1. Medicine
  2. Neuroscience

A latent clinical-anatomical dimension relating metabolic syndrome to brain structure and cognition

  1. Marvin Petersen  Is a corresponding author
  2. Felix Hoffstaedter
  3. Felix L Nägele
  4. Carola Mayer
  5. Maximilian Schell
  6. D Leander Rimmele
  7. Birgit-Christiane Zyriax
  8. Tanja Zeller
  9. Simone Kühn
  10. Jürgen Gallinat
  11. Jens Fiehler
  12. Raphael Twerenbold
  13. Amir Omidvarnia
  14. Kaustubh R Patil
  15. Simon B Eickhoff
  16. Goetz Thomalla
  17. Bastian Cheng
  1. Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany
  2. Institute for Systems Neuroscience, Medical Faculty, Heinrich-Heine University Düsseldorf, Germany
  3. Institute of Neuroscience and Medicine, Brain and Behaviour (INM-7), Research Center Jülich, Germany
  4. Midwifery Science-Health Services Research and Prevention, Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf, Germany
  5. Department of Cardiology, University Heart and Vascular Center, Germany
  6. German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Luebeck, Germany
  7. University Center of Cardiovascular Science, University Heart and Vascular Center, Germany
  8. Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Germany
  9. Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Germany
  10. Epidemiological Study Center, University Medical Center Hamburg-Eppendorf, Germany
https://doi.org/10.7554/eLife.93246.3
Share this article
Cite this article
  1. Marvin Petersen
  2. Felix Hoffstaedter
  3. Felix L Nägele
  4. Carola Mayer
  5. Maximilian Schell
  6. D Leander Rimmele
  7. Birgit-Christiane Zyriax
  8. Tanja Zeller
  9. Simone Kühn
  10. Jürgen Gallinat
  11. Jens Fiehler
  12. Raphael Twerenbold
  13. Amir Omidvarnia
  14. Kaustubh R Patil
  15. Simon B Eickhoff
  16. Goetz Thomalla
  17. Bastian Cheng
(2024)
A latent clinical-anatomical dimension relating metabolic syndrome to brain structure and cognition
eLife 12:RP93246.
https://doi.org/10.7554/eLife.93246.3
  2. Download BibTeX
  3. Download .RIS
12 figures, 9 tables and 4 additional files

Figures

Figure 1
Download asset Open asset
Methodology.

(a) Illustration of the partial least squares correlation analysis. Starting from two input matrices containing per-subject information of regional morphological measures as well as clinical data (demographic and metabolic syndrome (MetS)-related risk factors) a correlation matrix is computed. This matrix is subsequently subjected to singular value decomposition resulting in a set of mutually orthogonal latent variables. Latent variables each consist of a left singular vector (here, clinical covariance profile), singular value, and right singular vector (here, imaging covariance profile). In addition, subject-specific clinical and imaging scores are computed. (b) The interplay between MetS, brain structure, and cognition was investigated in a post-hoc mediation analysis. We tested whether the relationship between the clinical score, representing MetS severity, and different cognitive test performances was statistically mediated by the imaging score. (c) Contextualization analysis. Upper row: based on microarray gene expression data, the densities of different cell populations across the cortex were quantified. Middle and lower row: based on functional and structural group-consensus connectomes based on data from the Human Connectome Project, metrics of functional and structural brain network topology were derived. Cell density as well as connectomic measures were related to the bootstrap ratio via spatial correlations. Modified from Petersen et al., 2022b; Zeighami et al., 2019. Abbreviations: Astro – astrocytes; DWI – diffusion-weighted magnetic resonance imaging; Endo – endothelial cells; Ex – excitatory neuron populations (Ex1-8); In – inhibitory neuron populations (In1-8); Micro – microglia; Oligo – oligodendrocytes; rs-fMRI – resting-state functional magnetic resonance imaging; SVD – singular value decomposition.

Figure 2 with 4 supplements
Download asset Open asset
Partial least squares correlation analysis (PLS).

(a) Explained variance and p-values of latent variables. (b) Scatter plot relating subject-specific clinical and imaging PLS scores. Higher scores indicate higher adherence to the respective covariance profile. (c) Clinical covariance profile. 95% confidence intervals were calculated via bootstrap resampling. Note that confound removal for age, sex, education, and cohort was performed prior to the PLS. (d) Imaging covariance profile represented by bootstrap ratio. A high positive or negative bootstrap ratio indicates high contribution of a brain region to the overall covariance profile. Regions with a significant bootstrap ratio (>1.96 or <–1.96) are highlighted by colors. Abbreviations: BMI – Body mass index, HDL – high-density lipoprotein, LDL – low-density lipoprotein, rsp - Spearman correlation coefficient.

Figure 2—figure supplement 1
Download asset Open asset
Partial least squares correlation analysis – Latent variable 2.

The figure presents the results of latent variable 2 of the partial least squares correlation analysis. (a) Scatter plot relating subject-specific clinical and imaging PLS scores. (b) Clinical covariance profile. (c) Imaging covariance profile represented by bootstrap ratio. A high positive or negative bootstrap ratio indicates high contribution of a brain region to the overall covariance profile. Regions with a significant bootstrap ratio (>1.96 or <–1.96) are highlighted by colors. Abbreviations: BMI – Body mass index, HDL – high-density lipoprotein, LDL – low-density lipoprotein, rsp - Spearman correlation coefficient.

Figure 2—figure supplement 2
Download asset Open asset
Partial least squares correlation analysis – UK Biobank (including cognitive test results).

Partial least squares correlation analysis of the UK Biobank subsample including cognitive test results. (a) Explained variance and p-values of latent variables. (b) Scatter plot relating subject-specific clinical and imaging scores. Higher scores indicate higher adherence to the respective covariance profile. (c) Clinical covariance profile. 95% confidence intervals were calculated via bootstrap resampling. Note that confound removal for age, sex, and education was performed prior to the PLS. (d) Bootstrap ratio representing the covarying brain morphology pattern. A high positive or negative bootstrap ratio indicates high contribution of a brain region to the overall covariance profile. Regions with a significant bootstrap ratio (>1.96 or <–1.96) are highlighted by colors. Abbreviations: BMI – Body mass index, HDL – high-density lipoprotein, LDL – low-density lipoprotein, rsp – Spearman correlation coefficient; p – p-value; TMT-A – Trail Making Test A; TMT-B – Trail Making Test B.

Figure 2—figure supplement 3
Download asset Open asset
Partial least squares correlation analysis – Hamburg City Health Study (HCHS) (including cognitive test results).

Partial least squares correlation analysis of the HCHS subsample including cognitive test results. (a) Explained variance and p-values of latent variables. (b) Scatter plot relating subject-specific clinical and imaging scores. Higher scores indicate higher adherence to the respective covariance profile. (c) Clinical covariance profile. 95% confidence intervals were calculated via bootstrap resampling. Note that confound removal for age, sex, and education was performed prior to the PLS. (d) Bootstrap ratio representing the covarying brain morphology pattern. A high positive or negative bootstrap ratio indicates high contribution of a brain region to the overall covariance profile. Regions with a significant bootstrap ratio (>1.96 or <–1.96) are highlighted by colors. Abbreviations: BMI – Body mass index, HDL – high-density lipoprotein, LDL – low-density lipoprotein, rsp – Spearman correlation coefficient; p – p-value; TMT-A – Trail Making Test A; TMT-B – Trail Making Test B.

Figure 2—figure supplement 4
Download asset Open asset
Spatial correlation of effect size maps.

Spatial correlation matrix of all Schaefer 400-parcellated metabolic syndrome effect maps (bootstrap ratio and t-statistic). The upper triangle of the matrix displays Spearman correlations with dot size and color representing the magnitude of the coefficients. Asterisks highlight significant correlations after spin permutation testing and false discovery rate correction. The diagonal shows kernel density plots. The lower triangle illustrates the variables’ linear relationships via regression plots. Abbreviations: HCHS – Hamburg City Health Study, PLS – Partial least squares correlation analysis; rsp - Spearman correlation coefficient; pspin – false discovery rate-corrected p-value derived from spin permutations; UKB – UK Biobank.

Figure 3
Download asset Open asset
Mediation analysis results.

Mediation effects of subject-specific imaging PLS scores on the relationship between metabolic syndrome (MetS) represented by the clinical PLS score and cognitive test performances. Path plots display standardized effects and p-values: (a) clinical score to imaging score, (b) imaging score to cognitive score, (ab) indirect effect (c’) direct effect, and (c) total effect. Significant paths are highlighted in blue; non-significant in light gray. If the indirect effect ab was significant, the text for ab is highlighted in blue. A blue dot in the path plot indicates if a relationship is significantly mediated, i.e., the indirect effect ab was significant and the direct effect c’ was reduced or non-significant compared to the total effect c. An empty dot indicates a partial mediation, and a full dot indicates a full mediation. Abbreviations:pFDR - false discovery rate-corrected p-values; PLS – partial least squares correlation; TMT-A – Trail Making Test A; TMT-B – Trail Making Test B.

Figure 4 with 2 supplements
Download asset Open asset
Virtual histology analysis.

The regional correspondence between metabolic syndrome (MetS) effects (bootstrap ratio) and cell type-specific gene expression profiles was examined via an ensemble-based gene category enrichment analysis. (a) Barplot displaying spatial correlation results. The bar height displays the significance level. Colors encode the aggregate z-transformed Spearman correlation coefficient relating the Schaefer100-parcellated bootstrap ratio and respective cell population densities. Asterisks indicate statistical significance. The significance threshold of pFDR <0.05 is highlighted by a vertical dashed line. (b) Scatter plots illustrating spatial correlations between MetS effects and exemplary cortical gene expression profiles per cell population significantly associated across analyses – i.e., endothelium, microglia, and excitatory neurons type 8. Top 5 genes most strongly correlating with the bootstrap ratio map were visualized for each of these cell populations. Icons in the bottom right of each scatter plot indicate the corresponding cell type. A legend explaining the icons is provided at the bottom. First row: endothelium; second row: microglia; third row: excitatory neurons type 8. Virtual histology analysis results for the bootstrap ratios of latent variables 2 and 3 are shown in Figure 4—figure supplement 1. A corresponding plot illustrating the contextualization of the t-statistic derived from group statistics is shown in Figure 4—figure supplement 2. Abbreviations: -log(pFDR) – negative logarithm of the false discovery rate-corrected p-value derived from spatial lag models (Dukart et al., 2021; Burt et al., 2018); r – Spearman correlation coeffient. Z(rsp) – aggregate z-transformed Spearman correlation coefficient.

Figure 4—figure supplement 1
Download asset Open asset
Virtual histology analysis of latent variables 2 and 3.

Virtual histology analysis of the bootstrap ratio maps of latent variables 2 and 3 from the partial least squares (PLS) main analysis. Barplots display spatial correlation results of the bootstrap ratio of latent variables 2 and 3 and respective cell population densities computed via ensemble-based gene category enrichment analysis. (a) Results corresponding with the bootstrap ratio of latent variable 2. (b) Results corresponding with the bootstrap ratio of latent variable 3. Abbreviations: -log(pFDR) – negative logarithm of the false discovery rate-corrected p-value derived from spatial lag models; r – Spearman correlation coefficient. Z(rsp) – aggregate z-transformed Spearman correlation coefficient.

Figure 4—figure supplement 2
Download asset Open asset
Sensitivity virtual histology analysis based on t-statistic map from group comparison.

Virtual histology analysis of the t-statistic map derived from group comparison between individuals with metabolic syndrome and controls. (a) Barplot displaying spatial correlation results of the bootstrap ratio and respective cell population densities computed via ensemble-based gene category enrichment analysis. (b) Scatter plots illustrating per significantly associated cell population exemplary genes with top 5-highest correlation coefficients with the t-statistic map per significantly associated cell population across analyses (i.e. endothelium, microglia, excitatory neurons 8). Icons in the bottom right of each scatter plot indicate the corresponding cell type. First row: endothelium; second row: microglia; third row: excitatory neurons type 8. Abbreviations: -log(pFDR) – negative logarithm of the false discovery rate-corrected p-value derived from spatial lag models; r – Spearman correlation coefficient. Z(rsp) – aggregate z-transformed Spearman correlation coefficient.

Figure 5 with 2 supplements
Download asset Open asset
Brain network contextualization.

Spatial correlation results derived from relating Schaefer 400×7-parcellated maps of metabolic syndrome (MetS) effects (bootstrap ratio) to network topological indices (red: functional connectivity, blue: structural connectivity). Scatter plots that illustrate the spatial relationship are supplemented by surface plots for anatomical localization. The color coding of cortical regions and associated dots corresponds. (a and b) Functional and structural degree centrality rank. (c and d) Functional and structural neighborhood abnormality. (e and f) Intrinsic functional network hierarchy represented by functional connectivity gradients 1 and 2. Complementary results concerning t-statistic maps derived from group comparisons between MetS subjects and controls are presented in Figure 5—figure supplement 1. Corresponding results after reperforming the analysis with HCHS-derived group-consensus connectomes are presented in Figure 5—figure supplement 2. Abbreviations: HCHS – Hamburg City Health Study; prewire - p-value derived from network rewiring (Maslov et al., 2004); psmash - p-value derived from brainSMASH surrogates (Burt et al., 2020); pspin - p-value derived from spin permutation results (Alexander-Bloch et al., 2018); rsp - Spearman correlation coefficient.

Figure 5—figure supplement 1
Download asset Open asset
Sensitivity network contextualization analysis based on t-statistic map derived from group comparison.

Brain network contextualization analysis of group statistics results. Results are presented for t-statistics maps derived from group statistics considering the pooled sample of UK Biobank subjects and Hamburg City Health Study (HCHS) subjects. The upper row barplot summarizes the analysis results displaying the Spearman correlation with regard to each investigated index. Asterisks indicate statistical significance with respect to spin, brainSMASH, and network rewiring null models. The middle and lower rows display scatter plots of the significant association of the t-statistics map and the functional and structural neighborhood abnormality, respectively. The scatter plots are supplemented by surface plots for anatomical localization. Abbreviations: prewire - p-value derived from network rewiring (Maslov et al., 2004); psmash - p-value derived from brainSMASH surrogates (Burt et al., 2020); pspin - p-value derived from spin permutation results (Alexander-Bloch et al., 2018); rsp - Spearman correlation coefficient.

Figure 5—figure supplement 2
Download asset Open asset
Sensitivity network contextualization analysis based on group-consensus connectomes from the Hamburg City Health Study.

Brain network contextualization analysis of partial least squares correlation results (bootstrap ratio) based on group-consensus connectomes from the Hamburg City Health Study. Results are presented for bootstrap ratio maps derived from partial least squares correlation analysis considering the pooled sample. The upper row bar plot summarizes the analysis results displaying the Spearman correlation with regard to each investigated index. Asterisks indicate statistical significance with respect to spin, brainSMASH, and network rewiring null models. Scatter plots that illustrate the significant spatial relationships are presented below. The middle row displays the relationship of the bootstrap ratio map and the ranked functional and structural degree centrality. The lower row illustrates the association of the bootstrap ratio map and the functional and structural neighborhood abnormality. Abbreviations: prewire - p-value derived from network rewiring (Maslov et al., 2004); psmash - p-value derived from brainSMASH surrogates (Burt et al., 2020); pspin - p-value derived from spin permutation results (Alexander-Bloch et al., 2018); rsp - Spearman correlation coefficient.

Figure 6
Download asset Open asset
Graphical abstract.
Appendix 1—figure 1
Download asset Open asset
Flowchart sample selection procedure.
Appendix 1—figure 2
Download asset Open asset
Correlation matrix of metabolic syndrome-related risk factors.

The upper triangle of the matrix displays Pearson correlations with dot size and color representing the magnitude of the coefficients. The diagonal shows kernel density plots. The lower triangle illustrates the variables’ linear relationships via regression plots. Of note, non fasting plasma glucose was investigated in this analysis. Abbreviations: BP – blood pressure.

Appendix 2—figure 1
Download asset Open asset
Matching - UK Biobank.
Appendix 2—figure 2
Download asset Open asset
Matching – Hamburg City Health Study.
Appendix 2—figure 3
Download asset Open asset
Proportion of metabolic syndrome criteria.

Barplots indicate the percentage amount of metabolic syndrome (MetS) criteria that apply by group for the pooled sample. Significant group differences in χ2-tests are highlighted by asterisks.

Appendix 2—figure 4
Download asset Open asset
Vertix-wise group comparison of cortical thickness.

Vertex-level group comparison between individuals with metabolic syndrome and matched controls. Resulting surface maps of standardized t-statistic estimates encode the group-differences between patients and controls, with lower cortical thickness in the metabolic syndrome (MetS) group being represented by a positive t and lower by a negative t. The vertex-wise t-statistic map was Schaefer-parcellated for the downstream analyses.

Tables

Table 1
Descriptive statistics UKB and HCHS.
MetricStat*
Age (years)63.55±7.59 (40087)
Sex (% female)46.47 (40087)
Education (ISCED)2.62±0.73 (39944)
Metabolic syndrome components
Waist circumference (cm)88.47±12.71 (38800)
Hip circumference (cm)100.90±8.79 (38801)
Waist-hip ratio0.88±0.09 (38800)
Body mass index26.47±4.37 (38701)
RRsystolic (mmHg)138.30±18.57 (31234)
RRdiastolic (mmHg)78.88±10.09 (31238)
Antihypertensive therapy (%)6.96 (39976)
HDL (mg/dL)61.76±23.69 (34468)
LDL (mg/dL)137.38±36.29 (37456)
Cholesterol (mg/dL)211.29±56.42 (37531)
Triglycerides (mg/dL)148.90±83.84 (37510)
Lipid lowering therapy (%)14.44 (39976)
HbA1c (%)5.37±0.48 (37284)
Blood glucose (mg/dL)90.29±17.58 (34432)
Antidiabetic therapy (%)0.45 (39976)
Imaging
Mean cortical thickness (mm)2.40±0.09 (40087)
Cognitive variables of the UK Biobank
Fluid Intelligence6.63±2.06 (36510)
Matrix Pattern Completion7.99±2.13 (25771)
Numeric Memory Test6.69±1.52 (26780)
Paired Associate Learning6.92±2.63 (26048)
Prospective Memory1.07±0.39 (37192)
Reaction Time (sec)594.16±109.08 (37015)
Symbol Digit Substitution18.96±5.25 (25810)
Tower Rearranging Test9.91±3.23 (25555)
Trail Making Test A (sec)223.03±86.51 (26048)
Trail Making Test B (sec)550.01±270.09 (26048)
Cognitive variables of the Hamburg City Health Study
Animal Naming Test24.78±6.92 (2416)
Clock Drawing Test6.43±1.12 (2479)
Trail Making Test A (sec)40.09±14.33 (2290)
Trail Making Test B (sec)90.05±37.30 (2264)
Multiple-Choice Vocabulary Intelligence Test31.27±3.58 (2026)
Word List Recall7.75±1.84 (2342)
  1. *

    Presented as mean ± SD (N).

Appendix 1—table 1
Partial least squares analysis - latent variables.
Latent variableExplained variance (%)p-value
071.200.0002
122.330.0002
22.120.0002
31.840.0006
41.030.0026
50.520.0266
60.380.0100
70.230.0032
80.180.1178
90.160.2122
100.000.3137
110.000.0608
120.001
130.001
140.001
150.001
Appendix 1—table 2
Partial least squares analysis-Cross-validation.
CV foldrsp
00.17
10.21
20.22
30.16
40.15
50.18
60.23
70.13
80.20
90.22
Appendix 1—table 3
Virtual histology analysis - Bootstrap ratio (partial least squares, PLS).
Cell typeZrsppFDR
Endo0.1900.016
Micro0.2710.016
Ex80.1650.016
In10.3630.036
Ex60.1460.034
Oligo0.2070.057
In70.0790.083
Ex10.1220.144
In20.0580.179
In30.0470.208
Astro0.0710.259
In80.0550.299
Ex70.0440.336
In50.0370.388
Ex4–0.0200.776
Ex5–0.0550.924
In4–0.0560.949
In6–0.0990.949
Ex2–0.1020.967
Ex3–0.2890.999
Appendix 1—table 4
Virtual histology analysis - t-statistic (group comparison).
Cell typeZrsppFDR
Endo0.2080.020
Micro0.3210.040
Ex80.2080.040
Oligo0.2330.055
In10.4320.108
Ex60.1450.123
Ex10.1560.229
In30.0580.233
Astro0.1200.233
In70.0590.233
In20.0630.233
Ex70.0890.263
In50.0630.300
In80.0660.317
Ex40.0150.585
Ex5–0.0070.690
In6–0.0780.861
Ex2–0.0700.861
In4–0.0870.901
Ex3–0.3410.997
Appendix 1—table 5
UK Biobank field IDs.
Age21003
Sex31
Education6133*
Waist circumference48
Hip circumference49
Body mass index21001
RRsystolic4080
RRdiastolic4079
HDL30760
LDL30780
Cholesterol30690
Triglycerides30870
HbA1c30750
Blood glucose30740
Medication for cholesterol, blood pressure, diabetes6153
Fluid Intelligence20191
Matrix Pattern Completion6373
Numeric Memory Test20240
Paired Associate Learning20197
Prospective Memory20018
Reaction Time20023
Symbol Digit Substitution20159
Tower Rearranging Test21004
Trail Making Test A6348
Trail Making Test B6350

  1. Abbreviations: RR = blood pressure.

  2. *

    Converted to International Standard Classification of Education (ISCED) via the UKBB parser (https://github.com/USC-IGC/ukbb_parser; Zhu et al., 2019).

Appendix 1—table 6
Metabolic syndrome Criteria of the International Diabetes Federation (IDF) (Alberti et al., 2006).
Metabolic syndrome = obesity + two further criteria
Obesitywaist circumference ♀:≥80 cm; ♂:≥94 cm
Dyslipidemia (raised triglycerides)≥150 mg/dL (1.7 mmol/L) or lipid lowering medication
Dyslipidemia (reduced HDL cholesterol)♀:<50 mg/dL (1.29 mmol/L); ♂:<40 mg/dL (1.03 mmol/L) in males
Arterial hypertension (raised blood pressure)systolic BP ≥130 or diastolic BP ≥85 mm Hg or antihypertensive medication or diagnosis of hypertension
Insuline resistanceFasting plasma glucose ≥100 mg/dL (5.6 mmol/L) or antidiabetic therapy or diagnosis of diabetes mellitus type 2*
  1. *

    Measurements of fasting plasma glucose were not available for the study sample. Consequently, the criterion of insulin resistance was only based on the diagnosis of diabetes mellitus and administration of antidiabetic therapy.

Appendix 2—table 1
Descriptive group statistics - UK Biobank.
Metric*Individuals with MetSMatched controlsPuncorrPFDRStat†
Age (years)64.73±7.42 (6746)64.51±7.27 (6746)0.0950.154–0.03
Sex (% female)18.81 (6746)18.81 (6746)>0.99>0.990
Education (ISCED)2.63±0.73 (6746)2.67±0.71 (6746)0.0360.0690.04
Metabolic syndrome criteria
Waist circumference (cm)97.39±10.21 (6726)88.22±10.59 (6595)<0.001<0.001 ‡–0.88
RRsystolic (mmHg)146.41±15.38 (6213)135.57±17.71 (5397)<0.001<0.001 ‡–0.66
RRdiastolic (mmHg)82.26±9.39 (6214)77.58±9.79 (5397)<0.001<0.001 ‡–0.49
Antihypertensive therapy (%)9.96 (6746)9.68 (6746)<0.001<0.001 ‡7.07
HDL (mmol/L)1.18±0.26 (6225)1.49±0.32 (6332)<0.001<0.001 ‡1.08
Triglycerides (mmol/L)2.43±1.13 (6617)1.30±0.59 (6543)<0.001<0.001 ‡–1.25
Lipid-lowering therapy (%)39.05 (6746)7.07 (6746)<0.001<.001 ‡2446.5
Blood glucose (mmol/L)5.18±1.41 (6219)4.92±0.68 (6325)<0.001<.001 ‡–0.23
Antidiabetic therapy (%)0.06 (6746)0.19 (6746)0.0520.0973.77
Cognitive scores
Fluid Intelligence6.66±2.10 (6221)6.82±2.09 (6241)<0.001<0.001 ‡0.08
Matrix Pattern Completion8.02±2.13 (4283)8.14±2.06 (4355)0.0550.0960.06
Numeric Memory Test6.64±1.61 (4419)6.84±1.53 (4505)<0.001<0.001 ‡0.12
Paired Associate Learning6.45±2.60 (4337)6.73±2.61 (4392)<0.001<0.001 ‡0.10
Prospective Memory1.05±0.40 (6362)1.06±0.39 (6349)0.2210.3390.02
Reaction Time590.75±108.27 (6331)590.15±111.13 (6325)0.7920.858–0.005
Symbol Digit Substitution18.47±5.12 (4292)19.00±5.16 (4353)<0.001<0.001 ‡0.10
Tower Rearranging Test10.00±3.28 (4255)10.08±3.20 (4325)0.7470.8450.02
Trail Making Test A (sec)226.83±86.26 (4337)224.06±83.06 (4392)0.6430.836–0.03
Trail Making Test B (sec)561.81±271.39 (4337)553.62±282.55 (4392)0.6110.756–0.03
Imaging
Mean cortical thickness (mm)2.392±0.09 (6746)2.397±0.09 (6746)0.0350.0710.05

  1. Abbreviations: cm = centimeter, dL = deciliter, HDL = high-density lipoprotein, ISCED = International Standard Classification of Education, MetS = metabolic syndrome, mg = milligram, mm = millimeter, mmHg = millimeters of mercury, mmol/L = millimole perliter, PC = principal component, Puncor = uncorrected p-values, PFDR = false-discovery rate-corrected p-values, RR = Blood pressure, sec = seconds.

  2. *

    Presented as mean ± SD (N).

  3. †

    Presented as χ2 for categorical and Cohen’s d for continuous data.

  4. ‡

    Denotes statistical significance at FDR-corrected p<0.001

Appendix 2—table 2
Descriptive group statistics Hamburg City Health Study (HCHS).
Metric*Individuals with MetSMatched controlsPuncorrPFDRStat
Age (years)65.77±7.40 (759)65.97±7.52 (759)0.6130.6470.03
Sex (% female)33.4736.500.2360.2811.4
Education (ISCED)2.37±0.58 (759)2.42±0.60 (759)0.090.1140.09
Metabolic syndrome criteria
Waist circumference (cm)103.38±11.23 (754)91.45±11.36 (747)<0.001<0.001†–1.06
RRsystolic (mmHg)145.66±18.54 (740)140.17±21.10 (746)<0.001<0.001†–.28
RRdiastolic (mmHg)83.75±10.11 (740)82.00±10.40 (746)0.0010.002–.17
Antihypertensive therapy (%)52.60%26.22%<0.001<0.001†108.89
HDL (mg/dL)54.60±16.13 (751)67.63±17.46 (759)<0.001<0.001†0.78
Triglycerides (mg/dL)161.53±92.61 (751)91.23±30.62 (759)<0.001<0.001†–1.02
Lipid lowering therapy (%)40.85%7.64%<0.001<0.001†225.29
Blood glucose (mg/dL)107.47±28.59 (742)90.99±10.87 (753)<0.001<0.001†–0.76
Antidiabetic therapy (%)14.42%1.45%<0.001<0.001†85.47
Cognitive scores
Animal Naming Test23.71±6.46 (712)24.77±6.75 (711)0.0050.0090.16
Clock Drawing Test6.36±1.17 (730)6.39±1.16 (733)0.7740.7740.02
Trail Making Test A (sec)41.26±14.28 (685)40.42±14.54 (675)0.3210.359–0.06
Trail Making Test B (sec)93.74±37.30 (675)89.89±37.69 (671)0.0860.114–0.10
Multiple-Choice Vocabulary Intelligence Test31.18±3.43 (603)31.71±3.22 (619)0.0190.0340.16
Word List Recall7.42±1.89 (691)7.64±1.84 (673)0.0570.0830.12
Imaging
Mean cortical thickness (mm)2.327±0.08 (759)2.334±0.08 (757)0.0450.0710.1

  1. Abbreviations: cm = centimeter, dL = deciliter, HDL = high-density lipoprotein, ISCED = International Standard Classification of Education, MetS = metabolic syndrome, mg = milligram, mm = millimeter, mmHg = millimeters of mercury, Puncor = uncorrected p-values, PFDR = false-discovery rate-corrected p-values, RR = Blood pressure, sec = seconds.

  2. *

    Presented as mean ± SD (N).

  3. †

    Denotes statistical significance at FDR-corrected p<0.001.

Additional files

Supplementary file 1

Schaefer 400×7-parcellated maps of metabolic syndrome (MetS)-related brain morphological abnormalities (bootstrap ratio from PLS, t-statistic from group comparison).

https://cdn.elifesciences.org/articles/93246/elife-93246-supp1-v1.csv
Supplementary file 2

Schaefer 100×7-parcellated bootstrap ratio map.

https://cdn.elifesciences.org/articles/93246/elife-93246-supp2-v1.csv
Supplementary file 3

t-statistic from group comparison on fsLR.

https://cdn.elifesciences.org/articles/93246/elife-93246-supp3-v1.csv
MDAR checklist
https://cdn.elifesciences.org/articles/93246/elife-93246-mdarchecklist1-v1.pdf

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Marvin Petersen
  2. Felix Hoffstaedter
  3. Felix L Nägele
  4. Carola Mayer
  5. Maximilian Schell
  6. D Leander Rimmele
  7. Birgit-Christiane Zyriax
  8. Tanja Zeller
  9. Simone Kühn
  10. Jürgen Gallinat
  11. Jens Fiehler
  12. Raphael Twerenbold
  13. Amir Omidvarnia
  14. Kaustubh R Patil
  15. Simon B Eickhoff
  16. Goetz Thomalla
  17. Bastian Cheng
(2024)
A latent clinical-anatomical dimension relating metabolic syndrome to brain structure and cognition
eLife 12:RP93246.
https://doi.org/10.7554/eLife.93246.3