Neurocognitive Outcomes of Depression in the Elderly

Central hypothesis: the 5-year likelihood of each cognitive diagnostic outcome is associated with distinct clinical, cognitive, and neural phenotypes during acute LLD, which in turn have distinct genotypic correlates.

Specifically, CN individuals will have earlier first onset of depression (EOD) relative to AD, more negative life stress during acute depression compared with AD and PCI, and greater white matter integrity; CN will also be associated with the AA genotype of the COMT val158met polymorphism, which may confer both neuroprotection and higher stress sensitivity. PCI will have more EOD relative to AD, greater frailty, and lower white matter integrity than NC. AD will be associated with later age of depression onset (LOD), greater appetite loss, lower anxiety, smaller hippocampal volume, and greater memory impairment. To test these hypotheses, we propose the following

Inclusion criteria

For depressed group:

• Age > 60 years
• Major depression, single episode or recurrent
• Ability to read and write English
• MMSE >25
• Willingness to participate in the follow-up study for at least two years.

For non-depressed group:

• Age > 60 years
• Ability to read and write English
• MMSE >25
• Willingness to participate in the follow-up study for at least two years.

Exclusion criteria

• Lifetime alcohol or drug dependence
• conditions associated with MRI abnormalities such hydrocephalus, benign and cancerous brain tumors, epilepsy, Parkinson's disease, Huntington's chorea, dementia, demyelinating diseases, etc.
• endocrine disorder other than diabetes mellitus)
• Any physical or intellectual disability that may affect completion of self rating instruments
• Established clinical diagnosis of dementia
• Other primary psychiatric disorders, including panic disorder, social phobia, OCD, non-affective psychosis (including schizo-affective disorder), schizophrenia, bipolar disorder
• Any metal or pacemaker in the body which precludes MRI.