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Clinical outcomes up to 9 years after [18F]flutemetamol amyloid-PET in a symptomatic memory clinic population

Collij, Lyduine E. LU ; Farrar, Gill ; Zwan, Marissa ; van de Giessen, Elsmarieke ; Ossenkoppele, Rik LU ; Barkhof, Frederik ; Rozemuller, Annemieke J.M. ; Pijnenburg, Yolande A.L. ; van der Flier, Wiesje M. and Bouwman, Femke (2023) In Alzheimer's Research and Therapy 15(1).
Abstract

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... (More)

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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Diagnosis, Early-onset dementia, Neuropathology, Survival, [F]flutemetamol amyloid-PET
in
Alzheimer's Research and Therapy
volume
15
issue
1
article number
207
publisher
BioMed Central (BMC)
external identifiers
  • pmid:38012799
  • scopus:85177834353
ISSN
1758-9193
DOI
10.1186/s13195-023-01351-1
language
English
LU publication?
yes
id
63785eec-c51b-4684-b461-dc031cde63dc
date added to LUP
2023-12-18 14:41:53
date last changed
2024-04-03 00:43:59
@article{63785eec-c51b-4684-b461-dc031cde63dc,
  abstract     = {{<p>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 <sub>age</sub> = 61.8, 45.5% female, M <sub>MMSE</sub> = 23.3) suspected of early-onset dementia that underwent [<sup>18</sup>F]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 <sup>2</sup> = 26.03, p &lt; 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 &lt; 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.</p>}},
  author       = {{Collij, Lyduine E. and Farrar, Gill and Zwan, Marissa and van de Giessen, Elsmarieke and Ossenkoppele, Rik and Barkhof, Frederik and Rozemuller, Annemieke J.M. and Pijnenburg, Yolande A.L. and van der Flier, Wiesje M. and Bouwman, Femke}},
  issn         = {{1758-9193}},
  keywords     = {{Diagnosis; Early-onset dementia; Neuropathology; Survival; [F]flutemetamol amyloid-PET}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Alzheimer's Research and Therapy}},
  title        = {{Clinical outcomes up to 9 years after [<sup>18</sup>F]flutemetamol amyloid-PET in a symptomatic memory clinic population}},
  url          = {{http://dx.doi.org/10.1186/s13195-023-01351-1}},
  doi          = {{10.1186/s13195-023-01351-1}},
  volume       = {{15}},
  year         = {{2023}},
}