| 1. |
- Altomare, Daniele, et al.
(författare)
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Prognostic value of Alzheimer’s biomarkers in mild cognitive impairment : the effect of age at onset
- 2019
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 266:10, s. 2535-2545
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study is to assess the impact of age at onset on the prognostic value of Alzheimer’s biomarkers in a large sample of patients with mild cognitive impairment (MCI). Methods: We measured Aβ42, t-tau, hippocampal volume on magnetic resonance imaging (MRI) and cortical metabolism on fluorodeoxyglucose–positron emission tomography (FDG-PET) in 188 MCI patients followed for at least 1 year. We categorised patients into earlier and later onset (EO/LO). Receiver operating characteristic curves and corresponding areas under the curve (AUCs) were performed to assess and compar the biomarker prognostic performances in EO and LO groups. Linear Model was adopted for estimating the time-to-progression in relation with earlier/later onset MCI groups and biomarkers. Results: In earlier onset patients, all the assessed biomarkers were able to predict cognitive decline (p < 0.05), with FDG-PET showing the best performance. In later onset patients, all biomarkers but t-tau predicted cognitive decline (p < 0.05). Moreover, FDG-PET alone in earlier onset patients showed a higher prognostic value than the one resulting from the combination of all the biomarkers in later onset patients (earlier onset AUC 0.935 vs later onset AUC 0.753, p < 0.001). Finally, FDG-PET showed a different prognostic value between earlier and later onset patients (p = 0.040) in time-to-progression allowing an estimate of the time free from disease. Discussion: FDG-PET may represent the most universal tool for the establishment of a prognosis in MCI patients and may be used for obtaining an onset-related estimate of the time free from disease.
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| 2. |
- Caroli, Anna, et al.
(författare)
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Mild cognitive impairment with suspected nonamyloid pathology (SNAP) Prediction of progression
- 2015
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 84:5, s. 508-515
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non-Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI).Methods:We measured markers of amyloid pathology (CSF -amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [F-18]-fluorodeoxyglucose-PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A+/A- and N+/N- based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A-N+ cases.Results:The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A-N-, A+N-, SNAP, and A+N+, respectively; the proportion of APOE epsilon 4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A+N- and A+N+ groups (p 0.005). Hypometabolism in SNAP patients was comparable to A+N+ patients (p = 0.154), while hippocampal atrophy was more severe in SNAP patients (p = 0.002). Compared with A-N-, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N- patients did not (hazard ratio = 1.13, p = 0.771). In A+N- and A+N+ groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r = 0.42, p = 0.073).Conclusions:Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile.
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| 3. |
- Fällmar, David, et al.
(författare)
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Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.
- 2017
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 27:10, s. 4237-4246
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cerebral perfusion analysis based on arterial spin labeling (ASL) MRI has been proposed as an alternative to FDG-PET in patients with neurodegenerative disease. Z-maps show normal distribution values relating an image to a database of controls. They are routinely used for FDG-PET to demonstrate disease-specific patterns of hypometabolism at the individual level. This study aimed to compare the performance of Z-maps based on ASL to FDG-PET.METHODS: Data were combined from two separate sites, each cohort consisting of patients with Alzheimer's disease (n = 18 + 7), frontotemporal dementia (n = 12 + 8) and controls (n = 9 + 29). Subjects underwent pseudocontinuous ASL and FDG-PET. Z-maps were created for each subject and modality. Four experienced physicians visually assessed the 166 Z-maps in random order, blinded to modality and diagnosis.RESULTS: Discrimination of patients versus controls using ASL-based Z-maps yielded high specificity (84%) and positive predictive value (80%), but significantly lower sensitivity compared to FDG-PET-based Z-maps (53% vs. 96%, p < 0.001). Among true-positive cases, correct diagnoses were made in 76% (ASL) and 84% (FDG-PET) (p = 0.168).CONCLUSION: ASL-based Z-maps can be used for visual assessment of neurodegenerative dementia with high specificity and positive predictive value, but with inferior sensitivity compared to FDG-PET.KEY POINTS: • ASL-based Z-maps yielded high specificity and positive predictive value in neurodegenerative dementia. • ASL-based Z-maps had significantly lower sensitivity compared to FDG-PET-based Z-maps. • FDG-PET might be reserved for ASL-negative cases where clinical suspicion persists. • Findings were similar at two study sites.
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| 5. |
- Leuzy, Antoine, et al.
(författare)
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Derivation and utility of an A beta-PET pathology accumulation index to estimate A beta load
- 2020
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Ingår i: Neurology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0028-3878 .- 1526-632X. ; 95:21, s. E2834-E2844
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate a novel beta-amyloid (A beta)-PET-based quantitative measure (A beta accumulation index [A beta index]), including the assessment of its ability to discriminate between participants based on A beta status using visual read, CSF A beta(42)/A beta(40), and post-mortem neuritic plaque burden as standards of truth. Methods One thousand one hundred twenty-one participants (with and without cognitive impairment) were scanned with A beta-PET: Swedish BioFINDER, n = 392, [F-18]flutemetamol; Alzheimer's Disease Neuroimaging Initiative (ADNI), n = 692, [F-18]florbetapir; and a phase 3 end-of-life study, n = 100, [F-18] flutemetamol. The relationships between A beta index and standardized uptake values ratios (SUVR) from A beta-PET were assessed. The diagnostic performances of A beta index and SUVR were compared with visual reads, CSF A beta(42)/A beta(40), and A beta histopathology used as reference standards. Results Strong associations were observed between A beta index and SUVR (R-2: BioFINDER 0.951, ADNI 0.943, end-of-life, 0.916). Both measures performed equally well in differentiating A beta-positive from A beta-negative participants, with areas under the curve (AUCs) of 0.979 to 0.991 to detect abnormal visual reads, AUCs of 0.961 to 0.966 to detect abnormal CSF A beta(42)/A beta(40), and AUCs of 0.820 to 0.823 to detect abnormal A beta histopathology. Both measures also showed a similar distribution across postmortem-based A beta phases (based on anti-A beta 4G8 antibodies). Compared to models using visual read alone, the addition of the A beta index resulted in a significant increase in AUC and a decrease in Akaike information criterion to detect abnormal A beta histopathology. Conclusion The proposed A beta index showed a tight association to SUVR and carries an advantage over the latter in that it does not require the definition of regions of interest or the use of MRI. A beta index may thus prove simpler to implement in clinical settings and may also facilitate the comparison of findings using different A beta-PET tracers. Classification of evidence This study provides Class III evidence that the A beta accumulation index accurately differentiates A beta-positive from A beta-negative participants compared to A beta-PET visual reads, CSF A beta(42)/A beta(40), and A beta histopathology.
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| 6. |
- Prestia, Annapaola, et al.
(författare)
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Prediction of AD dementia by biomarkers following the NIA-AA and IWG diagnostic criteria in MCI patients from three European memory clinics
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:10, s. 1191-1201
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proposed diagnostic criteria (international working group and National Institute on Aging and Alzheimer's Association) for Alzheimer's disease (AD) include markers of amyloidosis (abnormal cerebrospinal fluid [CSF] amyloid beta [A beta]42) and neurodegeneration (hippocampal atrophy, temporo-parietal hypometabolism on [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), and abnormal CSF tau). We aim to compare the accuracy of these biomarkers, individually and in combination, in predicting AD among mild cognitive impairment (MCI) patients. Methods: In 73 MCI patients, followed to ascertain AD progression, markers were measured. Sensitivity and specificity, positive (LR+) and negative (LR-) likelihood ratios, and crude and adjusted hazard ratios were computed. Results: Twenty-nine MCI patients progressed and 44 remained stable. Positivity to any marker achieved the lowest LR- (0.0), whereas the combination A beta 42 plus FDG-PET achieved the highest LR+ (6.45). In a survival analysis, positivity to any marker was associated with 100% conversion rate, whereas negativity to all markers was associated with 100% stability. Discussion: The best criteria combined amyloidosis and neurodegeneration biomarkers, whereas the individual biomarker with the best performance was FDG-PET.
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| 7. |
- Prestia, Annapaola, et al.
(författare)
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Prediction of dementia in MCI patients based on core diagnostic markers for Alzheimer disease
- 2013
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 80:11, s. 1048-1056
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The current model of Alzheimer disease (AD) stipulates that brain amyloidosis biomarkers turn abnormal earliest, followed by cortical hypometabolism, and finally brain atrophy ones. The aim of this study is to provide clinical evidence of the model in patients with mild cognitive impairment (MCI). Methods: A total of 73 patients with MCI from 3 European memory clinics were included. Brain amyloidosis was assessed by CSF A beta 42 concentration, cortical metabolism by an index of temporoparietal hypometabolism on FDG-PET, and brain atrophy by automated hippocampal volume. Patients were divided into groups based on biomarker positivity: 1) A beta 422- FDG-PET- Hippo-, 2) A beta 42+ FDG-PET- Hippo-, 3) A beta 42+ FDG-PET + Hippo-, 4) A beta 42+ FDG-PET+ Hippo+, and 5) any other combination not in line with the model. Measures of validity were prevalence of group 5, increasing incidence of progression to dementia with increasing biological severity, and decreasing conversion time. Results: When patients with MCI underwent clinical follow-up, 29 progressed to dementia, while 44 remained stable. A total of 26% of patients were in group 5. Incident dementia was increasing with greater biological severity in groups 1 to 5 from 4% to 27%, 64%, and 100% (p for trend, 0.0001), and occurred increasingly earlier (p for trend = 0.024). Conclusions: The core biomarker pattern is in line with the current pathophysiologic model of AD. Fully normal and fully abnormal pattern is associated with exceptional and universal development of dementia. Cases not in line might be due to atypical neurobiology or inaccurate thresholds for biomarker (ab) normality.
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