Subjective Cognitive Impairment Cohort (SCIENCe): study design and first results

Slot, Rosalinde E.R.; Verfaillie, Sander C.J.; Overbeek, Jozefien M.; Timmers, Tessa; Wesselman, Linda M.P.; Teunissen, Charlotte E.; Dols, Annemiek; Bouwman, Femke H.; Prins, Niels D.; Barkhof, Frederik; Lammertsma, Adriaan A.; Berckel, Bart N.M. van; Scheltens, Philip; Sikkes, Sietske A.M.; Flier, Wiesje M. van der

doi:10.1186/s13195-018-0390-y

Cited by 103 publications

(120 citation statements)

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“…In line with earlier studies [8], we observed a tight link between CSF p-tau and [ 18 F]flortaucipir BP ND in SCD. However, other studies did not find a relationship between CSF p-tau and [ 18 F]flortaucipir within cognitively unimpaired controls [9][10][11], which could be related to the notion that individuals with SCD are at increased risk for AD [65,66,67]. However, p-tau may be more sensitive in early stages than [ 18 F]flortaucipir [11,26,52], as subtle increases in [ 18 F]flortaucipir binding has been shown in the preclinical stages of AD [15,19,60,68].…”

Section: Discussionmentioning

confidence: 98%

Regional [18F]flortaucipir PET is more closely associated with disease severity than CSF p-tau in Alzheimer’s disease

Wolters

Ossenkoppele

Verfaillie

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose In vivo Alzheimer's disease (AD) biomarkers for tau pathology are cerebrospinal fluid (CSF) phosphorylated tau (p-tau) and [ 18 F]flortaucipir positron emission tomography (PET). Our aim was to assess associations between CSF p-tau with [ 18 F]flortaucipir PET and the associations of both tau biomarkers with cognition and atrophy. Methods We included 78 amyloid positive cognitively impaired patients (clinical diagnoses mild cognitive impairment (MCI, n = 8) and AD dementia (n = 45) and 25 cognitively normal subjects with subjective cognitive decline (SCD) (40% amyloid-positive)). Dynamic 130 min [ 18 F]flortaucipir PET scans were acquired to generate binding potential (BP ND ) images using receptor parametric mapping and standardized uptake values ratios of 80-100 min (SUVr 80-100min ) post injection. We obtained regional BP ND and SUVr from entorhinal, limbic, and neocortical regions-of-interest (ROIs), closely aligning to the neuropathological tau staging schemes. Cognition was assessed using MMSE and composite scores of four cognitive domains, and atrophy was measured using gray matter volume covering the major brain lobes. First, we used linear regressions to investigate associations between CSF p-tau (independent variable) and tau PET (dependent variable). Second, we used linear regressions to investigate associations between CSF p-tau, tau PET (separate independent variables, model 1), and cognition (dependent variable). We then assessed the independent effects of CSF p-tau and tau PET on cognition by simultaneously adding the other tau biomarker as a predictor (model 2). Finally, we performed the same procedure for model 1 and 2, but replaced cognition with atrophy. Models were adjusted for age, sex, time lag between assessments, education (cognition only), and total intracranial volume (atrophy only). Results Higher [ 18 F]flortaucipir BP ND was associated with higher CSF p-tau (range of standardized betas (sβ) across ROIs, 0.43-0.46; all p < 0.01). [ 18 F]flortaucipir BP ND was more strongly associated with cognition and atrophy than CSF p-tau. When [ 18 F]flortaucipir BP ND and CSF p-tau were entered simultaneously, [ 18 F]flortaucipir BP ND (range sβ = − 0.20 to -0.57, all p < 0.05) was strongly associated with multiple cognitive domains and atrophy regions. SUVr showed comparable results to BP ND . Conclusion Regional [ 18 F]flortaucipir BP ND correlated stronger with cognition and neurodegeneration than CSF p-tau, suggesting that tau PET more accurately reflects disease severity in AD.

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Section: Discussionmentioning

confidence: 98%

Regional [18F]flortaucipir PET is more closely associated with disease severity than CSF p-tau in Alzheimer’s disease

Wolters

Ossenkoppele

Verfaillie

et al. 2020

Eur J Nucl Med Mol Imaging

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“…NC, normal control; SCD, subjective cognitive decline; aMCI, amnestic mild cognitive impairment; ATR, anterior thalamic radiation; CST, corticospinal tract; CgC, cingulum (cingulate gyrus); CgH, cingulum (hippocampus); Fmi, forceps minor; IFO, inferior fronto-occipital fasciculus; MD, mean diffusivity; L, left; R, right; WM, white matter; *P < 0.05; **P < 0.01; ***P < 0.001. processes and can offer a new insight into AD pathophysiology (Caso et al, 2016). Research interest is shifting to increasingly earlier stages, as the origin of AD and keys to treatment probably lie in the prevention of progression to a fully fledged disease (Slot et al, 2018). It should be noted that SCD has been shown to be the first clinical manifestation of AD, and there is increasing interest in the study of individuals meeting SCD criteria to assess the progression of this disease in the subjects who have a higher risk of cognitive decline (Sánchez-Benavides et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

White Matter Microstructural Damage as an Early Sign of Subjective Cognitive Decline

Luo

Qin

et al. 2020

Front. Aging Neurosci.

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Background and Objective: Subjective cognitive decline (SCD) is considered a preclinical state of Alzheimer's disease (AD) and may represent a more advanced preclinical status than amnestic mild cognitive impairment (aMCI). Our aim was to explore changes in the white matter (WM) microstructure and their correlation with cognitive function in these AD-spectrum patients.Methods: Diffusion tensor images from 43 individuals with normal cognition (NC), 38 SCD patients, and 36 aMCI patients were compared using an atlas-based segmentation strategy. The correlation between diffusion parameters and cognitive function was further analyzed.Results: The anatomical pattern of WM impairment was generally similar between SCD and aMCI patients. However, aMCI patients showed significantly lower fractional anisotropy (i.e., corpus callosum forceps major and forceps minor) and increased mean diffusivity [i.e., bilateral anterior thalamic radiation (ATR), left corticospinal tract (CST), forceps minor, left cingulum (cingulate gyrus), left cingulum hippocampus, and left inferior fronto-occipital fasciculus (IFO)] in some tracts than did SCD subjects, indicating a disruption in WM microstructural integrity in the aMCI. Individuals with microstructural disruption in forceps minor, left cingulum (cingulate gyrus), and left cingulum hippocampus tracts performed worse in general cognition and memory function tests, as indicated by line regression analysis.Conclusion: SCD individuals had extensive WM microstructural damage in a pattern similar to that seen in aMCI, although presenting a cognitive performance comparable with that of cognitively healthy individuals. Our results suggest that WM integrity might precede objectively measurable memory decline and may be a potential early biomarker for AD.

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“… followed up 122 SCD subjects for a mean time of 48 months and found a very poor accuracy of SCD‐plus criteria as predictors of AD. More recently, a cross‐sectional description of participant characteristics in an ongoing prospective cohort study on SCD showed that age ≥60 and ApoE ε4 were associated with positivity of cerebrospinal fluid biomarkers. In line with these data, our study showed that age at onset ≥60 years and ApoE ε4 increased the risk of conversion to AD in SCD subjects, by 3.5‐fold and 5‐fold respectively.…”

Section: Discussionmentioning

confidence: 99%

Assessing the effectiveness of subjective cognitive decline plus criteria in predicting the progression to Alzheimer’s disease: an 11‐year follow‐up study

Mazzeo

Padiglioni

Bagnoli

et al. 2020

Euro J of Neurology

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Background and purpose: Subjective cognitive decline (SCD) is a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests and has been shown to increase the risk of Alzheimer's disease (AD). SCD could also be related to other conditions such as normal aging, psychiatric, neurological or medical disorders. The SCD Initiative proposed a set of features (SCD-plus) that increase the likelihood of preclinical AD in individuals with SCD. Our aim was to assess the effect of these features on the risk of conversion from SCD to AD. Methods: In total 150 SCD subjects who underwent extensive neuropsychological investigation, assessment of cognitive complaints and apolipoprotein E (ApoE) genotyping at baseline and clinical-neuropsychological follow-up for a mean time of 11 years were included. Results: During the follow-up, 20 subjects developed AD. Considering SCDplus features, age at onset ≥60 years and ApoE e4 significantly increased the risk of conversion from SCD to AD. When our sample was stratified into three groups (no risk factor, one risk factor, two risk factors), the proportion of conversion was statistically significantly different between the three groups. Conclusions: Our model allows the risk of AD to be stratified in patients experiencing SCD according to age at onset and ApoE genotype.

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Subjective Cognitive Impairment Cohort (SCIENCe): study design and first results

Cited by 103 publications

References 65 publications

Regional [18F]flortaucipir PET is more closely associated with disease severity than CSF p-tau in Alzheimer’s disease

Regional [18F]flortaucipir PET is more closely associated with disease severity than CSF p-tau in Alzheimer’s disease

White Matter Microstructural Damage as an Early Sign of Subjective Cognitive Decline

Assessing the effectiveness of subjective cognitive decline plus criteria in predicting the progression to Alzheimer’s disease: an 11‐year follow‐up study

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