Four-month aerobic exercise training improves hippocampal volume in older adults at metabolic risk

1094 

Abstract Submission 

Svenja Schwarck^1,2, Jose Bernal², David Berron², Hannah Baumeister², Helena Gellersen², Marcel Daamen³, Anne Maass², Gabriel Ziegler^1,2, Henning Boecker³, Emrah Düzel^1,2

¹Institute of Cognitive Neurology and Dementia Research, Magdeburg, Germany, ²German Center of Neurodegenerative Diseases (DZNE), Magdeburg, Germany, ³German Center of Neurodegenerative Diseases (DZNE), Bonn, Germany

Svenja Schwarck  
Institute of Cognitive Neurology and Dementia Research|German Center of Neurodegenerative Diseases (DZNE)
Magdeburg, Germany|Magdeburg, Germany

Jose Bernal  
German Center of Neurodegenerative Diseases (DZNE)
Magdeburg, Germany

David Berron  
German Center of Neurodegenerative Diseases (DZNE)
Magdeburg, Germany

Hannah Baumeister  
German Center of Neurodegenerative Diseases (DZNE)
Magdeburg, Germany

Helena Gellersen  
German Center of Neurodegenerative Diseases (DZNE)
Magdeburg, Germany

Marcel Daamen  
German Center of Neurodegenerative Diseases (DZNE)
Bonn, Germany

Anne Maass  
German Center of Neurodegenerative Diseases (DZNE)
Magdeburg, Germany

Gabriel Ziegler  
Institute of Cognitive Neurology and Dementia Research|German Center of Neurodegenerative Diseases (DZNE)
Magdeburg, Germany|Magdeburg, Germany

Henning Boecker  
German Center of Neurodegenerative Diseases (DZNE)
Bonn, Germany

Emrah Düzel  
Institute of Cognitive Neurology and Dementia Research|German Center of Neurodegenerative Diseases (DZNE)
Magdeburg, Germany|Magdeburg, Germany

Higher metabolic risk is associated with poor cardiovascular health and greater risk of developing dementia (Duzel et al., 2016). Even though aerobic exercise training has been shown to improve cardiovascular and metabolic health, memory performance, and hippocampal volume in older healthy adults (Aghjayan et al., 2021), evidence of such effects in older adults with metabolic risk remains limited and conflicting. Here, we conducted a combined physical and cognitive training in older adults with metabolic risk to analyze the cumulative and analytically challenging immediate training effects.

Materials. We recruited thirty-five sedentary older adults (age: 67.77 ± 2.60 years; 12 female) with at least one metabolic risk factor and monitored them for four months, as they engaged in either aerobic exercise and cognitive training (n=17, 40 training sessions) or none (n = 18; pseudo-random allocation). At baseline and after four months, we assessed pre and post-intervention changes in neuropsychological tests, metabolic health, biomarkers (inter alia, Cathepsin-B), spiroergometric and structural MRI-based brain morphological features. The training regime comprised physical performance (PP, ratio Watt and heart rate) and subsequent memory picture recognition performance (MEM, reaction time corrected for error).
MRI features. We estimated whole hippocampal volumes (wHCV) from T2w MRI scans (3T TSE, 0.39x0.39x2.0 mm) with the T2-ASHS longitudinal segmentation algorithm (manual correction of 19 hemispheres); total gray matter volumes with CAT12 in SPM12; and white matter hyperintensities from their T1w MRI images (3T MPRAGE, 1.0x1.0x1.0 mm) with the SAMSEG longitudinal pipeline. We corrected all volumes for intracranial volume.
Statistical analysis. We tested for potential time x group interaction effects on each of the outcomes with linear mixed effects models with random intercepts (a model per outcome, age and sex as covariates). To overcome limitations of conventional longitudinal modelling approaches, we analyzed training effects using a hierarchical continuous-time dynamic model with two fully connected state variables, enabling bidirectional effects between PP and MEM over 40 measurement occasions.

Linear mixed effects. During the four-month intervention, the control group showed a decrease in left wHCV, while the volumes in the training group increased (time x group interaction: β = 161.70, 95%-CI[12.80, 310.26]). The training group also maintained their levels of Cathepsin-B and physical fitness over time, whereas the control group experienced a decline in both (physical fitness, maximal Wat: β = 11.45, 95%-CI[0.74, 21.79]; Cathepsin-B levels: β = 39.53, 95%-CI[6.71, 72.22]).
Dynamic modeling. In the training group only, PP improved MEM in subsequent dual-task session (-1.11, 95%-BCI[-1.22, -0.99]). Such effect lasted for up to 15 days. Higher baseline wHCV was associated with a stronger coupling-effect of PP on MEM (-0.15, 95%-BCI[-0.18, -0.11] ) and lower persistence of MEM (-0.145, 95-BCI[-0.21, -0.08]).

Four months of combined physical and cognitive training has a neuroprotective effect in older adults with metabolic risk factors. Specifically, training, as opposed to a sedentary lifestyle, helped to maintain Cathepsin-B levels and increase left hippocampal volume. Cognitive changes were nonetheless not evident within such a short time period. Using a sophisticated dynamic modelling approach, we demonstrated that exercise training is dynamically linked to cognition in a day-by-day manner, with higher levels of physical fitness improving memory performance in subsequent sessions. The observed benefits were midterm, i.e., lasting for up to 15 days after training session. Interestingly, this interaction was most pronounced in individuals with higher baseline hippocampal volume. Taken together, our data show some evidence for exercise-induced effects on brain health and plasticity in older adults at metabolic risk.

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)

Neural Plasticity and Recovery of Function ¹

Aging ²

Aging

Blood

Cognition

Modeling

MRI

Plasticity

Segmentation

Statistical Methods

Sub-Cortical

Other - physical exercise