scholarly journals Neuroinflammation characterizes the earliest changes in Alzheimer’s disease pathology and associated subjective cognitive impairment in adult hydrocephalus biopsies

2020 ◽  
Author(s):  
Wenrui Huang ◽  
Anne Marie Bartosch ◽  
Harrison Xiao ◽  
Xena Flowers ◽  
Sandra Leskinen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Status ◽  
Subjective Cognitive Decline ◽  
Cognitive Symptoms ◽  
Microglial Phenotype ◽  
Neuronal Genes ◽  
Early Alzheimer’S Disease ◽  
Disease Associated Genes ◽  
Microglial Response

AbstractIn an effort to better characterize the transcriptomic changes that accompany early Alzheimer’s disease (AD) pathology in living patients and correlate with contemporaneous cognitive data, we performed RNA-seq on 106 cortical biopsies that were taken during shunt placement for adult onset hydrocephalus with varying degrees of comorbid AD pathology. A restricted set of genes correlate with AD pathology in these biopsies, and co-expression network analysis demonstrates an evolution from microglial homeostasis to a disease-associated microglial phenotype in conjunction with increasing AD pathologic burden, along with a subset of additional astrocytic and neuronal genes that accompany these changes. Further analysis demonstrates that these correlations are driven by patients that report mild cognitive symptoms, despite similar levels of β-amyloid and tau pathology in comparison to patients who report no cognitive symptoms. Interestingly, downregulation of homeostatic genes and upregulation of disease-associated genes also correlate with microglial plaque invasion and an activated microglial morphology, and this change is not sensitive to cognitive status, suggesting that an initial microglial response to AD pathology is eventually maladaptive. Taken together, these findings highlight a restricted set of microglial and non-microglial genes and suggest that early AD pathology is largely characterized by a loss of homeostatic genes and an activated microglial phenotype that continues to evolve in conjunction with accumulating AD pathology in the setting of subjective cognitive decline.

scholarly journals An immune response characterizes early Alzheimer’s disease pathology and subjective cognitive impairment in hydrocephalus biopsies

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenrui Huang ◽  
Anne Marie Bartosch ◽  
Harrison Xiao ◽  
Suvrajit Maji ◽  
Elliot H. H. Youth ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Normal Pressure ◽  
Subjective Cognitive Decline ◽  
Cognitive Symptoms ◽  
Rna Seq ◽  
Microglial Phenotype ◽  
Neuronal Genes ◽  
Β Amyloid ◽  
Early Alzheimer’S Disease

AbstractEarly Alzheimer’s disease (AD) pathology can be found in cortical biopsies taken during shunt placement for Normal Pressure Hydrocephalus. This represents an opportunity to study early AD pathology in living patients. Here we report RNA-seq data on 106 cortical biopsies from this patient population. A restricted set of genes correlate with AD pathology in these biopsies, and co-expression network analysis demonstrates an evolution from microglial homeostasis to a disease-associated microglial phenotype in conjunction with increasing AD pathologic burden, along with a subset of additional astrocytic and neuronal genes that accompany these changes. Further analysis demonstrates that these correlations are driven by patients that report mild cognitive symptoms, despite similar levels of biopsy β-amyloid and tau pathology in comparison to patients who report no cognitive symptoms. Taken together, these findings highlight a restricted set of microglial and non-microglial genes that correlate with early AD pathology in the setting of subjective cognitive decline.

Blink rate study in patients with Alzheimer's disease, Mild Cognitive Impairment and Subjective Cognitive Decline

2021 ◽  
Vol 19 ◽  
Author(s):  
Fabrizia D’Antonio ◽  
Maria Ilenia De Bartolo ◽  
Gina Ferrazzano ◽  
Micaela Sepe Monti ◽  
Letizia Imbriano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Cognitive Status ◽  
Subjective Cognitive Decline ◽  
Blink Rate ◽  
Compensatory Mechanisms ◽  
Rate Study

Background: Blink rate (BR) is considered a marker of dopaminergic activity in humans. BR is increased in patients with Mild Cognitive Impairment (MCI), but no study has yet investigated whether BR changes with the progression of cognitive decline from MCI to Alzheimer’s disease (AD) and whether BR abnormalities are present in subjects with Subjective Cognitive Decline (SCD). Objective: The aim of our study was to assess BR in patients with AD, MCI, and SCD and to correlate BR with demographic and clinical features of cognitive decline. Methods: We enrolled 22 subjects with SCD, 23 with MCI, and 18 with AD and a group of 20 age-matched healthy controls (HCs). Cognitive function was assessed by testing global cognitive status and frontal, attentional, memory, verbal, and visuospatial functions. BR was measured by counting the number of blinks per minute. Results: MCI subjects had an increased BR (p<0.001), whereas AD subjects had a lower BR than HCs (p<0.05). Conversely, SCD subjects had a BR similar to HCs. No significant correlations emerged between neuropsychological scores and BR in SCD, MCI, and AD subjects. Conclusion: Increased BR in MCI likely reflects early compensatory mechanisms occurring before AD, whereas decreased BR in AD suggests dopaminergic system involvement in this condition.

Alzheimer’s Disease Genetics: A Dampened Microglial Response?

2021 ◽  
pp. 107385842110245
Author(s):  
Zena K. Chatila ◽  
Elizabeth M. Bradshaw
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immune ◽  
Regulatory Mechanisms ◽  
Innate Immune Cells ◽  
Genetic Studies ◽  
Age Related ◽  
Microglial Phenotype ◽  
The Central Nervous System ◽  
Microglial Response

Alzheimer’s disease (AD) is a debilitating age-related neurodegenerative condition. Unbiased genetic studies have implicated a central role for microglia, the resident innate immune cells of the central nervous system, in AD pathogenesis. On-going efforts are clarifying the biology underlying these associations and the microglial pathways that are dysfunctional in AD. Several genetic risk factors converge to decrease the function of activating microglial receptors and increase the function of inhibitory receptors, resulting in a seemingly dampened microglial phenotype in AD. Moreover, many of these microglial proteins that are genetically associated with AD appear to interact and share pathways or regulatory mechanisms, presenting several points of convergence that may be strategic targets for therapeutic intervention. Here, we review some of these studies and their implications for microglial participation in AD pathogenesis.

scholarly journals Neuropsychiatric and cognitive symptoms across the Alzheimer’s disease clinical spectrum: Cross-sectional and longitudinal associations

2021 ◽  
Author(s):  
Willem S. Eikelboom ◽  
Esther van den Berg ◽  
Ellen Singleton ◽  
Sara J. Baart ◽  
Michiel Coesmans ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Functioning ◽  
Neuropsychiatric Symptoms ◽  
Clinical Stage ◽  
Clinical Spectrum ◽  
Subjective Cognitive Decline ◽  
Cognitive Symptoms ◽  
Cross Sectional ◽  
Over Time

ABSTRACTObjectiveTo investigate the prevalence and trajectories of neuropsychiatric symptoms (NPS) in relation to cognitive functioning in a cohort of amyloid-β positive individuals across the Alzheimer’s disease (AD) clinical spectrum.MethodsWe included 1,524 amyloid-β positive individuals from the Amsterdam Dementia Cohort with subjective cognitive decline (SCD, n=113), mild cognitive impairment (MCI, n=321), or dementia (n=1,090). We measured NPS with the neuropsychiatric inventory (NPI), examining total scores and the presence of specific NPI-items. Cognition was assessed across five cognitive domains and with the MMSE. We examined trajectories including model based trends for NPS and cognitive functioning over time. We used linear mixed models to relate baseline NPI scores to cognitive functioning at baseline (whole-sample) and longitudinal time-points (subsample n=520, Mean=1.8 [SD=0.7] years follow-up).ResultsNPS were prevalent across all clinical AD stages (NPI total score ≥1 81.4% in SCD, 81.2% in MCI, 88.7% in dementia). Cognitive functioning showed an uniform gradual decline; while in contrast, large intra-individual heterogeneity of NPS was observed over time across all groups. At baseline, we found associations between NPS and cognition in dementia that were most pronounced for NPI total scores and MMSE (range β:-0.18–0.11, FDR-adjusted p<0.05), while there were no cross-sectional relationships in SCD and MCI (β:-0.32– 0.36, FDR-adjusted p>0.05). There were no associations between baseline NPS and cognitive functioning over time in any clinical stage (β:-0.13–0.44, FDR-adjusted p>0.05).ConclusionNPS and cognitive symptoms are both prevalent across the AD continuum, but show a different evolution during the course of the disease.

scholarly journals Cognitive Training Modulates Brain Hypersynchrony in a Population at Risk for Alzheimer’s Disease

2021 ◽  
Author(s):  
Isabel Suárez-Méndez ◽  
Ricardo Bruña ◽  
David López-Sanz ◽  
Pedro Montejo Carrasco ◽  
Mercedes Montenegro-Peña ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Training ◽  
Phase Locking ◽  
Cognitive Status ◽  
Subjective Cognitive Decline ◽  
Post Intervention ◽  
Preclinical Ad ◽  
Increased Risk ◽  
Before And After

Abstract BackgroundRecent neuroimaging studies in humans and animal models of Alzheimer’s disease (AD) demonstrated brain hyper-synchrony under amyloid burden, which is being identified as a proxy for conversion to dementia. The potential of non-pharmacological interventions to reverse this neurophysiological phenomenon in the early stages of the disease is still an open question. MethodBrain synchrony modulation by cognitive training (CogTr) was examined in a cohort of healthy controls (HC, n = 41, 22 trained) and individuals with subjective cognitive decline (SCD, n = 49, 24 trained). Magnetoencephalographic (MEG) activity and comprehensive neuropsychological scores were acquired before and after completion of a ten-week CogTr program aimed at improving cognitive function and daily living performance. Functional connectivity (FC) analyses were carried out using the phase-locking value. A mixed-effects ANOVA with factors stage (pre-intervention or post-intervention), CogTr (trained or non-trained), and cognitive status (HC or SCD) was used to estimate significant FC changes across MEG recordings.ResultsAlpha-band FC increases were observed for the whole sample (both trained and non-trained), but the effect was different in each group. For the trained group (both HC and SCD), we report a reduction in the FC increase within temporo-parietal and temporo-occipital connections. This effect was particularly manifest in trained participants with SCD, for whom the reduction in the FC increase also correlated with enhanced cognitive performance in different neuropsychological domains (memory, language, and executive function).ConclusionsCogTr programs could mitigate the increase in FC observed in preclinical AD, promoting brain synchrony normalization in groups at increased risk for developing the disease.

scholarly journals Alzheimer’s Disease: Pharmacotherapy of subjective cognitive decline

2018 ◽  
pp. 57-62
Author(s):  
Aslam Pathan ◽  
Abdulrahman Alshahrani
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Cognitive Decline ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Subjective Cognitive Decline ◽  
Cognitive Symptoms ◽  
Behavioral Impairment ◽  
Accurate Treatment

Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive and behavioral impairment that significantly interferes with social and occupational functioning. AD is progressive and fatal dementia of unknown cause characterized by loss of cognitive and physical functioning, commonly with behavior or cognitive symptoms. Cognitive decline is gradual and includes memory loss, aphasia, apraxia, agnosia, disorientation, and impaired executive function. physicians will often play a major role in diagnosing and treating dementia and related disorders in the community. Accurate treatment of cognitive symptoms is important. Accordingly, we reviewed the available pharmacotherapy in the clinical management of cognitive symptoms of dementia.

Case Studies in Dementia-Related Anxiety

GeroPsych ◽  
2020 ◽  
pp. 1-6
Author(s):  
Molly Maxfield ◽  
Jennifer R. Roberts ◽  
JoAnna Dieker
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Social Withdrawal ◽  
Cognitive Status ◽  
Generalized Anxiety ◽  
Neurocognitive Disorder ◽  
High Genetic Risk ◽  
Disease Case ◽  
Negative Perceptions

Abstract. Two clients seeking neuropsychological assessment reported anxiety about their cognitive status. We review the cases to increase our understanding of factors contributing to dementia-related anxiety. Case 1 met the criteria for mild neurocognitive disorder; the client’s memory was impaired, and she had a high genetic risk for Alzheimer’s disease. The client reported anxiety about negative perceptions of quality of life among individuals diagnosed with Alzheimer’s disease. Case 2 did not meet the criteria for a neurocognitive disorder. Anxiety about this client’s cognitive status appeared attributable to generalized anxiety disorder, given his anxiety about diverse topics. Both clients reported embarrassment about forgetfulness and social withdrawal. Dementia-related anxiety is believed to be relatively common, to exist on a continuum, to have unique social implications, and to stem from various sources, necessitating differing interventions.

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