Skip to main content
. Author manuscript; available in PMC: 2021 Nov 7.
Published in final edited form as: Rev Neurosci. 2019 Dec 18;31(1):1–57. doi: 10.1515/revneuro-2018-0096

Table 4:

Overview of prospective observation studies investigating level-change or correlated change associations of whole brain volume/CSF and cognitive abilities.

Brain measure/author, study Sample size at baseline (age range in years) Measurement occasions Time intervals in years Healthy cognitive aging:screening instruments at baseline Statistical method (change measure) Covariates Neuroanatomical measure (cf. Table 1) Brain regions Cognitive variables Brain-cognition relations (+= positive, −=negative)
Whole brain
Schmidt et al. (2005), Austrian Stroke Prevention Study 329 (50–75) 2–3 3 Nonea Repeated measures regression analysis (change ratiobrain) Age
Sex
Education (years)
VR
Diabetes Cardiac
disease Smoking
Cholesterol
Whole brain volume (NBV) - Episodic memory
Lern- und Gedächtnistest (immediate, delayed recall)
Reasoning
WCST
Attention and speed
Alters-Konzentrations-Test
TMT B
Digit span
Complex reaction time test
Level-change
Not reported
Correlated change
ΔNBV + Δepisodic memory, Δattention and speed
Charlton et al. (2010), GENIE 106 (50–90) 2 2 Nonea Correlation (change ratiobrain/cog) Age Whole brain volume (NBV) - Working memory
Digit span backwards, Letter-number sequencing
Level-change
No effect
Correlated change
No effect
Grimm et al. (2012), BLSA 149 (56–86) 6.8 ± 2.8 1 Nonea Bivariate LCSbbrain/cog None Ventricular volume (CSF) Lateral ventricles Episodic memory
CLVT
Level-change
No effect (in final model)
Correlated change (lagged)
ΔLateral ventricle volume (previous) − ΔCLVT (subsequent)
Mak et al. (2015a) 33 normal controls (76.7 ± 5.3) 2 1 No history of dementia or CAMCOG score <80 Correlation (change ratiobrain/cog) Age
Sex
Whole brain volume (TBV) - Global cognition
CAMCOG
Level-change
No effect
Correlated change
No effect
Ritchie et al. (2015b), Lothian Birth Cohort 657 (M age 73) 2 3 MMSE ≥ 24 Multivariate LCScbrain/cog Age,
Sex
Whole brain volume (TBV) - Fluid intelligence
Matrix reasoning
Block design
Digit span backward
Letter-number sequencing
Episodic memory
Logical memory (immediate, delayed recall)
Verbal paired associates
Spatial span (forward, backward)
Processing speed
Digit-symbol
Symbol search
Simple-/four-choice reaction time task
Inspection time task
Level-change
Episodic memory T1 + ΔTBV
Correlated change
No effect
Leong et al. (2017), Singapore Longitudinal Aging Brain Study 111 (56.1–83.1) 2–4 1.5–2 MMSE ≥ 26 Correlation (MLM slope estimatesbrain/cog) Age
Sex
Education
VR
BMI
ICV
Whole brain volume (TBV)
Ventricular volume (CSF)
- Global cognition
Composite of all abilities below
EF
Category fluency (three categories)
Design fluency
TMT B
Processing speed
TMT A
Symbol search
Symbol-digit modalities
Visuospatial memory
Visual paired associates test (immediate, delayed recall)
Verbal memory
AVLT (immediate, delayed recall)
Attention
Digit span
Spatial span (forward and backward)
Level-change
Not reported
Correlated change
ΔTBV+Δglobal cognition,
Δverbal memory
ΔTotal ventricular
volume−Δverbal memory,
ΔEF

brain, brain measurements; cog, cognitive measurements; GENIE, St GEorge’s Neuropsychology and Imaging in the Elderly; LCS, latent change score model; MLM, multilevel model; change ratio, a measure of change proportionalized on the baseline level and in some cases also on the time interval (for exact formula consult original publications); difference score, value at T1 – value at T2; CSF, cerebrospinal fluid; ICV, intracranial volume; TBV, total brain volume; NBV, normalized brain volume; TMT, trail making test; AVLT, Rey auditory verbal learning test; EF, executive functions; MMSE, mini-mental-state-examination; CAMCOG, Cambridge Cognitive Examination; VR, vascular risk (for details refer consult original publications); APOE-ε4, apolipoprotein E allele 4; BMI, body mass index; Δ, change.

a

No information provided on screening instruments and/or cut-offs used (for description of healthy aging criteria consult original publication).

b

Change was modeled over age (instead of time; consult original publication for details).

c

All cognitive variables were included in the same model.