Longitudinal associations between ß-amyloid and cortical thickness in mild cognitive impairment.

How beta-amyloid accumulation influences brain atrophy in Alzheimer's disease remains contentious with conflicting findings. We aimed to elucidate the correlations of regional longitudinal atrophy with cross-sectional regional and global amyloid in individuals with mild cognitive impairment and no cognitive impairment. We hypothesized that greater cortical thinning over time correlated with greater amyloid deposition, particularly within Alzheimer's disease characteristic regions in mild cognitive impairment, and weaker or no correlations in those with no cognitive impairment. 45 patients with mild cognitive impairment and 12 controls underwent a cross-sectional [11C]-Pittsburgh Compound B PET and two retrospective longitudinal structural imaging (follow-up: 23.65 ± 2.04 months) to assess global/regional amyloid and regional cortical thickness, respectively. Separate linear mixed models were constructed to evaluate relationships of either global or regional amyloid with regional cortical thinning longitudinally. In patients with mild cognitive impairment, regional amyloid in the right banks of the superior temporal sulcus was associated with longitudinal cortical thinning in the right medial orbitofrontal cortex (P = 0.04 after False Discovery Rate correction). In the mild cognitive impairment group, greater right banks amyloid burden and less cortical thickness in the right medial orbitofrontal cortex showed greater visual and verbal memory decline over time, which was not observed in controls. Global amyloid was not associated with longitudinal cortical thinning in any locations in either group. Our findings indicate an increasing influence of amyloid on neurodegeneration and memory along the preclinical to prodromal spectrum. Future multimodal studies that include additional biomarkers will be well-suited to delineate the interplay between various pathological processes and amyloid and memory decline, as well as clarify their additive or independent effects along the disease deterioration.

Validation of the Informant Quick Dementia Rating System (QDRS) among Older Adults in Singapore.

BACKGROUND: The Quick Dementia Rating System (QDRS) is a brief and rapid tool that can be administered by an informant without the need for a trained assessor. OBJECTIVE: Our objective was to examine the validity, reliability, and cost-effectiveness of the informant QDRS in a Singapore memory clinic sample. METHODS: We assessed a total of 177 older adults, among whom, 32 had no cognitive impairment (NCI), 61 had mild cognitive impairment (MCI), and 84 had dementia. Elderly underwent 1) the informant QDRS, 2) the Clinical Dementia Rating (CDR) as the gold standard diagnosis, 3) the Mini-Mental State Examination (MMSE), and 4) the Ascertain Dementia 8 (AD8) as comparisons to the QDRS. The extent to which the QDRS may reduce the recruitment cost (time) of clinical trials was also calculated. RESULTS: The QDRS had excellent internal consistency (Cronbach alpha = 0.939). It correlated highly with the CDR-global (R = 0.897), CDR Sum-of-Boxes (R = 0.915), MMSE (R = -0.848), and the AD8 (R = 0.747), showing good concurrent validity. With an optimal cut-off of 1.5 for MCI (sensitivity 85.2%, specificity 96.3%) and 6 for dementia (sensitivity 90.1%, specificity 89.2%), the QDRS achieved a higher overall accuracy of 85.0%, as compared to MMSE (71.2%) and AD8 (73.4%). A simulated clinical trial recruitment scenario demonstrated that pre-screening with the QDRS followed by a confirmatory CDR would reduce the time needed to identify NCI subjects by 23.3% and MCI subjects by 75.3%. CONCLUSION: The QDRS is a reliable cognitive impairment screening tool which is suitable for informant-administration, especially for identification of MCI.

SINgapore GERiatric intervention study to reduce physical frailty and cognitive decline (SINGER)-pilot: A feasibility study.

INTRODUCTION: The SINGER pilot randomized controlled trial aims to examine the feasibility and acceptability of the Finnish Geriatric Intervention Study (FINGER) multi-domain lifestyle interventions compared to Singaporean adaptations. METHODS: Seventy elderly participants were recruited and randomized into FINGER (n = 36) or SINGER (n = 34) interventions; involving physical exercise, cognitive training, diet, and vascular risk factors management, for 6 months. RESULTS: Both intervention groups were equally feasible and acceptable with participants completing at least 80% of the interventions. Body strength improved in both groups (Pupper body = .04, P lower body = .06, P core = .05). More participants in the SINGER group attained good blood pressure control at month-6 compared to FINGER (41% vs 19%; P = .06). DISCUSSION: This study is the first to compare the feasibility of multi-domain interventions adapted to local culture with the FINGER interventions. The findings will be utilized for a larger study to provide evidence for the efficacy of multi-domain lifestyle interventions in preventing cognitive decline.

Cerebral microinfarcts affect brain structural network topology in cognitively impaired patients.

Cerebral microinfarcts (CMIs), a novel cerebrovascular marker, are prevalent in Alzheimer's disease (AD) and associated with cognitive impairment. Nonetheless, the underlying mechanism of how CMIs influence cognition remains uncertain. We hypothesized that cortical-CMIs disrupted structural connectivity in the higher-order cognitive networks, leading to cognitive impairment. We analyzed diffusion-MRI data of 92 AD (26 with cortical-CMIs) and 110 cognitive impairment no dementia patients (CIND, 28 with cortical-CMIs). We compared structural network topology between groups with and without cortical-CMIs in AD/CIND, and tested whether structural connectivity mediated the association between cortical-CMIs and cognition. Cortical-CMIs correlated with impaired structural network topology (i.e. lower efficiency/degree centrality in the executive control/dorsal attention networks in CIND, and lower clustering coefficient in the default mode/dorsal attention networks in AD), which mediated the association of cortical-CMIs with visuoconstruction dysfunction. Our findings provide the first in vivo human evidence that cortical-CMIs impair cognition in elderly via disrupting structural connectivity.

Distinct BOLD variability changes in the default mode and salience networks in Alzheimer's disease spectrum and associations with cognitive decline.

Optimal levels of intrinsic Blood-Oxygenation-Level-Dependent (BOLD) signal variability (variability hereafter) are important for normative brain functioning. However, it remains largely unknown how network-specific and frequency-specific variability changes along the Alzheimer's disease (AD) spectrum and relates to cognitive decline. We hypothesized that cognitive impairment was related to distinct BOLD variability alterations in two brain networks with reciprocal relationship, i.e., the AD-specific default mode network (DMN) and the salience network (SN). We examined variability of resting-state fMRI data at two characteristic slow frequency-bands of slow4 (0.027-0.073 Hz) and slow5 (0.01-0.027 Hz) in 96 AD, 98 amnestic mild cognitive impairment (aMCI), and 48 age-matched healthy controls (HC) using two commonly used pre-processing pipelines. Cognition was measured with a neuropsychological assessment battery. Using both global signal regression (GSR) and independent component analysis (ICA), results generally showed a reciprocal DMN-SN variability balance in aMCI (vs. AD and/or HC), although there were distinct frequency-specific variability patterns in association with different pre-processing approaches. Importantly, lower slow4 posterior-DMN variability correlated with poorer baseline cognition/smaller hippocampus and predicted faster cognitive decline in all patients using both GSR and ICA. Altogether, our findings suggest that reciprocal DMN-SN variability balance in aMCI might represent an early signature in neurodegeneration and cognitive decline along the AD spectrum.