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Table 1 Study characteristics

From: Is intracranial volume a suitable proxy for brain reserve?

Study n Subjects Age Male (%) Education (years) Design Nuisance Corrected for Outcome Effect
Quantitative assessment
Mori, 1997* [41] 60 Mild to moderate AD 70.2 (7.1) 38.3 8.9 (2.3) Cross-sectional Age, sex, education Atrophy ADAS-Coga −0.12
      WAIS-R Full IQe 0.40
Staff, 2004 [58] 98 Unknown 79 57.6 9.8 (1.6) Cross-sectional Childhood IQ, sex WMH AVLT Memoryb 0.00
         RPMe 0.01
Christensen, 2009 [15] 416 Unknown 62.6 (1.4) 52 14 (2.6) Longitudinal, 4-year change Age, sex, education Atrophy and WMH SDMTc −0.22
      CVLT: Immediateb −0.39
         CVLT: Delayedb −1.45
Farias, 2012 [18] 401 Mixed HC, MCI and dementia 75 (6.9) 37.3 12.3 (4.8) Cross-sectional Sex, height TBV, hippocampal volume, and WMH SENAS: Semantic memoryb 0.20
        Episodic memoryb 0.08
         Executive functionc 0.27
         Spatial abilityd 0.16
Royle, 2013 [50] 327 HC 72.5 (0.7) 100 Cross-sectional Age TBV Composite scorea 0.19
       GM and WM 0.22
  297   72.6 (0.73) 0    TBV 0.21
         GM and WM 0.23
Groot, 2018 [22] 201 Aβ+ preclinical and prodromal AD 66.6 (7.5) 53 10–11** Cross-sectional Age, sex, education, scanner Atrophy Memoryb 0.12
      Attentionc 0.06
        Executivec 0.18
         Languagef −0.03
         Visuospatiald 0.14
         MMSEa 0.16
  462 Aβ+ probable AD 66.1 (7.4) 47 10–11**     Memoryb 0.10
        Attentionc 0.14
          Executivec 0.15
          Languagef 0.05
          Visuospatiald 0.13
          MMSEa 0.15
Categorical assessment
Wolf, 2004 [69] 73 HC, MCI 79.1 49.3 11.3 Cross-sectional Education Left hippocampus Predicting HC vs MCI (OR) 1.04***
  70 MCI, dementia 78.7 34.3 10.8   Age RBV Predicting MCI vs dementia (OR) 1.05***
Wolf, 2004 [70] 167 HC, MCI, AD, VaD 60.7 (9.9) 43 Cross-sectional Age, sex Hippocampal atrophy (visual assessment) HC vs cognitive impairment (OR compared with smallest quartile) 2.9
Silbert, 2009 [56] 49 HC (at baseline) 84.1 (6.2) 47 14.5 (2.7) Longitudinal, 10-year change Age, MMSE, APOEe4 status. ΔWMH, ΔvCSF, and hippocampal, vCSF and WMH Persistent cognitive decline (HR) 1.0
Negash, 2013 [44] 54 Aβ+ HC and AD 72.7 42.6 14.4 Cross-sectional Age, sex, education, APOEe4 status MTL volume Resilience (normal despite Aβ+; OR) 1.01
         Hippocampal and posterior cingulate volume   1.01
  1. Bold effects are reported to be significant according to study-specific statistical thresholds
  2. Aβ amyloid-beta, AD Alzheimer’s disease, ADAS-Cog Amsterdam dementia assessment scale—cognitive subscale, APOEε4 apolipoprotein ε4, AVLT auditory verbal learning test, CVLT California verbal learning test, GM gray matter, HC healthy controls, HR hazard ratio, ICV intracranial volume, IQ intelligence quotient, MCI mild cognitive impairment, MMSE Mini-Mental State Examination, MTL medial temporal lobe, OR odds ratio, RBV relative brain volume (brain volume to ICV ratio), RPM Raven’s progressive matrices, SDMT symbol-digit modalities test, SENAS Spanish-English neuropsychological assessment scale, TBV total brain volume, VaD vascular dementia, vCSF ventricular cerebrospinal fluid, WAIS-R Wechsler adult intelligence scale-revised, WM white matter, WMH white matter hyperintensity
  3. *Premorbid brain volume calculated as regression coefficient of (age + sex + ICV = whole brain volume) multiplied by ICV + constant
  4. **Categorization according to the Verhage scale [65] converted into years
  5. ***Odds ratios calculated from β coefficients using e^(β)
  6. This effect was considered an outlier and was not included in the meta-analysis
  7. aGlobal cognition
  8. bMemory
  9. cAttention/executive functions
  10. dVisuospatial ability
  11. eIntelligence
  12. fLanguage