Dr. Patrick Brown

Dr. Patrick Brown is a licensed clinical psychologist and an Assistant Professor of Clinical Psychology (in Psychiatry) in the Division of Geriatric Psychiatry at Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute. His research is focused on the interface between mood disorders and cognitive impairment in late life and the impact of the syndrome of frailty on assessment and treatment of depressive disorders in older individuals.

ElderBranch interviewed Dr. Brown to discuss his paper, “The nuances of cognition and depression in older adults: the need for a comprehensive assessment,” which he wrote along with Drs. Bret Rutherford, Joel Sneed, D.P. Devanand, and Steven Roose of the New York State Psychiatric Institute and the Columbia University College of Physicians and Surgeons.

Why did you decide to research the confluence of depression, cognitive impairment, and vascular risk factors in older adults? Why is this topic important?

In the last 10 years, our group in Geriatric Psychiatry at Columbia University has been discussing our approach towards the evaluation and treatment of the older individuals with depression. The simple fact is that a doctor cannot approach an older adult in the same manner in which he or she would approach a younger adult. With age comes an increased likelihood of comorbid medical illness, memory problems, and difficulties in day-to-day functioning. The increased likelihood of co-occurring illnesses or dysfunction has ramifications for making an accurate diagnosis and has implications on accurate treatment planning.

We focused on depression, vascular risk factors, and cognitive impairment because these three disorders represent the “axis of evil” for the older patient, resulting in increased likelihood of treatment resistance in older depressed individuals and a greater likelihood of poor prognosis.

Specifically, we focused on two types of cognitive impairment: episodic memory, or the ability to remember a story or event, and executive abilities, which refers to a group of processes that include organization, attention, planning, and reasoning.

These two types of cognition are particularly important because impairment in episodic memory denotes a stage in cognitive deterioration that deviates from cognitive problems considered “typical” of “normal aging” called amnestic mild cognitive impairment or amnestic MCI; older individuals with amnestic MCI are at greater risk of progression to dementia of the Alzheimer’s type, making this cognitive domain of great clinical importance to the patient, their family, and the clinician. Impairment in executive abilities has been associated with poorer treatment response to antidepressant medications in older depressed individuals; it is also associated with the presence of cerebrovascular disease and/or vascular risk factors such as hypertension, obesity, diabetes, and history of smoking.

Impairment in these two cognitive domains may denote impairment in specific brain regions resulting in differing clinical trajectories; knowing this information during the evaluation can positively impact the accuracy of diagnosis and better treatment planning by the clinician. By focusing on these three broad areas, we sought to highlight the complexity that accompanies the care of older adults and the need for comprehensive assessment to take place, particularly in the community.

Please describe your study. What were your in-going hypotheses?

Given that the episodic memory and executive dysfunction status of the older depressed individual independently communicate important information that should impact clinical management, we sought to examine the confluence of depression, cognitive impairment, and vascular risk factors in a diverse group of cognitively intact and cognitively impaired older individuals.

We hypothesized that the prevalence of depression would not differ between older adults with significant episodic memory problems (i.e., those with amnestic MCI) and those with cognitive impairment other than impairment in episodic memory (i.e. those with nonamnestic MCI).

Additionally, we hypothesized that depression would be more prevalent in cognitively impaired older adults than in cognitively intact older adults. We also hypothesized that depressed older adults with either amnestic MCI or nonamnestic MCI would have greater rates of executive dysfunction and vascular risk factors than nondepressed older adults.

To investigate these hypotheses, we used data from the National Alzheimer’s Coordinating Center, which runs a consortium of Alzheimer’s Disease Centers studying a large cohort of cognitively intact and cognitively impaired older adults, a subset of whom report significant depressive symptoms. By using these data gathered from older adults at 34 past and present Alzheimer’s Disease Centers, we could delineate these older adults by cognitive status, depression status, as well as by the presence of executive dysfunction and vascular risk factors.

What were the key findings from your research?

The findings from this study highlight the complexity of the confluence between depression and cognitive impairment in older adults. The data from this study show the following: (1) depression is common in older adults with both amnestic MCI and nonamnestic MCI; (2) executive dysfunction is common not only in older adults with nonamnestic MCI but also in older adults with amnestic MCI; and (3) vascular risk factors, specifically hypertension, are associated with the presence of executive dysfunction but not depression severity, as we had originally hypothesized.

These data highlight a basic but significant message to geriatric psychiatrists: the high frequency of the confluence between hypertension, episodic memory impairment, and executive dysfunction should result in systematic, thorough assessments in geriatric clinics.

Although research suggests that it is the presence of executive dysfunction (and the neuropathology that this dysfunction signifies) that predicts poor response to antidepressant treatment in late-life depression, antidepressant response may also be impacted by underlying Alzheimer’s pathology (of which episodic memory dysfunction is a marker) or the interaction between cerebrovascular disease and Alzheimer’s pathology. Without thorough assessment of our older patients at evaluation, however, it becomes difficult to disentangle these issues as well as enact an adequate treatment plan.

How can research in this field help clinicians create better treatment plans for depressed older adults?

These data have important clinical implications. Clinically, comprehensive assessment results in the formulation of more accurate treatment planning and can inform clinicians about patients’ long-term trajectory. A comprehensive assessment should provide the following: (1) the information necessary to make a DSM-V diagnosis of a mood disorder (i.e. depression or anxiety disorders) and a measurement of the severity of this disorder; (2) review of vascular risk factors (hypertension, obesity, diabetes, and/or history of smoking) that let the clinician estimate the probability that the patient has ischemic cerebrovascular disease even in the absence of neurological findings; and (3) testing of cognitive function so that the patient can be categorized as having normal cognitive status, nonamnestic MCI (i.e. cognitive impairment that does not include episodic memory dysfunction), amnestic MCI (i.e. impairment in episodic memory), and/or executive dysfunction.

There are a number of instruments that can accomplish each task, and each clinician can develop the systematic comprehensive assessment procedure that they prefer. For example, if a 72-year-old depressed man presents at a physician’s office with memory complaints, only a comprehensive medical, clinical, and neuropsychological assessment will lead to the implementation of the best treatment plan. Does this patient have executive dysfunction? Episodic memory dysfunction? History of hypertension or diabetes?

There are treatment implications based on the findings from each of these assessments. It allows for the differentiation between depression without cognitive impairment, depression with episodic memory dysfunction and no executive dysfunction (could signify either depression with depression-associated neuropathology or depression with Alzheimer’s neuropathology), depression with executive dysfunction (could signify a vascular depression), and depression with both executive and episodic memory dysfunctions (could signify a vascular depression with a high likelihood of underlying cerebrovascular disease and Alzheimer’s neuropathology).

The latter three scenarios require multifaceted treatment implementation: (1) the treatment of untreated vascular risk factors; (2) the treatment of depression (pharmacotherapy, therapy, or both); and/or (3) initiation of cholinesterase inhibitors, which may be warranted by the presence of episodic memory dysfunction.

Thorough assessment will also inform doctors of long-term prognosis. Early identification of incipient Alzheimer’s disease can lead to earlier enrollment of patients in clinical trials for treatment of cognitive impairment, earlier financial and estate planning, the designation of healthcare proxies, and the preparation of families for the future responsibility and cost of providing care for the older patient.

What are the next steps in terms of furthering the research in this area? What questions still need to be answered?

By and large, this work exemplifies a larger movement that is going on both specifically in geriatric psychiatry and more generally in psychiatry: this movement is based by in large on the question of who responds to treatment and who does not, and why do these individuals not respond to treatment. For researchers, these data highlight the need to make our intervention studies more inclusive.

In the past, treatment studies would exclude individuals with comorbid illnesses in order to pinpoint the effectiveness of medications on a specific disease (i.e. the clinical trial model). The problem with this method, while scientifically sound, is that it minimizes the generalizability of those research findings to community based psychiatrists and physicians. If the medication is effective in a highly selected population, it does not mean that it will be effective in an individual with other co-occurring illnesses. And as we discussed, when working with and treating older adults, co-occurring illness is far more the norm than it is the exception. For example, as mentioned earlier, we know that the presence of cerebrovascular disease in a depressed older adult is associated with poor response to antidepressant medication. We also know that older adults with cerebrovascular disease are more likely to have executive dysfunction and vascular risk factors such as hypertension, diabetes, and obesity.

The question now is: why? What is it about the neuropathology of this comorbid group that negatively effects the medication? So, the next steps to this research are really twofold: (1) To disseminate to clinicians the need to approach their older patients differently than their younger patients, with an eye towards comprehensive assessment towards those disorders that may impact treatment; and (2) To push researchers to focus on more complex older patients in their intervention trials to investigate those comorbid disorders that minimize treatment effectiveness and investigate what it is about these disorders that does so. In doing so, we can ultimately achieve a more personalized approach to medicine that maximizes the effectiveness of interventions through the utilization of information garnered through comprehensive assessment of our older patients.

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