FDG Uptake in the Basal Forebrain as Measured by Digital High-Resolution PET Is a Promising Marker of Basal Forebrain Degeneration in the Lewy Body Disease Spectrum

Abstract Introduction Sleep disturbances are common among patients with Lewy body disorders. Idiopathic REM sleep behavior disorder (iRBD) has been identified as a prodromal Lewy body condition with a significantly increased risk of conversion to either Parkinson’s disease (PD) or Dementia with Lewy Bodies (DLB). Pathological involvement of thalamic and brainstem structures involved in sleep regulation has been reported in these disorders, especially in later stages. We hypothesized that progression along the Lewy body disease spectrum may be associated with unique changes in spindle density and EEG power spectra during sleep reflecting involvement of these deep brain structures. Methods A cross-sectional design was used. 9 polysomnography confirmed iRBD, 18 early PD, 23 DLB and 13 controls underwent overnight polysomnography, neurological and neuropsychological assessment. Power spectrum analysis during NREM and REM sleep was undertaken using a previously validated quantitative EEG algorithm and compared between groups. Following artefact and outlier removal, results were analysed using the Cz derivation. Groups were statistically compared with a non-parametric Jonckheree-Terpstra test for ordered alternatives, controlling for age and sex. Results We found a significant and ordered reduction in power in the spindle frequency band (12-15 Hz) in NREM sleep across the Lewy body disease spectrum compared to controls (Controls > iRBD > early PD > DLB; TJT = 521.00, z = -2.902. p<0.001). In REM sleep we found a shift in power to slower frequencies with increased power in the theta (4.5-8 Hz) band in order of disease severity (DLB > early PD > iRBD > Controls; TJT = 950.00, z = 2.253. p=0.024). No differences were found across the other frequency bands in NREM or REM sleep. Conclusion There is a significant and progressive reduction in spindle density and corresponding slowing in REM sleep frequencies during sleep with clinical Lewy body staging. Thus, such measures have the potential to be useful biomarkers of progression towards Lewy body dementia from prodromal stages. Support This work was supported by a NHMRC Dementia Team Grant (#1095127), the NHMRC Postgraduate Scholarship and the University of Sydney Research Excellence Initiative 2020 grant.

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Diffuse Lewy body disease: Disease, spectrum disorder or variety of Alzheimer disease

International Journal of Geriatric Psychiatry ◽

10.1002/gps.930070403 ◽

1992 ◽

Vol 7 (4) ◽

pp. 229-234 ◽

Cited By ~ 15

Author(s):

E. Jane Byrne

Keyword(s):

Alzheimer Disease ◽

Lewy Body ◽

Lewy Body Disease ◽

Spectrum Disorder ◽

Diffuse Lewy Body Disease ◽

Disease Spectrum

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Alzheimer - Parkinson Disease Spectrum and Diffuse Lewy Body Disease

Basic, Clinical, and Therapeutic Aspects of Alzheimer’s and Parkinson’s Diseases - Advances in Behavioral Biology ◽

10.1007/978-1-4684-5844-2_79 ◽

1990 ◽

pp. 385-390

Author(s):

Dennis W. Dickson ◽

Howard Crystal ◽

Shu-Hui Yen ◽

Peter Davies

Keyword(s):

Parkinson Disease ◽

Lewy Body ◽

Lewy Body Disease ◽

Diffuse Lewy Body Disease ◽

Disease Spectrum

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Association of β-Amyloid and Basal Forebrain With Cortical Thickness and Cognition in Alzheimer and Lewy Body Disease Spectra

Neurology ◽

10.1212/wnl.0000000000013277 ◽

2021 ◽

pp. 10.1212/WNL.0000000000013277

Author(s):

Han Soo Yoo ◽

Seun Jeon ◽

Enrica Cavedo ◽

MinJin Ko ◽

Mijin Yun ◽

...

Keyword(s):

Cognitive Dysfunction ◽

Cortical Thickness ◽

Basal Forebrain ◽

Lewy Body ◽

Brain Magnetic Resonance Imaging ◽

Lewy Body Disease ◽

Cortical Atrophy ◽

Periventricular White Matter ◽

Intracranial Volume ◽

Β Amyloid

Objective:Cholinergic degeneration and β-amyloid contribute to brain atrophy and cognitive dysfunction in Alzheimer’s disease (AD) and Lewy body disease (LBD), but their relationship has not been comparatively evaluated.Methods:In this cross-sectional study, we recruited 28 normal controls (NC), 55 patients with AD mild cognitive impairment (MCI), 34 patients with AD dementia, 28 patients with LBD MCI, and 51 patients with LBD dementia. The subjects underwent cognitive evaluation, brain magnetic resonance imaging to measure the basal forebrain (BF) volume and global cortical thickness (CTh), and 18F-Florbetaben (FBB) positron emission tomography to measure the standardized uptake value ratio (SUVR). Using general linear models and path analyses, the association of FBB-SUVR and BF volume with the CTh and/or cognitive dysfunction were evaluated in AD spectrum (AD and NC) and LBD spectrum (LBD and NC), respectively. Covariates included age, sex, education, deep and periventricular white matter hyperintensities, intracranial volume, hypertension, diabetes mellitus, and hyperlipidemia.Results:BF volume mediated the association between FBB-SUVR and CTh both in AD and LBD spectra, while FBB-SUVR was associated with CTh independently of BF volume only in LBD spectrum. Significant correlation between voxel-wise FBB-SUVR and CTh was observed only in LBD group. FBB-SUVR was independently associated with widespread cognitive dysfunction both in AD and LBD spectra, especially in the memory domain [standardized beta (B) for AD spectrum = -0.60, B for LBD spectrum = -0.33]. In AD spectrum, BF volume was associated with memory dysfunction (B = 0.18), and CTh was associated with language (B = 0.21) and executive (B = 0.23) dysfunction. In LBD spectrum, however, BF volume and CTh were independently associated with widespread cognitive dysfunction.Conclusions:There is a common β-amyloid-related degenerative mechanism with or without the mediation of BF in AD and LBD spectra, while the association of BF atrophy with cognitive dysfunction is more profound and there is localized β-amyloid-cortical atrophy interaction in LBD spectrum.

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