Neuropsychologia 42 (2004) 1394–1413
Review
Relationship between hippocampal volume and memory ability in healthy
individuals across the lifespan: review and meta-analysis
Cyma Van Petten
∗
Department of Psychology, University of Arizona, Tucson, AZ 85721, USA
Received 29 September 2003; received in revised form 7 April 2004; accepted 12 April 2004
Abstract
Poor memory ability and small hippocampal volume measurements in magnetic resonance images co-occur in neurological patients.
Numerous studies have examined the relationship between memory performance and hippocampal volumes in participants without neuro-
logical or psychiatric disorders, with widely varying results. Three hypotheses about volume–memory relationships in the normal human
brain are discussed: “bigger is always better”, a neuropsychological view that volume decreases due to normal aging are accompanied
by memory decline, and a developmental perspective that regressive events in development may result in negative correlations between
hippocampal volume and memory ability. Meta-analysis of results from 33 studies led to little support for the bigger-is-better hypothesis.
A negative relationship between hippocampal volume and memory (smaller is better) was significant for studies with children, adolescents,
and youngadults. For studies with older adults, the most striking observationwas extreme variability: the evidencefor a positive relationship
between hippocampal size and episodic memory ability in older adults was surprisingly weak. Some of the variability in results from older
adults was associated with statistical methods of normalizing for age and head size, which are discussed.
© 2004 Elsevier Ltd. All rights reserved.
Keywords: Hippocampus; MR morphometry; Aging
1. Introduction
Most, if not all, of the cerebral cortex is likely to sub-
serve the learning and retrieval of facts and events, with
the engagement of specific regions dependent on the nature
of the material learned (see Damasio, 1989; McClelland,
McNaughton, & O’Reilly, 1995 for theoretical accounts,
and Köhler, Moscovitch, Wincocur, Houle, & McIntosh,
1998; Nyberg, Habib, McIntosh, & Tulving, 2000; Senkfor,
Van Petten, & Kutas, 2002; Wheeler, Peterson, & Buckner,
2000 for empirical reports). Despite general acceptance
of the idea that memory is not localized to one neural
structure, there is overwhelming evidence that the medial
temporal lobe (MTL) plays a central role in episodic mem-
ory for diverse material, via its interactions with distributed
cortical regions (Scoville & Milner, 1957). The MTL con-
sists of multiple cortical areas, including the hippocampal
formation, surrounding entorhinal, perirhinal, and posterior
parahippocampal regions within the parahippocampal gyrus
in humans, and part of the temporal pole (Insausti, Insausti,
Sobreviela, Salina, & Mart
´
ınez-Peñuela, 1998; Insausti,
∗
Fax: +1-520-621-9306.
E-mail address: vanpettc@u.arizona.edu (C. Van Petten).
Juottonen, et al., 1998). Although many cases of human
domain-general amnesia have damage to multiple regions of
the medial temporal lobe, or to the diencephalon (Aggleton
& Brown, 1999; Brown & Aggleton, 2001; Mayes, 2000;
Smith & Bigel, 2000), lesions restricted to the hippocampus
alone result in memory deficits in both humans and non-
human primates (Rempel-Clower, Zola, Squire, & Amaral,
1996; Zola & Squire, 2000). The latter conclusion was drawn
from postmortem examination of the affected brains, but the
availability of high-resolution magnetic resonance images
has led to a more widespread research effort to tie hippocam-
pal pathology to memory impairment over the last decade.
MR scans are used to identify and/or confirm the location
of damage after a frank neural insult such as stroke, hypoxia,
or closed head injury. But an additional advantage of a non-
invasive method is the possibility of identifying subtle neu-
ral damage when the insult is not as obvious. Recent studies
have examined hippocampal volumes in individuals with
childhood seizures, posttraumatic stress disorder, borderline
personality disorder, depression, high risk of schizophrenia
due to affected relatives, an ApoE-4 allele, and high estro-
gen levels (Bremner et al., 1995; Cohen, Small, Lalonde,
Friz, & Sunderland, 2001; den Heijer et al., 2003; Driessen
et al., 2000; Fennema-Notestine, Stein, Kennedy, Archibald,
0028-3932/$ – see front matter © 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.neuropsychologia.2004.04.006