Alzheimer Depression Research Articles

Decreased functional connectivity between the dorsal anterior cingulate cortex and lingual gyrus in Alzheimer's disease patients with depression

BackgroundDepression is one of the most common psychiatric symptoms in Alzheimer's disease (AD), occurring in up to 40% of AD patients. It influences the cognitive function of patients and increases the burden on their caregivers. Currently, there are few effective medical treatments for reducing the symptoms of depression in AD patients. Understanding the underlying neurobiological mechanisms in AD patients with depression (D-AD) is crucial for developing effective interventions. The anterior cingulate cortex (ACC) is an important brain region involved in emotional and cognitive processing. Several functional magnetic resonance imaging studies have shown that patients with major depressive disorder have structural, functional, and metabolic abnormalities in the ACC. MethodsWe investigated the resting-state functional connectivity (FC) of ACC subregions in 15 D-AD patients and 17 non-depressed AD (nD-AD) patients, by parcellating the ACC into the rostral and dorsal ACC (dACC). ResultsOur results revealed that D-AD patients have decreased FC between the dACC and the right occipital lobe and right lingual gyrus, compared with nD-AD patients. ConclusionsDecreased FC between the dACC and the right occipital lobe and right lingual gyrus may play an important role in the neuropathophysiology of depression in AD.

The Effect of Escitalopram on Mood and Cognition in Depressive Alzheimer’s Disease Subjects

Effective treatments to alleviate depression in Alzheimer's disease (AD) have been scarce. To investigate the efficacy and tolerability of escitalopram in the treatment of depression in AD. In this 12-week randomized, double-blind, placebo-controlled trial with open-label, 12-week extension, AD subjects over 50 years of age, with depression defined by Olin's provisional diagnostic criteria, were enrolled. The Cornell Scale for Depression in Dementia (CSDD), and other measures of depression and cognition were repeated. 91 subjects were screened, and 84 were randomized into either the study group or placebo group (n = 42 for both groups). Twenty-four subjects (29%) were unable to finish the study, yielding a per protocol population of 60 subjects (study group: n = 27; placebo group: n = 33). At week 12, differences in measures of depression and cognition between the two groups were not statistically significant. However, exploratory analysis suggested that further research on a subset of subjects with 'definite major depression' (baseline CSDD score ≥18) is needed. The number of treatment-related adverse-events (AE) did not differ between groups (p = 0.83) and no serious treatment-related AE were observed. The use of escitalopram was well tolerated in depressive dementia patients. Future studies focusing on subjects with more severe levels of depression, and with more statistical power, will be needed.

THE EFFECT OF ESCITALOPRAM ON MOOD AND COGNITION IN DEPRESSIVE ALZHEIMER’S DISEASE SUBJECTS

Background Effective treatments to alleviate depression in Alzheimer's disease (AD) have been scarce. Objective To investigate the efficacy and tolerability of escitalopram in the treatment of depression in AD. Methods In this 12-week randomized, double-blind, placebo-controlled trial with open-label, 12-week extension, AD subjects over 50 years of age, with depression defined by Olin's provisional diagnostic criteria, were enrolled. The Cornell Scale for Depression in Dementia (CSDD), and other measures of depression and cognition were repeated. Results 91 subjects were screened, and 84 were randomized into either the study group or placebo group (n = 42 for both groups). Twenty-four subjects (29%) were unable to finish the study, yielding a per protocol population of 60 subjects (study group: n = 27; placebo group: n = 33). At week 12, differences in measures of depression and cognition between the two groups were not statistically significant. However, exploratory analysis suggested that further research on a subset of subjects with 'definite major depression' (baseline CSDD score ≥18) is needed. The number of treatment-related adverse-events (AE) did not differ between groups (p = 0.83) and no serious treatment-related AE were observed. Conclusion The use of escitalopram was well tolerated in depressive dementia patients. Future studies focusing on subjects with more severe levels of depression, and with more statistical power, will be needed.

MEDICATIONS FOR DEPRESSION IN ALZHEIMER’S AND RISK OF MORTALITY: A LONGITUDINAL OBSERVATIONAL STUDY FROM THE ADTI

MEDICATIONS FOR DEPRESSION IN ALZHEIMER’S AND RISK OF MORTALITY: A LONGITUDINAL OBSERVATIONAL STUDY FROM THE ADTI

PT595. Incidence and course of depression in Alzheimer’s disease patients

PT595. Incidence and course of depression in Alzheimer’s disease patients

Major Depression Disorder with a Late Age-of-Onset as a Biological Model to Detect the Brain Features of Depression in Alzheimer's Disease and Behavioral Variant of Frontotemporal Dementia (P6.243)

Major Depression Disorder with a Late Age-of-Onset as a Biological Model to Detect the Brain Features of Depression in Alzheimer's Disease and Behavioral Variant of Frontotemporal Dementia (P6.243)

The Relationship between Serum Endocan Levels and Depression in Alzheimer's Disease.

Objectives. Growing evidence suggests that angiogenic vascular factors may be involved in the pathogenic mechanism of Alzheimer's disease (AD), and recently endocan has been proposed as an angiogenic biomarker. The aim of this study was to measure serum endocan levels according to the presence of depression in AD and to investigate the association among the serum endocan levels, cognitive function, and depression in these patients. Methods. Serum endocan levels were measured in 26 AD patients with depression, 29 AD patients without depression, and 29 healthy controls using an enzyme-linked immunosorbent assay kit. The Mini-Mental State Examination-Korean version (MMSE-KC) and the Korean version of the Geriatric Depression Scale-Short Form (SGDS-K) were used to evaluate cognitive function and depressive symptoms, respectively. Results. Serum endocan levels were significantly lower in AD patients with depression than in AD patients without depression or healthy controls. Serum endocan levels were negatively correlated with SGDS-K scores but not with MMSE-KC scores in AD patients. Conclusions. This study suggests that serum endocan levels might be associated with depression in AD. Future studies are needed to investigate the pathophysiological mechanisms or the role of endocan in AD with depression.

Neurometabolic characteristics in the anterior cingulate gyrus of Alzheimer's disease patients with depression: a (1)H magnetic resonance spectroscopy study.

BackgroundDepression is a common comorbid psychiatric symptom in patients with Alzheimer’s disease (AD), and the prevalence of depression is higher among people with AD compared with healthy older adults. Comorbid depression in AD may increase the risk of cognitive decline, impair patients’ function, and reduce their quality of life. However, the mechanisms of depression in AD remain unclear. Here, our aim was to identify neurometabolic characteristics in the brain that are associated with depression in patients with mild AD.MethodsThirty-seven patients were evaluated using the Neuropsychiatric Inventory (NPI) and Hamilton Depression Rating Scale (HAMD-17), and divided into two groups: 17 AD patients with depression (D-AD) and 20 non-depressed AD patients (nD-AD). Using proton magnetic resonance spectroscopy, we characterized neurometabolites in the anterior cingulate gyrus (ACG) of D-AD and nD-AD patients.ResultsCompared with nD-AD patients, D-AD patients showed lower N-acetylaspartate/creatine (NAA/Cr) and higher myo-inositol/creatine (mI/Cr) in the left ACG. NPI score correlated with NAA/Cr and mI/Cr in the left ACG, while HAMD correlated with NAA/Cr.ConclusionsOur findings show neurometabolic alterations in D-AD patients. Thus, D-AD pathogenesis may be attributed to abnormal activity of neurons and glial cells in the left ACG.

Altered relaxin family receptors RXFP1 and RXFP3 in the neocortex of depressed Alzheimer's disease patients.

The G-protein-coupled relaxin family receptors RXFP1 and RXFP3 are widely expressed in the cortex and are involved in stress responses and memory and emotional processing. However, the identification of these receptors in human cortex and their status in Alzheimer's disease (AD), which is characterized by both cognitive impairments and neuropsychiatric behaviours, have not been reported. In this study, we characterized RXFP receptors for immunoblotting and measured RXFP1 and RXFP3 immunoreactivities in the postmortem neocortex of AD patients longitudinally assessed for depressive symptoms. RXFP1 and RXFP3 antibodies were characterized by immunoblotting with lysates from transfected HEK cells and preadsorption with RXFP3 peptides. Also, postmortem neocortical tissues from behaviourally assessed AD and age-matched controls were processed for immunoblotting with RXFP1 and RXFP3 antibodies. Compared to controls, putative RXFP1 immunoreactivity was reduced in parietal cortex of non-depressed AD patients but unchanged in depressed patients. Furthermore, putative RXFP3 immunoreactivity was increased only in depressed AD patients. RXFP1 levels in the parietal cortex also correlated with severity of depression symptoms. In contrast, RXFP1 and RXFP3 levels did not correlate with dementia severity or β-amyloid burden. Alterations of RXFP1 and RXFP3 may be neurochemical markers of depression in AD, and relaxin family receptors warrant further preclinical investigations as possible therapeutic targets for neuropsychiatric symptoms in dementia.

A Review of Pharmacological Treatments for Depression in Alzheimer's Disease.

Depression in Alzheimer's disease (dAD) is one of the most common behavioral and psychological symptoms of dementia, with devastating consequences not only for the affected individuals, but for caregivers as well. So far, pharmacological treatment of dAD has been based on the "monoamine hypothesis". However, the reported moderate effects of approved antidepressants, as well as an increasing body of research evidence, suggest a more complex pathophysiologic mechanism. In the present paper, a systematic review of different treatments for dAD is presented that can inform the study of alternative neuropathological and neurobiological aspects of the disease aimed at the development of more effective treatment targets.

Phenomenology of Depression in Alzheimer's Disease.

Depression is among the most frequent psychiatric comorbid conditions in dementia. There is no strong consensus as to what criteria should be used to diagnose depression in AD. This is at least partially explained by the overlap between symptoms of depression and symptoms of AD. Recent studies using latent class analysis provided clarification to this diagnostic dilemma. All nine DSM-IV symptoms of major depression were found to characterize a class with a high chance (96% ) of having a clinical diagnosis of major depression, and symptoms of anxiety were also frequent. Other psychiatric symptoms may also be included under the construct of depression in AD, since both apathy and anxiety are among the most frequent comorbid conditions for major depression in AD. Subtypes of depression should also be validated in this condition. For instance, increased awareness of cognitive and functional deficits is significantly associated with dysthymia but not with major depression, suggesting that different depressive syndromes in AD may have different etiology.

Comprehensive analysis of patient and caregiver predictors for caregiver burden, anxiety and depression in Alzheimer's disease.

The primary aim of this study was to examine the correlations between patient and caregiver characteristics with caregiver burden, anxiety and depression in Alzheimer's Disease. Secondary aim was to determine which behavioural and psychological symptoms had the greatest impact on caregiver burden, anxiety and depression in Alzheimer's Disease. Caregivers of individuals with Alzheimer's Disease experience high levels of burden, both psychologically and physically. Previous studies have examined caregiver burden, anxiety and depression separately. However, no paper has examined these three psychological conditions simultaneously. A cross-sectional design. A total of 310 patients with probable Alzheimer's Disease and their primary caregivers were assessed. Cognitive impairment and neuropsychiatric symptoms were assessed with the Mini Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test and Neuropsychiatric Inventory, respectively. Caregiver burden, anxiety and depression were assessed with the ZBI, Generalised Anxiety Disorder Scale-7 and Patient Health Questionnaire-9, respectively. All 12 neuropsychiatric symptoms in the Neuropsychiatric Inventory were significantly correlated with caregiver burden, anxiety and depression, with the top three neuropsychiatric predictors being depression, apathy and anxiety. Furthermore, higher levels of caregiver anxiety were associated with a longer duration of being a caregiver. Within caregivers, higher levels of depression were independently associated with higher numbers of additional caregivers, lower educational background and being the spouse of the patient. Higher levels of burden were associated with a longer duration of being a caregiver and being the spouse of the patient. Caregiver burden, anxiety or depression were not significantly correlated with hours/day of caring for the patient. Caregiver burden, anxiety and depression were significantly correlated with different neuropsychiatric symptoms in the Neuropsychiatric Inventory. Practitioners are able to identify caregivers at risk for burden, anxiety and depression. Understanding which Neuropsychiatric Inventory symptom is more closely associated with distress in caregivers will help practitioners to be more specific and effective in detecting caregiver distress.

Validity of the geriatric depression scale and the collateral source version of the geriatric depression scale in nursing homes.

Depression is a common psychiatric disorder in older people. The study aimed to examine the screening accuracy of the Geriatric Depression Scale (GDS) and the Collateral Source version of the Geriatric Depression Scale (CS-GDS) in the nursing home setting. Eighty-eight residents from 14 nursing homes were assessed for depression using the GDS and the CS-GDS, and validated against clinician diagnosed depression using the Semi-structured Clinical Diagnostic Interview for DSM-IV-TR Axis I Disorders (SCID) for residents without dementia and the Provisional Diagnostic Criteria for Depression in Alzheimer Disease (PDCdAD) for those with dementia. The screening performances of five versions of the GDS (30-, 15-, 10-, 8-, and 4-item) and two versions of the CS-GDS (30- and 15-item) were analyzed using receiver operating characteristic (ROC) curves. Among residents without dementia, both the self-rated (AUC = 0.75-0.79) and proxy-rated (AUC = 0.67) GDS variations performed significantly better than chance in screening for depression. However, neither instrument adequately identified depression among residents with dementia (AUC between 0.57 and 0.70). Among the GDS variations, the 4- and 8-item scales had the highest AUC and the optimal cut-offs were >0 and >3, respectively. The validity of the GDS in detecting depression requires a certain level of cognitive functioning. While the CS-GDS is designed to remedy this issue by using an informant, it did not have adequate validity in detecting depression among residents with dementia. Further research is needed on informant selection and other factors that can potentially influence the validity of proxy-based measures in the nursing home setting.

Corpus Callosum Structure is Topographically Correlated with the Early Course of Cognition and Depression in Alzheimer's Disease.

Corpus callosum (CC) abnormalities may cause cognitive and neuropsychiatric complications due to reduced hemispheric integration. Over a one-year period, we investigated whether the CC structure of 20 patients with mild Alzheimer's disease (AD) was linked to the evolution of cognitive and neuropsychiatric symptoms. We also investigated whether this anatomical-clinical relationship was localized topographically on the CC by combining voxel-based morphometry and diffusion tensor imaging approaches. We assessed patients' global cognitive deterioration and neuropsychiatric symptoms with the Mini-Mental State Examination and the Neuropsychiatric Inventory. Increased global cognitive deterioration during the early course of AD was significantly related to reduced white matter density (p = 0.004) and fractional anisotropy (FA) (p = 0.012) and increased mean diffusivity (MD) (p = 0.017) at the level of the CC isthmus/splenium. Further, increased depression severity was significantly related to reduced FA (p = 0.008) and increased MD (p = 0.018) at the level of the CC rostrum. These results indicate that changes in early myelinated CC fibers, which subserve the lateral temporal and parietal cortices and are less vulnerable to damage, may be related to cognitive impairment. Furthermore, changes in late myelinated CC fibers, which connect the orbitofrontal cortices and are more vulnerable to damage, may be related to the earliest neuropsychiatric symptoms of AD, such as depression.

Brain structure and function related to depression in Alzheimer's disease: contributions from neuroimaging research.

The development of minimally invasive in vivo methods for imaging the brain has allowed for unprecedented advancement in our understanding of brain-behavior relationships. Structural, functional, and multimodal neuroimaging techniques have become more sophisticated in detecting structural and physiological abnormalities that may underlie various affective disorders and neurological illnesses such as depression in Alzheimer's disease (AD). In general, neuroimaging studies of depression in AD investigate whether depression is associated with damage to structures in specific neural networks involving frontal and subcortical structures or with functional disruption of cortical neural systems. This review provides an overview of how various imaging modalities have contributed to our understanding of the neurobiology of depression in AD. At present, the literature does not conclusively support any specific pathogenesis for depression, and it is not clear whether patients with AD and depression have histopathological and neurochemical characteristics that contribute to mood symptoms that are different from cognitively intact individuals with depression. Neuroimaging studies suggest that atrophy of temporal or frontal structures, white matter lesions in frontal lobe or subcortical systems, reduced activity in dorsolateral frontal cortex, or small vessel cerebrovascular disease may be associated with depression in AD. Conceptual, clinical, and methodological challenges in studying this relationship are discussed. Further work is needed to understand the specific brain structures, relevant white matter tracts, and interactions among them that are most important. This review concludes with potential directions for future research.

Neuropathology of depression in Alzheimer's disease: current knowledge and the potential for new treatments.

Depression is among the most common behavioral and psychological symptoms of dementia, and leads to more rapid decline and higher mortality. Treatment for depression in dementia has centered on conventional antidepressant drug treatment based around the monoamine hypothesis of depression. However, recent major studies have suggested that conventional antidepressant treatments that aim to correct underlying deficits in monoamine neurotransmitters are not effective for depression in dementia. Postmortem studies have also suggested that depression in dementia does not arise from serotonergic or noradrenergic abnormalities, or indeed from the degenerative pathology associated with Alzheimer's disease. In contrast, considerable recent evidence has suggested that alterations in glutamatergic transmission may contribute to the pathophysiology of depression. This supports the view that treatment-resistant depressed patients, such as many dementia patients, may benefit from agents affecting glutamate transmission. This review will thus draw together the wealth of pathological data examining the basis of depression in Alzheimer's disease and relate this to current thinking on treatment, with the aim of generating discussion on potential novel therapeutic strategies.

Impact of White Matter Lesions on Depression in the Patients with Alzheimer's Disease.

ObjectiveComorbid depression is common in patients with Alzheimer's disease (AD). An increase in white matter lesions (WMLs) has been associated with depression in both elderly individuals with normal cognition and patients with Alzheimer's disease. We investigated whether the severity and location of WMLs influence the association between WMLs and comorbid depression in AD.MethodsWe enrolled 93 AD patients from Seoul National University Bundang Hospital. We administered both the Mini International Neuropsychiatric Inventory (MINI) and the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K) clinical and neuropsychological battery. Subjects also underwent brain magnetic resonance imaging (MRI). We diagnosed AD according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. We diagnosed depressive disorders according to the DSM-IV diagnostic criteria, and evaluated the severity of depressive symptoms using the Korean version of the Geriatric Depression Scale (GDS-K). We quantified the WML volumes from the brain MRI using a fully automated segmentation algorithm.ResultsThe log of the WML volume in the frontal lobe was significantly associated with depressive disorders (odds ratio=1.905, 95% CI=1.027-3.533, p=0.041), but not with the severity of depressive symptoms as measured by the GDS-K.ConclusionThe WML volume in the frontal lobe conferred a risk of comorbid depressive disorders in AD, which implies that comorbid depression in AD may be attributed to vascular causes.

THE EFFECTS OF ADMINISTRATION OF VALPROIC ACID ON BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF) AND DEPRESSION OF ANIMAL ALZHEIMER’S DISEASE DURING EIGHT WEEK LONG ENDURANCE EXERCISES

Abstract. The objective of the present study is to analyze the effects of administration of valproic acid on Brain Derived Neurotrophic Factor (BDNF) and depression of alzheimer’s disease of desert rat during eight week long endurance exercises. In order to administer the study, 140 Sprague Dawley desert rats (70 of which are male and the other half, female) are categorized randomly into seven research groups, which includes 1) control group 2) sham group and testing groups 3) long distance training group 4) valproic acid 100 group 5) valproic acid 200 group 6) training group of valproic acid 100 7) training group of valproic acid 200. During the eight week period, research desert rats of groups 3, 6 and 7 run for 15 minutes and 30 seconds on zero gradient laboratory treadmill, with the speed of 15 to 20 meters per minute in each training lapse. The lapses are frequented five times a week. Furthermore, for a 14 day period, groups 4 and 6 are daily administered with 100 milligrams valproic acid on kilogram and groups 5 and 7 are daily administered with 200 milligrams valproic acid. Research Methodology For research data analysis, one-way variance test and post hoc Tukey’s test are utilized. The findings indicate that the level of BDNF in all the research groups is significantly higher than the sham group (p<0.05) and Tumor Necrosis Factor Alpha (TNF) and depression level of all the research groups are significantly lower than the sham group (p<0.05). Research Findings According to the research findings, it is indicated that endurance exercises, valproic acid and their synthetic administration increase the level of BDNF and decrease the levels of TNF and depression in desert rats with alzheimer’s disease.

Role of depression in Alzheimer’s disease

Role of depression in Alzheimer’s disease

Comparative efficacy of Ocimum sanctum L. and Ocimum basilicum L. essential oils against amyloid beta (1–42)-induced anxiety and depression in laboratory rats

The present study analyzed the possible anxiolytic and antidepressant proprieties of inhaled basil essential oils extracted from Ocimum sanctum L. (Os) and Ocimum basilicum L. (Ob) in β-amyloid (1–42) rat model of Alzheimer’s disease. The anxiolytic- and antidepressant-like effects of inhaled basil essential oils were studied by means of in vivo (elevated plus-maze and forced swimming tests) approaches. The β-amyloid (1–42)-treated rats exhibited the following: decrease of the exploratory activity (number of crossing), the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and increase of the swimming time and decrease of the immobility time within forced swimming test. The chemical composition varied from one sample to another. The main compounds found in both samples were linalool (31 %–Ob, 19 %–Os), camphor, β-elemene, α-bergamotene and bornyl-acetate, estragole (15.57 and 7.59 %, respectively), eugenol (2.64 and 1.39 %, respectively) and 1,8-cineole (3.29 and 3.90 %, respectively). As a result, exposure to basil essential oils significantly improved the behavior of the animals, suggesting anxiolytic- and antidepressant-like effects. Our results suggest that multiple exposures to basil essential oils can be useful as a mean to counteract anxiety and depression in Alzheimer’s disease conditions.