for Dementia of South Korea (CREDOS)

Self-reported memory complaints: Implications from a longitudinal cohort with autopsies

Contact Info

Product

Resources

About