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BACKGROUND: Late Life Depression (LLD) has been associated with alterations in intrinsic functional networks, best characterized in the Default Mode Network (DMN), the Cognitive Control Network (CCN), and the Salience Network (SN). However these findings often derive from small samples and it is not well understood how network findings relate to clinical and cognitive symptomatology. METHODS: We studied 100 older adults (n=79 with LLD, n=21 nondepressed) and collected resting state functional MRI, clinical measures of depression, and performance on cognitive tests. We selected canonical network regions for each intrinsic functional network (DMN, CCN, and SN) as seeds in seed-to-voxel analysis. We compared connectivity between depressed and non-depressed groups and correlated connectivity with depression severity among depressed subjects. We then investigated whether the observed connectivity findings were associated with greater severity of common neuropsychiatric symptoms or poorer cognitive performance. RESULTS: LLD was characterized by decreased DMN connectivity to the frontal pole, a CCN region (Wald χ(2)=22.33, P20.14, p4.65, p4.29, p

Objective Late-life depression is associated with cognitive deficits and increased risk for cognitive decline. The purpose of the study was to determine whether clinical characteristics could serve as phenotypes informative of subsequent cognitive decline. Age at depression onset and antidepressant remission at 3 months (acute response) and 12 months (chronic response) were examined. Methods In a longitudinal study of late-life depression in an academic center, 273 depressed and 164 never-depressed community-dwelling elders aged 60 years or older were followed on average for over 5 years. Participants completed annual neuropsychological testing. Neuropsychological measures were converted to z-scores derived from the baseline performance of all participants. Cognitive domain scores at each time were then created by averaging z-scores across tests, grouped into domains of episodic memory, attention-working memory, verbal fluency, and executive function. Results Depressed participants exhibited poorer performance at baseline and greater subsequent decline in all domains. Early-onset depressed individuals exhibited a greater decline in all domains than late-onset or nondepressed groups. For remission, remitters and nonremitters at both 3 and 12 month exhibited greater decline in episodic memory and attention-working memory than nondepressed subjects. Three-month remitters also exhibited a greater decline in verbal fluency and executive function, whereas 12-month nonremitters exhibited greater decline in executive function than other groups. Conclusion Consistent with past studies, depressed elders exhibit greater cognitive decline than nondepressed subjects, particularly individuals with early depression onset, supporting the theory that repeated depressive episodes may contribute to decline. Clinical remission is not associated with less cognitive decline.

The population of elderly adults will almost double from 43.1 million in 2012 to an estimated 83.7 million in 2050. These demographic changes will result in increased cases of dementia and illustrate the need for a better understanding of normal and pathological structural changes in the aging brain. Moreover, it highlights the need for better clinically focused tools to apply scientific findings at the individual level. A better understanding of how brain aging underlies changes in cognitive function and performance can allow us to better distinguish “normal” from pathological brain aging patterns, such as Alzheimer’s disease. This chapter will review our understanding of normal brain aging in older adults, at times highlighting specific findings that may have diagnostic or prognostic value for neurodegenerative disorders. Additionally, we will highlight advances in neuroimaging and automated tools for image analyses over the last decade and briefly discuss new approaches and commercial software programs designed to translate research into clinical neuroradiology.

Background Late-life depression (LLD) is associated with a fragile antidepressant response and high recurrence risk. This study examined what measures predict recurrence in remitted LLD. Methods Individuals of age 60 years or older with a Diagnostic and Statistical Manual - IV (DSM-IV) diagnosis of major depressive disorder were enrolled in the neurocognitive outcomes of depression in the elderly study. Participants received manualized antidepressant treatment and were followed longitudinally for an average of 5 years. Study analyses included participants who remitted. Measures included demographic and clinical measures, medical comorbidity, disability, life stress, social support, and neuropsychological testing. A subset underwent structural magnetic resonance imaging (MRI). Results Of 241 remitted elders, approximately over 4 years, 137 (56.8%) experienced recurrence and 104 (43.2%) maintained remission. In the final model, greater recurrence risk was associated with female sex (hazard ratio [HR] = 1.536; confidence interval [CI] = 1.027-2.297), younger age of onset (HR = 0.990; CI = 0.981-0.999), higher perceived stress (HR = 1.121; CI = 1.022-1.229), disability (HR = 1.060; CI = 1.005-1.119), and less support with activities (HR = 0.885; CI = 0.812-0.963). Recurrence risk was also associated with higher Montgomery-Asberg Depression Rating Scale (MADRS) scores prior to censoring (HR = 1.081; CI = 1.033-1.131) and baseline symptoms of suicidal thoughts by MADRS (HR = 1.175; CI = 1.002-1.377) and sadness by Center for Epidemiologic Studies-Depression (HR = 1.302; CI, 1.080-1.569). Sex, age of onset, and suicidal thoughts were no longer associated with recurrence in a model incorporating report of multiple prior episodes (HR = 2.107; CI = 1.252-3.548). Neither neuropsychological test performance nor MRI measures of aging pathology were associated with recurrence. Conclusions Over half of the depressed elders who remitted experienced recurrence, mostly within 2 years. Multiple clinical and environmental measures predict recurrence risk. Work is needed to develop instruments that stratify risk.

Introduction Dementia is the sixth leading cause of death in the United States with Alzheimer's disease being the leading cause of dementia. To avoid unnecessary suffering and even harmful resuscitation, patients with dementia, or their designated decision-makers, can choose to sign a do-not-resuscitate (DNR) or do-not-intubate (DNI) order when they are critically ill. These patients and their designated decision-makers may also choose to receive hospice care to treat their symptoms and improve their quality of life in their final days. The percentage of patients with dementia receiving hospice care in 2018 was 11%, and this percentage is fast growing of hospice patients. However, caring for patients with advanced dementia who are nearing end of life poses many challenges for inpatient psychiatrists and staff. This case aims to examine a patient with Major Neurocognitive Disorder due to Alzheimer's disease with behavioral disturbances and the challenges to honoring the patient's DNR/DNI status and coordinating discharge to hospice. Methods Case Description: Patient is a 78-year old male diagnosed with Major Neurocognitive Disorder due to Alzheimer's disease with behavioral disturbances admitted to Vanderbilt Psychiatric Hospital for uncontrollable physical aggression. This was his second psychiatric hospitalization in one year due to aggression. On initial evaluation, he was oriented to self only, which was his baseline. He was admitted on the following medications: donepezil 10mg daily, haloperidol 3 mg twice daily, melatonin 1.5 mg at bedtime, finasteride 5 mg daily, tamsulosin 0.8 mg at bedtime, aspirin 81 mg daily, a multivitamin daily, and comfort medications as needed. Behavioral interventions were initiated to reduce agitation. On hospital days 1-6, he was physically aggressive towards staff during activities of daily living. During this time, he was tapered off haloperidol and risperidone was titrated to target physically aggressive behavior, although this was eventually discontinued due to ineffectiveness. On hospital day 8, he was started on olanzapine for physical aggression, resulting in improvement. During this time, olanzapine was adjusted to 5 mg at bedtime and melatonin to 3 mg at bedtime. While his aggressive behavior improved, his food intake and mobility continued to decline. The geriatric psychiatry team recommended patient's POA consider hospice care. Palliative care was consulted, but declined to see the patient while he was hospitalized psychiatrically. On hospital day 26, the patient started displaying autonomic instability, though did not appear to be in distress. He was started on supplemental oxygen. The Geriatric Medicine consult team recommended morphine 5-10 mg every 2 hours as needed for dyspnea or pain. Two community hospice services were consulted and determined him appropriate for their facilities. The psychiatric nursing staff expressed concern his DNR/DNI could not be honored if he were to decompensate further prior to transfer. The Chief Medical Officer was involved who confirmed the DNR/DNI status could be honored as the policy had recently changed. On hospital day 28, the patient was discharged to a nursing home with hospice care, and he died nine days later. Results Discussion: Inpatient psychiatrists and staff are not as familiar as their counterparts at a medical center in managing end-of-life care and death of patients, despite geriatric psychiatrists commonly treating patients of advanced age or with terminal illness. An increasing number of patients with advanced dementia and associated behavioral disturbances are psychiatrically hospitalized, and they represent the fastest growing group of hospice patients. This patient's agitation needed stabilizing before he could transfer to a nursing home safely. When he began displaying autonomic instability, multiple members of his treatment team were concerned his advanced directives would not be honored if he died while on the psychiatric unit, and expressed additional concerns around the impact his death would have on staff and other patients. Conclusions Experts suggest the final stage of Alzheimer's disease include the inability to ambulate, speak, perform activities of daily living, and appropriately swallow. When these signs are present, it is important to recognize any limitations in the care available, involving hospice or palliative care experts if needed, to honor a patient's end of life wishes accordingly. This research was funded by Not applicable.

Background:Depression in late life is a risk factor for cognitive decline. Depression is also associated with increased disability and social support deficits; these may precede conversion to dementia and inform risk. In this study, we examined if baseline or one-year change in disability and social support predicted later cognitive deterioration.Methods:299 cognitively intact depressed older adults were followed for an average of approximately seven years. Participants received antidepressant treatment according to a standardized algorithm. Neuropsychological testing and assessment of disability and social support were assessed annually. Cognitive diagnosis was reviewed annually at a consensus conference to determine if participants remained cognitively normal, or if they progressed to either dementia or cognitively impaired, no dementia (CIND).Results:During study participation, 167 individuals remained cognitively normal (56%), 83 progressed to CIND (28%), and 49 progressed to dementia (16%). Greater baseline instrumental activities of daily living (IADL) deficits predicted subsequent conversion to a cognitive diagnosis (CIND or dementia). However, neither baseline measures nor one-year change in basic ADLs (BADLs) and social support predicted cognitive conversion. In post hoc analyses, two IADL measures (managing finances, preparing meals) significantly increased the odds of cognitive conversion.Conclusions:Greater IADL deficits predicted increased risk of cognitive conversion. Assessment of IADL deficits may provide clues about risk of later cognitive decline.