Reduced substantia innominata volume mediates contributions of microvascular and macrovascular disease to cognitive deficits in Alzheimer's disease

Jaswal, Gurpreet; Swardfager, Walter; Gao, Fuqiang; Nestor, Sean M.; Ganda, Anoop; Cogo-Moreira, Hugo; Sahlas, Demetrios J.; Stuss, Donald T.; Moody, Alan R.; Black, Sandra E.

doi:10.1016/j.neurobiolaging.2018.01.025

Cited by 7 publications

(3 citation statements)

References 43 publications

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“…67,68 Microvascular pathologies, including pericyte loss, BBB breakdown, and reduced vascular density (Figure 1(a)), have also been found at higher incidence in AD patients, as compared to controls. 69,70 The brain microinfarcts and microhemorrhages that are consequences of microvascular occlusions and ruptures are also found in increased number in AD patients as compared to controls. 71 The apolipoprotein E (APOE) e4 allele increases the risk of AD by 3-8-fold and lowers the onset age of AD symptoms by 7-15 years.…”

Section: Cerebral Blood Flow Reductions In Patients With Alzheimer's Diseasementioning

confidence: 99%

Causes and consequences of baseline cerebral blood flow reductions in Alzheimer’s disease

Bracko

Hernández

Park

et al. 2021

J Cereb Blood Flow Metab

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Reductions of baseline cerebral blood flow (CBF) of ∼10–20% are a common symptom of Alzheimer’s disease (AD) that appear early in disease progression and correlate with the severity of cognitive impairment. These CBF deficits are replicated in mouse models of AD and recent work shows that increasing baseline CBF can rapidly improve the performance of AD mice on short term memory tasks. Despite the potential role these data suggest for CBF reductions in causing cognitive symptoms and contributing to brain pathology in AD, there remains a poor understanding of the molecular and cellular mechanisms causing them. This review compiles data on CBF reductions and on the correlation of AD-related CBF deficits with disease comorbidities (e.g. cardiovascular and genetic risk factors) and outcomes (e.g. cognitive performance and brain pathology) from studies in both patients and mouse models, and discusses several potential mechanisms proposed to contribute to CBF reductions, based primarily on work in AD mouse models. Future research aimed at improving our understanding of the importance of and interplay between different mechanisms for CBF reduction, as well as at determining the role these mechanisms play in AD patients could guide the development of future therapies that target CBF reductions in AD.

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Section: Cerebral Blood Flow Reductions In Patients With Alzheimer's Diseasementioning

confidence: 99%

Causes and consequences of baseline cerebral blood flow reductions in Alzheimer’s disease

Bracko

Hernández

Park

et al. 2021

J Cereb Blood Flow Metab

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“…The LPO process induces the primary form of sporadic type of Parkinson disease (PD) [66]. Mainly, dopaminergic neuron damage occurs in the substantia nigra, locus ceruleus, dorsal motor nucleus and substantia innominata [67]. The sign of movement problems is festinating gait; rigidity of limbs; poverty of voluntary movement; and rolling type of tremor.…”

Section: Role Of Lpo In Parkinson Diseasementioning

confidence: 99%

Role of Lipid Peroxidation Process in Neurodegenerative Disorders

Muthuraman¹,

Rishitha²,

Paramakrishnan³

et al. 2020

Lipid Peroxidation Research

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Lipid peroxidation is one of the primary events of the cell injury process. In pathophysiological condition, it is undergoing the initiation of organ damage. Various free radicals are playing a key role in this lipid peroxidation process. Free radical associated organ damage involves the three major phases, that is, initiation, propagation and termination. The primary source of various free radical formations is mediated through the pathophysiological function of mitochondria. Lipid peroxidation is contributed to the multiple neurodegenerative disorders. Thus, the various endogenous cellular anti-oxidant systems are regulated lipid peroxidation process and control the neurodegenerative action. Some of the molecules are targeted to attenuate the lipid peroxidation and their mediators for the prevention of neurodegeneration.

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“…Furthermore, losses of cholinergic pathways assessed using the cholinergic pathways hyperintensities scale (CHIPS) were associated with vascular cognitive dysfunction [ 23 , 24 ]. However, although several studies have demonstrated the associations between SVD and some cholinergic markers (e.g., cerebral AChE activity [ 25 ] and substantia innominate/BF volume [ 26 , 27 ]) in AD, these findings are inconsistent and inadequate. Whether and how SVD impacts the integrity of the cholinergic NBM and WM pathways in AD progression remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Effect of cerebral small vessel disease on the integrity of cholinergic system in mild cognitive impairment patients: a longitudinal study

Qiu,

Hong,

Zeng

et al. 2024

J Neurol

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We aimed to investigate the effect of cerebral small vessel disease (SVD) on cholinergic system integrity in mild cognitive impairment (MCI) patients. Nucleus basalis of Meynert (NBM) volume and cholinergic pathways integrity was evaluated at baseline, 1-, 2-, and 4-year follow-ups in 40 cognitively unimpaired (CU) participants, 29 MCI patients without SVD, and 23 MCI patients with SVD. We compared cholinergic markers among three groups and examined their associations with SVD burden in MCI patients. We used linear mixed models to assess longitudinal changes in cholinergic markers over time among groups. Mediation analysis was employed to investigate the mediating role of cholinergic system degeneration between SVD and cognitive impairment. Increased mean diffusivity (MD) in medial and lateral pathways was observed in MCI patients with SVD compared to those without SVD and CU participants. Both MCI groups showed decreased NBM volume compared to CU participants, while there was no significant difference between the two MCI groups. Longitudinally, compared to CU participants, MCI patients with SVD displayed a more rapid change in MD in both pathways, but not in NBM volume. Furthermore, SVD burden was associated with cholinergic pathway disruption and its faster rate of change in MCI patients. However, mediation analyses showed that cholinergic pathways did not mediate significant indirect effects of SVD burden on cognitive impairment. Our findings suggest that SVD could accelerate the degeneration of cholinergic pathways in MCI patients. However, they do not provide evidence to support that SVD could contribute to cognitive impairment through cholinergic system injury.

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Reduced substantia innominata volume mediates contributions of microvascular and macrovascular disease to cognitive deficits in Alzheimer's disease

Cited by 7 publications

References 43 publications

Causes and consequences of baseline cerebral blood flow reductions in Alzheimer’s disease

Causes and consequences of baseline cerebral blood flow reductions in Alzheimer’s disease

Role of Lipid Peroxidation Process in Neurodegenerative Disorders

Effect of cerebral small vessel disease on the integrity of cholinergic system in mild cognitive impairment patients: a longitudinal study

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