Resilience to cognitive impairment in the oldest-old: design of the EMIF-AD 90+ study

Legdeur, Nienke; Badissi, Maryam; Carter, Stephen F.; Crom, Sophie de; Kreeke, Aleid van de; Vreeswijk, Ralph; Trappenburg, Marijke C.; Oudega, Mardien L.; Koek, Huiberdina L.; Campen, Jos P. van; Keijsers, Carolina J. P. W.; Amadi, Chinenye; Hinz, Rainer; Gordon, Mark Forrest; Novak, Gerald; Podhorná, Jana; Serné, Erik H.; Verbraak, Frank D.; Yaqub, Maqsood; Hillebrand, Arjan; Griffa, Alessandra; Pendleton, Neil; Kramer, Sophia E.; Teunissen, Charlotte E.; Lammertsma, Adriaan A.; Barkhof, Frederik; Berckel, Bart N.M. van; Scheltens, Philip; Muller, Majon; Maier, Andrea B.; Herholz, Karl; Visser, Pieter Jelle

doi:10.1186/s12877-018-0984-z

Cited by 31 publications

(48 citation statements)

References 134 publications

(102 reference statements)

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“…Individuals with normal cognition who underwent an amyloid positron emission tomography (PET) were selected from the Innovative Medicine Initiative European Medical Information Framework for AD (EMIF‐AD) 90+ Study conducted at the Amsterdam University Medical Center (UMC). Individuals were recruited through general practitioners or via advertisements, see Legdeur et al (2018) 17 for detailed description of this cohort and overall study design. Normal cognition was defined as a Clinical Dementia Rating (CDR) score of zero, and a Mini‐Mental State Examination (MMSE) score of ≥26.…”

Section: Methodsmentioning

confidence: 99%

Amyloid‐β, cortical thickness, and subsequent cognitive decline in cognitively normal oldest‐old

Pelkmans

Legdeur

Kate

et al. 2021

Ann Clin Transl Neurol

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Objective To investigate the relationship between amyloid‐β (Aβ) deposition and markers of brain structure on cognitive decline in oldest‐old individuals with initial normal cognition. Methods We studied cognitive functioning in four domains at baseline and change over time in fifty‐seven cognitively intact individuals from the EMIF‐AD 90+ study. Predictors were Aβ status determined by [18F]‐flutemetamol PET (normal = Aβ − vs. abnormal = Aβ+), cortical thickness in 34 regions and hippocampal volume. Mediation analyses were performed to test whether effects of Aβ on cognitive decline were mediated by atrophy of specific anatomical brain areas. Results Subjects had a mean age of 92.7 ± 2.9 years, of whom 19 (33%) were Aβ+. Compared to Aβ−, Aβ+ individuals showed steeper decline on memory (β ± SE = −0.26 ± 0.09), and processing speed (β ± SE = −0.18 ± 0.08) performance over 1.5 years (P < 0.05). Furthermore, medial and lateral temporal lobe atrophy was associated with steeper decline in memory and language across individuals. Mediation analyses revealed that part of the memory decline observed in Aβ+ individuals was mediated through parahippocampal atrophy. Interpretation These results show that Aβ abnormality even in the oldest old with initially normal cognition is not part of normal aging, but is associated with a decline in cognitive functioning. Other pathologies may also contribute to decline in the oldest old as cortical thickness predicted cognitive decline similarly in individuals with and without Aβ pathology.

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Section: Methodsmentioning

confidence: 99%

Amyloid‐β, cortical thickness, and subsequent cognitive decline in cognitively normal oldest‐old

Pelkmans

Legdeur

Kate

et al. 2021

Ann Clin Transl Neurol

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“…Specific procedures have been described for each cohort in detail elsewhere [ 21 – 26 ]. Briefly, HABS is a prospective community-based cohort that consists of individuals aged 65 years and older, who are considered cognitively normal at study inclusion [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

“…In the EMIF-AD PreclinAD Study, cognitively normal subjects aged 60 years and older were included [ 25 ]. The EMIF-AD 90+ Study focused on people aged 90 years and older who were either cognitively normal or who had some cognitive impairment [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

Decline in cognitively complex everyday activities accelerates along the Alzheimer’s disease continuum

et al. 2020

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Background Impairment in daily functioning is a clinical hallmark of dementia. Difficulties with “instrumental activities of daily living” (IADL) seem to increase gradually over the course of Alzheimer’s disease (AD), before dementia onset. However, it is currently not well established how difficulties develop along the preclinical and prodromal stages of AD. We aimed to investigate the trajectories of decline in IADL performance, as reported by a study partner, along the early stages of AD. Methods In a longitudinal multicenter study, combining data from community-based and memory clinic cohorts, we included 1555 individuals (mean age 72.5 ± 7.8 years; 50% female) based on availability of amyloid biomarkers, longitudinal IADL data, and clinical information at baseline. Median follow-up duration was 2.1 years. All amyloid-positive participants (n = 982) were classified into the National Institute on Aging–Alzheimer’s Association (NIA-AA) clinical stages ranging from preclinical AD (1) to overt dementia (4+). Cognitively normal amyloid-negative individuals (n = 573) served as a comparison group. The total scores of three study-partner reported IADL questionnaires were standardized. Results The rate of decline in cognitively normal (stage 1) individuals with and without abnormal amyloid did not differ (p = .453). However, from stage 2 onwards, decline was significantly faster in individuals on the AD continuum (B [95%CI] = − 0.32 [− 0.55, − 0.09], p = .007). The rate of decline increased with each successive stage: one standard deviation (SD) unit per year in stage 3 (− 1.06 [− 1.27, − 0.85], p < .001) and nearly two SD units per year in stage 4+ (1.93 [− 2.19, − 1.67], p < .001). Overall, results were similar between community-based and memory clinic study cohorts. Conclusions Our results suggest that the rate of functional decline accelerates along the AD continuum, as shown by steeper rates of decline in each successive NIA-AA clinical stage. These results imply that incremental changes in function are a meaningful measure for early disease monitoring. Combined with the low-cost assessment, this advocates the use of these functional questionnaires for capturing the effects of early AD-related cognitive decline on daily life.

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“…The 90+ study consists of cognitively healthy and cognitively impaired subjects, aged ≥90 or over. For extensive recruitment information we refer to our set-up paper of this study by Legdeur et al (17). The PreclinAD cohort (18) is a cohort consisting of cognitively healthy participants (monozygotic twins) aged ≥60, recruited from the Netherlands Twin Registry (19).…”

Section: Participantsmentioning

confidence: 99%

Ocular biomarkers for cognitive impairment in nonagenarians; a prospective cross-sectional study

Kreeke

Legdeur

Badissi

et al. 2019

Preprint

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Background: Ocular imaging receives much attention as a source of potential biomarkers for dementia. In the present study, we analyze these ocular biomarkers in cognitively impaired and healthy participants in a population aged over 90 years (= nonagenarian), and elucidate the effects of age on these biomarkers. Methods: For this prospective cross-sectional study, we included individuals from the EMIF-AD 90+ study, consisting of a cognitively healthy (N=67) and cognitively impaired group (N=33), and the EMIF-AD PreclinAD study, consisting of cognitively healthy controls aged ≥60 (N=198). Participants underwent Optical Coherence Tomography (OCT) and fundus photography of both eyes. OCT was used to asses total and individual inner retinal layer thickness in the macular region (Early Treatment Diabetic Retinopathy Study circles) as well as peripapillary retinal nerve fiber layer thickness, fundus images were analyzed with Singapore I Vessel Assessment to obtain 7 retinal vascular parameters. Values for both eyes were averaged. Differences in ocular biomarkers between the 2 nonagenarian groups were analyzed using linear regression, differences between the individual nonagenarian groups and controls were analyzed using generalized estimating equations. Results: Ocular biomarkers did not differ between the healthy and cognitively impaired nonagenarian groups. Both nonagenarian groups differed in most ocular biomarkers from the younger controls. Conclusion: Ocular biomarkers were not associated with cognitive impairment in nonagenarians, making their use as a screening tool for dementing disorders in this group limited. However, ocular biomarkers were significantly associated with chronological age, which were very similar to those ascribed to occur in Alzheimer’s Disease.

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Resilience to cognitive impairment in the oldest-old: design of the EMIF-AD 90+ study

Cited by 31 publications

References 134 publications

Amyloid‐β, cortical thickness, and subsequent cognitive decline in cognitively normal oldest‐old

Amyloid‐β, cortical thickness, and subsequent cognitive decline in cognitively normal oldest‐old

Decline in cognitively complex everyday activities accelerates along the Alzheimer’s disease continuum

Ocular biomarkers for cognitive impairment in nonagenarians; a prospective cross-sectional study

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