Neurovascular Correlates of Cobalamin, Folate, and Homocysteine in Dementia.

BACKGROUND: Cobalamin (Cbl) and folate are common supplements clinicians prescribe as an adjuvant therapy for dementia patients, on the presumption of their neurotrophic and/or homocysteine (Hcy) lowering effect. However, the treatment efficacy has been found mixed and the effects of Cbl/folate/Hcy on the human brain remain to be elucidated. OBJECTIVE: To explore the neurovascular correlates of Cbl/folate/Hcy in Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD). METHODS: Sixty-seven AD patients and 57 SIVD patients were prospectively and consecutively recruited from an outpatient clinic. Multimodal 3-Tesla magnetic resonance imaging was performed to quantitatively evaluate cerebral blood flow (CBF) and white matter integrity. The relationship between neuroimaging metrics and the serum levels of Cbl/folate/Hcy was examined by using the Kruskal-Wallis test, partial correlation analysis, and moderation analysis, at a significance level of 0.05. RESULTS: As a whole, CBF mainly associated with Cbl/folate while white matter hyperintensities exclusively associated with Hcy. As compared with AD, SIVD exhibited more noticeable CBF correlates (spatially widespread with Cbl and focal with folate). In SIVD, a bilateral Cbl-moderated CBF coupling was found between medial prefrontal cortex and ipsilateral basal ganglia, while in the fronto-subcortical white matter tracts, elevated Hcy was associated with imaging metrics indicative of increased injury in both axon and myelin sheath. CONCLUSIONS: We identified the neurovascular correlates of previously reported neurotrophic effect of Cbl/folate and neurotoxic effect of Hcy in dementia. The correlates exhibited distinct patterns in AD and SIVD. The findings may help improving the formulation of supplemental Cbl/folate treatment for dementia.

Effects of Mental Imagery on Prospective Memory: A Process Analysis in Individuals with Amnestic Mild Cognitive Impairment.

INTRODUCTION: Prospective memory (PM) is a multiphasic cognitive function important for autonomy and functional independence but is easily disrupted by pathological aging processes. Through cognitive simulation of perceptual experiences, mental imagery could be an effective compensatory strategy to enhance PM performance. Nevertheless, relevant research in individuals with amnestic mild cognitive impairment (MCI) has been limited, and the underlying mechanism of the therapeutic effect has not been sufficiently elucidated. The present study aimed to examine complex PM performances and the effect of mental imagery on each phase in older adults with MCI and to investigate the underlying cognitive mechanism from a process perspective. METHODS: Twenty-eight MCI and 32 normal aging controls completed a seminaturalistic PM task, in addition to a series of neuropsychological tests. Participants from each group were randomly assigned to a mental imagery condition or a standard repeated encoding condition before performing the PM task. Four indices were used to measure performance in the intention formation, intention retention, intention initiation, and intention execution phases of PM. Performances in each phase was compared between the 2 diagnostic groups and the 2 instruction conditions. RESULTS: The MCI group performed worse than the normal aging group in the intention formation and intention retention phases. The participants in the mental imagery condition performed significantly better than those in the standard condition during the intention formation, intention retention, and intention execution phases, regardless of the diagnostic group. Moreover, there was a significant interaction between the group and condition during intention retention, showing that people with MCI benefited even more from mental imagery than normal aging in this phase. Performance in the intention retention phase predicted performance in the intention initiation and intention execution phases. DISCUSSION: PM deficits in MCI mainly manifest during planning and retaining intentions. Mental imagery was able to promote performance in all but the initiation phase, although a trend for improvement was observed in this phase. The effects of mental imagery may be exerted in the intention retention phase by strengthening the PM cue-action bond, thereby facilitating the probability of intention initiation and bolstering fidelity to the original plan during intention execution.

Discriminating subcortical ischemic vascular disease and Alzheimer's disease by diffusion kurtosis imaging in segregated thalamic regions.

Differentiating between subcortical ischemic vascular disease (SIVD), Alzheimer's disease (AD), and normal cognition (NC) remains a challenge, and reliable neuroimaging biomarkers are needed. The current study, therefore, investigated the discriminative ability of diffusion kurtosis imaging (DKI) metrics in segregated thalamic regions and compare with diffusion tensor imaging (DTI) metrics. Twenty-three SIVD patients, 30 AD patients, and 24 NC participants underwent brain magnetic resonance imaging. The DKI metrics including mean kurtosis (MK), axial kurtosis (Kaxial ) and radial kurtosis (Kradial ) and the DTI metrics including diffusivity and fractional anisotropy (FA) were measured within the whole thalamus and segregated thalamic subregions. Strategic correlations by group, thalamo-frontal connectivity, and canonical discriminant analysis (CDA) were used to demonstrate the discriminative ability of DKI for SIVD, AD, and NC. Whole and segregated thalamus analysis suggested that DKI metrics are less affected by white matter hyperintensities compared to DTI metrics. Segregated thalamic analysis showed that MK and Kradial were notably different between SIVD and AD/NC. The correlation analysis between Kaxial and MK showed a nonsignificant relationship in SIVD group, a trend of negative relationship in AD group, and a significant positive relationship in NC group. A wider spatial distribution of thalamo-frontal connectivity differences across groups was shown by MK compared to FA. CDA showed a discriminant power of 97.4% correct classification using all DKI metrics. Our findings support that DKI metrics could be more sensitive than DTI metrics to reflect microstructural changes within the gray matter, hence providing complementary information for currently outlined pathogenesis of SIVD and AD.