scholarly journals The Cholinergic System, the Adrenergic System and the Neuropathology of Alzheimer’s Disease

2021 ◽  
Vol 22 (3) ◽  
pp. 1273
Author(s):  
Rola A. Bekdash
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinergic System ◽  
Wide Spectrum ◽  
Cholinergic Neurons ◽  
Public Health Problem ◽  
Brain Regions ◽  
Nucleus Basalis ◽  
Adrenergic System ◽  
Major Public Health Problem

Neurodegenerative diseases are a major public health problem worldwide with a wide spectrum of symptoms and physiological effects. It has been long reported that the dysregulation of the cholinergic system and the adrenergic system are linked to the etiology of Alzheimer’s disease. Cholinergic neurons are widely distributed in brain regions that play a role in cognitive functions and normal cholinergic signaling related to learning and memory is dependent on acetylcholine. The Locus Coeruleus norepinephrine (LC-NE) is the main noradrenergic nucleus that projects and supplies norepinephrine to different brain regions. Norepinephrine has been shown to be neuroprotective against neurodegeneration and plays a role in behavior and cognition. Cholinergic and adrenergic signaling are dysregulated in Alzheimer’s disease. The degeneration of cholinergic neurons in nucleus basalis of Meynert in the basal forebrain and the degeneration of LC-NE neurons were reported in Alzheimer’s disease. The aim of this review is to describe current literature on the role of the cholinergic system and the adrenergic system (LC-NE) in the pathology of Alzheimer’s disease and potential therapeutic implications.

scholarly journals Functional connectivity of the nucleus basalis of Meynert in Lewy body dementia and Alzheimer’s disease

2021 ◽  
pp. 1-6
Author(s):  
Julia Schumacher ◽  
Alan J. Thomas ◽  
Luis R. Peraza ◽  
Michael Firbank ◽  
John T. O’Brien ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Lewy Body ◽  
Cholinergic System ◽  
Structural Changes ◽  
Lewy Body Dementia ◽  
Occipital Cortex ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert

ABSTRACT Cholinergic deficits are a hallmark of Alzheimer’s disease (AD) and Lewy body dementia (LBD). The nucleus basalis of Meynert (NBM) provides the major source of cortical cholinergic input; studying its functional connectivity might, therefore, provide a tool for probing the cholinergic system and its degeneration in neurodegenerative diseases. Forty-six LBD patients, 29 AD patients, and 31 healthy age-matched controls underwent resting-state functional magnetic resonance imaging (fMRI). A seed-based analysis was applied with seeds in the left and right NBM to assess functional connectivity between the NBM and the rest of the brain. We found a shift from anticorrelation in controls to positive correlations in LBD between the right/left NBM and clusters in right/left occipital cortex. Our results indicate that there is an imbalance in functional connectivity between the NBM and primary visual areas in LBD, which provides new insights into alterations within a part of the corticopetal cholinergic system that go beyond structural changes.

scholarly journals Anhedonia as a Potential Risk Factor of Alzheimer’s Disease in a Community-Dwelling Elderly Sample: Results from the ZARADEMP Project

2021 ◽  
Vol 18 (4) ◽  
pp. 1370
Author(s):  
David Vaquero-Puyuelo ◽  
Concepción De-la-Cámara ◽  
Beatriz Olaya ◽  
Patricia Gracia-García ◽  
Antonio Lobo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Potential Risk ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Population Sample ◽  
Public Health Problem ◽  
Cox Proportional Hazards ◽  
Community Dwelling ◽  
Major Public Health Problem

(1) Introduction: Dementia is a major public health problem, and Alzheimer’s disease (AD) is the most frequent subtype. Clarifying the potential risk factors is necessary in order to improve dementia-prevention strategies and quality of life. Here, our purpose was to investigate the role of the absence of hedonic tone; anhedonia, understood as the reduction on previous enjoyable daily activities, which occasionally is underdetected and underdiagnosed; and the risk of developing AD in a cognitively unimpaired and non-depressed population sample. (2) Method: We used data from the Zaragoza Dementia and Depression (ZARADEMP) project, a longitudinal epidemiological study on dementia and depression. After excluding subjects with dementia, a sample of 2830 dwellers aged ≥65 years was followed for 4.5 years. The geriatric mental state examination was used to identify cases of anhedonia. AD was diagnosed by a panel of research psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. A multivariate survival analysis and Cox proportional hazards regression model were performed, and the analysis was controlled by an analysis for the presence of clinically significant depression. (3) Results: We found a significant association between anhedonia cases and AD risk in the univariate analysis (hazard ratio (HR): 2.37; 95% CI: 1.04–5.40). This association persisted more strongly in the fully adjusted model. (4) Conclusions: Identifying cognitively intact individuals with anhedonia is a priority to implement preventive strategies that could delay the progression of cognitive and functional impairment in subjects at risk of AD.

scholarly journals THE TRIAL-READY COHORT FOR PRECLINICAL/PRODROMAL ALZHEIMER’S DISEASE (TRC-PAD) – A FUNDAMENTAL ALLY IN AD PREVENTION RESEARCH

2020 ◽  
pp. 1-2
Author(s):  
A.P. Porsteinsson ◽  
E.D. Clark
Keyword(s):  
Public Health ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Financial Burden ◽  
Public Health Problem ◽  
Symptomatic Treatment ◽  
Health Impact ◽  
Major Public Health Problem ◽  
Medical Needs ◽  
Clinical Benefits

Alzheimer’s disease (AD) remains one of our greatest unmet medical needs, without any approved disease-modifying therapies. The emotional and financial burden of AD is enormous and predicted to grow exponentially with increasing median population age, posing a major public health problem. The potential to prevent or improve cognitive decline due to AD has important implications. There are medications currently approved for symptomatic treatment of AD, but they have limited clinical benefits and do not change the ultimate trajectory of the disease. The need to find effective treatments for AD that can prevent, slow, arrest, or even reverse the disease is ever more urgent and interventions that delay the symptomatic onset of AD would have a major public health impact (1).

scholarly journals Atrophy of Basal Forebrain Initiates with Tau Pathology in Individuals at Risk for Alzheimer’s Disease

2019 ◽  
Vol 30 (4) ◽  
pp. 2083-2098
Author(s):  
Jose L Cantero ◽  
Mercedes Atienza ◽  
Carmen Lage ◽  
Laszlo Zaborszky ◽  
Eduard Vilaplana ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Nucleus Basalis ◽  
Tau Pathology ◽  
Projection System ◽  
Prodromal Ad

Abstract Evidence suggests that the basal forebrain (BF) cholinergic system degenerates early in the course of Alzheimer’s disease (AD), likely due to the vulnerability of BF cholinergic neurons to tau pathology. However, it remains unclear whether the presence of tauopathy is the only requirement for initiating the BF degeneration in asymptomatic subjects at risk for AD (AR-AD), and how BF structural deficits evolve from normal aging to preclinical and prodromal AD. Here, we provide human in vivo magnetic resonance imaging evidence supporting that abnormal cerebrospinal fluid levels of phosphorylated tau (T+) are selectively associated with bilateral volume loss of the nucleus basalis of Meynert (nbM, Ch4) in AR-AD individuals. Spreading of atrophy to medial septum and vertical limb of diagonal band Broca (Ch1–Ch2) occurred in both preclinical and prodromal AD. With the exception of A+, all groups revealed significant correlations between volume reduction of BF cholinergic compartments and atrophy of their innervated regions. Overall, these results support the central role played by tauopathy in instigating the nbM degeneration in AR-AD individuals and the necessary coexistence of both AD proteinopathies for spreading damage to larger BF territories, thus affecting the core of the BF cholinergic projection system.

Amyloid-β, tau, and the cholinergic system in Alzheimer’s disease: seeking direction in a tangle of clues

2020 ◽  
Vol 31 (4) ◽  
pp. 391-413 ◽  
Author(s):  
Alireza Majdi ◽  
Saeed Sadigh-Eteghad ◽  
Sepideh Rahigh Aghsan ◽  
Fereshteh Farajdokht ◽  
Seyed Mehdi Vatandoust ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Basal Forebrain ◽  
Cholinergic System ◽  
Amyloid Β ◽  
Cholinergic Neurons ◽  
Clinical Findings ◽  
App Metabolism ◽  
Main Culprit

AbstractThe link between histopathological hallmarks of Alzheimer’s disease (AD), i.e. amyloid plaques, and neurofibrillary tangles, and AD-associated cognitive impairment, has long been established. However, the introduction of interactions between amyloid-beta (Aβ) as well as hyperphosphorylated tau, and the cholinergic system to the territory of descriptive neuropathology has drastically changed this field by adding the theory of synaptic neurotransmission to the toxic pas de deux in AD. Accumulating data show that a multitarget approach involving all amyloid, tau, and cholinergic hypotheses could better explain the evolution of events happening in AD. Various species of both Aβ and tau could be traced in cholinergic neurons of the basal forebrain system early in the course of the disease. These molecules induce degeneration in the neurons of this system. Reciprocally, aberrant cholinergic system modulation promotes changes in amyloid precursor protein (APP) metabolism and tau phosphorylation, resulting in neurotoxicity, neuroinflammation, and neuronal death. Altogether, these changes may better correlate with the clinical findings and cognitive impairment detected in AD patients. Failure of several of Aβ- and tau-related therapies further highlights the need for special attention to molecules that target all of these mentioned pathologic changes. Another noteworthy fact here is that none of the popular hypotheses of AD such as amyloidopathy or tauopathy seem to be responsible for the changes observed in AD alone. Thus, the main culprit should be sought higher in the stream somewhere in APP metabolism or Wnt signaling in the cholinergic system of the basal forebrain. Future studies should target these pathological events.

scholarly journals EEG alpha reactivity and cholinergic system integrity in Lewy body dementia and Alzheimer’s disease

2020 ◽  
Author(s):  
Julia Schumacher ◽  
Alan J. Thomas ◽  
Luis R. Peraza ◽  
Michael Firbank ◽  
Ruth Cromarty ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lewy Body ◽  
Cholinergic System ◽  
Lewy Body Dementia ◽  
Nucleus Basalis ◽  
Cholinergic Innervation ◽  
Alpha Power ◽  
System Integrity ◽  
Eeg Alpha

Abstract Background Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), is characterized by marked deficits within the cholinergic system which are more severe than in Alzheimer’s disease (AD) and are mainly caused by degeneration of the nucleus basalis of Meynert (NBM) whose widespread cholinergic projections provide the main source of cortical cholinergic innervation. EEG alpha reactivity, which refers to the reduction in alpha power over occipital electrodes upon opening the eyes, has been suggested as a potential marker of cholinergic system integrity. Methods Eyes-open and eyes-closed resting state EEG data were recorded from 41 LBD patients, 21 patients with AD, and 41 age-matched healthy controls. Alpha reactivity was calculated as the relative reduction in alpha power over occipital electrodes when opening the eyes. Structural MRI data were used to assess volumetric changes within the NBM using a probabilistic anatomical map. Results Alpha reactivity was reduced in AD and LBD patients compared to controls with a significantly greater reduction in LBD compared to AD. Reduced alpha reactivity was associated with smaller volumes of the NBM across all groups (ρ=0.42, p FDR =0.0001) and in the PDD group specifically (ρ=0.66, p FDR =0.01). Conclusions We demonstrate that LBD patients show an impairment in alpha reactivity upon opening the eyes which distinguishes this form of dementia from AD. Furthermore, our results suggest that reduced alpha reactivity might be related to a loss of cholinergic drive from the NBM, specifically in PDD.

scholarly journals Alzheimer's disease

2000 ◽  
Vol 2 (2) ◽  
pp. 91-100 ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Behavioral Problems ◽  
Imaging Techniques ◽  
Public Health Problem ◽  
Functional Brain Imaging ◽  
Mood Stabilizers ◽  
Major Public Health Problem ◽  
Double Blind ◽  
Cognitive Disturbance

Alzheimer's disease is one of the most devastating brain disorders of elderly humans. It is an undertreated and under-recognized disease that is becoming a major public health problem. The last decade has witnessed a steadily increasing effort directed at discovering the etiology of the disease and developing pharmacological treatment. Recent developments include improved clinical diagnostic guidelines and improved treatment of both cognitive disturbance and behavioral problems. Symptomatic treatment mainly focusing on cholinergic therapy has been clinically evaluated by randomized, double-blind, placebo-controlled, parallel-group studies measuring performance-based tests of cognitive function, activities of daily living, and behavior. Cholinesterase inhibitors, including donepezil, tacrine, rivastigmine, and galantamine are the recommended treatment of cognitive disturbance in patients with Alzheimer's disease. The role of estrogen replacement, anti-inflammatory agents, and antioxidants is controversial and needs further study. Antidepressants, antipsychotics, mood stabilizers, anxiolytics, and hypnotics are used for the treatment of behavioral disturbance. Future directions in the research and treatment of patients with Alzheimer's disease include: applying functional brain imaging techniques in early diagnosis and evaluation of treatment efficacy; development of new classes of medications working on different neurotransmitter systems (cholinergic, glutamatergic, etc), both for the treatment of the cognitive deficit and the treatment of the behavioral disturbances; and developing preventive methods (amyloid p-peptide immunizations and inhibitors of β-secretase and γ-secretase).

Neuropsychiatric Assessment and Intervention in Alzheimer's Disease

1996 ◽  
Vol 8 (S1) ◽  
pp. 25-30 ◽  
Author(s):  
Jeffrey L. Cummings
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Public Health Problem ◽  
The Elderly ◽  
The United States ◽  
Major Public Health Problem ◽  
Dementia Patients ◽  
Intellectual Abilities ◽  
The World ◽  
Eventual Death

Dementia is a major public health problem in the United States and the world, requiring the expenditure of enormous economic and human resources. Dementia is common in the elderly, and, as the size of the aged population increases, the number of dementia victims will rise. Many dementias are fatal, producing the gradual erosion of intellectual abilities and eventual death of the patient. Demands made on family members and caregivers of dementia patients are extraordinary and often result in their emotional and financial exhaustion. Although basic science efforts are devoted to finding a cure for Alzheimer's disease (AD) and other dementing illnesses, there is an urgent need for research that has immediate applicability to the 4 million current dementia patients.

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