Hippocampal volume is as
variable in young as in older
adults: Implications for the
notion of hippocampal atrophy in
humans
S.J. Lupien, A. Evans, C. Lord, J. Miles,
M. Pruessner, B. Pike, and J.C. Pruessner
NeuroImage
Volume 34, September 2006, Pages 479-485
The hippocampus
•Located bilaterally inside the temporal lobe
•Forms a part of the limbic system
• Plays a part in memory and spatial
navigation.
Hippocampal Volume
•Age
Dependant on:
•Psychiatric Disease (schizophrenia, depression,
PTSD)
•Pre-determined Individual difference?
Fig. 1. Schematic representation of the implicit
assumption resulting from the aging model. S.D.:
standard deviation.
Hypothesis
If aging and psychiatric disease lead to HC
atrophy in adult humans, it is implied that the
HC volume in young healthy adults should
present less variability than HC volume in older
adults and psychiatric populations.
Subjects
•177 men and women aged 18-85 years (70 men and 107
women)
•Participants were screened for history of neurological
disorder, psychiatric disorder, head trauma and conditions
preventing MRI assesment
•Participants with a psychiatric disorder, or participants using
antiseizure medication, antihypertensive medication,
anxiolytics or antidepressants were excluded from the study.
•Older patients were further screened for dementia and
depression using the Blessed Information-MemoryConcentration Test and the Geriatric Depression Questionaire
MRI image acquisition and
analysis
•Participants were split into 5 age
groups of approx. 40 individuals per
group.
•Age groups were:
18-24 years
25-40 years
41-59 years
60-75 years
76-85 years* (Only 16 individuals in
this group)
MRI image acquisition and
analysis
•All images were transferred to a silicon Graphics
workstation
•A combination of different algorithms was used to
prepare the raw MRI volume for manual
segmentation.
•Processing steps included: non-uniformity
correction, translation into standard stereotaxic
space, and signal intensity normalization.
Assessment of HC volume
•Principle orientation for the segmentation of the
HC was the coronal view for the tail and body of
the HC, and the axial view for the head.
•HC was segmented from posterior to anterior in
the coronal view, and superior to inferior in the
axial view.
•Does not comprise the amygdala
Results
Fig. 2. Scatterplot of the association between age
and HC volumes in males and females.
Results
Mean HC volume (cubic centimeters) and standard deviation in 177
men and women aged from 18 to 85 years
Age
Range
N
Total Mean
Min HC
Volume
Max HC Mean/lowes %
Volume t Quartile
difference
b/w means
18-24
41
4.23 +/- 0.36
3.65
5.13
3.82 +/- 0.12 12
25-40
38
4.13 +/- 0.48
3.31
5.12
3.55 +/- 0.13 16
41-59
42
3.97 +/- 0.36
3.07
4.96
3.56 +/- 0.18 12
60-75
40
3.78 +/- 0.46
2.89
4.54
3.28 +/- 0.20 15
76-85
16
3.20 +/- 0.48
2.57
4.26
2.64 +/- 0.08 21
Results
•Analysis established that there are differences in
mean HC volume associated with chronological
age
•Using Whites test it was established that there is
no evidence of different variance in different age
groups
•HC volume is therefore as variable in younger as
in older adults, although mean HC volume is
smaller is older groups when compared to younger
groups
Results
• % difference between the mean HC volume of each
age group and the mean HC volume of the lowest
quartiles in each age group were analyzed
•Results showed that within the same age group, the
% difference between the mean HC volume and the
mean of the lowest quartile of each group ranges
from 12-21%
•This % is greater than the % differences of HC
volume reported in patients suffering from
psychiatric disorders compared to age matched
controls.
Discussion
•Results show that the dispersion around the
mean of the HC volume is not different in young
and older adults
•25% of 18-24 year old subjects present HC
volumes as small as those observed in the
average older adults aged 60-75 years.
•Therefore it is possible that the HC volume at
any given age reflects a volume that was predetermined based on early experiences
Discussion
•HC “atrophy” due to the presence of a psychiatric
disease could in fact represent pre-determined
inter-individual differences in HC volume that
increase vulnerability to stress and/or mental
disorders.
•Case study: Monozygotic Twins and PTSD
-Study in 2002
-HC volume may be a pre-existing condition that
increases vulnerability to PTSD upon exposure to
a traumatic experience
Discussion
More Evidence:
•Other studies have revealed smaller HC volume
in first-episode untreated depressed patients and
first-episode untreated schizophrenics
•Finding goes against any neurotaxic effect of
depression and/or schizophrenia on HC volume
•Suggests that individual differences in HC
volume may render individuals more or less
vulnerable to the effects of stress and cognition on
mental health
Factors influencing HC Volume
•Genetics (40%)
•Experience (60%)
Experience factors influencing growth of HC
volume:
-Environmental enrichment *
-Nutritional factors*
-Stress (cortisol)*
-Gestational stress
*inducers of changes in neurogenesis and/or dendritic
arborization influencing HC volume
Conclusions
•HC volume is as variable in young as in older
adults
•Smaller HC volume attributed to the aging
process in previous studies could actually
represent HC volume early in life.
•Within similar age groups there is as much
variation in HC volume of healthy subjects as can
be found when comparing the HC volume of
psychiatric patients and age matched controls
Conclusion
Therefore: pre-determined individual
differences in HC volume in humans may
determine the vulnerability for age-related
cognitive impairments or psychopathology
throughout the lifetime.