Download بسم الله الرحمن الرحیم Late- versus early

Dr. Omranifard MD
12 may 2015
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Depression is one of the most prevalent
psychiatric disorders in late life with
devastating health consequences.
It could become the second most common
cause of disability by 2020.
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Furthermore late-onset depression (LOD)
becomes an important public health problem
and leads to increased risk of morbidity,
increased risk of suicide, increased risk of
physical, cognitive and psychosocial
impairment, all of which have been associated
with increased mortality.
However, depression may often be overlooked
and untreated in older patients.
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Age-of-onset has been suggested as a valid
alternative to recurrence and polarity for
classifying mood disorders
However, it is not clarified exactly how to
define the cut-off age…
according to age-of-onset, in most of studies
depression typically falls in three categories:
 childhood or adolescent onset Depression
(younger than 18-21years)
 adult depression (typically cut-off of 18-21
years)
 late-life onset of depression(onset after 55-65
years)
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So late-onset depression (LOD) means
depression with onset after 55-65 years and
early onset depression (EOD) means onset
before 55-65 years.
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Major depressive disorder is a highly prevalent
disease in old age.
Between 1% and 4% of the elderly experience
major depression and this prevalence increases
to between 6% and 32% among older nursing
home residents.
Though the elderly constitute a major
subgroup, depression frequently affects the
younger population as well.
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Epidemiologically, about 40% of cases of major
depression in old age are characterized by
recurrent depressive episodes, whereas only
30% reflect late-onset depression. In some
cases, recurrent and late-onset depression is
difficult to distinguish clinically.
Several evidences suggest that LOD is a distinctive
phenomenological entity a opposed to EOD…
EOD characteristics:
 earlier onset is associated with a more severe
course of the disorder . Depressive episodes in
childhood and adolescence, rather than those at
older ages, predict more episodes and longer
duration of depression in adult life and, thus, a
more chronic course of illness.
 An increased familial loading for depression
among EOD patients
 Less vascular risk factors
LOD characteristics:
 more often associated with cognitive impairment
 More neurologic comorbidity
 More vascular risk factors
 slow or poor response to antidepressant treatment.
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lower rate of family history of depression
higher prevalence of dementia suggesting a poorer
impact of genes and a higher correlation with
cognitive decline.
Comparison of cognitive profile:
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Cognitive deficits have been associated with
depression independently of age of onset.
However, cognitive impairment is significantly
greater in LOD than in EOD.
late-onset depression patients show greater
memory impairment, executive dysfunction
and greater impairment in episodic memory
tests than the early-onset group.
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hippocampal atrophy is more strongly
associated with late-onset than early-onset
depression. (The loss of hippocampal volume
and memory function observed in some elders
with late-life depression suggests that
depression may be a predispositional risk
factor for Alzheimer disease, because lower
hippocampal volumes predict subsequent
Alzheimer disease).
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In a study, over the four-year period, the LOD
group showed more cognitive decline on the
MMSE than did the EOD group.
The LOD group also exhibited lower gray
matter volume at baseline than did the EOD
group.
Some studies have identified more white
matter loss in LOD compared to EOD.
sociological variables:
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Late-onset depression patients are more frequently
married while early-onset depressives are more
often unmarried.
In elderly, Social isolation, physical inactivity, and
lack of leisure cognitive activity may result in
lowered reserve and therefore confer additional
risk for exhibiting clinical symptoms of dementia.
EOD group reported poorer social support than
did the LOD.
Comparison of depressive indices:
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EOD would be associated with more severe
indices of depressive disorder, poorer social
support, and more suicidal thoughts and
behaviors than would LOD. As predicted,
those with EOD had more depressive
symptoms at baseline than those with LOD.
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the EOD group have more residual symptoms
of depression over time.
those with EOD have more suicidal thoughts
and behaviors than did those with LOD.
Other differences:
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Patients with onset of depression in the early
adult age were characterised by a substantially
higher prevalence of co-morbid dependent PD
and borderline PD, a higher level of
neuroticism, a lower prevalence of stressful life
events, a higher prevalence of atypical features
compared to patients with later age-of onset.
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The patients with early onset reported more
subjective depressive symptoms after
treatment.
Patients with early onset had more drug abuse,
but this difference seemed to be – at least in
part – attributable to a higher prevalence of comorbid borderline PD in this group
Neuroimaging differences:
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LOD has been associated with more severe
structural brain abnormalities and cerebrovascular
pathology compared to age-matched controls and
EOD patients
patients with LOD have more pronounced atrophy
in cortical and sub-cortical regions. In particular
important local and global differences have been
found in prefrontal cortex and hippocampus.
Participants with LOD lost hippocampal volume at
a faster rate than did participants with EOD.
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LOD has been associated with frontostriatal
disruption caused by subcortical, white matter
and periventricular hyperintensities .
In particular, recent studies have demonstrated
that LOD and white matter lesions are strongly
related.
Interestingly, in a longitudinal stud white
matter hyperintensities in LOD have also been
associated with dementia.
Overall, the results are consistent with
the view that EOD is distinguished
from LOD by more frequent
association with persistent
disturbances in behaviors and
attitudes.
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EOD has been largely correlated to stress
factors and genes, while LOD has been
correlated principally to vascular dysfunction.
However, recent neuroimaging studies have
established that the prefrontal cortex and
hippocampus are the principle brain areas
involved in both types of depression. This
would suggest that the same brain areas are
implicated in two different neuropathologic
processes, with similar but not identical clinical
pictures.
The literature on depression and dementia has
always been somewhat contradictory. There is a
high comorbidity between depression and
cognitive impairment among older adults
There are three main hypotheses that attempt to
explain the association:
1.
depression may be a psychological reaction to
eroding cognitive capacities early in the course of
dementia;
2.
a common underlying central nervous system
disorder may be the cause of depression, as well as
cognitive decline in elderly persons; it has been
shown that elderly depressed people have more
frequent and more severe white matter and other
subcortical abnormalities on brain magnetic
resonance imaging;
depression may be associated with high levels of
cortisol, which can lead to neuronal death and
deregulation of the hypothalamic pituitary adrenal
axis resulting in hippocampal atrophy and
cognitive decline.
3.
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LOD increases risk of mild cognitive
impairment and dementia
cognitive decline in patients with dementia was
further accelerated by the presence of
depression. Taken together these data provide
evidence for some pathophysiolocal event
linking LOD, cognitive decline and dementia.
Some authors suggest a common
neuropathological platform based on vascular
dysfunctions linking these two major geriatric
pathologies
a recent longitudinal study found EOD had no
association with dementia and confirmed that
LOD is associated with an early manifestation of
dementia rather than increasing risk for dementia.
Geriatric depression may be a sign of brain
degeneration and the initial symptom of a
dementing disorder. It is important to consider
this in patients whose depressive symptoms begin
after the age of 60 years.