. Author manuscript; available in PMC: 2012 Oct 1.

Published in final edited form as: J Neuropsychiatry Clin Neurosci. 2011 Fall;23(1):6–15. doi: 10.1176/appi.neuropsych.23.1.6

Table 2.

Longitudinal Studies

	Study	N	Mean Age	Age Range	Gender (% Female)	Mean Education (Years)	Criteria for “Health”	Factors Measured Longitudinally	Study Interval: Mean (SD); Range	Imaging Modality	Image Analysis Method	Brain Measure(s)	Correction 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	Cohen et al., 2001{⁴⁷}	25	57.1	50+	100%	16.7	Physical, Cognitive	Brain and Cognition	~2 years	MRI	Mixed	Volume of hippocampus [L+R]	---	Attention/ Working Memory, Executive Function, Verbal & Visual Memory, Visuospatial Processing	↓ Hippo- campus	Volume changes unassociated with cognitive changes. Baseline hippo- campal volume* unassociated with baseline cognition*.	---
	Cook et al., 2004{⁶⁸}	29	74.8	60-89	58.6%	15.5	Physical, Psychological. Substance Abuse	Brain and Cognition	3.6 years (0.8); 2-6 years	MRI	Mixed	Volume of sulcal and ventricular CSF	ICV	Abstract Reasoning, Executive Function, Language, Processing Speed	↑ Sulcal & ventricular CSF	Minimal change in cognition, thus unable to examine longitudinal effects. Cognition at follow-up* unrelated to CSF at follow-up*.	---
	Du et al., 2003{⁴⁸}	23	76.5	---	30.4%	---	Physical, Cognitive, Psychological, Substance Abuse	Brain	1.8 years	MRI	Manual	Volume of entorhinal cortex [L&R]	ICV	Verbal Memory	↓ Entorhinal cortex [L&R]	Volume change not associated with memory*.	---
	Golomb et al., 1996{²⁷}	44	68.5	55+	59.1%	15.1	Physical, Cognitive, Psychological, Substance Abuse	Cognition	3.8 years (1.0); 2-6 years	MRI	Manual	Volume of HF, superior temporal gyrus, CSF [L+R]	ICV	Global, Verbal Memory	---	Smaller hippocampus (baseline)* = ↓ memory†.	---
	Marquis et al., 2002{¹⁹}	108	83.2	65+	63.0%	14.1	Physical, Cognitive, Substance Abuse	Cognition	6 years (2.6)	MRI	Manual	Volume of hippocampus, total volume [L+R]	---	Global, Verbal Memory	↓ Hippo- campus	Smaller hippo- campus [L+R], total volume (baseline)* = ↓ global cognition†. No relationships with memory.	---
	Tisserand et al., 2004{²²}	75	72.2	52-84	50.7%	“lower vocational education / intermediat e secondary education”	Physical, Cognitive, Substance Abuse	Cognition	~3 years	MRI	Automated	Total GM, WM, and CSF volume. VBM of GM. ROIs: PFC and medial temporal lobe (all measured at “follow- up”)	---	Global, Attention/ Working Memory, Executive Function, Processing Speed, Verbal Memory (“non- decliners” vs. “decliners”)	Overall: ↓ GM, ↑ CSF. Non- decliners: ↓ GM* (especially PFC [L&R], medial temporal lobe [L&R], striate cortex).	Non-decliners > Decliners in GM* (especially in PFC, R temporal lobe, and R posterior parietal cortex). Non-decliners < Decliners in CSF*.	---
	Visser et al., 1999{³⁶}	18	76.8	65-85	56%	8.2	Cognitive, Psychological	Cognition	~3 years	MRI	Mixed	Volume of hippocampus, parahippo- campal gyrus, medial temporal lobe [L+R]	ICV	Global, Verbal & Visual Memory	---	No relationship between volumes* and cognition* at baseline. Larger parahippocampal gyrus* = ↑ memory, global cognition	---
Samples of Younger and Older Adults	McArdle et al., 2004{²⁶}	225	---	30-80	51.6%	14.4	Physical, Psychological	Brain and Cognition	~ 7 years	CT	---	Lateral ventricle size [L+R]	Head size	Attention/ Working Memory, Verbal & Visual Memory	↑ Lateral ventricle size	↑ Lateral ventricle size = ↓ memory	Relationship between lateral ventricle size and memory strengthens with age
	Raz et al., 2005{⁶⁹}	72	52.6	20-77	58.3%	15.9	Physical, Cognitive, Psychological	Brain and Cognition	5.3 years (0.3); 4.8- 6.1 years	MRI	Manual	Volume of lateral PFC, orbital frontal cortex, prefrontal WM, inferior parietal lob- ule, inferior parietal WM, inferior temp- oral cortex, fusiform cortex, percalcarine cortex, hippocampus, entorhinal cortex, caudate, cerebellum [L+R]	ICV	Global	Mean ↓ all ROIs except visual cortex. Individual ↓ for all ROIs except inferior parietal lobule. O < Y in rate of ↓ in prefrontal WM, inferior temporal cortex, hippocampus, entorhinal cortex, cerebellar hemispheres.	Minimal change in cognition. No relationship with structural changes.	---
	Rodrigue and Raz, 2004{¹⁶}	48	57.6	26-82	60.4%	16	Physical, Cognitive, Psychological, Substance Abuse	Brain	5.2 years (0.2); 5.0- 5.9 years	MRI	Manual	Volume of entorhinal cortex, hippocampus, lateral PFC [L&R]	ICV	Verbal Memory	↓ PFC, hippocampus, and entorhinal cortex. Rate of ↓ increased with age in PFC and hippocampus, but not entorhinal cortex. [L+R]	↓ Entorhinal cortex = worse memory*†.	---
	Walhovd et al., 2004{⁷⁰}	54	51	20-88	53.7%	15.3	Physical, Cognitive	Cognition	79 days (42); 42- 241 days	MRI	Automated	Volume of WM, cortex, hippocampus [L+R]	ICV	Verbal Memory	↓ WM, cortical, hippocampal volumes*	Bigger cortical* and hippocampal volume* = better memory. Bigger hippocampal volume = better memory*†.	---

Key: Y = younger adults; O = older adults; GM = gray matter; WM = white matter; CSF = cerebrospinal fluid; PFC = prefrontal cortex; HF = hippocampal formation; VBM = voxel-based morphometry; ↑ = increase / positive association; ↓ = decrease / negative association; * = variable NOT measured longitudinally; † = 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.