Depressive Symptoms In Alzheimer's Disease Patients Research Articles

Abnormally decreased functional connectivity of the right nucleus basalis of Meynert in Alzheimer’s disease patients with depression symptoms

Dysfunction of the basal forebrain is the main pathological feature in patients with Alzheimer's disease (AD). The aim of this study was to explore whether depressive symptoms cause changes in the functional network of the basal forebrain in AD patients. We collected MRI data from depressed AD patients (n = 24), nondepressed AD patients (n = 14) and healthy controls (n = 20). Resting-state functional magnetic resonance imaging data and functional connectivity analysis were used to study the characteristics of the basal forebrain functional network of the three groups of participants. The functional connectivity differences among the three groups were compared using ANCOVA and post hoc analyses. Compared to healthy controls, depressed AD patients showed reduced functional connectivity between the right nucleus basalis of Meynert and the left supramarginal gyrus and the supplementary motor area. These results increase our understanding of the neural mechanism of depressive symptoms in AD patients.

Changes in serum brain-derived neurotrophic factor levels in patients with Alzheimer's disease

Objective To investigate changes in serum brain-derived neurotrophic factor(BDNF)levels in patients with Alzheimer's disease(AD). Methods Venous blood samples were collected from 40 AD patients, 40 amnestic mild cognitive impairment(aMCI)patients and 40 normal controls.Serum BDNF levels were analyzed by enzyme-linked immunosorbent assay(ELISA). The relationships of serum BDNF levels with age, gender, educational level, mini-mental state examination(MMSE)score and Beck depression scale-Ⅱ(BDⅠ-Ⅱ)score in AD patients were analyzed. Results Serum BDNF levels were lower in AD patients than in patients with aMCI and normal controls(4.6±1.9 μg/L vs.9.3±4.7 μg/L, 10.2±1.8 μg/L, F=71.083, P 0.05). Pearson correlation analysis showed that serum BDNF levels had a positive correlation with MMSE score(r=0.428, P<0.05). Conclusions Advanced age is associated with decreased serum levels of BDNF in AD patients.Decreased serum levels of BDNF in AD patients are related to the severity of cognitive impairment.There is no correlation between serum BDNF levels and depressive symptoms in AD patients. Key words: Alzheimer disease; Cognition disorders; Brain-derived neurotrophic factor

Antidepressant effects of creatine on amyloid β1–40-treated mice: The role of GSK-3β/Nrf2 pathway

Alzheimer's disease (AD) is characterized by progressive synaptic dysfunction and neuronal lost in specific brain areas including hippocampus, resulting in memory/learning deficits and cognitive impairments. In addition, non-cognitive symptoms are reported in AD patients, such as anxiety, apathy and depressed mood. The current antidepressant drugs present reduced efficacy to improve depressive symptoms in AD patients. Here, we investigated the ability of creatine, a compound with neuroprotective and antidepressant properties, to counteract amyloid β1–40 peptide-induced depressive-like behavior in mice. Moreover, we addressed the participation of the intracellular signaling pathway mediated by glycogen synthase kinase-3β (GSK-3β)/nuclear factor erythroid-2-related factor 2 (Nrf2) in the creatine effects. Aß1–40 administration (400 pmol/mouse, i.c.v.) increased the immobility time in the tail suspension test and decreased the grooming time and increased latency to grooming in the splash test, indicative of depressive-like behavior. These impairments were attenuated by creatine (0.01 and 10 mg/kg, p.o.) and fluoxetine (10 mg/kg, p.o., positive control). No significant alterations on locomotor performance were observed in the open field. Aß1–40 administration did not alter hippocampal phospho-GSK-3β (Ser9)/total GSK-3β, total GSK-3β and heme oxygenase-1 (HO-1) immunocontents. However, Aß1–40-infused mice treated with creatine (0.01 mg/kg) presented increased phosphorylation of GSK-3β(Ser9) and HO-1 immunocontent in the hippocampus. Fluoxetine per se increased GSK-3β(Ser9) phosphorylation, but did not alter HO-1 levels. In addition, Aß1–40 administration increased hippocampal glutathione (GSH) levels as well as glutathione reductase (GR) and thioredoxin reductase (TrxR) activities, and these effects were abolished by creatine and fluoxetine. This study provides the first evidence of the antidepressive-like effects of creatine in Aß1–40-treated mice, which were accompanied by hippocampal inhibition of GSK-3β and modulation of antioxidant defenses. These findings indicate the potential of creatine for the treatment of depression associated with AD.

Impaired Frontolimbic Connectivity and Depressive Symptoms in Patients with Alzheimer's Disease

Background/Aims: Depressive symptoms are commonly observed in Alzheimer's disease (AD). The underlying mechanisms of depressive symptoms in AD remain unclear; frontolimbic circuitry dysfunction may play a role. We aimed to investigate the microstructural integrity of frontolimbic connectivity of specific fiber tracts in AD patients with and without depressive symptoms using diffusion tensor imaging (DTI). Methods: Eleven AD patients with depressive symptoms (dep-AD), 18 AD patients without depressive symptoms (nondep-AD), and 18 normal control (NC) subjects were included. The cingulum bundle (CB), uncinate fasciculus (UF), and fornix, mainly frontolimbic connectivity, were measured by DTI tractography and the metrics of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD) were calculated. Results: Compared with NC subjects, both dep-AD and nondep-AD patients showed significant differences for all indices in the fornix and significantly decreased FA and increased MD and RD in the bilateral CB and UF. When compared to nondep-AD patients, dep-AD patients showed significantly increased MD and RD in the bilateral CB and right UF. Conclusion: Depressive symptoms in AD patients may be involved in greater microstructural abnormalities of frontolimbic connectivity and myelin injury in the bilateral CB and right UF might contribute to the pathophysiology of depressive symptoms in AD.

Subjective depressive mood and regional cerebral blood flow in mild Alzheimer's disease

Depressive symptoms are common in patients with Alzheimer's disease (AD) and increase the caregiver burden, although the etiology and pathologic mechanism of depressive symptoms in AD patients remain unclear. In this study, we tried to clarify the cerebral blood flow (CBF) correlates of subjective depressive symptoms in AD. Seventy-six consecutive patients with AD were recruited from outpatient units of the Memory Clinic of Okayama University Hospital. Subjective depressive symptoms were evaluated using the short version of the Geriatric Depression Scale (GDS). All patients underwent brain SPECT with 99mTc-ethylcysteinate dimer, and the SPECT images were analyzed by the Statistical Parametric Mapping 8 program. No significant differences between groups with high and low GDS scores were found with respect to age, sex, years of education, and revised Addenbrooke's Cognitive Examination scores. Compared to patients with low scores on GDS, patients with high scores showed significant hypoperfusion in the left inferior frontal region. The left inferior frontal region may be significantly involved in the pathogenesis of subjective depressive symptoms in AD. Subjective and objective depressive symptoms may have somewhat different neural substrates in AD.

Structural brain changes associated with depressive symptoms in the elderly with Alzheimer’s disease

ObjectiveTo examine neuroanatomical changes associated with depressive symptoms in Alzheimer's disease (AD) and the relationship between brain structure and cerebrospinal fluid (CSF) AD biomarkers in depressed and non-depressed patients.MethodsTwo independent...

Depressive symptoms and regional cerebral blood flow in Alzheimer's disease

Depressive symptoms are common in patients with Alzheimer's disease (AD) and increase the caregiver burden, although the etiology and pathologic mechanism of depressive symptoms in AD patients remain unclear. In this study, we tried to clarify the cerebral blood flow (CBF) correlates of depressive symptoms in AD, excluding the effect of apathy and anxiety. Seventy-nine consecutive patients with AD were recruited from outpatient units of the Memory Clinic of Okayama University Hospital. The level of depressive symptoms was evaluated using the depression domain of the Neuropsychiatric Inventory (NPI). The patients underwent brain SPECT with 99mTc-ethylcysteinate dimer. After removing the effects of age, anxiety and apathy scores of NPI, and five subscales of Addenbrooke's Cognitive Examination-revised (ACE-R), correlation analysis of NPI depression scores showed a significant cluster of voxels in the left middle frontal gyrus (Brodmann area 9), similar to the areas in the simple correlation analysis. The dorsolateral prefrontal area is significantly involved in the pathogenesis of depressive symptoms in AD, and the area on the left side especially may be closely related to the depressive symptoms revealed by NPI.

Prevalence and associated behavioral symptoms of depression in mild cognitive impairment and dementia due to Alzheimer's disease

Mild cognitive impairment (MCI) is a clinical concept that categorizes subjects who are in an intermediate cognitive state between normal aging and dementia. The aims of this study are to determine the prevalence of significant depressive symptoms in MCI and Alzheimer's disease (AD) patients and to characterize the behavior associated with significant depressive symptoms in MCI and AD patients. A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms of dementia and MCI was performed. The study population consisted of 270 MCI and 402 AD patients. Behavioral assessment was performed by means of Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) and Cohen-Mansfield Agitation Inventory. The presence of significant depressive symptoms was defined as a Cornell Scale for Depression in Dementia total score >7. The prevalence of significant depressive symptoms in AD patients (25%) was higher compared with MCI patients (16%) (p = 0.005). Patients with significant depressive symptoms showed an increased severity of frontal lobe symptoms, behavioral symptoms and agitation (Middelheim Frontality Score, Behave-AD and Cohen-Mansfield Agitation Inventory total scores; p < 0.001). Also, most of the individual frontal lobe and behavioral symptoms were more prevalent and severe, resulting in higher Behave-AD global scores. Mild cognitive impairment patients with depressive symptoms showed more severe behavioral symptoms and more severe verbally agitated behavior than AD patients without depressive symptoms (p < 0.001). Frontal lobe and behavioral symptoms are more prevalent and severe in MCI and AD patients with significant depressive symptoms as compared with patients without depressive symptoms.

No evidence for allelic association of serotonin 2A receptor and transporter gene polymorphisms with depression in Alzheimer disease

Patients with Alzheimer disease (AD) often exhibit psychiatric symptoms associated with cognitive impairment. The serotoninergic system may be involved in the development of depressive symptoms in AD patients, as suggested by the evidence that antidepressant drugs having the serotonin transporter as their target are effectively used to treat depressive AD patients. The aim of this study was to investigate the role of serotonin in depression, searching for association of two serotoninergic polymorphisms (T102C of serotonin receptor 5-HT2A and serotonin transporter linked polymorphic region -5-HTTLPR- of SLC6A4 gene) with depressive symptoms and considering their possible interactions with Apolipoprotein E (ApoE) and between themselves, in a sample of 208 sporadic AD patients and 116 normal controls from Italy. 5-HTTLPR and T102C are not associated with AD when separately analysed. However, we found out an interaction between the two polymorphisms in L/L and C/C genotype carriers increasing the risk for the disease (p=0.015, OR=8.048; 95% CI: 1.497-43.262). No association of the polymorphisms was detected with depression linked to AD. No interaction between 5-HTTLPR and T102C was detected in depressive AD subjects, even after stratification according to the presence of ApoE4 allele. These results suggest that the serotoninergic system may be not involved in the pathogenesis of depressive symptoms in AD patients, and it may be involved in other aspects of disease pathophysiology like cognitive symptoms and psychosis.