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  • Ovid Technologies (Wolters Kluwer Health)  (3)
  • Verfaillie, Sander C.J.  (3)
  • 1
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    Online Resource
    ATN classification and clinical progression in subjective cognitive decline : The SCIENCe project
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Neurology Vol. 95, No. 1 ( 2020-07-07), p. e46-e58
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 95, No. 1 ( 2020-07-07), p. e46-e58
    Abstract: To investigate the relationship between the ATN classification system (amyloid, tau, neurodegeneration) and risk of dementia and cognitive decline in individuals with subjective cognitive decline (SCD). Methods We classified 693 participants with SCD (60 ± 9 years, 41% women, Mini-Mental State Examination score 28 ± 2) from the Amsterdam Dementia Cohort and Subjective Cognitive Impairment Cohort (SCIENCe) project according to the ATN model, as determined by amyloid PET or CSF β-amyloid (A), CSF p-tau (T), and MRI-based medial temporal lobe atrophy (N). All underwent extensive neuropsychological assessment. For 342 participants, follow-up was available (3 ± 2 years). As a control population, we included 124 participants without SCD. Results Fifty-six (n = 385) participants had normal Alzheimer disease (AD) biomarkers (A–T–N–), 27% (n = 186) had non-AD pathologic change (A–T–N+, A–T+N–, A–T+N+), 18% (n = 122) fell within the Alzheimer continuum (A+T–N–, A+T–N+, A+T+N–, A+T+N+). ATN profiles were unevenly distributed, with A–T+N+, A+T–N+, and A+T+N+ containing very few participants. Cox regression showed that compared to A–T–N–, participants in A+ profiles had a higher risk of dementia with a dose–response pattern for number of biomarkers affected. Linear mixed models showed participants in A+ profiles showed a steeper decline on tests addressing memory, attention, language, and executive functions. In the control group, there was no association between ATN and cognition. Conclusions Among individuals presenting with SCD at a memory clinic, those with a biomarker profile A–T+N+, A+T–N–, A+T+N–, and A+T+N+ were at increased risk of dementia, and showed steeper cognitive decline compared to A–T–N– individuals. These results suggest a future where biomarker results could be used for individualized risk profiling in cognitively normal individuals presenting at a memory clinic.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000009724
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    Location Call Number Limitation Availability
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  • 2
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    Online Resource
    [18F]Flortaucipir PET Across Various MAPT Mutations in Presymptomatic and Symptomatic Carriers
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Neurology Vol. 97, No. 10 ( 2021-09-7), p. e1017-e1030
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 97, No. 10 ( 2021-09-7), p. e1017-e1030
    Abstract: To assess the [ 18 F]flortaucipir binding distribution across MAPT mutations in presymptomatic and symptomatic carriers. Methods We compared regional [ 18 F]flortaucipir binding potential (BP ND ) derived from a 130-minute dynamic [ 18 F]flortaucipir PET scan in 9 (pre)symptomatic MAPT mutation carriers (4 with P301L [1 symptomatic], 2 with R406W [1 symptomatic] , 1 presymptomatic L315R, 1 presymptomatic S320F, and 1 symptomatic G272V carrier) with 30 cognitively normal controls and 52 patients with Alzheimer disease. Results [ 18 F]Flortaucipir BP ND images showed overall highest binding in the symptomatic carriers. This was most pronounced in the symptomatic R406W carrier in whom tau binding exceeded the normal control range in the anterior cingulate cortex, insula, amygdala, temporal, parietal, and frontal lobe. Elevated medial temporal lobe BP ND was observed in a presymptomatic R406W carrier. The single symptomatic carrier and 1 of the 3 presymptomatic P301L carriers showed elevated [ 18 F]flortaucipir BP ND in the insula, parietal, and frontal lobe compared to controls. The symptomatic G272V carrier exhibited a widespread elevated cortical BP ND , with at neuropathologic examination a combination of 3R pathology and encephalitis. The L315R presymptomatic mutation carrier showed higher frontal BP ND compared to controls. The BP ND values of the S320F presymptomatic mutation carrier fell within the range of controls. Conclusion Presymptomatic MAPT mutation carriers already showed subtle elevated tau binding, whereas symptomatic MAPT mutation carriers showed a more marked increase in [ 18 F]flortaucipir BP ND . Tau deposition was most pronounced in R406W MAPT (pre)symptomatic mutation carriers, which is associated with both 3R and 4R tau accumulation. Thus, [ 18 F]flortaucipir may serve as an early biomarker for MAPT mutation carriers in mutations that cause 3R/4R tauopathies.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000012448
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Association of CSF, Plasma, and Imaging Markers of Neurodegeneration With Clinical Progression in People With Subjective Cognitive Decline
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Neurology Vol. 98, No. 13 ( 2022-03-29), p. e1315-e1326
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 13 ( 2022-03-29), p. e1315-e1326
    Abstract: Multiple biomarkers have been suggested to measure neurodegeneration (N) in the AT(N) framework, leading to inconsistencies between studies. We investigated the association of 5 N biomarkers with clinical progression and cognitive decline in individuals with subjective cognitive decline (SCD). Methods We included individuals with SCD from the Amsterdam Dementia Cohort and SCIENCe project, a longitudinal cohort study (follow-up 4±3 years). We used the following N biomarkers: CSF total tau (t-tau), medial temporal atrophy visual rating on MRI, hippocampal volume (HV), serum neurofilament light (NfL), and serum glial fibrillary acidic protein (GFAP). We determined correlations between biomarkers. We assessed associations between N biomarkers and clinical progression to mild cognitive impairment or dementia (Cox regression) and Mini-Mental State Examination (MMSE) over time (linear mixed models). Models included age, sex, CSF β-amyloid (Aβ) (A), and CSF p-tau (T) as covariates, in addition to the N biomarker. Result We included 401 individuals (61±9 years, 42% female, MMSE 28 ± 2, vascular comorbidities 8%–19%). N biomarkers were modestly to moderately correlated (range r −0.28 – 0.58). Serum NfL and GFAP correlated most strongly ( r 0.58, p 〈 0.01). T-tau was strongly correlated with p-tau ( r 0.89, p 〈 0.01), although these biomarkers supposedly represent separate biomarker groups. All N biomarkers individually predicted clinical progression, but only HV, NfL, and GFAP added predictive value beyond Aβ and p-tau (hazard ratio 1.52 [95% CI 1.11–2.09]; 1.51 [1.05–2.17] ; 1.50 [1.04–2.15]). T-tau, HV, and GFAP individually predicted MMSE slope (range β −0.17 to −0.11, p 〈 0.05), but only HV remained associated beyond Aβ and p-tau (β −0.13 [SE 0.04]; p 〈 0.05). Discussion In cognitively unimpaired older adults, correlations between different N biomarkers were only moderate, indicating they reflect different aspects of neurodegeneration and should not be used interchangeably. T-tau was strongly associated with p-tau (T), which makes it less desirable to use as a measure for N. HV, NfL, and GFAP predicted clinical progression beyond A and T. Our results do not allow to choose one most suitable biomarker for N, but illustrate the added prognostic value of N beyond A and T. Classification of Evidence This study provides Class II evidence that HV, NfL, and GFAP predicted clinical progression beyond A and T in individuals with SCD.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000200035
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    Location Call Number Limitation Availability
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    Online Resource
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