Effects of interventions on cerebral perfusion in the Alzheimer's disease spectrum: A systematic review.

Cerebral perfusion dysfunctions are seen in the early stages of Alzheimer's disease (AD). We systematically reviewed the literature to investigate the effect of pharmacological and non-pharmacological interventions on cerebral hemodynamics in randomized controlled trials involving AD patients or Mild Cognitive Impairment (MCI) due to AD. Studies involving other dementia types were excluded. Data was searched in April 2021 on MEDLINE, Embase, and Web of Science. Risk of bias was assessed using Cochrane Risk of Bias Tool. A meta-synthesis was performed separating results from MCI and AD studies. 31 studies were included and involved 310 MCI and 792 CE patients. The MCI studies (n = 8) included physical, cognitive, dietary, and pharmacological interventions. The AD studies (n = 23) included pharmacological, physical interventions, and phytotherapy. Cerebral perfusion was assessed with PET, ASL, Doppler, fNIRS, DSC-MRI, Xe-CT, and SPECT. Randomization and allocation concealment methods and subject characteristics such as AD-onset, education, and ethnicity were missing in several papers. Positive effects on hemodynamics were seen in 75 % of the MCI studies, and 52 % of the AD studies. Inserting cerebral perfusion outcome measures, together with established AD biomarkers, is fundamental to target all disease mechanisms and understand the role of cerebral perfusion in AD.

Topography of Cholinergic Changes in Dementia With Lewy Bodies and Key Neural Network Hubs.

OBJECTIVES: The authors investigated the topography of cholinergic vulnerability in patients with dementia with Lewy bodies (DLB) using positron emission tomography (PET) imaging with the vesicular acetylcholine transporter (VAChT) [18F]-fluoroethoxybenzovesamicol ([18F]-FEOBV) radioligand. METHODS: Five elderly participants with DLB (mean age, 77.8 years [SD=4.2]) and 21 elderly healthy control subjects (mean age, 73.62 years [SD=8.37]) underwent clinical assessment and [18F]-FEOBV PET. RESULTS: Compared with the healthy control group, reduced VAChT binding in patients with DLB demonstrated nondiffuse regionally distinct and prominent reductions in bilateral opercula and anterior cingulate to mid-cingulate cortices, bilateral insula, right (more than left) lateral geniculate nuclei, pulvinar, right proximal optic radiation, bilateral anterior and superior thalami, and posterior hippocampal fimbria and fornices. CONCLUSIONS: The topography of cholinergic vulnerability in DLB comprises key neural hubs involved in tonic alertness (cingulo-opercular), saliency (insula), visual attention (visual thalamus), and spatial navigation (fimbria/fornix) networks. The distinct denervation pattern suggests an important cholinergic role in specific clinical disease-defining features, such as cognitive fluctuations, visuoperceptual abnormalities causing visual hallucinations, visuospatial changes, and loss of balance caused by DLB.