Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder that is associated with cognitive and memory deterioration, progressive impairment of activities of daily living, a variety of neuropsychiatric symptoms, and behavioral disturbances (Robinson). This disease is seen in about 2-4 million Americans and is usually occurs after the age of 65 years (Robinson).
According to Teri and Wagner (1992) there is growing agreement among physicians that Alzheimer’s disease is often accompanied by mood and behavior disturbances, especially depression. Depression and Alzheimer’s dementia are two separate disorders, one is disorder of affect other disorder of cognition (Terri, & Wagner 1992). Despite this, depression and dementia share a number of characteristics and frequently coexist.
Impact of Associated Depression with Alzheimer’s disease on Patients and Caregivers
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According to Terry & Wagner (1992) depression is one of the most frequent comorbid psychiatric disorders in Alzheimer's disease and other dementias and is associated with poor quality of life, a great degree of disability in activities of daily living, a faster cognitive decline, a high rate of nursing home placement and high mortality rate. AD patients with coexistent depression exhibit significantly more functional disability due to presence of depressive symptoms like: dysphoric mood, vegetative signs, social withdrawal, loss of interest, feelings of guilt and worthlessness, and suicidal ideation etc (Terry, & Wagner 1992).
According to Newcomer, Yordi, DuNah, Fox, & Wilkinson (1999) depression in the patient is often a major source of stress, burden, and depression for care providers Caregivers of people with dementia and depression have been shown to experience depression, anger, anxiety, guilt, and to report negative attitudes toward the patient and other family members All these problems in patients with AD and depression can lead to massively increased health care costs (Terry and Wagner, 1992). Assessment of the Problem Gathering data on depression in order to accurately assess the prevalence of depression amongst the patients suffering from AD is a very difficult problem due to many reasons as mentioned below: Lack of established procedures to ascertain depressive symptoms in AD: Absence of a standardized procedure for assessment of depression in patients with AD was probably the main factor which has contributed to the variable rates of depression (15%-86%) in different studies (Terri, & Wagner 1992). Different versions of the DSM III  and DSM-III-R  criteria were used in various studies which gave rise to different rates of prevalence of depression in patients with Alzheimer’s disease.
AD and depression are now often clearly defined by using well-accepted diagnostic criteria, such as the Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. , rev. (DSM-III-R); and the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA), and well-established measures pning the range of self-report and interviewer assessment (Terri, & Wagner, 1992).
Other more established measures are also been used now, including the Hamilton Depression Rating Scale (HDRS) and the Geriatric Depression Scale. Using DSM-III-R criteria, Teri, and Wagner (1991) reported prevalence of depression among AD patients in their study as 29%.. Overlap of symptoms between depression and AD: Since there can be overlap of symptoms between the two, it is difficult to attribute the symptom to a particular disorder. This overlap can often confound the diagnosis of depression (Terri, & Wagner 1992).
Existent measures can identify the presence of specific symptomatology, but they cannot clarify its cause. For e. g. : a person might be experiencing “loss of interest," Now this loss could be due to the cognitive deterioration of dementia or due to anhedonia (loss of pleasure) related to depression.. Thus it becomes very difficult to differentiate dementia from depression in some cases. The primary source from which the history of depressive symptoms is obtained:
According to a number of studies (Gilley, et al. 1996; Teri, & Wegner1991), the traditional methods of obtaining a history of depressive symptoms like a patient interview and self-reporting questionnaires might not prove accurate to assess the patient’s symptoms as the patient with Alzheimer’s disease might be suffering from significant cognitive impairment. As a result of this cognitive impairment AD patients are unable to provide accurate information about their symptoms of depression.
As an alternative to patient-report methods, the use of collateral informants (patient’s care provider) to ascertain depressive symptomatology in cognitively impaired patients has been employed nowadays. In 1991 Teri and Wegner conducted a study in AD patients to show that the reports given by the patients themselves indicated less depression than reports from either their caregivers or reports given by clinicians after clinical observation of the patient. The results of their study indicated that most of the patients suffering from AD and dementia seemed to be unaware of their depression.
Although the use of collateral informants seems to be an attractive alternative approach for the assessment of depression in AD patients, it is not without important potential limitations. Caregivers may be unavailable for many patients or the care provider may not be living with the patient (Terry &Wegner 1992). If the care provider does not stay with the patient he might not get an opportunity to routinely observe the patient and will not be able to provide accurate information. The relationship between the care provider and the patient also needs to be considered.
According to many studies (Terri, & Wegner 1992; Gilley, et al. 1995) child or spouse of the patient has been identified as the most accurate informant. Inaccurate data may be obtained if other sources of collateral informants are used. Caregivers may also provide inaccurate history as they may rely more on observable behaviors than on other sources of information because they are unable to evaluate the patient's emotional state, or conversely, caregivers may rely more on inference, using their subjective beliefs to evaluate how the patient is feeling (Teri& Wegner 1991).
In cases where the care provider is not available, it typically becomes the responsibility of the clinician to make a diagnosis of depression. However clinician’s diagnosis is based on brief periods of patient’s observation and thus might not yield accurate results (Terri & Wegner 1992).
Effect of Depression on Cognitive Deficits
Associated with AD. Pronounced episodic memory impairment is one of the cardinal manifestations of AD. Depression on its own is also related to some amount of memory loss.
Since both depression and AD have been found to result in memory deficits, it may be hypothesized that the simultaneous occurrence of both these diseases would add to the memory problems resulting from AD alone (Terry & Wagner 1992). Many neuropathological and clinical studies have attempted to determine whether the existence of one disorder predisposes an individual to the development of the other and whether the cognitive deficits seen in AD become more pronounced if the person also suffers from depression.
The results of the study performed by Fahlander, Berger & Wahlin (1999) indicated that depression does not further impair episodic memory performance in patients with AD. This result was in agreement with prior research done by Backman, Hassing, Forsell, and Viitanen (1996) who determined the comorbidity effects of AD and depression on episodic memory performance in very old persons (90-100 years of age) with and without dementia and depression. Overall, Backman, et al. found no differences between depressed patients and healthy old controls or between patients with AD and depression and those with AD alone.
Backman, et al explained this finding as follows: Symptoms of depression which are most likely to exert negative effects on memory include motivational and attention factors like lack of interest, loss of energy, concentration difficulties etc. Some amount of memory impairment is already present among AD patients as a result of similar symptoms like lack of interest, loss of energy etc associated with dementia. Therefore, a diagnosis of major depression may not cause further impairment of memory in persons suffering from AD.
Backman, et al also suggested that although depression influences memory performance in normal aging individuals, in dementia, this effect seems to be overshadowed by the neurodegenerative changes of AD itself . Backman et al reached a conclusion that since such symptoms are more likely to be part of normal aging in the ’90s compared with earlier decades, the effects of major depression on memory would be more prevalent among younger old persons(in7-8th decade of life) as compared to the oldest old(in the 9-10th decade of life).
Tests for Differentiating Alzheimer’s disease and Depression
The utility of the Fuld profile in the differentiation of AD and depression: Bornstein, Termeer, Longbrake, Heger, & North (1989) have examined the incidence of the Fuld profile in a sample of patients diagnosed to be suffering from major depression. Fuld’s profile refers to a pattern of performance on the Wechsler Adult Intelligence Scale-Revised (WAIS-R) that appears to be associated with cholinergic deficits and thus is found to be associated with Alzheimer's disease (Bornstein, et al).
Since a large number of patients with AD have been seen to show negative profiles, a negative profile does not prove that AD is not present. Bornstein, et al. have suggested that one should not rely on the results obtained from the Fuld profile to make a diagnosis of AD. A diagnosis of AD should be made only after a thorough medical and neurological history and a complete neuropsychological examination. According to Bornstein, et al this profile was significantly less frequent in the depressed patients as compared to that reported in previous studies in Alzheimer's disease patients.
The study by Bornstein, et al does provide some support regarding the diagnostic specificity of the Fuld profile in the diagnosis of depression. Although this study and previous data are encouraging, considerable further investigation is needed to document the specificity and diagnostic contribution of this profile for diagnosis of depression. Measurement of a potential biological marker in the CSF: Increased CSF concentrations of a phosphorylated brain protein called tau protein, has been seen in patients with Alzheimer’s disease. Phosphorylated tau protein (tau) has been suggested as a biomarker for Alzheimer's disease.
Since the levels of this protein are not elevated in patients with depression, measurement of this biological marker in cerebrospinal fluid (CSF) can diagnose patients with AD and thus help in differentiating them from those suffering from depression. (Vernon 2003).
Treatment of Depression in Alzheimer’s Disease Patient
Treatment of Alzheimer's disease has proved to be quite difficult. The disease is progressive and the use of drugs (like cholinesterase inhibitors) just helps in bringing about a little improvement (20-30%) in cognitive symptoms (Zepf 2005).
However, the drugs used for improving cognitive functions have no effect on depressive symptoms. Treatment of depression must form an important part of the overall treatment of this disease. This is so as treatment of depression in patients with Alzheimer's disease can have a significant impact on the well-being of these patients as well as their caregivers [Lyketsos, et al. 2003 (as cited in Miller 2004)]. Continuing research is taking place in order to treat depression in AD patients. Many drugs have been tried to treat depression among patients with AD.
Drugs like tricyclic antidepressants often used in cases of depression without AD are usually avoided in patients with AD, owing to their anticholinergic properties (Zepf, 2005). Lyketsos et al, 2003 (as cited in Miller 2004) showed the drug sertraline (selective serotonin uptake inhibitor) to be much superior as compared to placebo in treatment of depression in patients with AD. According to USA Today (Society for the advancement of education), the drug sertraline (Zoloft) significantly improves the quality of life and prevents disruption in daily activities for patients with Alzheimer's disease with depression.
Use of this drug has been shown to lessen the behavioral disturbances and improve the activities of daily living but has no effect on patients' cognitive abilities, such as thinking, remembering and learning.
Despite the great deal of research which has recently taken place in the field of Alzheimer’s disease with depression, more research is still required in this field as the physicians are still are not clear about the pathophysiology of AD or about the exact prevalence of depression in patients of AD or it’s etiology.
The questions of whether depression and dementia are similar or different, whether one leads to the other or whether their coexistence has any etiological significance are far from resolved. The complete knowledge and understanding in this field will help the physicians in developing effective treatment strategies for the care of such patients. Once the psychologists are able to understand the risk factors for coexistent depression in dementia and find its effective cure, they would be able to significantly improve the quality of life of the patients as well as their care providers and greatly reduce the health care costs.
Several questions regarding the management of depression in AD still need to be answered. The comparative efficacy of anti-depressants from various classes still needs to be explored by performing larger clinical trials. The role of non-pharmacological methods for the treatment of depression also needs to be explored. Further research and studies are required in the future to address these topics. The number of studies at present is quite small and the need for further investigation in the future persists.
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