Clinical, Neuropsychological, and Neuroimaging Characteristics of Amyloid- positive vs. Amyloid-negative Patients with Clinically Diagnosed Alzheimer’s Disease and Amnestic Mild Cognitive Impairment

Abstract

Background: A significant proportion of patients with clinically diagnosed Alzheimer’s disease (AD) and an even higher proportion of patients with amnestic mild cognitive impairment (aMCI) do not show evidence of amyloid deposition on positron emission tomography (PET) with amyloid-binding tracers such as 11C-labeled Pittsburgh Compound B (PiB). Objective: This study aimed to identify clinical, neuropsychological and neuroimaging factors that might suggest amyloid neuropathology in patients with clinically suspected AD or aMCI. Methods: Forty patients with mild to moderate AD and 23 patients with aMCI who were clinically diagnosed in our memory clinic and had PiB PET scans were included. Clinical, neuropsychologi- cal, and imaging characteristics, such as medial temporal lobe atrophy (MTA) and white matter hy- perintensities (WMH) on MRI and metabolic pattern on 18F-labeled fluorodeoxyglucose (FDG) PET, were compared between patients with PiB positive and negative PET results for AD, aMCI, and all subjects combined, respectively. Results: Compared with PiB positive patients, PiB negative patients had a higher prevalence of hy- pertension history, better performance on the Mini-Mental State Examination, the Rey Auditory Verbal Learning Test, and the Judgement of Line Orientation, lower score of MTA, and were less likely to have temporoparietal-predominant hypometabolism on FDG PET. Affective symptoms were less common in PiB negative patients diagnosed with AD, and the Animal Fluency Test score was higher in PiB negative patients diagnosed with aMCI. Conclusion: : In patients with clinically diagnosed AD or aMCI, absence of a history of hyperten- sion, deficits in verbal learning and memory, visuospatial function, semantic verbal fluency, pres- ence of affective symptoms, MTA on MRI, and temporoparietal hypometabolism on FDG PET suggested amyloid deposition in the brain.

A neuropsychological profile and its correlation with neuroimaging markers in patients with subcortical ischaemic vascular dementia

“…Language function composite was calculated by the average Z score of the Animal Verbal Fluency Test (AVFT), 24 the Vegetable Verbal Fluency Test, 25 the Boston Naming Test (BNT), 26 and the Controlled Oral Word Association Test 27 . Visuospatial function was evaluated by the Z score of the Judgement of Line Orientation Test (JLO) 26 . Because the distributions for the timed cognitive measures of the TMT‐A and the TMT‐B were strongly skewed, these variables were log transformed for analysis.…”

“…The executive function composite was calculated by the average Z score of the Trail Making Test‐B (TMT‐B) 18 and colour‐word condition of the SCWT (SCWT‐CW) 23 . Language function composite was calculated by the average Z score of the Animal Verbal Fluency Test (AVFT), 24 the Vegetable Verbal Fluency Test, 25 the Boston Naming Test (BNT), 26 and the Controlled Oral Word Association Test 27 . Visuospatial function was evaluated by the Z score of the Judgement of Line Orientation Test (JLO) 26 .…”

“…27 Visuospatial function was evaluated by the Z score of the Judgement of Line Orientation Test (JLO). 26 Because the distributions for the timed cognitive measures of the TMT-A and the TMT-B were strongly skewed, these variables were log transformed for analysis. Then, the Z scores of the TMT-A and the TMT-B were multiplied by minus 1 to be consistent with other tests, with a higher score indicating better performance.…”

“…periventricular white matter using the Fazekas scale. 29 PVS was scored as 0 (none), 1 (1-10), 2 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20), 3 (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), and 4 (>40) according to the numbers in basal ganglia (BG) and centrum semiovale (CSO), respectively. 30 The higher score of the left or right hemisphere was used in the analysis for both WMH and PVS.…”

Patients with Alzheimer’s disease dementia show partially preserved parietal ‘hubs’ modeled from resting-state alpha electroencephalographic rhythms

“…In this area of research, previous structural and resting-state functional magnetic resonance imaging (sMRI and rs-fMRI) studies showed colocalized abnormalities in both interhemispheric and intrahemispheric cortical connectivity in ADD patients compared with healthy elderly people (Nold) with unimpaired cognition ( Delbeuck et al, 2003 ; Busche and Konnerth, 2016 ; Nakamura et al, 2017 ). Thanks to the high spatial resolution of MRI techniques (i.e., millimeters), those abnormalities were mainly localized as follows: (1) in the posterior parietal (precuneus) and cingulate cortices of the cortical default mode network (DMN; Bokde et al, 2006 ; Sorg et al, 2007 ; Brier et al, 2012 ; Wang et al, 2013 , 2015 ; Joo et al, 2016 ; Eyler et al, 2019 ; Talwar et al, 2021 ; Zhang et al, 2021 ); (2) in the occipital and inferior parietal gyrus ( Wang et al, 2021 ); and (3) in the medial temporal lobe and other nodes of the limbic system ( Talwar et al, 2021 ).…”