Differential microstructural and morphological abnormalities in mild cognitive impairment and Alzheimer's disease: Evidence from cortical and deep gray matter.

One aim of this study is to use non-Gaussian diffusion kurtosis imaging (DKI) for capturing microstructural abnormalities in gray matter of Alzheimer's disease (AD). The other aim is to compare DKI metrics against thickness of cortical gray matter and volume of deep gray matter, respectively. A cohort of 18 patients with AD, 18 patients with amnestic mild cognitive impairment (MCI), and 18 normal controls underwent morphological and DKI MR imaging. Images were investigated using regions-of-interest-based analyses for deep gray matter and vertex-wise analyses for cortical gray matter. In deep gray matter, more regions showed DKI parametric abnormalities than atrophies at the early MCI stage. Mean kurtosis (MK) exhibited the largest number of significant abnormalities among all DKI metrics. At the later AD stage, diffusional abnormalities were observed in fewer regions than atrophies. In cortical gray matter, abnormalities in thickness were mainly in the medial and lateral temporal lobes, which fit the locations of known early pathological changes. Microstructural abnormalities were predominantly in the parietal and even frontal lobes, which fit the locations of known late pathological changes. In conclusion, MK can complement conventional diffusion metrics for detecting microstructural changes, especially in deep gray matter. This study also provides evidence supporting the notion that microstructural changes predate morphological changes. Hum Brain Mapp 38:2495-2508, 2017. © 2017 Wiley Periodicals, Inc.

Hemisphere, gender and age-related effects on iron deposition in deep gray matter revealed by quantitative susceptibility mapping.

The purpose of this work was to investigate the effects of hemispheric location, gender and age on susceptibility value, as well as the association between susceptibility value and diffusional metrics, in deep gray matter. Iron content was estimated in vivo using quantitative susceptibility mapping. Microstructure was probed using diffusional kurtosis imaging. Regional susceptibility and diffusional metrics were measured for the putamen, caudate nucleus, globus pallidus, thalamus, substantia nigra and red nucleus in 42 healthy adults (age range 25-78 years). Susceptibility value was significantly higher in the left than the right side of the caudate nucleus (P = 0.043) and substantia nigra (P < 0.001). Women exhibited lower susceptibility values than men in the thalamus (P < 0.001) and red nucleus (P = 0.032). Significant age-related increases of susceptibility were observed in the putamen (P < 0.001), red nucleus (P < 0.001), substantia nigra (P = 0.004), caudate nucleus (P < 0.001) and globus pallidus (P = 0.017). The putamen exhibited the highest rate of iron accumulation with aging (slope of linear regression = 0.73 × 10(-3) ppm/year), which was nearly twice those in substantia nigra (slope = 0.40 × 10(-3) ppm/year) and caudate nucleus (slope = 0.39 × 10(-3) ppm/year). Significant positive correlations between the susceptibility value and diffusion measurements were observed for fractional anisotropy (P = 0.045) and mean kurtosis (P = 0.048) in the putamen without controlling for age. Neither correlation was significant after controlling for age. Hemisphere, gender and age-related differences in iron measurements were observed in deep gray matter. Notably, the putamen exhibited the highest rate of increase in susceptibility with aging. Correlations between susceptibility value and microstructural measurements were inconclusive. These findings could provide new clues for unveiling mechanisms underlying iron-related neurodegenerative diseases.

Montreal Cognitive Assessment - Single Cutoff Achieves Screening Purpose.

BACKGROUND AND PURPOSE: The study evaluated the performance between norm-derived age and education adjusted vs single cutoff scores of the Montreal Cognitive Assessment, Hong Kong version (HK-MoCA) in classifying cognitive impairment in Chinese older adults. METHODS: Total scores of HK-MoCA were collected from 315 subjects (128 with dementia, 122 with mild cognitive impairment (MCI) and 65 normal) attending a public district hospital-based cognition clinic from 2012 to 2017. The HK-MoCA total scores were evaluated using different cutoffs. Norm-derived age and education adjusted cutoff scores were at 16th, 7th, and 2nd percentiles. Comparison was made with the single cutoff scores validated in a local study with 21/22 for MCI and 18/19 for dementia. RESULTS: Single cutoff score of HK-MoCA differentiated MCI from normal with sensitivity of 0.861 and specificity of 0.723. To detect dementia, its sensitivity was 0.922, and specificity was 0.923. In identifying cognitive impairment, the sensitivity and specificity were 0.932 and 0.723, respectively. However, age and education adjusted cutoff scores achieved high specificities at all levels of cognitive impairment with trade-off of sensitivities. The accuracy of correctly classifying tested subjects into appropriate groups was 85.3% if single cutoff was used though the consistency between norm-derived cutoffs and expert diagnoses were only 59.0%, 54.2%, and 53.9% at 16th, 7th, and 2nd percentiles, respectively. The consistency decreased with older age and lower education level, and majority of misclassifications were false negatives. CONCLUSION: HK-MoCA is a convenient screening tool to detect cognitive impairment. Administration time is relatively short, and it has incorporated essential cognitive domains. Single cutoff scores with inherent simple education adjustment achieved screening purpose of mild cognitive impairment and dementia in Chinese older adults.

Behavioral activation for dementia caregivers: scheduling pleasant events and enhancing communications.

BACKGROUND: Dementia caregiving is often associated with increase in depressive symptoms and strained relationships. This study tested whether telephone-delivered psychoeducation combined with an enhanced behavioral activation (BA) module had a better effect on the well-being of Alzheimer's caregivers than psychoeducation alone. The focus is on enhancing the competent use of coping skills via BA. The program is delivered by telephone to increase accessibility and sustainability for caregivers. Senior citizens are trained as paraprofessionals to deliver the BA module to increase the potential for sustainability of the program. METHODS AND SUBJECTS: The study compared two telephone interventions using a 4-month longitudinal randomized controlled trial. For the first 4 weeks, all participants received the same psychoeducation program via telephone. Then for the following 4 months, eight biweekly telephone follow-up calls were carried out. For these eight follow-up calls, participants were randomized into either one of the two following groups with different conditions. For the psychoeducation with BA (PsyED-BA) group, participants received eight biweekly sessions of BA practice focused on pleasant event scheduling and improving communications. For the psychoeducation only (PsyED only) group, participants received eight biweekly sessions of general discussion of psychoeducation and related information. A total of 62 family caregivers of persons living with dementia were recruited and 59 (29 in the PsyED-BA group and 30 in the PsyED only group) completed the whole study. RESULTS: As compared to the group with psychoeducation and discussion, the group with enhanced BA had decreased levels of depressive symptoms. The study had a low attrition rate. CONCLUSION: Results suggested that competence-based training could be effectively administered through the telephone with the help of senior citizens trained and engaged as paraprofessionals. Results contribute to the present literature by offering some framework for developing effective, accessible, sustainable, and less costly interventions.

Community-Based HIV-1 Early Diagnosis and Risk Behavior Analysis of Men Having Sex with Men in Hong Kong.

The increasing prevalence of HIV-1 among men having sex with men (MSM) calls for an investigation of HIV-1 prevalence and incidence in MSM by early diagnosis to assist with early preventive interventions in Hong Kong. The participants were recruited randomly from MSM communities within a one-year period. Rapid HIV Test (RHT) and real-time dried blood spot (DBS)-based quantitative polymerase chain reaction (DBS-qPCR) were used for the early diagnosis of 474 participants. Risk behavior analysis was performed by studying information obtained from the participants during the study period. The HIV-1 prevalence and incident rates in the studied MSM population were 4.01% (19/474) and 1.47% (7/474), respectively. Three infected participants were found at the acute phase of infection by DBS-qPCR. Only 46.4% (220/474) MSM were using condoms regularly for anal sex. HIV infection significantly correlated with unprotected receptive anal sex and syphilis infection. An increased number of infections was found among foreign MSM in Hong Kong. This study is the first to use DBS-qPCR to identify acutely infected individuals in a community setting and to provide both the prevalence and incident rates of HIV-1 infection among MSM in Hong Kong. The risk analysis provided evidence that behavior intervention strengthening is necessary to fight against the increasing HIV-1 epidemic among MSM in Hong Kong and surrounding regions in Asia.

Aging in deep gray matter and white matter revealed by diffusional kurtosis imaging.

Diffusion tensor imaging has already been extensively used to probe microstructural alterations in white matter tracts, and scarcely, in deep gray matter. However, results in literature regarding age-related degenerative mechanisms in white matter tracts and parametric changes in the putamen are inconsistent. Diffusional kurtosis imaging is a mathematical extension of diffusion tensor imaging, which could more comprehensively mirror microstructure, particularly in isotropic tissues such as gray matter. In this study, we used the diffusional kurtosis imaging method and a white-matter model that provided metrics of explicit neurobiological interpretations in healthy participants (58 in total, aged from 25 to 84 years). Tract-based whole-brain analyses and regions-of-interest (anterior and posterior limbs of the internal capsule, cerebral peduncle, fornix, genu and splenium of corpus callosum, globus pallidus, substantia nigra, red nucleus, putamen, caudate nucleus, and thalamus) analyses were performed to examine parametric differences across regions and correlations with age. In white matter tracts, evidence was found supportive for anterior-posterior gradient and not completely supportive for retrogenesis theory. Age-related degenerations appeared to be broadly driven by axonal loss. Demyelination may also be a major driving mechanism, although confined to the anterior brain. In terms of deep gray matter, higher mean kurtosis and fractional anisotropy in the globus pallidus, substantia nigra, and red nucleus reflected higher microstructural complexity and directionality compared with the putamen, caudate nucleus, and thalamus. In particular, the unique age-related positive correlations for fractional anisotropy, mean kurtosis, and radial kurtosis in the putamen opposite to those in other regions call for further investigation of exact underlying mechanisms. In summary, the results suggested that diffusional kurtosis can provide measurements in a new dimension that were complementary to diffusivity metrics. Kurtosis together with diffusivity can more comprehensively characterize microstructural compositions and age-related changes than diffusivity alone. Combined with proper model, it may also assist in providing neurobiological interpretations of the identified alterations.

Correlations between microstructural alterations and severity of cognitive deficiency in Alzheimer's disease and mild cognitive impairment: a diffusional kurtosis imaging study.

OBJECT: Diffusional kurtosis imaging (DKI), a natural extension of diffusion tensor imaging (DTI), can characterize non-Gaussian diffusion in the brain. We investigated the capability of DKI parameters for detecting microstructural changes in both gray matter (GM) and white matter (WM) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and sought to determine whether these DKI parameters could serve as imaging biomarkers to indicate the severity of cognitive deficiency. MATERIALS AND METHODS: DKI was performed on 18AD patients and 12 MCI patients. Fractional anisotropy, kurtosis and diffusivity parameters in the temporal, parietal, frontal and occipital lobes were compared between the two groups using Mann-Whitney U test. The correlations between regional DKI parameters and mini-mental state examination (MMSE) score were tested using Pearson's correlation. RESULTS: In ADs, significantly increased diffusivity and decreased kurtosis parameters were observed in both the GM and WM of the parietal and occipital lobes as compared to MCIs. Significantly decreased fractional anisotropy was also observed in the WM of these lobes in ADs. With the exception of fractional anisotropy and radial kurtosis, all the five other DKI parameters exhibited significant correlations with MMSE score in both GM and WM. CONCLUSION: Bearing additional information, the DKI model can provide sensitive imaging biomarkers for assessing the severity of cognitive deficiency in reference to MMSE score and potentially improve early detection and progression monitoring of AD based on characterizing microstructures in both the WM and especially the GM.