Depression 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.

The Characteristics of Entorhinal Cortex Functional Connectivity in Alzheimer's Disease Patients with Depression.

Depression is one of the most common neuropsychiatric symptoms of Alzheimer's disease (AD) which decreases the life quality of both patients and caregivers. There are currently no effective drugs. It is therefore important to explore the pathogenesis of depression in AD patients. The present study aimed to investigate the characteristics of the entorhinal cortex (EC) functional connectivity (FC) in the whole brain neural network of AD patients with depression (D-AD). Twenty-four D-AD patients, 14 AD patients without depression (nD-AD), and 20 healthy controls underwent resting-state functional magnetic resonance imaging. We set the EC as the seed and used FC analysis. One-way analysis of variance was used to examine FC differences among the three groups. Using the left EC as the seed point, there were FC differences among the three groups in the left EC-inferior occipital gyrus. Using the right EC as the seed point, there were FC differences among the three groups in the right EC-middle frontal gyrus, -superior parietal gyrus, -superior medial frontal gyrus, and -precentral gyrus. Compared with the nD-AD group, the D-AD group had increased FC between the right EC and right postcentral gyrus. Asymmetry of FC in the EC and increased FC between the EC and right postcentral gyrus may be important in the pathogenesis of depression in AD.

Transcranial pulse stimulation (TPS) improves depression in AD patients on state-of-the-art treatment.

IntroductionUltrasound‐based brain stimulation is a novel, non‐invasive therapeutic approach to precisely target regions of interest. Data from a first clinical trial of patients with Alzheimer's disease (AD) receiving 2‐4 weeks transcranial pulse stimulation (TPS) have shown memory and cognitive improvements for up to 3 months, despite ongoing state‐of‐the‐art treatment. Importantly, depressive symptoms also improved.MethodsWe analyzed changes in Beck Depression Inventory (BDI‐II) and functional connectivity (FC) changes with functional magnetic resonance imaging in 18 AD patients.ResultsWe found significant improvement in BDI‐II after TPS therapy. FC analysis showed a normalization of the FC between the salience network (right anterior insula) and the ventromedial network (left frontal orbital cortex).DiscussionStimulation of areas related to depression (including extended dorsolateral prefrontal cortex) appears to alleviate depressive symptoms and induces FC changes in AD patients. TPS may be a novel add‐on therapy for depression in AD and as a neuropsychiatric diagnosis.

Depressive symptoms and olfactory function in patients with subjective cognitive decline, mild cognitive impairment and Alzheimer's disease

Objective: Olfactory function appears to be a potential marker for the discrimination and early detection of Alzheimer's disease (AD) and depression. The aim of this study is to compare olfactory function in patients with different stages of cognitive impairment under the additional aspect of depression. Methods: Overall, 37 AD patients, 162 patients with amnestic mild cognitive impairment (MCI), 209 patients with non-amnestic MCI, 70 patients with subjective cognitive decline (SCD), and 158 healthy controls (HC) were examined. We investigated the difference in olfactory function for the diagnostic groups as well as for depressed and non-depressed participants. Results: Considering the whole sample, no significant difference in Sniffin’ Sticks performance was found between depressed and non-depressed individuals. Analysis on a single-group basis revealed that non-depressed participants in the HC group scored significantly higher compared with the depressed participants. On the contrary, depressed AD patients showed better olfactory identification scores than non-depressed AD patients.In the total sample, a negative relationship between the Beck Depression Inventory-II (BDI-II) and Sniffin’ Sticks tests was found. A significant explanatory value of depressiveness for olfaction was found in the HC group. In the other diagnostic groups, no significant results were found. Conclusion: No difference was found between depressed and non-depressed individuals considering the whole sample, which does not support our hypothesis that olfactory function can be used to distinguish between depression and early stages of cognitive impairment.

Analysis of risk factors for depression in Alzheimer’s disease patients

Purpose: Depression, which affects about 52% of Alzheimer's disease (AD) patients, can worsen cognitive impairment and increase mortality and suicide rates. We hope to provide clinical evidence for the prevention and treatment of depression in AD patients by investigating related risk factors of depression in AD patients.Methods: 158 AD inpatients of the Department of Neurology, Daping Hospital from September 2017 to March 2019 were enrolled. General information, laboratory tests, cognitive and emotional function assessments of the inpatients were collected. Logistic regression was used to analyze the risk factors of depression in AD patients, and the relationship between 17 Hamilton depression scale scores and HbA1c levels in AD patients was further analyzed.Results: The prevalence of age, gender, hypertension, hyperlipidemia, Type 2 diabetes mellitus (T2DM), and white matter lesions (WML) in the AD with depression group was significantly different from without depression group. Hypertension, T2DM, and WML are independent risk factors for depression in AD patients. The depression scores of AD patients with HbA1c>6.5% were significantly higher than AD patients with HbA1c ≤ 6.5%, and there were significant difference in depression scale scores between using anti-diabetes drugs group and not using anti-diabetes drugs group whose HbA1c level is >6.5%, while no difference in depression scores between using anti-diabetes drugs group and not using anti-diabetes drugs group whose HbA1c level is ≤6.5%.Conclusion: T2DM is an independent risk factor for AD patients with depression. Increased HbA1c levels aggravate depression in AD patients, and controlling HbA1c levels and anti-diabetes drugs can reduce the severity of depression in AD patients.

Identification of Key Regulatory Genes and Pathways in Prefrontal Cortex of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder partly induced by dysregulation of different brain regions. Prefrontal cortex (PFC) dysregulation has been reported to associate with mental symptoms such as delusion, apathy, and depression in AD patients. However, the internal mechanisms have not yet been well-understood. This study aims to identify the potential therapeutic target genes and related pathways in PFC of AD. First, differential expression analyses were performed on transcriptome microarray of PFC between AD specimens and non-AD controls. Second, protein-protein interaction networks were constructed based on the identified differentially expressed genes to explore candidate therapeutic target genes. Finally, these candidate genes were validated through biological experiments. The enrichment analyses showed that the differentially expressed genes were significantly enriched in protein functions and pathways related to AD. Furthermore, the top ten hub genes in the protein-protein interaction network (ELAVL1, CUL3, MAPK6, FBXW11, YWHAE, YWHAZ, GRB2, CLTC, YWHAQ, and PDHA1) were proved to be directly or indirectly related to AD. Besides, six genes (PDHA1, CLTC, YWHAE, MAPK6, YWHAZ, and GRB2) of which were validated to significantly altered in AD mice by biological experiments. Importantly, the most significantly changed gene, PDHA1, was proposed for the first time that may be serve as a target gene in AD treatment. In summary, several genes and pathways that play critical roles in PFC of AD patients have been uncovered, which will provide novel insights on molecular targets for treatment and diagnostic biomarkers of AD.

The Abnormal Functional Connectivity between the Hypothalamus and the Temporal Gyrus Underlying Depression in Alzheimer's Disease Patients.

Hypothalamic communication with the rest of the brain is critical for accomplishing a wide variety of physiological and psychological functions, including the maintenance of neuroendocrine circadian rhythms and the management of affective processes. Evidence has shown that major depressive disorder (MDD) patients exhibit increased functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Neurofibrillary tangles are also found in the hypothalamus of Alzheimer’s disease (AD) patients, and AD patients exhibit abnormal changes in the HPA. However, little is known of how the hypothalamus interacts with other brain regions in AD patients with depression (D-AD). Functional connectivity (FC) analysis explores the connectivity between brain regions that share functional properties. Here, we used resting-state (rs) magnetic resonance imaging (MRI) technology and the FC method to measure hypothalamic connectivity across the whole brain in 22 D-AD patients and 21 non-depressed AD patients (nD-AD). Our results showed that D-AD patients had reduced FC among the hypothalamus, the right middle temporal gyrus (MTG) and the right superior temporal gyrus (STG) compared with the FC of nD-AD patients, suggesting that the abnormal FC between the hypothalamus and the temporal lobe may play a key role in the pathophysiology of depression in AD patients.

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.

Abnormal degree centrality in Alzheimer's disease patients with depression: A resting-state functional magnetic resonance imaging study

Depression is common in Alzheimer's disease (AD) and occurs in AD patients with a prevalence of up to 40%. It reduces cognitive function and increases the burden on caregivers. Currently, there are very few medications that are useful for treating depression in AD patients. Therefore, understanding the brain abnormalities in AD patients with depression (D-AD) is crucial for developing effective interventions. The aim of this study was to investigate the intrinsic dysconnectivity pattern of whole-brain functional networks at the voxel level in D-AD patients based on degree centrality (DC) as measured by resting-state functional magnetic resonance imaging (R-fMRI). Our study included 32 AD patients. All patients were evaluated using the Neuropsychiatric Inventory and Hamilton Depression Rating Scale and further divided into two groups: 15 D-AD patients and 17 non-depressed AD (nD-AD) patients. R-fMRI datasets were acquired from these D-AD and nD-AD patients. First, we performed a DC analysis to identify voxels that showed altered whole brain functional connectivity (FC) with other voxels. We then further investigated FC using the abnormal DC regions to examine in more detail the connectivity patterns of the identified DC changes. D-AD patients had lower DC values in the right middle frontal, precentral, and postcentral gyrus than nD-AD patients. Seed-based analysis revealed decreased connectivity between the precentral and postcentral gyrus to the supplementary motor area and middle cingulum. FC also decreased in the right middle frontal, precentral, and postcentral gyrus. Thus, AD patients with depression fit a ‘network dysfunction model’ distinct from major depressive disorder and AD.

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.

Regional Cerebral Blood Flow Abnormalities Associated With Apathy and Depression in Alzheimer Disease

The aim of this study was to identify brain areas related to apathy or depression in patients with Alzheimer disease (AD). Eighty-one AD patients were enrolled in this prospective study. (99m)Tc-HMPAO single photon emission computed tomography was performed to evaluate regional cerebral blood flow (rCBF). According to the Neuropsychiatric Inventory subscores of apathy and depression, 9 patients were classified as clinically significant (cs) depressed and non-cs-apathetic (D+) groups and 9 were classified as cs-apathetic and non-cs-depressed (A+) groups. In addition, 18 patients were classified as age-matched and Mini-Mental State Examination-matched disease control groups (D-, A-). The significance of rCBF differences between groups and the correlation between rCBF and subscores in 81 AD patients were estimated by SPM (uncorrected P < 0.005) analysis. D+ patients had significantly lower perfusion in the right orbitofrontal and inferior frontal gyri than D- patients, whereas A+ patients had this in the right amygdala, temporal, posterior cingulate, right superior frontal, postcentral, and left superior temporal gyri than A- patients. The negatively correlated areas with depression subscores included the left inferior frontal and the right middle frontal gyri and those with apathy subscores included the right temporal and right medial frontal gyri. We suggest that this finding may indicate that apathy and depression in AD patients involve distinct functional circuits.

Depression in Taiwanese patients with Alzheimer's disease determined by the National Institutes of Mental Health Provisional Criteria

Depression is a common behavioral and psychological symptom of Alzheimer's disease (AD). The aims of the present study were to determine the rate of depression in Taiwanese patients with AD using the National Institutes of Mental Health Provisional Criteria for Depression in AD (NIMH-dAD criteria) and to investigate the association of depression with other behavioral and psychological symptoms. A consecutive series of 302 AD patients registered in a dementia clinic were investigated in this study. All patients met the criteria of the National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association for probable AD. The rates of depression were determined according to the criteria of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders for major depression (DSM-IV), the International Classification of Diseases-9-Clinical Modification (ICD-9-CM) for neurotic depression, the depression subscale of the Neuropsychiatric Inventory (NPI), and the NIMH-dAD criteria. Depression severity was assessed using the 17-item Hamilton Depression Rating Scale. The rates of depression determined by the NIMH-dAD criteria were compared with the rates derived from each of the other instruments. Other behavioral and psychological symptoms were assessed using NPI. A behavioral neurologist or a geriatric psychiatrist interviewed all the patients. Using the NIMH-dAD criteria, it was found that 90 (29.8%) of the AD patients had depression, and all depressive symptoms in NIMH-dAD were significantly higher among depressed patients. Among other depression instruments, the frequency of depression was lowest using the DSM-IV major depression criteria (9.3%) and highest with the NPI depression subscale (54%). Behavioral and psychological symptoms determined with NPI were significantly higher among depressed patients in all domains except euphoria. This is the first study of depression in Taiwanese patients with AD using the NIMH-dAD criteria. Our findings suggest that comorbid depression is high in Taiwanese patients with AD. It is clinically important to note the high frequency of most behavioral and psychological symptoms among depressed AD patients.

Depression and Brain-derived Neurotrophic Factor Levels in Alzheimer's Disease

Background: Depression is often viewed as a risk factor for the development of Alzheimer's disease (AD), however little is known regarding the underlying biological mechanisms linking these two diseases. Brain-derived neurotrophic factor (BDNF) has been linked to both cognitive impairment and depression in past research; however few studies have ex-amined this relation in a sample of Alzheimer's patients. The present study sought to address this gap in the literature by examining the relation between serum BDNF levels and depression assessed by the Geriatric Depression Scale (GDS) in a group of patients diagnosed with probable Alzheimer's disease. Methods: Participants included 169 individuals diagnosed with Probable AD enrolled in the TARC Longitudinal Research Cohort with available BDNF levels and GDS scores. The participants were divided into Depressed (N = 20) and Not Depressed (N = 149) based on GDS scores. Re-sults: BDNF levels significantly predicted level (High vs. Low) of depression (β = 0.066, SE = 0.031, p = 0.034). BDNF levels for the Depressed group were significantly higher than those observed in the Not Depressed group (p. > 0.036). Conclusions: These findings suggest that an upregulation of BDNF possibly exists among depressed AD patients as a response to the chronic inflammatory processes that occur in depression. This upregulation of BDNF appears to persist at least into early stages of Alzheimer's.

Antidepressants are a rational complementary therapy for the treatment of Alzheimer's disease

There is a high prevalence rate (30-50%) of Alzheimer's disease (AD) and depression comorbidity. Depression can be a risk factor for the development of AD or it can be developed secondary to the neurodegenerative process. There are numerous documented diagnosis and treatment challenges for the patients who suffer comorbidity between these two diseases. Meta analysis studies have provided evidence for the safety and efficacy of antidepressants in treatment of depression in AD patients. Preclinical and clinical studies show the positive role of chronic administration of selective serotonin reuptake inhibitor (SSRI) antidepressants in hindering the progression of the AD and improving patient performance. A number of clinical studies suggest a beneficial role of combinatorial therapies that pair antidepressants with FDA approved AD drugs. Preclinical studies also demonstrate a favorable effect of natural antidepressants for AD patients. Based on the preclinical studies there are a number of plausible antidepressants effects that may modulate the progression of AD. These effects include an increase in neurogenesis, improvement in learning and memory, elevation in the levels of neurotrophic factors and pCREB and a reduction of amyloid peptide burden. Based on this preclinical and clinical evidence, antidepressants represent a rational complimentary strategy for the treatment of AD patients with depression comorbidity.

Hypothalamic Vasopressin and Oxytocin mRNA Expression in Relation to Depressive State in Alzheimer’s Disease: A Difference With Major Depressive Disorder

Arginine vasopressin (AVP) and oxytocin (OXT), produced in the hypothalamic paraventricular (PVN) and supraoptic nucleus (SON), are considered to be involved in the pathophysiology of major depressive disorder (MDD). The objective of this study was to determine, for the first time, the relationship between AVP and OXT gene expression and depressive state in Alzheimer's disease (AD). Post-mortem brain tissue was obtained from six control subjects, and from a prospectively studied cohort of 23 AD patients, using the DSM-IIIR and the Cornell Scale for Depression in Dementia to determine depression diagnosis and severity. The amount of AVP and OXT mRNA was determined by in situ hybridisation. AD patients did not differ from controls with respect to the amount of AVP or OXT mRNA in the PVN or SON. Also, no differences were found between depressed and nondepressed AD patients and no relationship was found between the depression severity and AVP or OXT mRNA expression. The results indicate that AVP and OXT gene expression in the PVN and SON is unchanged in depressed AD patients compared to nondepressed AD patients. This is in contrast with the enhanced AVP gene expression in MDD, suggesting a difference in pathophysiology between MDD and depression in AD.

Resolving the relationship between ApolipoproteinE and depression

Several studies have reported an association between the ApolipoproteinE-ɛ4 (APOE4) allele and depression among elders. However others have failed to find an association. Since APOE4 is a well recognized risk factor for Alzheimer dementia, cognitive status may represent an important confounder between APOE4 and depression. In this investigation, we examined the relationship between the ApolipoproteinE-ɛ4 allele and depression among elders accounting for cognitive status. Using a case-control design ( n = 1052), we investigated the association between ApolipoproteinE-ɛ4 and depression in Alzheimer disease patients ( n = 528) and in cognitively intact controls ( n = 524). We demonstrated an apparent association between the APOE4 allele and depression in the combined dataset ( p = 0.001) when not controlling for cognitive status. However, once stratified by the presence of Alzheimer disease, there was no association in either the Alzheimer group ( p = 0.290) or the cognitively intact controls ( p = 0.494). In this dataset there is no association between the ApolipoproteinE-ɛ4 allele and depression among those with Alzheimer disease or among cognitively intact elders. However there is a significant association between female gender and depression in the cognitively intact ( p = 0.003) but not among those with Alzheimer disease. Additionally, individuals with Alzheimer disease and depression had a significantly younger age of onset for their Alzheimer disease than those without depression ( p = 0.017).

Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease

Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts.

Comparison of three rating scales as outcome measures for treatment trials of depression in Alzheimer disease: findings from DIADS

Major depression affects about 25% of patients with Alzheimer's disease (AD) and has serious adverse consequences for patients as well as caregivers. Studies of treatments for depression in AD, like most treatment studies, depend on the ability of the scales used to measure outcome to detect a difference between the effects of treatment and control, particularly in trials conducted over waves. To compare the ability of three depression scales, and some of their subscales, to detect the difference in the effects of drug (treatment) and placebo (control). Comparison of three scales of depression in terms of percent variance explained as indicated by the adjusted or partial eta-squared for the effect of drug versus placebo, controlling for baseline depression, in a randomized, placebo-controlled, parallel, 12-week, clinical trial of sertraline for the treatment of depression with AD. University outpatient clinic. Forty-four patients with probable Alzheimer's disease and Major Depressive Episode. The Cornell Scale for Depression in Dementia (CSDD), the Hamilton Depression Rating Scale (HDRS), and the Neuropsychiatric-Inventory Mood Domains (NPI-M). Examination of the treatment effects as indicated by the partial eta-squared's for each scale at each wave, revealed a slight, but not significant, advantage for the use of the CSDD over the HDRS, and a significant advantage for the use of either of these over the NPI-M. Treatment effects, as reflected in the partial eta-squared's computed for the subscales at each wave, were significant for all four subscales, and were largest for the CSDD 'mood' subscale although they were not significantly greater than for the other subscales. The CSDD, and particularly its mood subscale, appears to be more sensitive than the HDRS, it's subscales or the NPI-M, for comparing drug to placebo in treating major depression in AD patients. Treatment effects as reflected in the partial eta-squared's were largest on the CSDD mood subscale and increased over time. The pattern for the other subscales was non-monotonic over waves and resembled the pattern for the entire scale. Perhaps combining the CSDD two subscales obscures the treatment effects for the separate subscales.

P4-203: The effect of cognitive function and depressive mood on the activity of daily living and quality of life in Chinese elderly patients with Alzheimer’s disease

Patients with Alzheimer's disease (AD) are characterized by cognitive decline and depressive mood, resulting in deterioration of their activity of daily living (ADL) and quality of life (QoL). However, how their ADL and QoL are affected have been greatly ignored and not been emphasized in Hong Kong. To validate the assessment “Chinese Version of Quality of Life in Alzheimer's Disease” (CQoL–AD) and to evaluate the effect of cognitive function and depressive mood on ADL and QoL in Chinese patients with AD. This is a cross–sectional study. 121 Chinese AD patients and their caregivers were recruited from three clinical settings by purposeful sampling. The cognitive function was measured by the Cantonese version of Mini Mental State Examination (CMMSE); the depressive mood was measured by the Chinese version of Geriatric Depressive Scale (CGDS); the ADL was measured by the Chinese version of Disability Assessment for Dementia (DAD) and the QoL was measured by the Chinese version of Quality of Life in Alzheimer's Disease (CQoL–AD). Internal consistency, test–retest reliability and inter–rater reliability of CQoL–AD measure from patient report were 0.917, 0.964 and 0.993 respectively, while those from caregiver report were 0.746, 0.966 and 0.996 respectively. Both CQoL–AD scores from patient and caregiver report were not correlated with CMMSE score but had a moderate negative correlation with the CGDS score (r=–0.668 and r=–0.313 respectively). The mean CQoL–AD scores from both patient and caregiver reports were significantly higher in the non–depressed group (34.2 and 31.0 respectively) than in the depressed group (23.8 and 28.9 respectively). The CDAD score was positively correlated with CMMSE score (r=0.652) and negatively correlated with CGDS score (r=– 0.191). The mean CDAD score was significantly higher for those with mild AD (37.8) than those with severe AD (20.6). The mean CDAD score was significantly higher for those non–depressed AD patients (30.2) than those depressed AD patients (26.9). The CQoL–AD is a promising instrument in Chinese AD patients. AD patients with higher cognitive function and lesser depressive symptoms had better performance of ADL than those with lower cognitive function and greater depressive symptoms.

Increased cerebrospinal fluid cortisol level in Alzheimer's disease is not related to depression

Hypothalamo-pituitary-adrenal (HPA)-axis hyperactivity is well established in a large proportion of both Alzheimer's disease (AD) patients and idiopathic depression patients, resulting in, e.g. increased cerebrospinal fluid (CSF) cortisol levels. We hypothesized that HPA-axis activity in depressed AD patients is even more increased than in non-depressed AD patients, resulting in higher CSF cortisol levels. Cortisol levels were measured in post mortem CSF of depressed and non-depressed AD patients and in controls. Cortisol levels in AD patients were more than double those of controls, while no significant differences were found between depressed and non-depressed AD patients. These results suggest a different pathogenetic mechanism in depression in AD than in idiopathic depression.