Depression and Alzheimer’s Disease Term Paper

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Updated: Mar 9th, 2024

Introduction

Alzheimer’s disease is often referred to as the “disease of the century” and is found to afflict approximately 4 million Americans, mostly those over the age of 65. It is the harshest of all incurable diseases because it hits its victim twice. First, the mind dies, slowly and irrevocably, until even the simplest tasks become insurmountable. Then, after many years, the body dies. Alzheimer’s disease is even more devastating for the families and caregivers of its victims.

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It is identified as “dementia of the Alzheimer’s type” in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (Handy et al, 1998). The disease is the outcome of mental deterioration occurring especially in later life and is an irreversible condition. Major characteristics include short- and long-term memory loss, impaired judgment, slovenly appearance, and poor hygiene. Depression is a mental health disorder that can affect the way a person eats, sleeps, the way he feels about himself and the way he thinks about things. It describes both a mood and a syndrome. Studies show that people afflicted with Alzheimer’s disease often suffer from depression as well.

The objective of the paper is to analyze the link between Alzheimer’s disease and depression.

Survey of literature

Lyketsos and Lee (2004) point to the fact that over 80% of patients with Alzheimer’s disease (AD) develop ‘non-cognitive’ neuropsychiatric symptoms at some point during the course of their illness and depression is among the most frequent of such comorbidities. According to Lyketsos, depression affects 50% of AD patients and has severe negative consequences for patients and caregivers. Lyketsos and Lee also add that depression in AD patients can be detected and quantified reliably, and can be differentiated from the other neuropsychiatric symptoms of AD. It can also be treated in several ways.

Moretti et al (2002) have studied the relationship between depression and Alzheimer’s disease and explored whether depression is a symptom of AD or comorbidity. Alzheimer’s disease is a commonly occurring form of dementia which is characterized by disruptive behavioral and cognitive systems. Depression, apathy, anxiety, and other conduct disorders are the complaints most often reported in the case of patients with AD.

In this study, Moretti et al gave inhibitors of cholinesterase (Donepezil, 5 mg/ day) alone, or inhibitors of cholinesterase plus selective seratonin reuptake inhibitors (SSRIs) (citalopram HBr, 20 mg/day) to fifty subjects with a diagnosis of probable AD. Results over a period of time indicated that SSRI intake seems to be effective for depression, decreasing it and improving quality of life for both patients with AD and their caregivers clearly indicating the depression is a co-morbidity with AD that can be treated as a symptom.

Meltzer et al (1998) begin with an analysis of major depression in late life and Alzheimer’s disease. They cite various studies indicating that depression often affects AD patients and higher rates of depression happen among institutionalized aged persons. The researchers, in order to examine the relationship between depression and dementia of AD have used vivo functional imaging of the 5-HT neurotransmitter system with positron emission tomography (PET).

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Extensive evidence implicates a deficit in serotonergic neurotransmission in the development of major depression. It has been further suggested that the age related changes in 5-HT neurons may predispose the elderly to develop depression. There is also increasing evidence that a combination of disturbances in cholinergic and serotonergic function may play a role in cognitive impairment in Alzheimer’s disease (AD), with serotonergic dysfunction potentially responsible for causing depression.

Major depression is generally characterized by deficits in various cognitive domains and key symptoms of major depression are normally present in patients with mild to moderate Alzheimer’s disease and these overlapping conditions include depressed mood, apathy, social restraint, or loss of interests. Apathy has been detectable in 37% of Alzheimer’s disease patients as well as in 32% of depressed non-demented patients.

Buerger et al (2003) have focused on differentiation of geriatric major depression from Alzheimer’s disease despite overlapping symptoms. Increased CSF concentrations of tau protein phosphorylated at threonine 231 (p-tau231) has been used as a biomarker for Alzheimer’s disease and p-tau231 levels were analyzed to mark differences between geriatric major depression and Alzheimer’s disease. It was found that P-tau231 levels were significantly higher in Alzheimer’s disease than in geriatric major depression patients and healthy comparison subjects.

In their study on treating depression in Alzheimer disease Lyketsos et al (2003) have assessed the efficacy and safety of sertraline hydrochloride for the treatment of major depression in Alzheimer disease, and have evaluated the effect of depression reduction on daily activities.

Forty-four outpatients with probable Alzheimer disease and major depressive episodes participated in this study and intervention Sertraline hydrochloride, mean dosage of 95 mg/d, and an identical placebo were randomly assigned. It was found that in the sertraline-treated group 9 patients (38%) were full responders and 11 (46%) were partial responders compared with 3 (20%) and 4 (15%), respectively, in the placebo-treated group (P =.007). It is concluded that Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease. It was also found that depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living, but not improved cognition.

In the article titled “Depression in Alzheimer’s disease: is there a temporal relationship between the onset of depression and the onset of dementia?” Heun et al (2002) have investigated the reasons for the comorbidity of major depression and Alzheimer’s disease. It was explored whether major depression was a risk factor for AD or whether both disorders have a common neurobiology. Temporal relationship between the first onset of Alzheimer’s disease and major depression was investigated. There was no significant correlation between the onset of AD and of major depression.

However, the incidence of major depression 5 years before and after the onset of AD was significantly higher implying that there may be a common neurobiological process that causes cognitive decline and depression in a subsample of AD patients (Heun et al, 2002).

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Theoretical background of the topic- according to different points of views

First described by Alois Alzheimer in 1906, Alzheimer’s disease (pronounced ALTS-hi-merz) is a fatal, progressive, degenerative condition. It attacks the brain, resulting in impaired memory, cognition, and behavior, and it is the most common form of dementia (Thies, 2004). Depression or depressive symptoms are common in Alzheimer’s disease. But the difficulties of making the diagnosis of depression are suggested by the wide variation in rates of prevalence.

From 0 to 86 percent of people with Alzheimer’s suffer depression or manifest some of its symptoms (Migliorelli et al., 1995). Major depression in late life and Alzheimer’s disease (AD) are disorders of enormous and increasing public health significance. Depression, as we understand it, is more frequently observed during the early to middle stages of AD, but it can develop in the later stages. Depression and Alzheimer’s may be linked in some other ways. Some researchers believe severe depression may cause damage that makes the brain more vulnerable to a disease process such as Alzheimer’s (Gruetzner, 2001).

Others believe that damage associated with Alzheimer’s makes the brain more susceptible to depression. Some depressive signs such as loss of interest in daily activities and apathy have been identified as early indications of AD. These do not occur as psychological reactions to cognitive impairment because the cognitive impairment is not yet very evident. They are the result of behavioral and affective changes associated with changing chemical and physical properties of the brain (Gruetzner, 2001).

Persons with dementia of AD, particularly early onset, can experience a great sense of loss of themselves and the life they had envisioned. The activities that had supported their sense of self as spouse, parent, and employee are threatened. These circumstances can precipitate depression. Thus depression related to AD can also be a result of psychosocial changes; it can also be related to changes in brain chemistry created by brain damage.

When it occurs early in the disease process, AD depression looks much like non-AD depression. There may be several types of depression affecting people with AD. Some precede signs of dementia. Others develop after symptoms of dementia have been identified.

When suffering from depression, people with Alzheimer’s disease are known to be more distressed and agitated and to have greater problems with functioning and performing activities of daily living. Family members experience more stress and burden because of the increased dysfunction and mood-related disturbances experienced by their loved ones. Identifying depression with AD is more difficult because depressive symptoms are often transitory, or less severe and pervasive, than those seen in major depressive disorders. Depression and Alzheimer’s share symptoms, and some symptoms of depression may actually represent early signs of AD (Gruetzner, 2001).

It has been found that people who are aware of dementia symptoms and understand what it means to have Alzheimer’s might have a greater risk of becoming depressed at an early stage of dementia and people with AD who have less severe cognitive impairment or more severe functional impairment have a higher risk of becoming depressed (Payne, 1998). Depression and Alzheimer’s may be linked in some other ways.

Some researchers believe severe depression may cause damage that makes the brain more vulnerable to a disease process such as Alzheimer’s. Others believe that damage associated with Alzheimer’s makes the brain more susceptible to depression. Some depressive signs such as loss of interest in daily activities and apathy have been identified as early indications of AD (Gruetzner, 2001). These do not occur as psychological reactions to cognitive impairment because the cognitive impairment is not yet very evident. They are the result of behavioral and affective changes associated with changing chemical and physical properties of the brain.

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Recent research has determined that depressive symptoms may develop as long as 3 years before some people are diagnosed with Alzheimer’s disease (Visser, 2000). While some depression is mild and has transitory symptoms, depressive disorders found with Alzheimer’s disease can be severe. One can conclude several things about depression with Alzheimer’s disease: it is common, has multiple causes, and occurs at different points in the disease process. The severity of symptoms varies and the presentation of symptoms may depend on the stage during which depression develops. Differences in onset and symptom presentation may actually characterize different types of depression.

Depression and Alzheimer’s share some symptoms, which can be an obstacle in identifying AD with coexisting depression. Poor concentration may create problems with memory that resemble the impairment characteristic of Alzheimer’s; the apathy of Alzheimer’s resembles the loss of interest or desire common with depression. Nevertheless, major depression affects from 30 to 50 percent of the individuals who develop Alzheimer’s (Backman et al., 1996). Some persons with Alzheimer’s have a higher risk for depression. A personal or family history of depression increases the risk of developing depression with Alzheimer’s. Women with AD have a greater risk for depression. The presence of delusions and early-onset dementia increase the risk for depression (Gruetzner, 2001).

Some depressive symptoms resemble symptoms of Alzheimer’s disease more than others do. These are called passive symptoms. They include apathy, social withdrawal, and lower level of activity. Loss of interest and spontaneity, slowed gait and motor responses, limited emotional expressions, and a decrease in talking are examples of other passive symptoms shared by depression and dementia. Passive symptoms due to dementia tend to increase as the severity of the disease progresses. When Alzheimer’s is more advanced and passive symptoms are predominant, recognizing depression is even more difficult (Gruetzner, 2001).

Alzheimer’s with depression has many different faces. Some depressive episodes that occur for the first time in later life are suspected of being precursors of Alzheimer’s. It is possible that certain presentations of depression seen with Alzheimer’s may represent a subtype of Alzheimer’s (Gruetzner, 2001). Depressive symptoms may appear before symptoms of dementia because of specific areas of structural damage to the brain and neurochemical changes that have been activated by the disease process.

Signs and symptoms of dementia become evident later in the disease progression. Having the first episode of depression late in life may be an early sign of AD, especially when significant cognitive impairment characterizes the depression. Depression can be treated successfully when it coexists with Alzheimer’s. Memory problems related to depression abate with improvement in depressive symptoms.

Studies show that major depression afflicts 17-31% of patients with dementia and depressive symptoms occur in 50% of patients with dementia (Wragg and Jeste, 1989). The prevalence rates for depression in Alzheimer’s disease (17-29%) and vascular dementia (19-27%) are about equal (Fisher et al., 1990). Patients with dementia who develop concurrent depression tend to have a genetic vulnerability to depression. The depression is often characterized by self-pity, rejection sensitivity, and anhedonia. A depressed mood has been associated with a subsequent threefold increase in dementia risk (Devanand et al., 1996).

Identifying depression with AD is more difficult because depressive symptoms are often transitory, or less severe and pervasive, than those seen in major depressive disorders. Depression and Alzheimer’s share symptoms, and some symptoms of depression may actually represent early signs of AD. People who are aware of dementia symptoms and understand what it means to have Alzheimer’s disease might have a greater risk of becoming depressed at an early stage of dementia. This psychological reaction to loss does not, however, explain the fact that depression occurs in people who not only have little awareness of dementia symptoms but who have more severely advanced dementia (Devanand, 1996).

Some problems attributed to dementia may be caused by depression. Depressed people with Alzheimer’s are more likely to be agitated and have behavioral problems that are more difficult to manage. They are more likely to suffer delusions. They are prone to exhibit greater impairment in dressing, grooming, eating, bathing, and other activities of daily living. Persons with depression and AD may exhibit more cognitive impairment. Depression may be difficult to identify with Alzheimer’s, but unlike Alzheimer’s disease, it can be treated.

Recognizing and treating depression creates significant benefits for persons with AD and their caregivers. It reduces their distress and suffering. In some instances, depression may herald the arrival of Alzheimer’s. Depressive symptoms may be seen when cognitive impairment is not yet severe enough to meet the criteria for dementia. Depressive symptoms may represent a prodromal stage of AD—that is, signs that appear before the symptoms of the disease can be recognized. Early recognition and treatment of AD and depression are important.

Depression with Alzheimer’s is usually responsive to antidepressant medication. Newer antidepressants are called new-generation antidepressants and include several different classifications. The most familiar class is known as selective serotonin reuptake inhibitors, or SSRIs. Zoloft, Prozac, Paxil, Celexa, and Luvox are the trade names of current SSRIs. They work by selectively preventing nerve cells from eliminating the neurotransmitter serotonin. Other new-generation antidepressants include Effexor, Wellbutrin, Remeron, and Serzone (Gruetzner, 2001). These antidepressants act on chemical changes in neurotransmitters thought to be involved in depression.

Conclusion

Depression and Alzheimer’s disease have been found to be linked both at the psychological and at the physiological levels. There are many reasons why depression occurs in people with AD. Some people who develop Alzheimer’s may be more genetically vulnerable to depression. Some have had previous episodes of depression or have continued to suffer chronic depression. Some cases of Alzheimer’s actually appear to begin as depression. It is only later that symptoms of a dementia are recognized. AD causes brain damage that result in a loss of neurons and neurotransmitters. A greater loss of neurons in some parts of the brain predisposes some individuals with AD to depression. Realizing the causes of depression in patients with Alzheimer’s disease can lead to better treatment of the depression.

Bibliography

Backman, L., et al (1996). Episodic Remembering in a Population-Based Sample of Nonagenarians: Does Major Depression Exacerbate the Memory Deficits Seen in Alzheimer’s Disease? Psychology and Aging. Volume 11. 1996. 649–657.

Buerger, Katharina; Zinkowski, Raymond; Stefan J. Teipel; Hiroyuki Arai; John DeBernardis; Daniel Kerkman; Cheryl McCulloch; Frank Padberg; Frank Faltraco; Alexander Goernitz; Tero Tapiola; Stanley I. Rapoport; Tuula Pirttilä; Hans-Jürgen Möller and Harald Hampel (2003). Differentiation of Geriatric Major Depression From Alzheimer’s Disease With CSF Tau Protein Phosphorylated at Threonine 23. American Journal of Psychiatry. Volume 160, Issue 2. 376-379.

Devanand D, Sano M, Tang M-X, Taylor S, Gurland B, Wilder D, Stern Y, Mayneux R (1996). Depressed mood and the incidence of Alzheimer’s disease in the elderly living in the community. Arch General Psychiatry. Volume 53. 175– 182.

Fisher P, Simanyi M and Danielczyk W (1990): Depression in dementia of the Alzheimer type and in multi-infarct dementia. American Journal of Psychiatry. Volume 147. 1484–1487.

Gruetzner, Howard (2001). Alzheimer’s: A Caregiver’s Guide and Sourcebook. Wiley Publishers. New York.

Heun, Reinhard; Kockler, Martin and Ptok, Ursula (2002). Depression in Alzheimer’s disease: is there a temporal relationship between the onset of depression and the onset of dementia? European Psychiatry. Volume 17, Issue 5.

Lyketsos, G. Constantine and Lee, B. Hochang (2004). Diagnosis and Treatment of Depression in Alzheimer’s Disease. Dementia Geriatric Cognitive Disorders. Volume 17. 55-64.

Lyketsos, G. Constantine; DelCampo, Lourdes; Steinberg, Martin; Miles, Quincy; Steele, D. Cynthia; Munro, Cynthia; Baker, S. Alva; Sheppard, e. Jeannie-Marie; Frangakis, Constantine; Brant, Jason and Rabins, V. Peter (2003). Treating Depression in Alzheimer Disease – Efficacy and Safety of Sertraline Therapy, and the Benefits of Depression Reduction: The DIADS. General Psychiatry. Vol. 60 No. 7.

Meltzer, Carolyn Cidis; Gwenn Smith; Steven T. DeKosky; Bruce G. Pollock; Chester A. Mathis; Robert Y. Moore; David J. Kupfer and Charles F. Reynolds (1998). Serotonin in Aging, Late-Life Depression, and Alzheimer’s Disease: The Emerging Role of Functional Imaging. Neuropsychopharmacology. Vol. 19, Issue 6.

Migliorelli, R., et al (1995). Prevalence and Correlates of Dysthymia and Major Depression Among Patients with Alzheimer’s Disease. American Journal of Psychiatry. Volume 152.

Moretti, Rita; Tore, Paola; Antonella, M. Rodolfo and Cazzato, Giuseppe (2002). Depression and Alzheimer’s disease: Symptom or comorbidity? American Journal of Alzheimer’s Disease and Other Dementias®, Vol. 17, No. 6, 338-344.

Payne, J. L., et al (1998). Relationship of Cognitive and Functional Impairment to Depressive Features in Alzheimer’s Disease and Other Dementias. Journal of Neuropsychiatry and Clinical Neurosciences. Volume 10, Fall 1998. 440–447.

Thies, William (2004). The Devastating Toll of Alzheimer’s Disease on Patients and Caregivers: “The Impact of the Disease Extends Well beyond Those Who Have It… at Least 70% of Those Stricken Live at Home, Where Their Families Provide 75% of the Needed Care”. USA Today. Volume: 132. Issue: 2704. Page Number: 56+.

Visser, P. J., et al (2000). Distinction Between Preclinical Alzheimer’s Disease and Depression.Journal of the American Geriatric Society. Volume 48. 467–605.

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