Read Full Text: Depression in neurodegenerative diseases: Common mechanisms and current treatment options
Journal: Neuroscience and Biobehavioral Reviews
Year Published: 2019
Ranked 8th on our 2019-2023 list of the 100 Most Influential OT Journal Articles
CEU Podcast: #56: Depression in Neurodegenerative Diseases with Rachel Wiley
Today’ article drives home the complex connection between depression and three neurodegenerative diseases:
- Alzheimer’s Disease
- Parkinson’s Disease
- Huntington’s Disease
Even though depression has a high comorbidity with all of these diagnoses, the authors argue that it should not be an assumed part of the disease process. Instead, depression should be recognized as distinct—and treated as such.
But, here’s where things get complicated:
In some cases, the medications traditionally used to treat depression do not work for this population—and can in fact be actively harmful. So, OT approaches like environmental enrichment and physical exercise could actually be the frontline defense for helping these patients manage their depression.
To unpack all of this, I am so thankful to have dementia care expert Rachel Wiley, MS, OTR/L, CDP, join us on the podcast next week.
Let’s dive in.
Quick intro to major depressive disorder (MDD)
Major depressive disorder is a highly prevalent psychiatric condition impacting people across all demographics.
In the United States, the lifetime prevalence of MDD is an estimated 17%—and it is one of the leading causes of disability worldwide.
The typical presentation of MDD can include:
- Depressed mood
- Reduced interest in pleasurable activities (anhedonia)
- Cognitive impairment
- Feelings of guilt and worthlessness
- Suicidal ideation
Depression and neurodegenerative diseases
Even though MDD can present at any age, there are certain circumstances in which clinicians must be hypervigilant in recognizing a client’s increased risk of mood disorder (for example: after the diagnosis of a chronic and/or untreatable condition such as a neurodegenerative disease).
However, diagnosing depression in this context can be difficult, as one of the criteria for diagnosis of depression is that the symptoms cannot be explained by another condition.
So, in the article we’re looking at today, the authors walk us through our current understanding of the mechanisms behind depression and three neurodegenerative diseases:
- Alzheimer’s Disease (AD)
- Parkinson’s Disease (PD)
- Huntington’s Disease (HD)
They highlight not only the distinct features of depression in this context, but also the similarities between the mechanisms of depression and the mechanisms of these three diseases.
The authors also discuss what this means for treatment.
What causes depression?
Before diving into how depression intersects with these three diseases, the authors examine what we know about the causes of depression.
The common understanding that depression results from a chemical imbalance is actually oversimplified.
In reality, there is no universal mechanism to explain the causes of depression.
The authors go in-depth on some of the proposed mechanisms, which are illustrated on the infographic below. I encourage you to review the full article for more details on each one.
What are the mechanisms behind neurodegenerative disease?
Different neurodegenerative diseases have different causes and distinct presentations. But, there is significant overlap in the mechanisms behind them.
These include:
- Atypical protein assembly
- Excitotoxicity
- Reduced trophic support and neuroplasticity
- Oxidative stress and mitochondrial dysfunction
- Neuroinflammation
You can see how these mechanisms overlap with the causes of depression. This creates a complex web in which these disorders can influence and exacerbate each other.
Okay. Let’s look very high-level at depression that co-occurs with these three disorders, particularly with respect to treatment.
1. Alzheimer’s Disease and MDD
MDD is highly prevalent in patients with Alzheimer’s Disease. There is a wide range of reported incidence due to variations in diagnostic criteria, but to give you a general sense of where we stand, this study reported that MDD is present in about 40% of AD cases.
Compared to patients who are diagnosed with AD or MDD alone, the number of hospitalizations is considerably higher for patients who present with both AD and MDD. Most significantly, there’s an increased mortality rate for individuals with comorbid depression and AD.
Treatment
The evidence is variable in quality, but there are a few non-pharmacological strategies that appear to alter the course of MDD in AD:
- Specific regimens of music therapy have shown effectiveness. (2017)
- Reminiscence therapy, multisensory stimulation therapy, and behavioral management with occupational therapy may also be beneficial, but more research is needed in these areas. (2017)
- Exercise has mixed reports as a treatment. But, it should be noted that physical activity can reduce the risk for both depression and neurodegeneration.
Regarding medication, there is evidence against the effectiveness of common depression medications (like SSRIs, SNRIs, and MAOIs) for this population. Non-traditional agents like omega-3 supplementation show promise, but more research is needed.
2. Parkinson’s Disease and MDD
Studies show that 10–45% of PD patients are affected by clinically significant depression.
Compared to all other motor and non-motor symptoms, MDD has been identified as the greatest predictor of quality of life for individuals with Parkinson’s Disease. Unfortunately, depression is often under-recognized by physicians.
Treatment
This clinical study found that aerobic physical exercise had a positive effect on both motor symptoms and scores on the Beck Depression Inventory.
Deep brain stimulation and repetitive transcranial stimulation have also been shown to improve depressive symptoms.
Regarding medication, the article provides an in-depth examination of pharmacological options. While some have shown effectiveness, they are also associated with negative side effects.
3. Huntington’s Disease and MDD
Most studies suggest the prevalence of depression in HD ranges between 15–69%. The wide variability may be due to the use of different testing tools, including:
- Beck Depression Inventory (BDI)
- Hamilton Rating Scale for Depression (HAM-D)
- Hospital Anxiety and Depression Scale (HADS)
- Unified Huntington’s Disease Rating Scale (UHDRS)
Depression is the most common psychiatric complaint in HD patients. And, studies have found that depressive symptoms may precede motor and cognitive symptoms by years, if not decades.
It has been proposed that the psychiatric symptoms of HD may affect quality of life more than the classic motor symptoms. It is also critical to note that suicide rates among individuals with HD are 4–6x higher than the general population.
Hence, it is paramount to diagnose and treat MDD early.
Treatment
MDD has been markedly undertreated in patients with HD. In fact, about half of HD patients who show depressive symptoms end up receiving no treatment.
Unfortunately, even when patients do receive treatment, there is a significant lack of evidence to guide their care path.
Regarding non-pharmacological treatment, a 2001 study showed an improved quality of life for HD patients who engaged in motivational therapy. Physical exercise and environmental enrichment have also shown promise in HD mice.
There is also a dearth of evidence with regard to medication. The article does call out one medication that is not recommended, and provides mechanistic support for some others.
Discussion
Despite years of research, there is still no effective treatment to prevent the progression of AD, PD, and HD.
Depressive symptoms are very common in patients with these diagnoses, and depression increases the overall burden of disease. Therefore, appropriate non-pharmacological and/or pharmacological treatment is essential.
The demand for new, effective interventions is further underscored by the poor effectiveness of standard antidepressant therapy to treat depression that co-occurs with these diseases. Instead, interventions used with these patients must target the specific mechanisms that contribute to their depression.
For instance, physical exercise and environmental enrichment improve neuroplasticity by increasing BDNF, a protein that contributes to neuroplasticity. These interventions have shown positive effects in patients with MDD and neurodegenerative conditions, but more studies are needed to prove their effectiveness.
Takeaways for OT practitioners
(Please note: These are my personal takeaways. They are not mentioned specifically in the article.)
1. This article went deep into the mechanisms of these diseases and their treatments. This is the future of OT.
Not gonna lie—this was a hard read.
But, it really illustrates how much we are learning about the mechanisms behind diseases and their treatments. As OTs, we must not shy away from science like this. As this article demonstrated, our treatments can have just as strong of a neurobiological impact as the medications often prescribed to these patients. And, it is up to us to have a basic understanding of the body systems we are impacting—and why different treatments are more beneficial for certain populations.
2. OTs have such an important role to play in dementia care.
This article really drove home the complexity of dementia care. And, for me, it highlighted the need for skilled OTs and systems to support their work. Non-pharmacological approaches like ours are often the best route to increasing quality of life for patients and their care partners. On that note, I’m so thankful to be joined by Rachel Wiley next week for a discussion on what this holistic care looks like in practice.
Here’s the full APA citation for this article:
Galts, C. P. C., Bettio, L. E. B., Jewett, D. C., Yang, C. C., Brocardo, P. S., Rodrigues, A. L. S., Thacker, J. S., & Gil-Mohapel, J. (2019). Depression in neurodegenerative diseases: Common mechanisms and current treatment options. Neuroscience and biobehavioral reviews, 102, 56–84.
Earn one hour of continuing education by listening to the podcast on this article!!
In this podcast episode, we dive even deeper into this topic, with OT (and Club member!), Rachel Wiley. You may be eligible for continuing education credit for listening to this podcast. Please read our course page for more details!