Hanna Lu

Disturbance of attention network functions in Chinese healthy older adults: an intra-individual perspective.

BACKGROUND Intra-individual variability (IIV) and the change of attentional functions have been reported to be susceptible to both healthy ageing and pathological ageing. The current study aimed to evaluate the IIV of attention and the age-related effect on alerting, orienting, and executive control in cognitively healthy older adults. METHOD We evaluated 145 Chinese older adults (age range of 65-80 years, mean age of 72.41 years) with a comprehensive neuropsychological battery and the Attention network test (ANT). A two-step strategy of analytical methods was used: Firstly, the IIV of older adults was evaluated by the intraindividual coefficient of variation of reaction time (ICV-RT). The correlation between ICV-RT and age was used to evaluate the necessity of subgrouping. Further, the comparisons of ANT performance among three age groups were performed with processing speed adjusted. RESULTS Persons correlation revealed significant positive correlations between age and IIV (r = 0.185, p = 0.032), age and executive control (r = 0.253, p = 0.003). Furthermore, one-way ANOVA comparisons among three age groups revealed a significant age-related disturbance on executive control (F = 4.55, p = 0.01), in which oldest group (group with age >75 years) showed less efficient executive control than young-old (group with age 65-70 years) (Conventional score, p = 0.012; Ratio score, p = 0.020). CONCLUSION Advancing age has an effect on both IIV and executive attention in cognitively healthy older adults, suggesting that the disturbance of executive attention is a sensitive indicator to reflect healthy ageing. Its significance to predict further deterioration should be carefully evaluated with prospective studies.

Efficiency of Attentional Components in Elderly with Mild Neurocognitive Disorders Shown by the Attention Network Test.

Aims: Complex attention, serving as a main diagnostic item of mild neurocognitive disorders (NCD), has been reported to be susceptible to pathological ageing. This study aimed to evaluate the attention network functions in older adults with subtypes of NCD. Methods: 36 adults with NCD due to Alzheimers disease (NCD-AD), 31 adults with NCD due to vascular disease (NCD-vascular) and 137 healthy controls were recruited. Attention Network Test (ANT) was conducted to assess the efficiency of alerting, orienting and executive control. Results: Significant between-group differences were found in executive control (conventional score: F = 11.472, p < 0.001; ratio score: F = 8.430, p < 0.001) and processing speed (F = 4.958, p = 0.008). NCD subgroups demonstrated poorer performance on the ANT, particularly on executive control (healthy 59.9 ± 45.9, NCD-vascular 88.9 ± 44.8, NCD-AD 97.0 ± 53.9). Moreover, the NCD-AD group showed both less efficient executive control and prominent slowing processing speed (reaction time: healthy 687.5 ± 106.0 ms, NCD-vascular 685.3 ± 97.1 ms, NCD-AD 750.6 ± 132.6 ms). Conclusions: The NCD-vascular group appeared to be less efficient in executive control, while the NCD-AD group demonstrated less effective executive control and also slower processing speed. These results suggest that the characterized performance of ANT, processing speed and executive control in particular, might help differentiate adults at risk of different forms of cognitive impairment.

Associations between Intra-Individual Variability of Reaction Time and Cognitive Function in Cognitively Normal Senior Adults: Still beyond Good or Bad?

Background: Intra-individual (IIV) of reaction time (RT), as the short-term fluctuations of RT-based performance, has been reported to be susceptible to cognitive ageing. The current study aimed to examine IIV of RT and its relationships with cognitive performance in cognitively normal senior adults. Methods: We evaluated 137 community-dwelling elderly (mean age: 72.41 ± 3.99) with a comprehensive neuropsychological battery and a RT-based test. Intraindividual coefficient of variation of reaction time (ICV-RT) was used to evaluate the IIV. Pearson’s correlation and hierarchical multiple regression analyses were employed to assess the relationships between IIV and the scores of cognitive function. Results: Advancing age was accompanied with declined cognitive function and increased IIV. ICV-RT was negatively correlated with the score of Montreal Cognitive Assessment Hong Kong version (HK MoCA) across three types of flanker. Hierarchical multiple regression showed that ICV-RT was a significant predictor of HK MoCA (β = −0.294, p = 0.001). Conclusion: Increased IIV is consistently associated with and contributed to the age-related decline of cognitive performance in senior adults. The utility of IIV in predicting further deterioration should be carefully postulated with prospective studies.

‘Two-level’ measurements of processing speed as cognitive markers in the differential diagnosis of DSM-5 mild neurocognitive disorders (NCD)

Processing speed is an updated diagnostic factor for neurocognitive disorders (NCD) in DSM-5. This study investigated the characteristics of processing speed and their diagnostic values in NCD patients. A flanker test was conducted in 31 adults with NCD due to vascular disease (NCD-vascular), 36 patients with NCD due to Alzheimer’s disease (NCD-AD), and 137 healthy controls. The processing speed was evaluated using two measurements: mean reaction time (RT) and intra-individual variability of RT. Mean RT represents the global processing speed. Intra-individual variability of RT is the short-term fluctuation of RT and consists of two indices, which are intra-individual coefficient of variation of reaction time (ICV-RT) and intra-individual standard deviations (iSD). We observed elevated ICV-RT and iSD in NCD-AD and NCD-vascular patients. Additionally, there was a slowed RT in NCD-AD patients. The intra-individual variability of RT had a moderate power to differentiate NCD subgroups. The mean RT was able to discriminate the NCD-AD from NCD-vascular patients. Our findings highlight the clinical utility of the combined ‘two-level’ measurements of processing speed to distinguish between individuals with different cognitive status. Furthermore, the ‘two-level’ features of processing speed embedded in the psychometric property may also reflect the diverse aetiology underlying certain ‘disease-specific’ neurocognitive disorders.

Utility of Montreal Cognitive Assessment (Hong Kong Version) in the Diagnosis of Mild Neurocognitive Disorders (NCD): NCD due to Alzheimer Disease (NCD-AD) and NCD due to Vascular Disease (NCD-Vascular)

To the Editor: We read with great interest of the study investigating the clinical utility of the Montreal Cognitive Assessment (MoCA) in DSM-5 major and mild neurocognitive disorders (NCD).1 Through receiver operating (ROC) characteristic curve analysis, the diagnostic performance of MoCA by area under the curve (AUC) for MoCA was high for major NCD (AUC value 1⁄4 0.99, 95% confidence interval [CI] 0.98e1.0) and modest for mild NCD (AUC value 1⁄4 0.77, 95% CI 0.67e0.86). The different discriminative powers of MoCA in NCD triggers the underlying concerns that greater heterogeneity of mild NCD would be the possible reason. Indeed, the heterogeneity of NCD could be evaluated from 2 levels. The first level is from the diagnostic classification: NCD refers to a heterogeneous community with diverse etiology, cognitive profiles, and clinical outcomings. Particularly, NCD contains NCD due toAlzheimer disease (NCD-AD) andNCDdue to vascular disease (NCD-vascular).2 The second level is from the individual with old age: intraindividual variability (IIV), as a facet of short-term fluctuations of speed-based test, is a stable characteristic that appears to

The effects of apolipoprotein ε 4 on aging brain in cognitively normal Chinese elderly: a surface-based morphometry study.

BACKGROUND Default mode network (DMN) has been reported to be susceptible to APOE ε 4 genotype. However, the APOE ε 4-related brain changes in young carriers are different from the ones in elderly carriers. The current study aimed to evaluate the cortical morphometry of DMN subregions in cognitively normal elderly with APOE ε 4. METHOD 11 cognitively normal senior APOE ε 4 carriers and 27 matched healthy controls (HC) participated the neuropsychological tests, genotyping, and magnetic resonance imaging (MRI) scanning. Voxel-based morphometry (VBM) analysis was used to assess the global volumetric changes. Surface-based morphometry (SBM) analysis was performed to measure regional gray matter volume (GMV) and gray matter thickness (GMT). RESULTS Advancing age was associated with decreased GMV of DMN subregions. Compared to HC, APOE ε 4 carriers presented cortical atrophy in right cingulate gyrus (R_CG) (GMV: APOE carriers: 8475.23 ± 1940.73 mm3, HC: 9727.34 ± 1311.57 mm3, t = 2.314, p = 0.026, corrected) and left insular (GMT: APOE ε 4 carriers: 3.83 ± 0.37 mm, HC: 4.05 ± 0.25 mm, t = 2.197, p = 0.033, corrected). CONCLUSIONS Our results highlight the difference between different cortical measures and suggest that the cortical reduction of CG and insular maybe a potential neuroimaging marker for APOE 4 ε senior carriers, even in the context of relatively intact cognition.

Mapping the Proxies of Memory and Learning Function in Senior Adults with High-performing, Normal Aging and Neurocognitive Disorders

BACKGROUND Memory and learning, as the core brain function, shows controversial results across studies focusing on aging and dementia. One of the reasons is because of the multi-faceted nature of memory and learning. However, there is still a dearth of comparable proxies with psychometric and morphometric portrait in clinical and non-clinical populations. OBJECTIVE We aim to investigate the proxies of memory and learning function with direct and derived measures and examine their associations with morphometric features in senior adults with different cognitive status. METHODS Based on two modality-driven tests, we assessed the component-specific memory and learning in the individuals with high performing (HP), normal aging, and neurocognitive disorders (NCD) (n = 488). Structural magnetic resonance imaging was used to measure the regional cortical thickness with surface-based morphometry analysis in a subsample (n = 52). METHODS Compared with HP elderly, the ones with normal aging and minor NCD showed declined recognition memory and working memory, whereas had better learning performance (derived scores). Meanwhile, major NCD patients showed more breakdowns of memory and learning function. The correlation between proxies of memory and learning and cortical thickness exhibited the overlapped and unique neural underpinnings. CONCLUSIONS The proxies of memory and learning could be characterized by component-specific constructs with psychometric and morphometric bases. Overall, the constructs of memory are more likely related to the pathological changes, and the constructs of learning tend to reflect the cognitive abilities of compensation.

Impacts of ‘two-level’ variability on the differential power for Montreal Cognitive Assessment (MoCA) in prodromal dementia

We read with great interest of the study defining and validating the screening accuracy of short form Montreal Cognitive Assessment (s-MoCA) in individuals with different cognitive status.1 This 5-min s-MoCA is attractive because it achieves the goal for adequate screening of cognitive impairment in an ageing population. Of particular interest, the ‘disease-specific’ versions of s-MoCA enrolling the items from full MoCA, present different classification accuracy. It is noteworthy to postulate that the alternative items between versions of s-MoCA may due to the underlying heterogeneity driven by two-level variability. The first-level is interindividual variability due to the diagnostic classification: mild cognitive impairment (MCI) and dementia refer to a highly heterogeneous community with diverse aetiology, cognitive profiles and clinical outcomes. It is not surprising to find some commonalities given that the underlying neural basis for cognitive impairment in patients with MCI may present with similar impaired cognitive domain …

Beyond a Differential Diagnosis: Cognitive and Morphometric Decoding of Information Processing Speed in Senior Adults with DSM-5 Mild Neurocognitive Disorders

BACKGROUND Processing speed has been highlighted as a diagnostic item for neurocognitive disorders (NCD) in DSM-5. The utility of information processing speed (IPS) enclosed with multiscale constructs in the diagnosis of NCD warrants exploration. OBJECTIVE We aimed to investigate the IPS with two types of measurements in the patients with NCD due to vascular disease (NCD-vascular) and NCD due to Alzheimers disease (NCD-AD), and examine the associations between IPS measures and morphometric features. METHODS The IPS was evaluated using trail making test (TMT) and flanker test (n = 204). Direct scores, derived scores, and reaction time (RT) were used as IPS measures. Further, surface-based morphometry cortical volume was calculated in a subsample (n = 44) with structural MRI data. RESULTS All IPS measures showed a significant value to differentiate NCD patients from healthy subjects. Only mean RT could distinguish NCD-AD from NCD-vascular groups. TMT-B score and difference score were correlated with gray matter volume (GMV) of inferior frontal gyrus, precuneus and superior temporal cortex. Mean RT was associated with the GMV of post-central gyrus (r = -0.327, p = 0.035), and executive speed was associated with inferior frontal cortex (r = -0.475, p = 0.001), cingulate gyrus (r = -0.497, p = 0.001), and superior temporal gyrus (r = -0.36, p = 0.019). CONCLUSION The cognitive and morphometric correlates of IPS measures indicate that complex IPS might be decomposed into the domain-specific components with corresponding neural underpinnings. Our findings may also provide essential insights into the diagnostic item of NCD.

Aberrant interhemispheric functional connectivity within default mode network and its relationships with neurocognitive features in cognitively normal APOE ε 4 elderly carriers

BACKGROUND Default mode network (DMN) is vulnerable to the effects of APOE genotype. Given the reduced brain volumes and APOE ε 4-related brain changes in elderly carriers, it is less known that whether these changes would influence the functional connectivity and to what extent. This study aimed to examine the functional connectivity within DMN, and its diagnostic value with age-related morphometric alterations considered. METHODS Whole brain and seed-based resting-state functional connectivity (RSFC) analysis were conducted in cognitively normal APOE ε 4 carriers and matched non-carriers (N=38). The absolute values of mean correlation coefficients (z-values) were used as a measure of functional connectivity strength (FCS) between DMN subregions, which were also used to estimate their diagnostic value by receiver-operating characteristic (ROC) curves. RESULTS APOE ε 4 carriers demonstrated decreased interhemispheric FCS, particularly between right hippocampal formation (R.HF) and left inferior parietal lobular (L.IPL) (t=3.487, p<0.001). ROC analysis showed that the FCS of R.HF and L.IPL could differentiate APOE ε 4 carriers from healthy counterparts (AUC value=0.734, p=0.025). Moreover, after adjusting the impact of morphometry, the differentiated value of FCS of R.HF and L.IPL was markedly improved (AUC value=0.828, p=0.002). CONCLUSIONS Our findings suggest that APOE ε 4 allele affects the functional connectivity within posterior DMN, particularly the atrophy-corrected interhemispheric FCS before the clinical expression of neurodegenerative disease.