scholarly journals Neuroinflammation, Depressive Affect, and Amyloid Burden in Alzheimer's Disease: Insights from the Kynurenine Pathway

2020 ◽  
Author(s):  
Auriel Willette ◽  
Colleen Pappas ◽  
Nathan Hoth ◽  
Qian Wang ◽  
Brandon Klinedinst ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Gray Matter ◽  
Functional Outcomes ◽  
Executive Dysfunction ◽  
Functional Independence ◽  
Anterior Cingulate ◽  
Inflammatory Factors ◽  
Depressive Affect

Background: Depressive symptoms in Alzheimer's disease (AD) predict worse cognitive and functional outcomes. Both AD and major depression are characterized by shunted tryptophan metabolism away from serotonin (5-HT) and toward the neuroinflammatory kynurenine (Kyn) pathway. The present study assessed the role of Kyn across the AD continuum in behavioral, neuroanatomical, neuropathological, and physiological outcomes. Methods: In 746 participants from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI1) cohort, serum markers of 5-HT, tryptophan, and Kyn were measured and their relationships investigated with immunologic markers, affect and functional outcomes, CSF markers of beta-amyloid (Aβ) and tau, and regional gray matter. Results: A higher Kyn/Tryptophan ratio was linked to many inflammatory markers, as well as lower functional independence and memory scores. A higher Kyn/5-HT ratio showed similar associations, but also strong relationships with depressive affect and neuropsychiatric disturbance, executive dysfunction, and global cognitive decline. Further, gray matter atrophy was seen in hippocampus, anterior cingulate, and prefrontal cortices, as well as greater amyloid and total tau deposition. Finally, using moderated-mediation, several pro-inflammatory factors partially mediated Kyn/5-HT and depressive affect scores in participants with subclinical Aβ (i.e., Aβ-), whereas such associations were fully mediated by Complement 3 in Aβ+ participants. Conclusions: These findings suggest that neuroinflammatory signaling cascades may occur during AD, resulting in increased Kyn metabolism that influences the pathogenesis of depressive symptoms. Aβ and the complement system may be critical contributing factors in this process.

Depressive Symptoms and APOE ε2 Broad the Natural History in Presenilin-1 E280A Familial Early-Onset Alzheimer's Disease

2018 ◽  
Author(s):  
Natalia Acosta-Baena ◽  
Carlos Mario Lopera-Gómez ◽  
Mario César Jaramillo-Elorza ◽  
Margarita Giraldo-Chica ◽  
Mauricio Arcos-Burgos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Natural History ◽  
Early Onset ◽  
Presenilin 1 ◽  
Early Onset Alzheimer’S Disease

scholarly journals Topographic patterns of white matter hyperintensities are associated with multimodal neuroimaging biomarkers of Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Malo Gaubert ◽  
Catharina Lange ◽  
Antoine Garnier-Crussard ◽  
Theresa Köbe ◽  
Salma Bougacha ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Glucose Metabolism ◽  
Corpus Callosum ◽  
Gray Matter ◽  
Fdg Pet ◽  
White Matter Hyperintensities ◽  
Gray Matter Volume ◽  
Matter Volume

Abstract Background White matter hyperintensities (WMH) are frequently found in Alzheimer’s disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with Aβ burden, glucose hypometabolism, and gray matter volume reduction. Methods In a total of 155 participants (IMAP+ cohort) across the cognitive continuum from normal cognition to AD dementia, FLAIR MRI, AV45-PET, FDG-PET, and T1 MRI were acquired. WMH were automatically segmented from FLAIR images. Mean levels of neocortical Aβ deposition (AV45-PET), temporo-parietal glucose metabolism (FDG-PET), and medial-temporal gray matter volume (GMV) were extracted from processed images using established AD meta-signature templates. Associations between AD brain biomarkers and WMH, as assessed in region-of-interest and voxel-wise, were examined, adjusting for age, sex, education, and systolic blood pressure. Results There were no significant associations between global Aβ burden and region-specific WMH. Voxel-wise WMH in the splenium of the corpus callosum correlated with greater Aβ deposition at a more liberal threshold. Region- and voxel-based WMH in the posterior corpus callosum, along with parietal, occipital, and frontal areas, were associated with lower temporo-parietal glucose metabolism. Similarly, lower medial-temporal GMV correlated with WMH in the posterior corpus callosum in addition to parietal, occipital, and fontal areas. Conclusions This study demonstrates that local white matter damage is correlated with multimodal brain biomarkers of AD. Our results highlight modality-specific topographic patterns of WMH, which converged in the posterior white matter. Overall, these cross-sectional findings corroborate associations of regional WMH with AD-typical Aß deposition and neurodegeneration.

Reproducibility of Brain Volume Changes in Longitudinal Voxel-Based Morphometry Between Non-Accelerated and Accelerated Magnetic Resonance Imaging

2021 ◽  
pp. 1-10
Author(s):  
Hidemasa Takao ◽  
Shiori Amemiya ◽  
Osamu Abe ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Magnetic Resonance ◽  
Gray Matter ◽  
Gray Matter Volume ◽  
Elderly Subjects ◽  
Voxel Based Morphometry ◽  
Volume Changes ◽  
Matter Volume ◽  
Healthy Elderly

Background: Scan acceleration techniques, such as parallel imaging, can reduce scan times, but reliability is essential to implement these techniques in neuroimaging. Objective: To evaluate the reproducibility of the longitudinal changes in brain morphology determined by longitudinal voxel-based morphometry (VBM) between non-accelerated and accelerated magnetic resonance images (MRI) in normal aging, mild cognitive impairment (MCI), and Alzheimer’s disease (AD). Methods: Using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 2 database, comprising subjects who underwent non-accelerated and accelerated structural T1-weighted MRI at screening and at a 2-year follow-up on 3.0 T Philips scanners, we examined the reproducibility of longitudinal gray matter volume changes determined by longitudinal VBM processing between non-accelerated and accelerated imaging in 50 healthy elderly subjects, 54 MCI patients, and eight AD patients. Results: The intraclass correlation coefficient (ICC) maps differed among the three groups. The mean ICC was 0.72 overall (healthy elderly, 0.63; MCI, 0.75; AD, 0.63), and the ICC was good to excellent (0.6–1.0) for 81.4%of voxels (healthy elderly, 64.8%; MCI, 85.0%; AD, 65.0%). The differences in image quality (head motion) were not significant (Kruskal–Wallis test, p = 0.18) and the within-subject standard deviations of longitudinal gray matter volume changes were similar among the groups. Conclusion: The results indicate that the reproducibility of longitudinal gray matter volume changes determined by VBM between non-accelerated and accelerated MRI is good to excellent for many regions but may vary between diseases and regions.

scholarly journals Anhedonia in Semantic Dementia—Exploring Right Hemispheric Contributions to the Loss of Pleasure

2021 ◽  
Vol 11 (8) ◽  
pp. 998
Author(s):  
Siobhán R. Shaw ◽  
Hashim El-Omar ◽  
Siddharth Ramanan ◽  
Olivier Piguet ◽  
Rebekah M. Ahmed ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Rating Scale ◽  
Right Hemisphere ◽  
Semantic Knowledge ◽  
Semantic Dementia ◽  
Anterior Cingulate ◽  
Functional Impairments ◽  
Lobe Atrophy

Semantic dementia (SD) is a younger-onset neurodegenerative disease characterised by progressive deterioration of the semantic knowledge base in the context of predominantly left-lateralised anterior temporal lobe (ATL) atrophy. Mounting evidence indicates the emergence of florid socioemotional changes in SD as atrophy encroaches into right temporal regions. How lateralisation of temporal lobe pathology impacts the hedonic experience in SD remains largely unknown yet has important implications for understanding socioemotional and functional impairments in this syndrome. Here, we explored how lateralisation of temporal lobe atrophy impacts anhedonia severity on the Snaith–Hamilton Pleasure Scale in 28 SD patients presenting with variable right- (SD-R) and left-predominant (SD-L) profiles of temporal lobe atrophy compared to that of 30 participants with Alzheimer’s disease and 30 healthy older Control participants. Relative to Controls, SD-R but not SD-L or Alzheimer’s patients showed clinically significant anhedonia, representing a clear departure from premorbid levels. Overall, anhedonia was more strongly associated with functional impairment on the Frontotemporal Dementia Functional Rating Scale and motivational changes on the Cambridge Behavioural Inventory in SD than in Alzheimer’s disease patients. Voxel-based morphometry analyses revealed that anhedonia severity correlated with reduced grey matter intensity in a restricted set of regions centred on right orbitofrontal and temporopolar cortices, bilateral posterior temporal cortices, as well as the anterior cingulate gyrus and parahippocampal gyrus, bilaterally. Finally, regression and mediation analysis indicated a unique role for right temporal lobe structures in modulating anhedonia in SD. Our findings suggest that degeneration of predominantly right-hemisphere structures deleteriously impacts the capacity to experience pleasure in SD. These findings offer important insights into hemispheric lateralisation of motivational disturbances in dementia and suggest that anhedonia may emerge at different timescales in the SD disease trajectory depending on the integrity of the right hemisphere.

scholarly journals Overlap of Pain and Depression Among Nursing Home Residents With Advanced Alzheimer’s Disease and Related Dementia

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 42-43
Author(s):  
Emmanuelle Belanger ◽  
Richard Jones ◽  
Gary Epstein-Lubow ◽  
Kate Lapane
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nursing Home ◽  
Depressive Symptoms ◽  
Hospice Care ◽  
Care Delivery ◽  
Nursing Home Residents ◽  
National Sample ◽  
Fee For Service ◽  
Minimum Dataset

Abstract Physical and psychological suffering are interrelated and should be assessed together as part of palliative care delivery. We aimed to describe the overlap of pain and depressive symptoms among long-stay nursing home (NH) residents with advanced Alzheimer’s disease and related dementia (ADRD), and to determine the incidence of pain and depressive symptoms. We conducted a retrospective study of a US national sample of fee-for-Service Medicare beneficiaries who became long-stay NH residents in 2014-2015, had two consecutive quarterly Minimum Dataset assessments (90 and 180 days +/- 30 days), and had a diagnosis of ADRD in the Chronic Condition Warehouse and moderate to severe cognitive impairment (N= 92,682). We used descriptive statistics and Poisson regression models to examine the incidence of each symptom controlling for age, sex, and concurrent hospice care. Sub-groups with self-reported and observer-rated symptoms (pain/PHQ-9) were modelled separately, as were those switching between the two. The prevalence of depressive symptoms was low (5.7%), while pain was more common (18.2%). Across various subgroups, 2% to 4% had both pain and depression, but between 20% and 25% were treated with both antidepressants and scheduled analgesia. Depressed residents at baseline had an incidence rate ratio (IRR) of pain of 1.2 at the second assessment, while the residents with pain at baseline had an IRR of depressive symptoms of 1.3 at the second assessment. Our results support the expected relationship between pain and depressive symptoms in a national sample of long-stay NH residents with advanced ADRD, suggesting the need for simultaneous clinical management.

scholarly journals Perceived stress and depressive symptoms not neuropsychiatric symptoms predict caregiver burden in Alzheimer’s disease: a cross-sectional study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Manee Pinyopornpanish ◽  
Kanokporn Pinyopornpanish ◽  
Atiwat Soontornpun ◽  
Surat Tanprawate ◽  
Angkana Nadsasarn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Caregiver Burden ◽  
Perceived Stress ◽  
Neuropsychiatric Symptoms ◽  
Cross Sectional Study ◽  
Assessment Tools ◽  
Sectional Study ◽  
Cross Sectional

Abstract Background Caregiver burden affects the caregiver’s health and is related to the quality of care received by patients. This study aimed to determine the extent to which caregivers feel burdened when caring for patients with Alzheimer’s Disease (AD) and to investigate the predictors for caregiving burden. Methods A cross-sectional study was conducted. One hundred two caregivers of patients with AD at Maharaj Nakorn Chiang Mai Hospital, a tertiary care hospital, were recruited. Assessment tools included the perceived stress scale (stress), PHQ-9 (depressive symptoms), Zarit Burden Interview-12 (burden), Clinical Dementia Rating (disease severity), Neuropsychiatric Inventory Questionnaires (neuropsychiatric symptoms), and Barthel Activities Daily Living Index (dependency). The mediation analysis model was used to determine any associations. Results A higher level of severity of neuropsychiatric symptoms (r = 0.37, p < 0.01), higher level of perceived stress (r = 0.57, p < 0.01), and higher level of depressive symptoms (r = 0.54, p < 0.01) were related to a higher level of caregiver burden. The direct effect of neuropsychiatric symptoms on caregiver burden was fully mediated by perceived stress and depressive symptoms (r = 0.13, p = 0.177), rendering an increase of 46% of variance in caregiver burden by this parallel mediation model. The significant indirect effect of neuropsychiatric symptoms by these two mediators was (r = 0.21, p = 0.001). Conclusion Caregiver burden is associated with patients’ neuropsychiatric symptoms indirectly through the caregiver’s depressive symptoms and perception of stress. Early detection and provision of appropriate interventions and skills to manage stress and depression could be useful in reducing and preventing caregiver burden.

scholarly journals Brain mechanisms underlying neuropsychiatric symptoms in Alzheimer’s disease: a systematic review of symptom-general and –specific lesion patterns

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yaojing Chen ◽  
Mingxi Dang ◽  
Zhanjun Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Neuropsychiatric Symptoms ◽  
Onset Time ◽  
Anterior Cingulate ◽  
Neural Basis ◽  
Preclinical Ad ◽  
Disease Stages ◽  
Mild Cognitive Impairment Stage

AbstractNeuropsychiatric symptoms (NPSs) are common in patients with Alzheimer’s disease (AD) and are associated with accelerated cognitive impairment and earlier deaths. This review aims to explore the neural pathogenesis of NPSs in AD and its association with the progression of AD. We first provide a literature overview on the onset times of NPSs. Different NPSs occur in different disease stages of AD, but most symptoms appear in the preclinical AD or mild cognitive impairment stage and develop progressively. Next, we describe symptom-general and -specific patterns of brain lesions. Generally, the anterior cingulate cortex is a commonly damaged region across all symptoms, and the prefrontal cortex, especially the orbitofrontal cortex, is also a critical region associated with most NPSs. In contrast, the anterior cingulate-subcortical circuit is specifically related to apathy in AD, the frontal-limbic circuit is related to depression, and the amygdala circuit is related to anxiety. Finally, we elucidate the associations between the NPSs and AD by combining the onset time with the neural basis of NPSs.

Relation between neuritic plaques and depressive state in Alzheimer's disease

2010 ◽  
Vol 22 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Gerben Meynen ◽  
Heleen Van Stralen ◽  
Jan H. Smit ◽  
Wouter Kamphorst ◽  
Dick F. Swaab ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Temporal Cortex ◽  
Clinical Severity ◽  
Depressive State ◽  
Neuritic Plaques ◽  
Prospective Longitudinal Study ◽  
Severity Of Dementia ◽  
Prospective Longitudinal

Meynen G, Van Stralen H, Smit JH, Kamphorst W, Swaab DF, Hoogendijk WJG. Relation between neuritic plaques and depressive state in Alzheimer's disease.Background:To investigate for the first time in a prospective study the relationship between depressive state and the neuropathological hallmarks of Alzheimer's disease, using a scale for depressive symptoms in dementia, while controlling for clinical severity of dementia.Method:Within the framework of a prospective longitudinal study of depression in Alzheimer's disease, patients with dementia underwent a clinical evaluation every six months during the last years of their lives, using the Cornell scale for depression in dementia to assess depressive symptoms and using the Functional Assessment Staging scale to control for clinical severity of dementia. The brains of 43 Alzheimer patients were obtained. The last clinical evaluations prior to death together with post-mortem neuropathology measures were analysed.Results:We found a correlation between the Cornell scores and the sum score for the density of neuritic plaques in the entire cortex (p = 0.027), and even stronger in the temporal cortex (p = 0.012). The observed correlations were independent of sex, age of death, clinical dementia severity and duration of Alzheimer's disease.Conclusions:This study shows a positive relationship between depressive state at time of death and the presence of neuritic plaques in Alzheimer's disease, which is independent of the clinical severity of dementia.

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