TY - JOUR
T1 - Clinical outcomes up to 9 years after [18F]flutemetamol amyloid-PET in a symptomatic memory clinic population
AU - Collij, Lyduine E.
AU - Farrar, Gill
AU - Zwan, Marissa
AU - Ossenkoppele, Rik
AU - Barkhof, Frederik
AU - Rozemuller, Annemieke J.M.
AU - Pijnenburg, Yolande A.L.
AU - van der Flier, Wiesje M.
AU - Bouwman, Femke
N1 - Funding Information: Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting Steun Alzheimercentrum Amsterdam. WMvdF holds the Pasman chair. WMvdF is a recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007), Alzheimer Nederland and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). More than 30 partners contribute to ABOARD. We thank Prof. van Berckel for his significant contribution to the acquisition and visual assessment of the amyloid-PET images. This work received an in-kind contribution of the [F]flutemetamol/Vizamyl® radiotracer by GE Healthcare. 18 Funding Information: Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting Steun Alzheimercentrum Amsterdam. WMvdF holds the Pasman chair. WMvdF is a recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007), Alzheimer Nederland and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). More than 30 partners contribute to ABOARD. We thank Prof. van Berckel for his significant contribution to the acquisition and visual assessment of the amyloid-PET images. This work received an in-kind contribution of the [18F]flutemetamol/Vizamyl® radiotracer by GE Healthcare. Funding Information: Wiesje M. van der Flier Research programs of Wiesje van der Flier have been funded by ZonMW, NWO, EU-FP7, EU-JPND, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Health~Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Pasman stichting, stichting Alzheimer & Neuropsychiatrie Foundation, Biogen MA Inc, Boehringer Ingelheim, Life-MI, AVID, Roche BV, Fujifilm, Combinostics. WF holds the Pasman chair. WF is a recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). WF has performed contract research for Biogen MA Inc., and Boehringer Ingelheim. WF has been an invited speaker at Boehringer Ingelheim, Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape), Springer Healthcare. WF is a consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA Inc. WF participated in advisory boards of Biogen MA Inc and Roche. All funding is paid to her institution. WF was associate editor of Alzheimer, Research & Therapy in 2020/2021. WF is an associate editor at Brain. Publisher Copyright: © 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Background: Previous studies demonstrated increases in diagnostic confidence and change in patient management after amyloid-PET. However, studies investigating longitudinal outcomes over an extended period of time are limited. Therefore, we aimed to investigate clinical outcomes up to 9 years after amyloid-PET to support the clinical validity of the imaging technique. Methods: We analyzed longitudinal data from 200 patients (M age = 61.8, 45.5% female, M MMSE = 23.3) suspected of early-onset dementia that underwent [18F]flutemetamol-PET. Baseline amyloid status was determined through visual read (VR). Information on mortality was available with a mean follow-up of 6.7 years (range = 1.1–9.3). In a subset of 108 patients, longitudinal cognitive scores and clinical etiological diagnosis (eDx) at least 1 year after amyloid-PET acquisition were available (M = 3.06 years, range = 1.00–7.02). VR − and VR + patients were compared on mortality rates with Cox Hazard’s model, prevalence of stable eDx using chi-square test, and longitudinal cognition with linear mixed models. Neuropathological data was available for 4 patients (mean delay = 3.59 ± 1.82 years, range = 1.2–6.3). Results: At baseline, 184 (92.0%) patients were considered to have dementia. The majority of VR + patients had a primary etiological diagnosis of AD (122/128, 95.3%), while the VR − group consisted mostly of non-AD etiologies, most commonly frontotemporal lobar degeneration (30/72, 40.2%). Overall mortality rate was 48.5% and did not differ between VR − and VR + patients. eDx at follow-up was consistent with baseline diagnosis for 92/108 (85.2%) patients, with most changes observed in VR − cases (VR − = 14/35, 40% vs VR + = 2/73, 2.7%, χ 2 = 26.03, p < 0.001), who at no time received an AD diagnosis. VR + patients declined faster than VR − patients based on MMSE (β = − 1.17, p = 0.004), episodic memory (β = − 0.78, p = 0.003), fluency (β = − 1.44, p < 0.001), and attention scores (β = 16.76, p = 0.03). Amyloid-PET assessment was in line with post-mortem confirmation in all cases; two cases were VR + and showed widespread AD pathology, while the other two cases were VR − and showed limited amyloid pathology. Conclusion: In a symptomatic population, we observed that amyloid-status did not impact mortality rates, but is predictive of cognitive functioning over time across several domains. Also, we show particular validity for a negative amyloid-PET assessment, as these patients did not receive an AD diagnosis at follow-up.
AB - Background: Previous studies demonstrated increases in diagnostic confidence and change in patient management after amyloid-PET. However, studies investigating longitudinal outcomes over an extended period of time are limited. Therefore, we aimed to investigate clinical outcomes up to 9 years after amyloid-PET to support the clinical validity of the imaging technique. Methods: We analyzed longitudinal data from 200 patients (M age = 61.8, 45.5% female, M MMSE = 23.3) suspected of early-onset dementia that underwent [18F]flutemetamol-PET. Baseline amyloid status was determined through visual read (VR). Information on mortality was available with a mean follow-up of 6.7 years (range = 1.1–9.3). In a subset of 108 patients, longitudinal cognitive scores and clinical etiological diagnosis (eDx) at least 1 year after amyloid-PET acquisition were available (M = 3.06 years, range = 1.00–7.02). VR − and VR + patients were compared on mortality rates with Cox Hazard’s model, prevalence of stable eDx using chi-square test, and longitudinal cognition with linear mixed models. Neuropathological data was available for 4 patients (mean delay = 3.59 ± 1.82 years, range = 1.2–6.3). Results: At baseline, 184 (92.0%) patients were considered to have dementia. The majority of VR + patients had a primary etiological diagnosis of AD (122/128, 95.3%), while the VR − group consisted mostly of non-AD etiologies, most commonly frontotemporal lobar degeneration (30/72, 40.2%). Overall mortality rate was 48.5% and did not differ between VR − and VR + patients. eDx at follow-up was consistent with baseline diagnosis for 92/108 (85.2%) patients, with most changes observed in VR − cases (VR − = 14/35, 40% vs VR + = 2/73, 2.7%, χ 2 = 26.03, p < 0.001), who at no time received an AD diagnosis. VR + patients declined faster than VR − patients based on MMSE (β = − 1.17, p = 0.004), episodic memory (β = − 0.78, p = 0.003), fluency (β = − 1.44, p < 0.001), and attention scores (β = 16.76, p = 0.03). Amyloid-PET assessment was in line with post-mortem confirmation in all cases; two cases were VR + and showed widespread AD pathology, while the other two cases were VR − and showed limited amyloid pathology. Conclusion: In a symptomatic population, we observed that amyloid-status did not impact mortality rates, but is predictive of cognitive functioning over time across several domains. Also, we show particular validity for a negative amyloid-PET assessment, as these patients did not receive an AD diagnosis at follow-up.
KW - Diagnosis
KW - Early-onset dementia
KW - Neuropathology
KW - Survival
KW - [F]flutemetamol amyloid-PET
UR - http://www.scopus.com/inward/record.url?scp=85177834353&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13195-023-01351-1
DO - https://doi.org/10.1186/s13195-023-01351-1
M3 - Article
C2 - 38012799
SN - 1758-9193
VL - 15
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 207
ER -