Thalamic Involvement in Fluctuating Cognition in Dementia with Lewy Bodies: Magnetic Resonance Evidences

Abstract

Dementia with Lewy bodies (DLB) is characterized by fluctuation in cognition and attention. Thalamocortical connectivity and integrity of thalami are central to attentional function. We hypothesize that DLB patients with marked and frequent fluctuating cognition (flCog) have a loss of thalamocortical connectivity, an intrinsic disruption to thalamic structure and imbalances in thalamic neurotransmitter levels. To test this, magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and proton MR spectroscopy on thalami were performed on 16 DLB, 16 Alzheimer's disease (AD) and 13 healthy subjects. MRI and DTI were combined to subdivide thalami according to their cortical connectivity and to investigate microstructural changes in connectivity-defined thalamic regions. Compared with controls, lower N-acetyl-aspartate/total creatine (NAA/tCr) and higher total choline/total creatine (tCho/tCr) values were observed within thalami of DLB patients. tCho/tCr increase was found within right thalamus of DLB patients as compared with AD. This increase correlated with severity and frequency of flCog. As compared with controls, DLB patients showed bilateral damage within thalamic regions projecting to prefrontal and parieto-occipital cortices, whereas AD patients showed bilateral alteration within thalamic region projecting to temporal cortex. We posit that microstructural thalamic damage and cholinergic imbalance may be central to the etiology of flCog in DLB.

123I-Iodobenzovesamicol SPECT Imaging of Cholinergic Systems in Dementia with Lewy Bodies

“…The present study confirms and complements previous in vivo PET studies as, to date, thalamic cholinergic denervation has been found in only a single small sample of 6 DLB patients (9). In addition, the critical role of the thalamus in DLB was recently highlighted in a multimodal MRI study, and this finding suggested a close relationship between thalamic cholinergic imbalance and fluctuating cognition in DLB (28). At the subcortical level, our findings could provide a differential diagnosis approach with other dementias, such as AD and parkinsonian dementia, which share clinical features with DLB.…”

Structural grey matter changes in the substantia innominata in Alzheimer's disease and dementia with Lewy bodies: a DARTEL‐VBM study

“…Deficits in cognition and cognitive fluctuations are key symptoms in DLB (McKeith et al ., 2005), and whilst the cholinergic system has a key role in cognitive and attentional function (Baxter and Chiba, 1999; Niewiadomska et al ., 2009), the influence of the cholinergic system upon cognitive fluctuations is not currently well understood in DLB. The present study therefore suggests that the SI contributes to the symptom of cognitive fluctuations in DLB, although other evidence has suggested that cognitive fluctuations may also depend upon changes in other brain networks and neurotransmitter systems, as well as cortico‐thalamic disturbances (Delli Pizzi et al ., 2015; Francis et al ., 2006; Peraza et al ., 2014). There was no association between visual hallucinations and SI volume, despite the support for the role of cholinergic dysfunction in visual hallucinations (McKeith et al ., 2000; Perry et al ., 1990a).…”

GABA content within the ventromedial prefrontal cortex is related to trait anxiety

“…a neuronal marker of energetic metabolism whose levels are typically stable in normal conditions (Christiansen et al, 1993;Bogner et al, 2009). TCr has been widely used as an internal reference in 1 H-MRS studies (Gao et al, 2013;Delli Pizzi et al, 2015).…”

“…Peak shifts were restricted to 6 0.05 ppm of the theoretical location. Spectra with artifact and metabolites fits with Cramer Rao Lower Bounds above 20% were excluded (Delli Pizzi et al, 2015). Thus, water signal was used as an internal reference standard to perform absolute tCr quantification (Christiansen et al, 1993;Delli Pizzi et al, 2012, 2013, 2015.…”