Regional functional synchronizations in dementia with Lewy bodies and Alzheimer's disease

Abstract

Background:Dementia with Lewy bodies (DLB) is a common cause of dementia in the elderly population after Alzheimer's disease (AD), and at early stages differential diagnosis between DLB and AD might be difficult due to their symptomatic overlap, e.g. cognitive and memory impairments. We aimed to investigate functional brain differences between both diseases in patients recently diagnosed.Methods:We investigated regional functional synchronizations using regional homogeneity (ReHo) in patients clinically diagnosed with DLB (n = 19) and AD (n = 18), and for comparisons we also included healthy controls (HC, n = 16). Patient groups were matched by age, education, and by the level of cognitive impairment (MMSE p-value = 0.36). Additionally, correlations between ReHo values and clinical scores were investigated.Results:The DLB group showed lower ReHo in sensory-motor cortices and higher ReHo in left middle temporal gyrus when compared with HCs (p-value < 0.001 uncorrected). The AD group demonstrated lower ReHo in the cerebellum and higher ReHo in the left/right lingual gyri, precuneus cortex, and other occipital and parietal regions (p-value < 0.001 uncorrected).Conclusions:Our results agree with previous ReHo investigations in Parkinson's disease (PD), suggesting that functional alterations in motor-related regions might be a characteristic of the Lewy body disease spectrum. However, our results in AD contradict previously reported findings for this disease and ReHo, which we speculate are a reflection of compensatory brain responses at early disease stages. ReHo differences between patient groups were at regions related to the default mode and sensory-motor resting state networks which might reflect the aetiological divergences in the underlying disease processes between AD and DLB.

Functional connectivity in dementia with Lewy bodies: A within‐ and between‐network analysis

“…The right motor network showed large clusters of decreased connectivity in DLB within primary motor areas. Sensorimotor networks have been commonly shown to be altered in Lewy body diseases (Tessitore, Giordano, de Micco, Russo, & Tedeschi, ; Wu et al, ; Yu, Liu, Wang, Chen, & Liu, ) and lower connectivity within the motor cortex has been reported previously in DLB (Peraza et al, ; Taylor, Colloby, McKeith, & O'Brien, ). In addition to reduced connectivity within the motor network itself we found that cognitive control areas, such as frontal and default mode areas, were less strongly involved in this network in DLB, which might be related to impairments of voluntary movement control in this disease group.…”

Quantitative electroencephalography as a marker of cognitive fluctuations in dementia with Lewy bodies and an aid to differential diagnosis

“…These findings could be part of the pathology or alternatively, the result of a compensation mechanism that may occur at early stages of AD. At rest, early stage AD patients may have increased activity and functional connectivity in resting state networks which correlate with a lower MMSE score ( Peraza et al, 2016 ). However, at more advanced stages activity and connectivity decrease to levels lower than those seen in controls ( Agosta et al, 2012 ).…”

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

“…Therefore, the pathogenesis of AD is associated with aberrantly increased excitatory transmission and calcium degranulation [101]. Neurodegeneration with defects in the gene encoding IGF-1, IGF-2 and their receptors were observed in AD patients after postmortem examination [102]. Neuronal functions like central and peripheral brain functions are insulin dependent and regulate vasodilatation and vasoconstriction via the PI3K → Akt pathway and MAPK → ET, respectively [100].…”

“…Receptor-mediated vasodilatation through PI3K → Akt by nitric oxide synthase results in the production of nitric oxide and vascular relaxation [100]. In diabetic patients, there is reduced vasodilatation due to aberrant insulin signaling which reduces nitric oxide production and cerebral blood flow resulting in dysfunctional neurons and AD progression [102]. Diabetes affects neuropathological mechanisms in the brain by epigenetic modifications which result in increased susceptibility to insults associated with neurodegenerative impairment [104, 105].…”