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Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up.

ABSTRACT: We aimed to longitudinally assess the relationship between changing brain energy metabolism (glucose and acetoacetate) and cognition during healthy aging. Participants aged 71 ± 5 year underwent cognitive evaluation and quantitative positron emission tomography (PET) and magnetic resonance imaging (MRI) scans at baseline (N = 25) and two (N = 25) and four (N = 16) years later. During the follow-up, the rate constant for brain extraction of glucose (Kglc) declined by 6%-12% mainly in the temporo-parietal lobes and cingulate gyri (p ? 0.05), whereas brain acetoacetate extraction (Kacac) and utilization remained unchanged in all brain regions (p ? 0.06). Over the 4 years, cognitive results remained within the normal age range but an age-related decline was observed in processing speed. Kglc in the caudate was directly related to performance on several cognitive tests (r = +0.41 to +0.43, all p ? 0.04). Peripheral insulin resistance assessed by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely related to Kglc in the thalamus (r = -0.44, p = 0.04) and in the caudate (r = -0.43, p = 0.05), and also inversely related to executive function, attention and processing speed (r = -0.45 to -0.53, all p ? 0.03). We confirm in a longitudinal setting that the age-related decline in Kglc is directly associated with declining performance on some tests of cognition but does not significantly affect Kacac.

SUBMITTER: Castellano CA

PROVIDER: S-EPMC6384269 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up.

Castellano Christian-Alexandre CA Hudon Carol C Croteau Etienne E Fortier Mélanie M St-Pierre Valérie V Vandenberghe Camille C Nugent Scott S Tremblay Sébastien S Paquet Nancy N Lepage Martin M Fülöp Tamàs T Turcotte Éric E ÉE Dionne Isabelle J IJ Potvin Olivier O Duchesne Simon S Cunnane Stephen C SC

Frontiers in aging neuroscience 20190115

We aimed to longitudinally assess the relationship between changing brain energy metabolism (glucose and acetoacetate) and cognition during healthy aging. Participants aged 71 ± 5 year underwent cognitive evaluation and quantitative positron emission tomography (PET) and magnetic resonance imaging (MRI) scans at baseline (N = 25) and two (N = 25) and four (N = 16) years later. During the follow-up, the rate constant for brain extraction of glucose (Kglc) declined ...[more]

PMID: 30828297

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Project description:ObjectiveTo understand the role of depressive symptoms in preclinical Alzheimer's disease, it is essential to define their temporal relationship to Alzheimer's proteinopathies in cognitively normal older adults. The study objective was to examine associations of brain amyloid beta and longitudinal measures of depression and depressive symptom clusters in a cognitively normal sample of older adults.MethodA total of 270 community-dwelling, cognitively normal elderly individuals underwent baseline Pittsburgh compound B (PiB) positron emission tomography (PET) measures of cortical aggregate amyloid beta and annual assessments with the 30-item Geriatric Depression Scale (GDS). The authors evaluated continuous PiB binding as a predictor of GDS score or GDS cluster, calculated as total scores and mean scores for three GDS item clusters (apathy-anhedonia, dysphoria, and anxiety-concentration), across time (1-5 years; mean=3.8 years) in separate mixed-effects models with backward elimination. Initial predictors included PiB binding, age, sex, Hollingshead score, American National Adult Reading Test (AMNART) score, apolipoprotein E ε4 status, depression history, and their interactions with time.ResultsHigher PiB binding predicted accelerated rates of increase in GDS score over time, adjusting for depression history. Higher PiB binding also predicted steeper rates of increase for anxiety-concentration scores, adjusting for depression history and the AMNART score-by-time interaction. In a post hoc model estimating anxiety scores without concentration disturbance items, the PiB binding-by-time interaction remained significant.ConclusionsHigher amyloid beta burden was associated with increasing anxious-depressive symptoms over time in cognitively normal older individuals. Prior depression history was related to higher but not worsening symptom ratings. These results suggest a direct or indirect association of elevated amyloid beta levels with worsening anxious-depressive symptoms and support the hypothesis that emerging neuropsychiatric symptoms represent an early manifestation of preclinical Alzheimer's disease.

Project description:BackgroundCharacterization of blood supply changes in older individuals is important in understanding brain aging and diseases. However, prior studies largely focused on cross-sectional design, thus change in cerebral blood flow (CBF) could not be assessed on an individual level.PurposeTo evaluate longitudinal short-term changes in global CBF in cognitively normal older adults.Study typeProspective, longitudinal, and cohort.PopulationOne-hundred twenty-seven cognitive-normal participants (mean age 69 ± 7 years, 47 males) underwent serial MRI with an average follow-up time of 2.1 years.Field strength/sequence3 T phase-contrast (PC), three-dimensional magnetization-prepared-rapid-acquisition-of-gradient-echo (MPRAGE) and fluid-attenuated inversion recovery (FLAIR) MRI.AssessmentTotal CBF was measured with PC MRI allowing assessment of quantitative flow in four major feeding arteries by a trained radiologist with >3 years' experience (O.K.). Brain volume was obtained from MPRAGE MRI and measured by T1-MultiAtlas MRICloud tool. The ratio between total CBF and brain volume yielded global CBF in mL/100 g/min. White matter hyperintensity (WMH) was measured automatically using a Bayesian probability approach on FLAIR.Statistical testsLinear mixed effect model was used to simultaneously assess cross-sectional age-differences and longitudinal age-changes in CBF. Spearman rank correlation was used to evaluate the relationship between CBF change and WMH progression. A P-value of <0.05 (two-tailed) was considered significant.ResultsGlobal CBF decreased with age at a longitudinal rate of -0.56 mL/100 g/min/year (95% confidence interval [CI]: -1.09, -0.03), compared to a cross-sectional rate of -0.26 mL/100 g/min/year (95% CI: -0.41, -0.11). Changes in CBF were significantly associated with progression of WMH (Spearman rank correlation r = -0.25), as those participants who had a more rapid CBF reduction had greater increases in WMH volumes and the relationship remained significant when adjusting for baseline vascular risk scores. Additionally, age-related changes in whole-brain volume were found to be -0.151%/year (95% CI: -0.186, -0.116).Data conclusionThese findings suggest that brain aging in older adults is accompanied by a rapid longitudinal reduction in CBF, the rate of which is associated with white matter damage.Level of evidence1 TECHNICAL EFFICACY STAGE: 2.

Dataset Information

Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up.

Publications

Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up.

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