2. Dr. Omranifard MD 12 may 2015

3. 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.

4. 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.

5. 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…

6. 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)

7. So late-onset depression (LOD) means depression with onset after 55-65 years and early onset depression (EOD) means onset before 55-65 years.

8. 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.

9. 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.

10. Several evidences suggest that LOD is a distinctive phenomenological entity a opposed to EOD…

11. 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

12. LOD characteristics: more often associated with cognitive impairment More neurologic comorbidity More vascular risk factors slow or poor response to antidepressant treatment. lower rate of family history of depression higher prevalence of dementia suggesting a poorer impact of genes and a higher correlation with cognitive decline.

13. Comparison of cognitive profile: 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.

14. 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).

15. 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.

16. sociological variables: 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.

17. Comparison of depressive indices: 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.

18. 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.

19. Other differences: 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.

20. 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 co- morbid borderline PD in this group

21. Neuroimaging differences : 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.

22. 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.

23. 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.

24. 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.

25. 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:

26. 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; 3. 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.

27. 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

28. 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.

29. 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.