1
Journal of Alzheimer’s Disease xx (20xx) x–xx DOI 10.3233/JAD-140324 IOS Press
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Review
Depression in Alzheimer’s Disease: Epidemiology, Mechanisms, and Management
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Song Chia,b , Jin-Tai Yub,∗ , Meng-Shan Tanc and Lan Tanb,c,∗
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a Department
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b Department
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of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, China c Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, China
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Accepted 21 April 2014
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Keywords: Alzheimer’s disease, depression, epidemiology, mechanism, therapy
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INTRODUCTION
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Abstract. Depression occurs with a high prevalence of up to 50% in patients with Alzheimer’s disease (AD) and increases the caregivers’ burden. Depression symptoms can precede clinical diagnosis of AD for years or occurs around the onset of AD, although the etiology and pathologic mechanism of depression in AD pathogenesis remain unclear. Here, we provide an overview on recent studies, indicating that genetic factors, neuroanatomic changes, vascular risk factors, and the imbalance of neurotransmitters might contribute to depressive symptoms in AD. Tau pathology and amyloid- accumulation also correlate with depression in AD. In addition, the alteration of hypothalamic-pituitary-adrenal axis, inflammatory pathway, and neurotrophin deficiency are the possible biological mechanisms linking depression and AD, and might become the potential targets for AD treatment. Current data support that antidepressants are promising to alleviate the symptom, though the efficacy is controversial. Moreover, antidementia medication and non-pharmacological interventions can be potential choices. In this review, we describe the prevalence and clinical course of depression in AD, analyze the underlying mechanisms, and discuss the possible management strategies for depression in patients with AD.
10
Alzheimer’s disease (AD) is a major neurodegenerative problem characterized by progressive deterioration in multiple cognitive areas. In spite of the hallmark of gradual cognitive decline, AD patients can also suffer from a wide range of psychiatric and behavioral problems, among which depression is one of the critically important issues. The prevalence of depression can amount to as high as 50% in individuals ∗ Correspondence
to: Lan Tan and Jin-Tai Yu, Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao 266071, PR China. Tel.: +86 532 8890 5659; Fax: +86 532 85968434; Emails: [email protected] (L. Tan) or [email protected] (J.T. Yu).
with AD [1–3], which is associated with great social, medical, and economic burden [4]. Some findings in the neurodegenerative process of AD have been suggested to contribute to depression as well. Small hippocampus volumes, the macroscopic alterations in AD, were confirmed in patients with major depressive disorders [5]. Similar association was also found at the microscopic level, with the changes in amyloid metabolism suggested to be affected in depression [6, 7]. However, it is still controversial whether depression acts as a risk factor or a prodromal of AD, and what the underlying mechanism is for depression in AD. Given the high prevalence and poorly understood association, a better understanding of depression in AD is therefore
ISSN 1387-2877/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
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EPIDEMIOLOGY Prevalence of depression in AD It was found that about half of AD patients suffer from a depressive episode at least once during the clinical course [8, 9]. However, the prevalence varies greatly in different investigations, depending on the diversity in research methodology, diagnostic criteria for depression, and patient samples. For example, studies using specific diagnostic criteria for depression in AD such as Olin’s criteria [10] suggested high depressive prevalence of around 50% [1, 2, 11], while those using categorical diagnostic criteria such as the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the International Classification of Diseases (ICD-10) indicated comparatively lower prevalence of around 10%–40% [1, 11]. The most probable reason is that the diagnostic criteria of the latter are astrictive and more symptoms are required to be fulfilled. It is noteworthy that complicated factors exist in the diagnosis of depression in AD [12]. Patients with AD appear to have less common core symptoms of depression like sadness, sleep disturbances, and appetite loss [10, 13]. On the other hand, symptoms such as loss of interest are also evident in AD patients without significant depressive symptoms. Therefore, the diagnostic criteria of idiopathic depression are not entirely appropriate for depression in AD. The prevalence of depression seems to be closely correlated with different stages of depression and AD. Structured interview of individuals with AD and their caregivers showed that the prevalence of minor depression was from 20% to 30%, while that of major depression was comparatively lower from 20% to 25% [9, 14]. Nevertheless, the value was much lower in another two studies based on 481 and 2,947 AD patients, respectively, with the prevalence of major
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depression in AD being only 3.2% to 5.1% and that of minor depression being 2% [15, 16]. Regardless of the discrepancy in prevalence, in these studies, patients with minor depression had a comparatively higher prevalence than those of major depression, but both minor and major depression were correlated with significant functional impairment [9]. Similarly, the prevalence of depression was much higher in moderate and advanced stage of AD than those in mild stage [17], and the prevalence tended to increase with the progression of cognitive decline longitudinally [18]. However, the results were inconclusive in other studies [19, 20]. A systematic review based on 24 studies provided more information and found no such association, either with respect to the symptoms or with categorical diagnosis [21]. It is known that cognitive impairment in AD patients can limit their ability to report depressive symptoms to clinicians, whereas caregivers often overreport depressive symptoms in the patient. Therefore, complicated factors are involved in the assessment of depression and its prevalence in AD. It is noteworthy that depression and apathy are the most prevalent neuropsychiatric symptoms in AD. Differentiating apathy from depression in AD is sometimes difficult because of the overlapping features and high morbidities. However, apathy is a symptom to some extent distinct from depression in AD both clinically and pathophysiologically [22, 23]. The dysphoric symptoms such as sadness, guilt feelings, self-criticism, helplessness, and hopelessness are typically present in depression but absent in apathy, which is characterized by a lack of emotional responsiveness and diminished motivation [22, 23]. Compared with depression, the neuropathological changes of apathy in AD are more in the anterior cingulate frontal–subcortical circuit and cholinergic deficiency contribute to the neurobiological process, while those of depression are more in the frontal-striatal and subcortical limbic circuits and serotoninergic deficiency, or an imbalance between dopamine and norepinepherine plays the role [22, 23]. Therefore, a careful differentiation of the two symptoms would be helpful to the further management.
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of great importance both for optimal treatment and prevention. In the present review, we conducted a comprehensive search for potentially relevant studies in the electronic bibliographic databases of PubMed and EMBASE with terms ‘(depression or depress*) AND (Alzheim* OR dement*)’. Then we elucidated depression in AD from the perspective of epidemiology, and mainly focused on the evidence of whether depression is a risk factor for AD. At the same time, we discussed the potential mechanism underlying the depressive symptom in AD, and gave special attention to the current possible treatments.
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Un
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S. Chi et al. / Depression in Alzheimer’s Disease
uth
2
Incidence and clinical course of depression in AD Few studies have investigated the incidence and clinical course of depression in AD longitudinally. The incidence of depression or depressive symptoms in AD varied greatly in different studies [24–26], from no more than 2% per year [27, 28] to around 20% per year [29–31] depending greatly on the study meth-
95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137
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S. Chi et al. / Depression in Alzheimer’s Disease
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Depression and risk of AD development
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a 2-year follow-up indicated that baseline depressed affection predicted all-type dementia, though the association was less strong of AD compared with that of vascular dementia [38]. Another two studies claimed that only severe depression or those higher educated depressed individuals were prone to develop AD 4 years later [39, 40]. Nonetheless, in a study with 3-year follow-up, no such significant association was found [41]. Of interest, the peak incidence of major depression was reported to occur 5 years around the onset of AD [26]. Thus, in that condition, depression was more of a symptom during the neurodegenerative process of AD. It has been considered that late-onset depression might be a prodromal condition of AD due to short time lag between the onsets. A recent meta-analysis, which included 23 community-based prospective cohort studies, concluded that late-life depression significantly increased the risk of AD incidence for 1.65 fold, even after controlling all possible cofounders [42]. The result was consistent with the pooled findings of almost 2-fold increased risk in another meta-analysis, which was constituted mostly by case–control studies. However, those with mid-life depression were also included in these studies [37]. More evidence was obtained from a recent published study, in which significant association only occurred in those within 75 years cut-off. The association became even more notable when combined with current depressive symptom [43]. Therefore, only when late-onset depression is proximal to dementia diagnosis and simultaneously without clinical remission, it might be elucidated as a preclinical manifestation of AD.
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ods such as the study duration and evaluation tools (Table 1). In general, most procedures were no more than 2 years, and the DSM criteria was most often used for AD diagnosis. There is little agreement on the natural course of depression in AD because of the fluctuation of depressive symptoms over time and heterogeneity in research methodology [12] (Table 2). Data from the Chicago Health and Aging Project showed that depressive symptoms barely changed during an average course of 2–3 years in patients after the diagnosis of AD, both via informant report or self-report of depression [32, 33]. Of note, in the two studies, it was the depression score but not the prevalence that was compared. Similarly, in an early study, AD patients from a multicenter were enrolled and followed up for 3 years at 6-month intervals, during which depressed mood was persistent with a moderate prevalence of around 25% [34]. However, other studies found that depression tends to be persistent over the first few months, and remit over time [19, 24, 31, 35]. In a study with a large sample size, patients with probable AD were followed every 6 months for up to 14 years. The prevalence of depressive symptoms was stable over the first 3 years of follow-up but significantly dropped in the fourth and fifth years [20]. It seems that depression occurred at certain stages of dementia and decreased toward the terminal stages [36]. Nevertheless, the decrease of depressive symptoms in the follow-up period cannot be explained totally by cognitive decline and impaired functional ability. A systematic review based on 24 studies failed to find association between the severity of AD and the prevalence of comorbid depressive symptoms or diagnosed depression [21]. Therefore, more long-term studies are needed to identify the clinic course of depression in patients with AD.
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The issue of whether depression is an AD-associated prodromal condition or a risk factor is controversial. One important issue in understanding the association is the interval between the onset of depression and AD. As a matter of fact, if there was a long time lag between the onsets, depression was usually considered more of a risk factor than a prodromal condition [37]. In the past decade, most studies that focused on the issue were prospectively designed with a follow-up period of around 5 years, and only a few studies lasted for more than 10 years. Few studies explored the association with a short follow-up period less than 5 years and arrived at conflicting conclusions. A recent study with
195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227
POTENTIAL MECHANISMS
228
Neuroanatomic changes
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Neurodegeneration in the frontal-limbic circuits or frontal-subcortical circuits has been proven critical for the pathogenesis of idopathogenic depression. Similarly, the structural and functional changes in brains of AD patients have also been investigated by means of magnetic resonance imaging, single photon emission computed tomography (SPECT), and positron emission tomography (PET). A disruption of cerebral frontal-subcortical pathways, due to either volumetric changes in prefrontal gray [44, 45] or subcortical changes such as white matter hyperintensities [46] and lacunas in the basal ganglia [47], has been proposed to contribute to depression in AD patients in most structural studies. Moreover, a greater number
230 231 232 233 234 235 236 237 238 239 240 241 242 243
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Study
Design and years of follow up
Characteristic of study participants
[23]
Perspective, every 6 month for 2 years Perspective, every 6 month for 4 years Perspective, every 6 month for 1 year Retrospective, 5 years Perspective, every 6 month for 3 years Perspective, for mean 3.5 years Perspective, every 3 month for 1 year Perspective, 3 years and 2 years
98 young-onset AD; 123 late-onset AD 312 cases
[28] [22] [24] [26] [29] [27] [25]
No data 146 cases 389 and 586 cases
Measure of depression
Measure of AD
Newly identified depression (%)
NPI
DSM-IV, Text Revision
NPI
DSM-IV and NINCDS/ADRDA; mild to moderate AD NINCDS/ADRDA
Young-onset: 28.8%/2 year; Late-onset: 48.6/2 year 17.45%/ per year 6 month: 1.8%; 12 month: 6.4%
ICD-10 NINCDS/ADRDA
2.46% per year
Journal of Alzheimer’s Disease xx (20xx) x–xx DOI 10.3233/JAD-140324 IOS Press
3
4
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2
Review
Depression in Alzheimer’s Disease: Epidemiology, Mechanisms, and Management
5
Song Chia,b , Jin-Tai Yub,∗ , Meng-Shan Tanc and Lan Tanb,c,∗
6
a Department
7
b Department
uth
9
of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, China c Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, China
dA
8
or P
1
Accepted 21 April 2014
21
Keywords: Alzheimer’s disease, depression, epidemiology, mechanism, therapy
22
INTRODUCTION
14 15 16 17 18 19
23 24 25 26 27 28 29 30
rre
13
co
12
Un
11
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20
Abstract. Depression occurs with a high prevalence of up to 50% in patients with Alzheimer’s disease (AD) and increases the caregivers’ burden. Depression symptoms can precede clinical diagnosis of AD for years or occurs around the onset of AD, although the etiology and pathologic mechanism of depression in AD pathogenesis remain unclear. Here, we provide an overview on recent studies, indicating that genetic factors, neuroanatomic changes, vascular risk factors, and the imbalance of neurotransmitters might contribute to depressive symptoms in AD. Tau pathology and amyloid- accumulation also correlate with depression in AD. In addition, the alteration of hypothalamic-pituitary-adrenal axis, inflammatory pathway, and neurotrophin deficiency are the possible biological mechanisms linking depression and AD, and might become the potential targets for AD treatment. Current data support that antidepressants are promising to alleviate the symptom, though the efficacy is controversial. Moreover, antidementia medication and non-pharmacological interventions can be potential choices. In this review, we describe the prevalence and clinical course of depression in AD, analyze the underlying mechanisms, and discuss the possible management strategies for depression in patients with AD.
10
Alzheimer’s disease (AD) is a major neurodegenerative problem characterized by progressive deterioration in multiple cognitive areas. In spite of the hallmark of gradual cognitive decline, AD patients can also suffer from a wide range of psychiatric and behavioral problems, among which depression is one of the critically important issues. The prevalence of depression can amount to as high as 50% in individuals ∗ Correspondence
to: Lan Tan and Jin-Tai Yu, Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao 266071, PR China. Tel.: +86 532 8890 5659; Fax: +86 532 85968434; Emails: [email protected] (L. Tan) or [email protected] (J.T. Yu).
with AD [1–3], which is associated with great social, medical, and economic burden [4]. Some findings in the neurodegenerative process of AD have been suggested to contribute to depression as well. Small hippocampus volumes, the macroscopic alterations in AD, were confirmed in patients with major depressive disorders [5]. Similar association was also found at the microscopic level, with the changes in amyloid metabolism suggested to be affected in depression [6, 7]. However, it is still controversial whether depression acts as a risk factor or a prodromal of AD, and what the underlying mechanism is for depression in AD. Given the high prevalence and poorly understood association, a better understanding of depression in AD is therefore
ISSN 1387-2877/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
31 32 33 34 35 36 37 38 39 40 41 42 43 44 45
53 54 55 56 57 58
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61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94
EPIDEMIOLOGY Prevalence of depression in AD It was found that about half of AD patients suffer from a depressive episode at least once during the clinical course [8, 9]. However, the prevalence varies greatly in different investigations, depending on the diversity in research methodology, diagnostic criteria for depression, and patient samples. For example, studies using specific diagnostic criteria for depression in AD such as Olin’s criteria [10] suggested high depressive prevalence of around 50% [1, 2, 11], while those using categorical diagnostic criteria such as the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the International Classification of Diseases (ICD-10) indicated comparatively lower prevalence of around 10%–40% [1, 11]. The most probable reason is that the diagnostic criteria of the latter are astrictive and more symptoms are required to be fulfilled. It is noteworthy that complicated factors exist in the diagnosis of depression in AD [12]. Patients with AD appear to have less common core symptoms of depression like sadness, sleep disturbances, and appetite loss [10, 13]. On the other hand, symptoms such as loss of interest are also evident in AD patients without significant depressive symptoms. Therefore, the diagnostic criteria of idiopathic depression are not entirely appropriate for depression in AD. The prevalence of depression seems to be closely correlated with different stages of depression and AD. Structured interview of individuals with AD and their caregivers showed that the prevalence of minor depression was from 20% to 30%, while that of major depression was comparatively lower from 20% to 25% [9, 14]. Nevertheless, the value was much lower in another two studies based on 481 and 2,947 AD patients, respectively, with the prevalence of major
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depression in AD being only 3.2% to 5.1% and that of minor depression being 2% [15, 16]. Regardless of the discrepancy in prevalence, in these studies, patients with minor depression had a comparatively higher prevalence than those of major depression, but both minor and major depression were correlated with significant functional impairment [9]. Similarly, the prevalence of depression was much higher in moderate and advanced stage of AD than those in mild stage [17], and the prevalence tended to increase with the progression of cognitive decline longitudinally [18]. However, the results were inconclusive in other studies [19, 20]. A systematic review based on 24 studies provided more information and found no such association, either with respect to the symptoms or with categorical diagnosis [21]. It is known that cognitive impairment in AD patients can limit their ability to report depressive symptoms to clinicians, whereas caregivers often overreport depressive symptoms in the patient. Therefore, complicated factors are involved in the assessment of depression and its prevalence in AD. It is noteworthy that depression and apathy are the most prevalent neuropsychiatric symptoms in AD. Differentiating apathy from depression in AD is sometimes difficult because of the overlapping features and high morbidities. However, apathy is a symptom to some extent distinct from depression in AD both clinically and pathophysiologically [22, 23]. The dysphoric symptoms such as sadness, guilt feelings, self-criticism, helplessness, and hopelessness are typically present in depression but absent in apathy, which is characterized by a lack of emotional responsiveness and diminished motivation [22, 23]. Compared with depression, the neuropathological changes of apathy in AD are more in the anterior cingulate frontal–subcortical circuit and cholinergic deficiency contribute to the neurobiological process, while those of depression are more in the frontal-striatal and subcortical limbic circuits and serotoninergic deficiency, or an imbalance between dopamine and norepinepherine plays the role [22, 23]. Therefore, a careful differentiation of the two symptoms would be helpful to the further management.
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of great importance both for optimal treatment and prevention. In the present review, we conducted a comprehensive search for potentially relevant studies in the electronic bibliographic databases of PubMed and EMBASE with terms ‘(depression or depress*) AND (Alzheim* OR dement*)’. Then we elucidated depression in AD from the perspective of epidemiology, and mainly focused on the evidence of whether depression is a risk factor for AD. At the same time, we discussed the potential mechanism underlying the depressive symptom in AD, and gave special attention to the current possible treatments.
co
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46
S. Chi et al. / Depression in Alzheimer’s Disease
uth
2
Incidence and clinical course of depression in AD Few studies have investigated the incidence and clinical course of depression in AD longitudinally. The incidence of depression or depressive symptoms in AD varied greatly in different studies [24–26], from no more than 2% per year [27, 28] to around 20% per year [29–31] depending greatly on the study meth-
95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137
138
139 140 141 142 143 144
S. Chi et al. / Depression in Alzheimer’s Disease
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182 183 184 185 186 187 188 189 190 191 192 193 194
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Depression and risk of AD development
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a 2-year follow-up indicated that baseline depressed affection predicted all-type dementia, though the association was less strong of AD compared with that of vascular dementia [38]. Another two studies claimed that only severe depression or those higher educated depressed individuals were prone to develop AD 4 years later [39, 40]. Nonetheless, in a study with 3-year follow-up, no such significant association was found [41]. Of interest, the peak incidence of major depression was reported to occur 5 years around the onset of AD [26]. Thus, in that condition, depression was more of a symptom during the neurodegenerative process of AD. It has been considered that late-onset depression might be a prodromal condition of AD due to short time lag between the onsets. A recent meta-analysis, which included 23 community-based prospective cohort studies, concluded that late-life depression significantly increased the risk of AD incidence for 1.65 fold, even after controlling all possible cofounders [42]. The result was consistent with the pooled findings of almost 2-fold increased risk in another meta-analysis, which was constituted mostly by case–control studies. However, those with mid-life depression were also included in these studies [37]. More evidence was obtained from a recent published study, in which significant association only occurred in those within 75 years cut-off. The association became even more notable when combined with current depressive symptom [43]. Therefore, only when late-onset depression is proximal to dementia diagnosis and simultaneously without clinical remission, it might be elucidated as a preclinical manifestation of AD.
dA
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ods such as the study duration and evaluation tools (Table 1). In general, most procedures were no more than 2 years, and the DSM criteria was most often used for AD diagnosis. There is little agreement on the natural course of depression in AD because of the fluctuation of depressive symptoms over time and heterogeneity in research methodology [12] (Table 2). Data from the Chicago Health and Aging Project showed that depressive symptoms barely changed during an average course of 2–3 years in patients after the diagnosis of AD, both via informant report or self-report of depression [32, 33]. Of note, in the two studies, it was the depression score but not the prevalence that was compared. Similarly, in an early study, AD patients from a multicenter were enrolled and followed up for 3 years at 6-month intervals, during which depressed mood was persistent with a moderate prevalence of around 25% [34]. However, other studies found that depression tends to be persistent over the first few months, and remit over time [19, 24, 31, 35]. In a study with a large sample size, patients with probable AD were followed every 6 months for up to 14 years. The prevalence of depressive symptoms was stable over the first 3 years of follow-up but significantly dropped in the fourth and fifth years [20]. It seems that depression occurred at certain stages of dementia and decreased toward the terminal stages [36]. Nevertheless, the decrease of depressive symptoms in the follow-up period cannot be explained totally by cognitive decline and impaired functional ability. A systematic review based on 24 studies failed to find association between the severity of AD and the prevalence of comorbid depressive symptoms or diagnosed depression [21]. Therefore, more long-term studies are needed to identify the clinic course of depression in patients with AD.
145
3
The issue of whether depression is an AD-associated prodromal condition or a risk factor is controversial. One important issue in understanding the association is the interval between the onset of depression and AD. As a matter of fact, if there was a long time lag between the onsets, depression was usually considered more of a risk factor than a prodromal condition [37]. In the past decade, most studies that focused on the issue were prospectively designed with a follow-up period of around 5 years, and only a few studies lasted for more than 10 years. Few studies explored the association with a short follow-up period less than 5 years and arrived at conflicting conclusions. A recent study with
195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227
POTENTIAL MECHANISMS
228
Neuroanatomic changes
229
Neurodegeneration in the frontal-limbic circuits or frontal-subcortical circuits has been proven critical for the pathogenesis of idopathogenic depression. Similarly, the structural and functional changes in brains of AD patients have also been investigated by means of magnetic resonance imaging, single photon emission computed tomography (SPECT), and positron emission tomography (PET). A disruption of cerebral frontal-subcortical pathways, due to either volumetric changes in prefrontal gray [44, 45] or subcortical changes such as white matter hyperintensities [46] and lacunas in the basal ganglia [47], has been proposed to contribute to depression in AD patients in most structural studies. Moreover, a greater number
230 231 232 233 234 235 236 237 238 239 240 241 242 243
4
Un
rre
Study
Design and years of follow up
Characteristic of study participants
[23]
Perspective, every 6 month for 2 years Perspective, every 6 month for 4 years Perspective, every 6 month for 1 year Retrospective, 5 years Perspective, every 6 month for 3 years Perspective, for mean 3.5 years Perspective, every 3 month for 1 year Perspective, 3 years and 2 years
98 young-onset AD; 123 late-onset AD 312 cases
[28] [22] [24] [26] [29] [27] [25]
No data 146 cases 389 and 586 cases
Measure of depression
Measure of AD
Newly identified depression (%)
NPI
DSM-IV, Text Revision
NPI
DSM-IV and NINCDS/ADRDA; mild to moderate AD NINCDS/ADRDA
Young-onset: 28.8%/2 year; Late-onset: 48.6/2 year 17.45%/ per year 6 month: 1.8%; 12 month: 6.4%
ICD-10 NINCDS/ADRDA
2.46% per year
