Table 1.
Cross-Sectional Studies
| Study | N | Mean Age |
Age Range |
Gender (% Female) |
Mean Edu- cation (Years) |
Criteria for “Health” |
Imaging Modality |
Image Analysis Method |
Brain Measure(s) |
Correct- ion to Brain Measures |
Cognitive Domains Measured |
Age Effect on Brain Structure |
Relationship between Brain Structure and Cognition |
Comparison of Structure-Cognition Relationships in Older Adults vs. Younger Adults |
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Samples
of Older Adults |
Convit et al., 2003{18} |
30 | 68.6 | 53-89 | 56.7% | 16.2 | Physical, Cognitive, Psychological |
MRI | Manual | Volume of hippocampus, parahippocam- pal gyrus, superior tempo- ral gyrus, global atrophy [L+R] |
Volume of cere- bral vault |
Global, Verbal Memory |
↑ Global atrophy. ↓ Hippocampus (trend). |
↑ Hippocampus & memory† |
--- |
| Dickerson et al., 2009{45} |
47 | 76.2 | 66-90 | 63.8% | --- | Physical, Cognitive, Psychological |
MRI | Mixed | Mean thick- ness, surface area, and volume of L&R entorhinal, perirhinal, posterior para- hippocampal cortices |
ICV | Verbal Memory |
O < Y in L&R entorhinal cortex volume, surface area (trend for thickness). O < Y in L&R posterior parahippocampal cortex volume, surface area. |
↑ Entorhinal cortex thickness & memory (trend). |
--- | |
| Earnest et al., 1979{25} |
59 | 78 | 60-99 | 81.4% | 13.2 | Physical, Cognitive, Substance Abuse |
CT | Manual | Widths of 4 largest sulci, size of lateral ventricles |
None | Attention/ Working Memory, Executive Function, Processing Speed, Visual Memory, Visuospatial Processing |
↑ Size of largest sulci and ventricle size. 80-99 year-olds > 60-79 year- olds in widths of largest sulci and ventricle size. |
↓ Ventricles & processing speed† |
--- | |
| Golomb et al., 1993{38} |
145 | 70 | 55-88 | 52.6% | --- | Physical, Cognitive, Psychological, Substance Abuse |
MRI or CT |
Manual | Hippocampal atrophy [L+R] |
None | Attention/ Working Memory, Verbal & Visual Memory |
Hippocampal atrophy group > no hippocampal atrophy group in age |
No hippocampal atrophy group > hippocampal atrophy group in verbal memory†. No hippocampal atrophy group > hippocampal atrophy group in non- verbal memory (trend)†. |
--- | |
| Golomb et al., 1994{24} |
54 | 69 | 55-87 | 57.4% | 15.0 | Physical, Cognitive, Psychological, Substance Abuse |
MRI | Manual | Volume of HF, superior temporal gyrus, CSF [L+R] |
Head Size | Attention/ Working Memory, Verbal & Visual Memory |
↓ Hippocampus, superior temporal gyrus. ↑ CSF. |
↑ Hippocampus & memory†, ↓ CSF & memory† |
--- | |
| Gunning- Dixon and Raz, 2003{29} |
139 | 63.7 | 50-81 | 59.7% | --- | Physical, Cognitive, Psychological, Substance Abuse |
MRI | Manual | Volume of PFC, fusiform gyrus [L+R] |
Height | Attention/ Working Memory, Executive Function |
↓ PFC and fusiform gyrus. |
↑ PFC & executive function† |
--- | |
| Hackert et al., 2002{34} |
511 | 73 | 60-90 | 48.9% | “primary” : 31%, “inter- mediate/ higher”: 60%, “college”: 9% |
Cognitive | MRI | Manual | Volume of hippocampus [L&R] |
ICV | Global, Verbal Memory |
↓ Hippocampal head, body, and tail [L&R] |
↑ Hippocampus (L&R total, L & R head) & memory†. ↑ Hippocampus (L&R head) & global cognitive performance†. |
--- | |
| Hanninen et al., 1997{28} |
90 | 70.5 | 50+ | 61.3 | 9.1 | Cognitive, Psychological |
MRI | Manual | Volume of frontal lobe [L&R] |
--- | Executive Function, Verbal & Visual Memory |
--- |
Controls: ↑ Frontal lobe [L&R] & executive function†. Age- Associated Memory Impairment group: ↑R frontal lobe & executive function†. |
--- | |
| Laasko et al., 2000{37} |
34 | 72 | 64-79 | 58.8% | --- | Physical, Cognitive, Psychological, Substance Abuse |
MRI | Manual | Volume of hippocampus [L&R] |
ICV | Global, Visual Memory |
--- | Hippocampal volume unassociated with cognition. |
--- | |
| Lupien et al., 1998{39} |
9 | 73.9 | --- | --- | 11.2 | Physical, Cognitive |
MRI | Mixed | Volume of hippocampus, parahippocam- pal gyrus, fusiform gyrus, middle -inferior temporal gyrus, superior tempo- ral gyrus [L+R] |
Head Size | Visual Memory | No relationship between age and volumes. |
↑ Hippocampus & memory. ↑ Middle inferior gyrus & memory. |
--- | |
| Lye et al., 2004{40} |
57 | 85.1 | 80+ | 50.9% | 10.4 | Cognitive | MRI | Mixed | Volume of hippocampus [L&R] |
Total volume |
Verbal & Visual Memory |
--- | ↑ L hippocampus & memory (depending on memory measure)†. |
--- | |
| MacLullich et al., 2002{17} |
97 | 67.8 | 65-70 | 0.0% | --- | Physical | MRI | Mixed | Volume of hippocampus, temporal lobes, frontal lobes [L&R]; Intracranial area. |
Intracrani al area |
Abstract Reasoning, Executive Function, Premorbid Function, Processing Speed, Verbal & Visual Memory |
--- | ↑ General brain size factor & general cognitive factor. |
--- | |
| O’Brien, 1997{35} |
40 | 71.6 | 55-96 | 50% | 11.9 | Physical, Cognitive, Psychological, Substance Abuse |
MRI | Manual | Hippocampal/ amygdala atrophy [L+R] |
--- | Global, Abstract Reasoning, Executive Function, Language, Motor Skills, Verbal & Visual Memory |
↑ Hippocampal/ amygdala atrophy |
No hippocampal/ amygdala atrophy group > hippocampal/ amygdala atrophy group in memory, global cognition† |
--- | |
| Reiman, et al. 1998{41} |
33 | 56 | 50-62 | 72.7% | 15.9 | Physical, Cognitive, Psychological |
MRI | Manual | Volume of hippocampus [L&R] |
ICV | Verbal Memory |
No relationship between age and hippocampal volume. |
↑ Hippocampus [L&R] & memory |
--- | |
| Rosen et al., 2003{42} |
14 | 70.0 | --- | 85.7% | 16.1 | Physical, Cognitive, Psychological |
MRI | Manual | Volumes of entorhinal cortex, hippocampus [L&R] |
ICV | Verbal Memory |
--- |
High Memory group > Low Memory group in entorhinal cortex, hippo- campus [L&R]. ↑ L entorhinal cortex & memory (immediate and delayed). ↑ L hippo- campus & delayed memory. |
--- | |
| Salat et al., 2002{32} |
31 | 84 | 72-94 | 51.6% | 14.9 | Physical, Cognitive, Psychological |
MRI | Manual | Total PFC volume, PFC WM volume, and PFC GM volume; Sup- erior, middle, inferior, orbital, anterior cingulate PFC ROIs [L+R] |
ICV | Attention/ Working Memory, Executive Function, Other (“Conditional Association Learning”) |
↑ Orbital PFC. | ↓ Superior PFC & learning. ↓ Orbital PFC (relative to other ROIs) & working memory, executive function. |
--- | |
| Soininen, 1994{49} |
32 | 69.0 | --- | --- | 10.2 | Physical, Cognitive |
MRI | Manual | Volume of hippocampus, amygdala [L&R] |
Total volume |
Verbal & Visual Memory |
No relationship between age and volumes. |
Controls = Age- Associated Memory Impairment group in hippocampal, amygdala volumes. Controls > Age-Associated Memory Impairment group in hippocampal asymmetry (R > L). Groups combined: ↑ R hippocampus & visual memory, ↑ hippocampal asymmetry & visual memory, ↑ amygdala [L&R] & verbal memory. |
--- | |
| Staff et al., 2006{21} |
98 | --- | 79-80 | --- | --- | Physical, Cognitive |
MRI | Automated | VBM; Total GM and WM |
ICV | Abstract Reasoning, Premorbid Function, Processing Speed, Verbal Memory |
--- | ↑ WM & processing speed, abstract reasoning. ↑ GM & processing speed, abstract reasoning, general intelligence. |
--- | |
| de Toledo et al., 2000{46} |
30 | 72.4 | 64-84 | --- | --- | Physical, Cognitive, Psychological, Substance Abuse |
MRI | Manual | Volume of hippocampus, parahippocam- pal gyrus, temporal lobe [L&R] |
ICV | Verbal & Visual Memory |
--- | Volumes unassociated with memory† |
--- | |
| Tullberg et al., 2004{31} |
78 | 77.5 | --- | --- | --- | Physical, Cognitive |
MRI | Mixed | Frontal and posterior cortical GM volumes [L+R] |
ICV | Attention/ Working Memory, Executive Function, Verbal Memory (Executive Function and Memory composites) |
--- | ↑ Frontal cortical GM & memory. |
--- | |
| Van Petten et al., 2004{20} |
48 | 73.2 | 65.5- 85.8 |
68.8% | 15.0 | Physical, Cognitive, Psychological, Substance Abuse |
MRI | Manual | Total cerebral volume; GM volume of frontal (superior, middle, inferior gyri), temporal (HF; superior, middle, inferior, fusiform, and parahippocam- pal gyri), occipital regions [L&R] |
Both raw and ICV- corrected measures reported |
Attention/ Working Memory, Executive Function, Verbal & Visual Memory (Memory and “Frontal factor” composites) |
↓ Total cerebral volume, GM in temporal lobe (superior and middle temporal gyri, L temporal neocortex), and frontal lobe (inferior frontal gryus, sum of frontal ROIs). |
↓ GM in middle frontal gyrus and most temporal ROIs including hippo- campus & memory. ↑ Cranial vault & “frontal factor”. |
--- | |
| Zimmerman et al., 2008{44} |
48 | 81.8 | >70 | 47.9% | 13.1 | Physical, Cognitive |
MRI | Manual | Volume of hippocampus [L&R] |
ICV (midsag- ittal area) |
Executive Function, Processing Speed, Verbal Memory |
↓ Hippocampus [L+R] |
↑ Hippocampus [L+R] & memory (for 1 out of 2 measures)†. When analyzed by group, relationship held in Normal Memory group but not Mild Memory Impairment group† |
--- | |
|
Samples
of Younger and Older Adults |
Brickman et al., 2006{57} |
Y: 77, M: 82, O: 40 |
Y: 25.2; M: 43.7; O: 63.2 |
Y: 21- 30; M: 31-54; O: 55- 79 |
Y: 62%; M: 46%; O: 42% |
Y: 14.7; M: 14.1; O:12.2 |
Physical, Psychological, Substance Abuse |
MRI | Automated | VBM; WM volume in frontal, temporal, parietal, occipital lobes [L&R] |
Total WM volume |
Attention/ Working Memory, Executive Function, Verbal Memory |
O < Y & M in global WM (Y = M). O < Y in frontal and temporal WM (M < Y but not O). Quadratic relationship in L&R frontal, L&R temporal, L&R parietal, and R occipital WM. |
↑ R frontal WM & cognition (especially executive function, memory). ↑ R temporal WM & cognition (especially executive function, memory). ↑ L frontal WM & executive function, memory. ↑ L temporal WM & executive function, memory. |
Age-memory relationship partially mediated by L&R frontal WM. Age- executive function relationship partially mediated by L frontal WM. Age x structure interaction not directly tested. |
| Driscoll et al., 2003{58} |
Y: 16; O: 16 |
Y: 26.1; O: 77.6 |
Y: 20- 39; O: 60-85 |
Y: 50%; O: 50% |
--- | Physical, Cognitive, Psychological |
MRI | Automated | Volume of hippocampus [L&R] |
ICV | Visual Memory, Visuospatial Processing |
O < Y in hippocampus [L&R] |
↑ Hippocampal volume [L+R] & visuospatial performance |
--- | |
| Fjell et al., 2006{23} |
Y: 35, O: 39 |
Y: 35.5; O: 70.7 |
20-88 | 55.4% | Y: 15.8; O: 14.6 |
Physical, Cognitive |
MRI | Automated | Cortical thickness at each vertex of cortical mantle [L&R] |
--- | Abstract Reasoning, Attention/ Working Memory, Executive Function,, Visuospatial Processing (combined into “Fluid” Function and Executive Function domains) |
O with High Fluid Function vs. Y: Thinner cortex in most regions, but thicker cortex in R posterior cingulate gyrus and L subcallosal gyrus. O with Average Fluid Function vs. Y: Thinner cortex in all regions. |
--- |
O with High vs. O with Average Fluid Function: Thicker cortex especially in R posterior cingulate gyrus, frontal and prefrontal regions, medial structure, gyrus of cingulate isthmus. Y with High vs. Y with Average Fluid Function: No differences in R posterior cingulate or L subcallosal region. O with High vs. O with Average Executive Function: Thicker cortex in R middle frontal gyrus. |
|
| Head et al., 2002{59} |
68 | 48.9 | 22-80 | 61.8% | --- | Physical, Cognitive, Psychological, Substance Abuse |
MRI | Manual | Volume of lateral PFC, HF, caudate nucleus, putamen, visual cortex, cerebellar hemispheres [L+R] |
Height | Attention/ Working Memory, Executive Function, Visuospatial Processing |
↓ Lateral PFC, putamen, cerebellar hemispheres |
↑ Lateral PFC & working memory in early-stage skill acquisition (only when including individuals with hypertension)†. |
--- | |
| Kennedy and Raz, 2005{33} |
Y: 30, M: 29, O: 26 |
47.4 | Y: 20- 39; M: 40-60; O: 60- 80 |
56.5% | 16.0 | Physical, Psychological |
MRI | Manual | Volume of lateral PFC, hippocampus, caudate, cerebellar hemispheres [L+R] |
Height | Motor Skills, Visuospatial Processing (“Perceptual- Motor Skill Acquisition”) |
--- | Brain not associated with cognitive performance across all ages. |
O: ↑ Lateral PFC volume & skill acquisition (strengthened with practice). Y: No similar “practice effect.” |
|
| Paul et al., 2009{60} |
Y: 158; M: 67; O: 26 |
Y: 26.5; M: 49.8; O: 66.2 |
Y:18- 39; M: 40-59; O: 60- 79 |
Y: 55.1%; M: 67.2%; O: 53.8% |
Y: 14.5; M: 14.5; O: 13.3 |
Physical, Cognitive, Psychological, Substance Abuse |
MRI | Automated | Volume of PFC, cerebellar GM, cerbellar vermis [L+R] |
PFC volume or cerebellar GM volume |
Attention/ Working Memory, Executive Function, Motor Skills, Visuospatial Processing, Other (Time Estimation) |
O < Y and M in total cerebellar GM. O < Y in posterior superior vermian GM. O < Y and M in prefrontal volume. |
Mixed results for relationship between PFC and executive function. ↑ PFC & processing speed. ↑ PFC & visuospatial processing. |
--- | |
| Pfefferbaum et al., 1990{15} |
105 | 62.2 | 20-82 | 60.0% | 16 | Physical | CT | Mixed | CSF in lateral ventricles, vertex sulci, frontal sulci, Sylvian fissures, parieto- occipital sulci, third ventricle |
--- | Abstract Reasoning, Attention/ Working Memory, Executive Function, Language, Processing Speed, Verbal & Visual Memory, Visuospatial Processing, Vocabulary |
↑ CSF in all ROIs |
↓ CSF in vertex sulci and Sylvian fissure & performance IQ measures. ↓ CSF in Sylvian fissure & language. Brain measures no longer associated with cognition†. |
--- | |
| Raz et al., 1993{61} |
29 | 43.8 | 18-78 | 41.40% | 15 | Physical, Cognitive, Psychological, Substance Abuse |
MRI | Manual | Volume of cerebrum, inferior parietal lobule, HF. Cross-sectional area of dorso- lateral PFC, postcentral gyrus, prefrontal WM [L+R, asymmetry] |
Head Size | Global, Vocabulary |
↓ Cerebral volume, dorso- lateral PFC area, prefrontal WM area. |
↑ Cerebrum & “fluid” intelligence. ↑ Cerebral asymmetry (L>R) & “fluid” intelligence, vocabulary. ↑ Dorso- lateral PFC & “fluid” intelligence. ↑ Prefrontal WM asymmetry (L>R) & fluid” intelligence. ↑ Cerebral asymmetry (L>R)& fluid intelligence, vocabulary†. All other relationships became non-significant†. |
--- | |
| Raz et al., 1998{43} |
95 | 44 | 18-77 | 56.8% | 16.1 | Physical, Cognitive, Psychological, Substance Abuse |
MRI | Manual | Volume of dorsolateral PFC, orbito- frontal cortex, visual cortex, fusiform gyrus, inferior parietal lobe, parahip- pocampal gyrus, HF. [L+R] |
Height | Attention/ Working Memory, Executive Function, Verbal & Visual Memory, Visuospatial Processing |
↓ PFC, fusiform gyrus, hippo- campus, visual cortex. |
↑ PFC volume & executive function†. ↑ Visual cortex & working memory†. |
60-77 year-olds with poorest memory scores: ↑ hippocampus & memory. Relationship not found in whole sample. |
|
| Raz et al., 1999{62} |
60 | 47.5 | 19-77 | 58.3% | 16.3 | Physical, Psychological, Substance Abuse |
MRI | Manual | Volume of dorsolateral PFC, inferior temporal gyrus, fusiform gyrus, occipital cortex [L+R] |
Height | Attention/ Working Memory, Visuospatial Processing |
↓ Dorsolateral PFC, fusiform gyrus |
↑ Dorsolateral PFC & visuospatial processing†. |
--- | |
| Raz et al., 2000{63} |
68 | 45.5 | 22-80 | 55.9% | --- | Physical, Cognitive, Psychological, Substance Abuse |
MRI | Manual | Volume of dorsolateral PFC, hippo- campus, caudate, putamen, cerebellum [L+R] |
Height | Attention/ Working Memory, Visuospatial Processing, Motor Skills |
↓ Dorsolateral PFC, hippo- campus, putamen, cerebellum. |
↑ Cerebellum & motor skills†. ↑ Putamen & motor skills†. ↑ Cerebellum & working memory†. |
--- | |
| Schretlen et al., 2000{64} |
112 | 54 | --- | 57.1% | 13.5 | Physical, Cognitive, Psychological, Substance Abuse |
MRI | Mixed | Frontal and nonfrontal volume [L+R] |
Non- frontal volume |
Abstract Reasoning, Attention/ Working Memory, Executive Function, Premorbid Function, Processing Speed, Verbal & Visual Memory, Visuospatial Processing, Vocabulary |
↓ Frontal volume. |
↑ Frontal volume = & executive function. ↑ Frontal volume & fluid- spatial ability†. |
--- | |
| Seidman et al., 2002{65} |
47 | 40.1 | 20-68 | 43.7% | 15.1 | Physical, Psychological, Substance Abuse |
MRI | Mixed | Volume of hippocampus [L&R] |
Total cerebral volume |
Premorbid Function, Verbal Memory, Visuospatial Processing, Vocabulary |
--- | ↑ Hippocampus [L&R] & memory. |
--- | |
| Sullivan et al., 1995{66} |
64 | 43.9 | 21-70 | 0% | 16.3 | Cognitive, Psychological, Substance Abuse |
MRI | Mixed | Volume of hippocampus, temporal lobe GM and WM, CSF [L&R] |
Head size | Attention/ Working Memory, Premorbid Function, Verbal & Visual Memory, Vocabulary |
↓ L&R temporal GM. ↑ CSF. |
↑ Hippocampus [L&R] & verbal memory. ↓ Hippocampus [L&R] & visual memory. ↓ L hippocampus & attention/working memory. ↑ R temporal GM & visual memory, attention/working memory. ↓ CSF & memory, attention/ working memory. ↑ Cortical GM & attention/working memory. |
--- | |
| Tisserand et al., 2000{67} |
61 | 55.7 | 21- 81 | 57.4% | 2.6 (“1 = primary school, 5 = university degree”) |
Physical, Cognitive, Psychological |
MRI | Mixed | Volume of hippocampus, parahippocam- pal gyri [L&R]; mammillary bodies, CSF in third ventricle |
ICV | Attention/ Working Memory, Executive Function, Verbal Memory |
↓ Total volume. ↓ Hippocampus [L&R]. ↓ Para- hippocampal gyri [L&R]. ↑ CSF. |
↑ Hippocampus [L+R] & memory, executive function. ↑ Parahippo- campal gyrus [L+R] & memory, executive function. ↑ Total volume & memory, executive function. ↓ CSF & memory, executive function. Brain measures no longer associated with cognition†. |
--- | |
| Woodruff- Pak et al., 2001{50} |
Y: 8; O: 8 |
Y: 27.3; O: 82.5 |
Y: 21- 35; O: 77-95 |
Y: 62.5%; O: 50% |
--- | Cognitive | MRI | Manual | Volume of cerebellum [L+R] |
ICV | Other (Acquisition of conditioned response) |
O < Y in cerebellar volume |
Y and O combined: ↑ cerebellum & acquisition of conditioned response. |
Y: ↑ Cerebellum & acquisition of conditioned response (trend). O: Scatter plot suggests same relationship holds. |
|
| Zimmerman et al., 2006{30} |
148 | 40.1 | 21-76 | 49.0% | 14.6 | Physical, Psychological , Substance Abuse |
MRI | Automated | GM volume in hippocampus, amygdala, putamen, lateral frontal lobe, medial frontal lobe, orbital frontal lobe [L+R] |
--- | Attention/ Working Memory, Executive Function |
↓ Hippocampus, amygdala, putamen, lateral frontal, medial frontal, and orbital frontal. Quadratic relationship in caudate and thalamus (↓ until age 50, then ↑). |
--- | From graph, <40 years old: lateral frontal volume not associated with executive function; >40 years old: ↑ Lateral frontal volume & executive function. ↓ Lateral frontal volume & attention regardless of age. ↑ Orbital frontal volume & attention regardless of age. |
Key: Y = younger adults; M = middle-aged adults; O = older adults; GM = gray matter; WM = white matter; CSF = cerebrospinal fluid; PFC = prefrontal cortex; HF = hippocampal formation; ROI = region of interest; VBM = voxel-based morphometry; ↑ = positive association; ↓ = negative association; † = controlling for age; [L+R] = bilateral regions combined in analyses; [L&R] = both hemispheres analyzed separately.
Note: Only statistically significant results are reported, except when otherwise noted.