Changes in
memory occur with age but memory changes are also the
earliest cognitive change seen in Alzheimer's disease
(AD). Recent studies indicate that there is a considerable
difference between the nature of the memory changes in
aging and in AD and the underlying neurobiology responsible
for those changes.
There are substantial
changes with age in explicit secondary memory, in contrast
to the minimal age changes in sensory and primary memory.
The age at which changes in secondary memory occur depends
upon the methods that are used to test the memory store.
Difficult explicit memory tasks (e.g., delayed recall)
demonstrate statistically significant differences by subjects
in their fifties, in comparison to younger individuals.
Non-human primates demonstrate age-related differences
on difficult memory tasks at an equivalent point in their
life span (i.e., 16 - 23 years).
A close examination
of the human data indicates that the older individuals
are not more rapidly forgetting what they learned, but
rather they are taking longer to learn the new information.
For example, if one compares the difference between immediate
and delayed recall over the life span, several studies
demonstrate no statistically significant age differences.
The alterations
in memory associated with early Alzheimer's disease (AD)
differ in important ways from those associated with age-related
changes in memory. Difficulty with delayed recall is generally
the first and most salient symptom to emerge in patients
with Alzheimer's disease (AD). Moreover, when compared
with a variety of patient groups with amnesic and dementing
disorders, AD patients retain less information over a
brief delay than any groups tested to date.
These findings
suggest that selected, and differing, alterations in the
brain are responsible for the differing pattern of memory
loss seen in normal aging and in AD. The most likely explanation
for the abnormalities in memory that characterize the
early stage of AD pertains to the damage to the hippocampal
formation seen in these patients. In the hippocampal formation,
neuronal loss and abnormal formations with the cells (e.g.,
neurofibrillary tangles and neuritic plaques) are seen
primarily in the entorhinal cortex and subiculum, the
primary pathways that convey information into and out
of the hippocampus. The entorhinal cortex appears to undergo
the most profound changes in the early stages of AD, with
a 32% loss of neurons overall, even among very mildly
impaired patients.
Neuronal loss
with age, however, appears to be minimal in the hippocampus,
and recent positron emission tomography and functional
magnetic resonance imaging studies demonstrate robust
responses during memory tasks among both elderly and young
individuals. In addition, among the brain regions examined
to date, neuronal loss in the cortex is either not significant
or not as extensive as earlier reports suggested. However,
with advancing age, there is substantial neuronal loss
in selected subcortical regions responsible for the production
of neurotransmitters important for memory function, such
as the basal forebrain and the locus coeruleus, and significant
alterations in the composition and volume of the white
matter.
Understanding
the nature of these cognitive changes and the brain alterations
associated with them, is the first step in developing
methods of changing them.
