Dataset Information

Risk Factors, Neuroanatomical Correlates, and Outcome of Neuropsychiatric Symptoms in Alzheimer's Disease.

ABSTRACT: An integrative model of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) is lacking.In this study, we investigated the risk factors, anatomy, biology, and outcomes of NPS in AD.181 subjects were included from the Alzheimer's Disease Neuroimaging Study (ADNI). NPS were assessed with the Neuropsychiatric Inventory Questionnaire at baseline and 6 months. NPI?>3 was used as a threshold for NPS positivity. Three NPS courses were characterized: 1) minimal/absent (negative at 0 and 6 months, n?=?77); 2) fluctuating (positive only at one time point, n?=?53); 3) persistent (positive at both time points, n?=?51). We examined the association between NPS course and family history of dementia, personal history of psychiatric disorders, cerebrospinal fluid biomarkers, atrophy patterns, as well as longitudinal cognitive and functional measures at 12 and 24 months (MMSE, CDR-SOB, FAQ).AD subjects with absent, fluctuating, or persistent NPS had similar CSF amyloid-? and tau levels. AD subjects with minimal/absent NPS had less personal history of psychiatric disorders (35%) than those with fluctuating (57%; p?=?0.015) or persistent NPS (47%, not significant). At 24 months, AD subjects with persistent NPS had worse cognitive (MMSE; p?=?0.05) and functional (CDR-SOB; p?=?0.016) outcomes. Dorsolateral prefrontal atrophy was seen in persistent NPS, but not in fluctuating NPS.Our results suggest that individuals with personal history of psychiatric disorders might be more vulnerable to develop NPS throughout the course of AD. The worst cognitive and functional outcomes associated with NPS in AD underscores the importance of monitoring NPS early in the disease course.

SUBMITTER: Poulin SP

PROVIDER: S-EPMC5963953 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Risk Factors, Neuroanatomical Correlates, and Outcome of Neuropsychiatric Symptoms in Alzheimer's Disease.

Poulin Stéphane P SP Bergeron David D Dickerson Bradford C BC

Journal of Alzheimer's disease : JAD 20170101 2

<h4>Background</h4>An integrative model of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) is lacking.<h4>Objective</h4>In this study, we investigated the risk factors, anatomy, biology, and outcomes of NPS in AD.<h4>Methods</h4>181 subjects were included from the Alzheimer's Disease Neuroimaging Study (ADNI). NPS were assessed with the Neuropsychiatric Inventory Questionnaire at baseline and 6 months. NPI >3 was used as a threshold for NPS positivity. Three NPS courses were characte ...[more]

PMID: 28869463

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Project description:Background: Neuropsychiatric symptoms due to Alzheimer's disease (AD) and mild cognitive impairment (MCI) can decrease quality of life for patients and increase caregiver burden. Better characterization of neuropsychiatric symptoms and methods of analysis are needed to identify effective treatment targets. The current investigation leveraged the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) to examine the network structure of neuropsychiatric symptoms among symptomatic older adults with cognitive impairment. Methods: The network relationships of behavioral symptoms was estimated from Neuropsychiatric Inventory Questionnaire (NPI-Q) data acquired from 12,494 older adults with MCI and AD during their initial visit. Network analysis provides insight into the relationships among sets of symptoms and allows calculation of the strengths of the relationships. Nodes represented individual NPI-Q symptoms and edges represented the pairwise dependency between symptoms. Node centrality was calculated to determine the relative importance of each symptom in the network. Results: The analysis showed patterns of connectivity among the symptoms of the NPI-Q. The network ( M =.28) consisted of mostly positive edges. The strongest edges connected nodes within symptom domain. Disinhibition and agitation/aggression were the most central symptoms in the network. Depression/dysphoria was the most frequently endorsed symptom, but it was not central in the network. Conclusions: Neuropsychiatric symptoms in MCI and AD are highly comorbid and mutually reinforcing. The presence of disinhibition and agitation/aggression yielded a higher probability of additional neuropsychiatric symptoms. Interventions targeting these symptoms may lead to greater neuropsychiatric symptom improvement overall. Future work will compare neuropsychiatric symptom networks across dementia etiologies, informant relationships, and ethnic/racial groups, and will explore the utility of network analysis as a means of interrogating treatment effects.

Project description:BackgroundThe causes of behavioral and psychological symptoms of dementia (BPSD) vary according to the dementia subtype and associated neuropathology. The present study aimed to (i) compare BPSD between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD) across stages, and (ii) explore the associations with diffusion tensor imaging (DTI) in the corpus callosum (CC) and other major fibers.MethodsTwenty-four patients with SIVD and 32 with AD were recruited. Four domains of the Neuropsychiatric Inventory (NPI) (hyperactivity, psychosis, affective, and apathy) and two DTI parameters [fractional anisotropy (FA) and mean diffusivity (MD)] within the genu, body (BCC), and splenium (SCC) of the CC and other major fibers were assessed.ResultsOverall, the patients with clinical dementia rating (CDR) 1 ~ 2 had higher scores in apathy domain than those with CDR0.5. Among those with CDR1 ~ 2, SIVD had higher scores in apathy domain than AD. MD values in the BCC/SCC were positively correlated with total NPI score and psychosis, hyperactivity, and apathy domains. FA values in the SCC were inversely correlated with total NPI score and psychosis domain. The correlations were modified by age, the CASI, and CDR scores. Stepwise linear regression models suggested that FA value within the left superior longitudinal fasciculus predicted the hyperactivity domain. MD value within the SCC/left uncinate fasciculus and FA value within the GCC/left forceps major predicted the psychosis domain. MD value within the right superior longitudinal fasciculus and CDR predicted the apathy domain. Further analysis suggested distinct patterns of regression models between SIVD and AD patients.ConclusionWhite matter integrity within the BCC/SCC had associations with multi-domains of BPSD. Our study also identified important roles of regions other than the CC to individual domain of BPSD, including the left superior longitudinal fasciculus to the hyperactivity domain, the left uncinate fasciculus/forceps major to the psychosis domain, and the right superior longitudinal fasciculus to the apathy domain. The neuronal substrates in predicting BPSD were different between SIVD and AD patients. Of note, apathy, which was more profound in SIVD, was associated with corresponding fiber disconnection in line with dementia severity and global cognition decline.

Project description:Early Alzheimer's disease can involve social disinvestment, possibly as a consequence of impairment of nonverbal communication skills. This study explores whether patients with Alzheimer's disease at the mild cognitive impairment or mild dementia stage have impaired recognition of emotions in facial expressions, and describes neuroanatomical correlates of emotion processing impairment. As part of the ongoing PACO study (personality, Alzheimer's disease and behaviour), 39 patients with Alzheimer's disease at the mild cognitive impairment or mild dementia stage and 39 matched controls completed tests involving discrimination of four basic emotions-happiness, fear, anger, and disgust-on photographs of faces. In patients, automatic volumetry of 83 brain regions was performed on structural magnetic resonance images using MAPER (multi-atlas propagation with enhanced registration). From the literature, we identified for each of the four basic emotions one brain region thought to be primarily associated with the function of recognizing that emotion. We hypothesized that the volume of each of these regions would be correlated with subjects' performance in recognizing the associated emotion. Patients showed deficits of basic emotion recognition, and these impairments were correlated with the volumes of the expected regions of interest. Unexpectedly, most of these correlations were negative: better emotional facial recognition was associated with lower brain volume. In particular, recognition of fear was negatively correlated with the volume of amygdala, disgust with pallidum, and happiness with fusiform gyrus. Recognition impairment in mild stages of Alzheimer's disease for a given emotion was thus associated with less visible atrophy of functionally responsible brain structures within the patient group. Possible explanations for this counterintuitive result include neuroinflammation, regional β-amyloid deposition, or transient overcompensation during early stages of Alzheimer's disease.

Project description:BackgroundNeuropsychiatric symptoms (NPS) are common in individuals with Alzheimer's disease (AD) dementia, but substantial heterogeneity exists in the manifestation of NPS. Sex differences may explain this clinical variability. We aimed to investigate the sex differences in the prevalence and severity of NPS in AD dementia.MethodsLiterature searches were conducted in Embase, MEDLINE/PubMed, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, PsycINFO, and Google Scholar from inception to February 2021. Study selection, data extraction, and quality assessment were conducted in duplicate. Effect sizes were calculated as odds ratios (OR) for NPS prevalence and Hedges' g for NPS severity. Data were pooled using random-effects models. Sources of heterogeneity were examined using meta-regression analyses.ResultsSixty-two studies were eligible representing 21,554 patients (61.2% females). The majority of the included studies had an overall rating of fair quality (71.0%), with ten studies of good quality (16.1%) and eight studies of poor quality (12.9%). There was no sex difference in the presence of any NPS (k = 4, OR = 1.35 [95% confidence interval 0.78, 2.35]) and overall NPS severity (k = 13, g = 0.04 [- 0.04, 0.12]). Regarding specific symptoms, female sex was associated with more prevalent depressive symptoms (k = 20, OR = 1.60 [1.28, 1.98]), psychotic symptoms (general psychosis k = 4, OR = 1.62 [1.12, 2.33]; delusions k = 12, OR = 1.56 [1.28, 1.89]), and aberrant motor behavior (k = 6, OR = 1.47 [1.09, 1.98]). In addition, female sex was related to more severe depressive symptoms (k = 16, g = 0.24 [0.14, 0.34]), delusions (k = 10, g = 0.19 [0.04, 0.34]), and aberrant motor behavior (k = 9, g = 0.17 [0.08, 0.26]), while apathy was more severe among males compared to females (k = 11, g = - 0.10 [- 0.18, - 0.01]). There was no association between sex and the prevalence and severity of agitation, anxiety, disinhibition, eating behavior, euphoria, hallucinations, irritability, and sleep disturbances. Meta-regression analyses revealed no consistent association between the effect sizes across studies and method of NPS assessment and demographic and clinical characteristics.DiscussionFemale sex was associated with a higher prevalence and greater severity of several specific NPS, while male sex was associated with more severe apathy. While more research is needed into factors underlying these sex differences, our findings may guide tailored treatment approaches of NPS in AD dementia.

Dataset Information

Risk Factors, Neuroanatomical Correlates, and Outcome of Neuropsychiatric Symptoms in Alzheimer's Disease.

Publications

Risk Factors, Neuroanatomical Correlates, and Outcome of Neuropsychiatric Symptoms in Alzheimer's Disease.

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