This study seeks to examine clinical, genetic, and neuroanatomical variables related to mood
and cognitive outcomes of depression in late life. We plan to study the following SPECIFIC
Aim 1. To compare cognitive outcomes among older adults with and without depression, and to
examine depression and cognitive outcomes in patients with cognitive impairment or
Aim 2. To examine the role of genes in long-term depression outcomes in the elderly.
Aim 3. To determine neuroanatomical and neuropathological correlates of late-life depression
We will test the following hypotheses:
Hypothesis 1. Compared with non-depressed elderly controls, depressed elderly patients will
have an increased incidence of development of mild cognitive impairment and dementia.
Hypothesis 2. Depressed subjects with mild cognitive impairment will have a worse depression
course compared with depressed subjects who do not have mild cognitive impairment.
Hypothesis 3. Depressed subjects with worsening deep white matter disease and smaller
hippocampal volumes on longitudinal (baseline to two year) magnetic resonance imaging brain
scans will have a worse depression course and more cognitive decline compared with depressed
subjects without these brain changes.
Hypothesis 4. Depressed subjects with the 5HTTLPR short allele will have a worse depression
course compared with depressed subjects without these risk genes.
Hypothesis 5. Depressed subjects with the apolipoprotein E (APOE) epsilon-4 allele and
vascular risk gene polymorphisms such as ACE receptor will have an increased risk of
cognitive decline compared with depressed subjects without these risk genes.
Hypothesis 6. Compared with brains of non-depressed controls, brains of depressed subjects
will demonstrate increased density of blood vessels in the prefrontal cortex, including
orbital frontal cortex and dorsolateral prefrontal cortex.
Hypothesis 7. Compared with brains of non-depressed controls, brains of depressed subjects
will demonstrate decreased packing density of prefrontal cortex neurons with pyramidal
Hypothesis 8. Compared with non-demented depressed subjects, depressed individuals who
become demented will have more neuritic plaques, neurofibrillary tangles and cerebrovascular
We will examine secondary aims related to 1) mortality and 2) social factors, with the
1. Depressed subjects with a larger increase in volume of hyperintensities will have a
higher mortality rate.
2. Subjects with poor social support and functional status will have worse depression and
For depressed group:
1. Age > 60 years
2. Major depression, single episode or recurrent
3. Ability to read and write English
4. MMSE >25
5. Willingness to participate in the follow-up study for at least two years.
For non-depressed group:
1. Age > 60 years
2. Ability to read and write English
3. MMSE >25
4. Willingness to participate in the follow-up study for at least two years.
1. Lifetime alcohol or drug dependence
2. conditions associated with MRI abnormalities such hydrocephalus, benign and cancerous
brain tumors, epilepsy, Parkinson's disease, Huntington's chorea, dementia,
demyelinating diseases, etc.
3. endocrine disorder other than diabetes mellitus)
4. Any physical or intellectual disability that may affect completion of self rating
5. Established clinical diagnosis of dementia
6. Other primary psychiatric disorders, including panic disorder, social phobia, OCD,
non-affective psychosis (including schizo-affective disorder), schizophrenia, bipolar
7. Any metal or pacemaker in the body which precludes MRI.