Steady-state visual evoked potential temporal dynamics reveal correlates of cognitive decline

Nelly, Richard; Nikolic, Miki; Mortensen, Erik Lykke; Osler, Merete; Lauritzen, Martin; Benedek, Krisztina

doi:10.1016/j.clinph.2020.01.010

Cited by 7 publications

(5 citation statements)

References 34 publications

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“…Study on the age-related change in cognitive function and Aβ accumulation, cerebral glucose consumption or permeability of the blood-brain barrier in the same subjects has been published elsewhere [23,24]. Studies based on other subsamples of the Metropolit 1953 Danish Male Birth Cohort have examined age-related changes in brain structures [25,26] and electrical activity [27,28].…”

Section: Methodsmentioning

confidence: 99%

The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation

Vestergaard,

Bakhtiari,

Osler

et al. 2024

Preprint

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Background Accumulation of β-amyloid (Aβ) in the brain is a hallmark of Alzheimer’s Disease (AD). Cerebral deposition of Aβ initiates deteriorating pathways which eventually can lead to AD. However, the exact mechanisms are not known. A possible pathway could be that Aβ affects the cerebral vessels, causing inadequate cerebrovascular function. In the present study, we examined if Aβ accumulation is associated with a reduced cerebral blood flow response (CBF) to neuronal activation by visual stimulation (DCBFVis.Act) in cognitively normal subjects from the Metropolit Danish Male Birth Cohort. Methods 64 subjects participated in the present study. DCBFVis.Act was measured using arterial spin labelling (ASL) combined with blood-oxygen-level-dependent (BOLD) MRI. Neuronal activation was obtained by visual stimulation by a flickering checkerboard presented on a screen in the MRI-scanner. Brain Aβ accumulation and cerebral glucose metabolism were assessed by PET imaging using the radiotracers [11C]Pittsburgh Compound-B (PiB) and [18F]Fluorodeoxyglucose (FDG), respectively. Cortical thickness was measured from structural MRI. Results DCBFVis.Act correlated negatively (\(\beta\) = -32.1 [95% confidence interval (CI): -60.2 ; -4.1], r = -0.30, p = 0.025) with PiB standardized uptake value ratio (SUVr) in the brain regions activated by visual stimulation. DCBFVis.Act did not correlate with FDG SUVr (\(\beta\) = 1.9 [CI: -23.8 ; 27.6], r = 0.02, p = 0.88) or cortical thickness (\(\beta\) = 10.3 [CI: -8.4 ; 29.0], r = 0.15, p = 0.27) in the activated brain regions. Resting CBF did not correlate with PiB SUVr neither in the regions activated by visual stimulation (\(\beta\) = -17.8 [CI:-71.9 ; 36.2], r = 0.09, p = 0.51) nor in the remaining cortex (\(\beta\) = 5.2 [CI:-3.9 ; 14.2], r = 0.15, p = 0.26). Conclusion We found a correlation between high PiB SUVr and reduced CBF response to neuronal activation, indicating a link between Aβ accumulation and impaired cerebrovascular function. The impairment was not associated with cortical thinning or hypometabolism, suggesting that Aβ accumulation affecting brain vessel function could be a very early pathology leading to neurodegenerative disease.

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Section: Methodsmentioning

confidence: 99%

The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation

Vestergaard,

Bakhtiari,

Osler

et al. 2024

Preprint

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“…Studies based on the Metropolit Danish Male Birth Cohort on age-related changes in brain structures [ 20 , 21 ] and electrical activity [ 22 , 23 ] and its relationship to cognition have previously been published; however, the participants in present study were not part of the former studies.…”

Section: Methodsmentioning

confidence: 99%

Subclinical cognitive deficits are associated with reduced cerebrovascular response to visual stimulation in mid-sixties men

et al. 2022

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Reduced cerebrovascular response to neuronal activation is observed in patients with neurodegenerative disease. In the present study, we examined the correlation between reduced cerebrovascular response to visual activation (ΔCBFVis.Act) and subclinical cognitive deficits in a human population of mid-sixties individuals without neurodegenerative disease. Such a correlation would suggest that impaired cerebrovascular function occurs before overt neurodegenerative disease. A total of 187 subjects (age 64–67 years) of the Metropolit Danish Male Birth Cohort participated in the study. ΔCBFVis.Act was measured using arterial spin labelling (ASL) MRI. ΔCBFVis.Act correlated positively with cognitive performance in: Global cognition (p = 0.046), paired associative memory (p = 0.025), spatial recognition (p = 0.026), planning (p = 0.016), simple processing speed (p < 0.01), and with highly significant correlations with current intelligence (p < 10−5), and more complex processing speed (p < 10−3), the latter two explaining approximately 11–13% of the variance. Reduced ΔCBFVis.Act was independent of brain atrophy. Our findings suggest that inhibited cerebrovascular response to neuronal activation is an early deficit in the ageing brain and associated with subclinical cognitive deficits. Cerebrovascular dysfunction could be an early sign of a trajectory pointing towards the development of neurodegenerative disease. Future efforts should elucidate if maintenance of a healthy cerebrovascular function can protect against the development of dementia.

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“…The participants were examined physiologically and cognitively at several time points throughout their lives, making them ideal for a longitudinal ageing study. Previous studies from this cohort have focused on age-related changes in brain structures [26], electrical activity [27][28][29][30] and cerebrovascular function [31]. For the present study, we recruited a subset of participants from the cohort who had been examined at three different timepoints 5 years apart, with the first examination taking place in 2011/2012 (T1), the second in 2015/2016 (T2) and the third in 2021/2022 (T3).…”

Section: Participantsmentioning

confidence: 99%

Changes in hippocampal volume during a preceding 10-year period do not correlate with cognitive performance and hippocampal blood‒brain barrier permeability in cognitively normal late-middle-aged men

et al. 2022

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Hippocampal blood–brain barrier (BBB) permeability may increase in normal healthy ageing and contribute to neurodegenerative disease. To examine this hypothesis, we investigated the correlation between blood–brain barrier (BBB) permeability, regional brain volume, memory functions and health and lifestyle factors in The Metropolit 1953 Danish Male Birth Cohort. We used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a gadolinium-based contrast agent to assess BBB permeability in 77 participants in the cohort. BBB permeability was measured as Ki values in the hippocampus, thalamus and white matter. Over a 10-year period, we observed progressive atrophy of both the left and right hippocampus (p = 0.001). There was no significant correlation between current BBB permeability and hippocampal volume, prior atrophy or cognition. The hippocampus volume ratio was associated with better visual and verbal memory scores (p < 0.01). Regional BBB differences revealed higher Ki values in the hippocampus and white matter than in the thalamus (p < 0.001). Participants diagnosed with type II diabetes had significantly higher BBB permeability in the white matter (p = 0.015) and thalamus (p = 0.016), which was associated with a higher Fazekas score (p = 0.024). We do not find evidence that BBB integrity is correlated with age-related hippocampal atrophy or cognitive functions. The association between diabetes, white matter hyperintensities and increased BBB permeability is consistent with the idea that cerebrovascular disease compromises BBB integrity. Our findings suggest that the hippocampus is particularly prone to age-related atrophy, which may explain some of the cognitive changes that accompany older age, but this prior atrophy is not correlated with current BBB permeability.

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Steady-state visual evoked potential temporal dynamics reveal correlates of cognitive decline

Cited by 7 publications

References 34 publications

The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation

The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation

Subclinical cognitive deficits are associated with reduced cerebrovascular response to visual stimulation in mid-sixties men

Changes in hippocampal volume during a preceding 10-year period do not correlate with cognitive performance and hippocampal blood‒brain barrier permeability in cognitively normal late-middle-aged men

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