Objective: Deficits in the semantic learning strategy were observed in subjects with amnestic mild cognitive impairment (aMCI) in our previous study. In the present study, we explored the contributions of executive function and brain structure changes to the decline in the semantic learning strategy in aMCI. Methods: A neuropsychological battery was used to test memory and executive function in 96 aMCI subjects and 90 age- and gender-matched healthy controls (HCs). The semantic clustering ratio on the verbal learning test was calculated to evaluate learning strategy. Medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) were measured on MRI with the MTA and Fazekas visual rating scales, respectively. Results: Compared to HCs, aMCI subjects had poorer performance in terms of memory, executive function, and the semantic clustering ratio (P < .001). In aMCI subjects, no significant correlation between learning strategy and executive function was observed. aMCI subjects with obvious MTA demonstrated a lower semantic clustering ratio than those without MTA (P < .001). There was no significant difference in the learning strategies between subjects with high-grade WMH and subjects with low-grade WMH. Conclusion: aMCI subjects showed obvious impairment in the semantic learning strategy, which was attributable to MTA but independent of executive dysfunction and subcortical WMH. These findings need to be further validated in large cohorts with biomarkers identified using volumetric brain measurements. (JINS, 2019, 25, 706–717)

This study explored the efficacy of aerobic training (AT) in mitigating white matter hyperintensity (WMH) progression and whether these changes are sex dependent. This was an exploratory analysis of a randomized controlled trial assessing the effect of AT on cognition in people with vascular cognitive impairment. Participants were randomized to a 6 month AT or usual care (control [CON]) group. A subset completed magnetic resonance imaging to quantify WMH volume. Using an analysis of covariance model, we found a significant sex × group interaction (p = .03). Over the 6 month study, AT females demonstrated greater WMH progression than CON females (p = .05). Among males, there was no significant between-group difference (p = .31). Within the AT group, males demonstrated significantly less WMH progression than females (p = .01) at 6 months. Therefore, the effects of AT on WMH progression may vary by sex; that is, AT may curtail WMH progression in males but not females.

Background: To assess the prevalence of three nociceptive primitive reflexes (nPR), i.e., glabellar tap, snout reflex, and palmomental reflex, in neurologically and cognitively healthy (NCH) aging subjects. Objective: To investigate whether nPR are cross-sectionally associated with white matter hyperintensities (WMH), lacunes, atrophy of the caudate nuclei, and global brain atrophy. Methods: A total of 1246 NCH subjects aged 45–91 years were included in the study and underwent standard brain MRI. Atrophy of the caudate nuclei and global brain atrophy were assessed through the bicaudate ratio (BCr) and lateral ventricles to brain ratio (LVBr), respectively. WMH were assessed through visual rating scales. Lacunes were also rated. Association of nPR with vascular risk factors/diseases and imaging findings was evaluated using logistic regression analysis. Results: nPR were exhibited by 33.1% of subjects and increased with age. Subjects with nPR performed less than subjects without nPR in tests evaluating global cognition, executive functions, attention, and language. Snout reflex was the most common nPR, followed by glabellar tap and palmomental reflex. Glabellar tap was associated with parieto-temporal WMH, BCr, and LVBr; snout reflex was associated with frontal lacunes, temporal WMH, BCr, and LVBr; palmomental reflex was associated with parieto-occipital WMH, basal ganglia lacunes, BCr, and LVBr. Conclusions: This study demonstrates that in NCH aging individuals, nPR are associated with WMH, lacunes, BCr, and LVBr and are probably a warning sign of incipient cognitive decline. Therefore, NCH subjects presenting nPR should manage their vascular risk factors/vascular diseases rigorously in order to prevent or delay progression of small vessel disease, and future neurological and cognitive disabilities.

The ventromedial prefrontal cortex's (vMPFC) role in regulating emotions in late life depression (LLD) remains unclarified. We assessed vMPFC activation in an emotional valence blood oxygenation level-dependent (BOLD) functional magnetic neuroimaging (fMRI) task and related the findings to extent of white matter hyperintensities (WMH). Sixteen participants with mild to moderate LLD were compared to 14 similar aged comparison participants. Participants in the scanner viewed words matched for length and arousal, indicated the perceived valence by pressing one of the three buttons i.e. “positive, negative, or neutral.” WMH volume was greater in LLD participants than comparison participants. There were no differences in activations between groups to any valence contrast. Female LLD participants showed greater activation for negative versus positive and negative versus neutral words as compared to female comparison participants. Female LLD participants respond differently to emotionally laden words compared to comparison participants. WMH could play a role in etiopathology of emotional perception in female LLD participants.

Structural brain magnetic resonance imaging (MRI) traits share part of their genetic variance with cognitive traits. Here, we use genetic association results from large meta-analytic studies of genome-wide association (GWA) for brain infarcts (BI), white matter hyperintensities, intracranial, hippocampal, and total brain volumes to estimate polygenic scores for these traits in three Scottish samples: Generation Scotland: Scottish Family Health Study (GS:SFHS), and the Lothian Birth Cohorts of 1936 (LBC1936) and 1921 (LBC1921). These five brain MRI trait polygenic scores were then used to: (1) predict corresponding MRI traits in the LBC1936 (numbers ranged 573 to 630 across traits), and (2) predict cognitive traits in all three cohorts (in 8,115–8,250 persons). In the LBC1936, all MRI phenotypic traits were correlated with at least one cognitive measure, and polygenic prediction of MRI traits was observed for intracranial volume. Meta-analysis of the correlations between MRI polygenic scores and cognitive traits revealed a significant negative correlation (maximal r = 0.08) between the HV polygenic score and measures of global cognitive ability collected in childhood and in old age in the Lothian Birth Cohorts. The lack of association to a related general cognitive measure when including the GS:SFHS points to either type 1 error or the importance of using prediction samples that closely match the demographics of the GWA samples from which prediction is based. Ideally, these analyses should be repeated in larger samples with data on both MRI and cognition, and using MRI GWA results from even larger meta-analysis studies.

Intraindividual variability (IIV) refers to reaction time (RT) variation across the trials of a given cognitive task. Little research has contrasted different measures of IIV or assessed how many RT trials are required to provide a robust measure of the construct. We, therefore, investigated three measures of IIV (raw SD, coefficient of variation, and intraindividual SD statistically removing time-on-task effects) in relation to frontal white matter hyperintensities (obtained through structural MRI) in 415 cognitively normal community-dwelling adults aged 44 to 48 years. Results indicated the three IIV measures did not differ greatly in predictions of white matter hyperintensities, although it is possible that time-on-task effects were influential. As few as 20 trials taking approximately 52 s to administer provided a reliable prediction of frontal white matter hyperintensities. We conclude that future work should evaluate the comparative utility of different IIV measures in relation to persons exhibiting clear neuropathology. (JINS, 2013, 19, 1–6)

Background: White matter hyperintensities (WMH) have frequently been associated with lower executive function performance. Little is known, however, about the effects of hippocampal atrophy on executive control in Alzheimer's disease (AD). The present study focused on the association of hippocampal atrophy with executive function in AD patients and examined whether a threshold effect is present, indicating that a certain amount of brain damage must be present before cognitive function becomes impaired. Finally, we examined the combined effect of hippocampal atrophy and WMH on cognitive task performance.

Methods: We retrospectively collected neuropsychological and neuroimaging data of 94 AD patients. These patients completed tasks of general cognitive function, executive function, memory, and processing speed. With magnetic resonance imaging (MRI), hippocampal atrophy was rated as medial temporal lobe atrophy (MTA) and cerebrovascular disease was rated as WMH using validated visual rating scales.

Results: Medial temporal lobe atrophy (MTA) was associated with lower executive function, general cognitive function, and episodic memory performance. A threshold effect was present, indicating that severe to very severe, but not moderate, MTA was associated with lower executive function. WMH were significantly associated with a single executive test only, whereas the interaction between WMH and MTA was not significantly related to any of the cognitive tasks.

Conclusions: Our findings suggest that AD neuropathology in itself may be responsible for executive dysfunction. Potential explanations for these findings are discussed, focusing on the role of the hippocampus in executive function tests and reduced frontal-posterior connectivity in this patient sample.

‘Cerebral small vessel disease’ is common in older adults and is an important cause of morbidity, functional impairment and cognitive decline. Small vessel disease is a collective term used to describe a number of underlying pathological processes and neuroimaging findings, such as lacunar infarcts, white matter lesions and microhaemorrhages.

With readily available neuroimaging, diagnostic accuracy has improved; however, the management of small vessel disease and prevention of cognitive decline remains uncertain. Treatment of conventional vascular risk factors may be appropriate, but future research is required to provide definitive answers. We have conducted a comprehensive literature review of cerebral small vessel disease in older adults. This highlights the clinical sequelae and underlying pathological processes, whilst discussing novel diagnostic neuroimaging and therapeutic strategies.

Few studies have applied multiple imaging modalities to examine cognitive correlates of white matter. We examined the utility of T2-weighted magnetic resonance imaging (MRI) -derived white matter hyperintensities (WMH) and diffusion tensor imaging-derived fractional anisotropy (FA) to predict cognitive functioning among older adults. Quantitative MRI and neuropsychological evaluations were performed in 112 older participants from an ongoing study of the genetics of Alzheimer's disease (AD) in African Americans. Regional WMH volumes and FA were measured in multiple regions of interest. We examined the association of regional WMH and an FA summary score with cognitive test performance. Differences in WMH and FA were compared across diagnostic groups (i.e., normal controls, mild cognitive impairment, and probable AD). Increased WMH volume in frontal lobes was associated with poorer delayed memory performance. FA did not emerge as a significant predictor of cognition. White matter hyperintensity volume in the frontal and parietal lobes was increased in MCI participants and more so in AD patients relative to controls. These results highlight the importance of regionally distributed small vessel cerebrovascular disease in memory performance and AD among African American older adults. White matter microstructural changes, quantified with diffusion tensor imaging, appear to play a lesser role in our sample. (JINS, 2012, 18, 414–427)

While post-stroke dementia has been extensively investigated, the large number of patients with mild cognitive impairment (MCI) following stroke has received less attention, and reports on the longitudinal course of such impairment are inconsistent in their findings. We examined patients with MCI (n = 45) or no cognitive impairment (NCI) (n = 59), based on consensus criteria following detailed neuropsychological assessments and magnetic resonance imaging (MRI) scans, and compared them with healthy control subjects (n = 84), all of whom were assessed at two time points, 3 years apart. The MCI at baseline in this group was judged to be vascular in etiology (vaMCI). Incident dementia was diagnosed in 24.4% of vaMCI and 8.5% of NCI subjects and no control subjects over 3 years, giving a rate of conversion of approximately 8% per year in post-stroke vaMCI. The vaMCI group showed greater decline in logical memory than the NCI group. Within the vaMCI group, those who developed dementia had great decline in language and executive function. Compared with NCI patients, those with vaMCI had more vascular risk factors and more white matter hyperintensities on MRI at baseline, but did not differ in their brain or hippocampal volumes. Neither MRI volumetric measures nor interval cerebrovascular events predicted decline in function. The major determinant of decline and categorical transition was impaired performance at baseline, suggesting that those with mild impairment post-stroke are more vulnerable to subsequent decline. (JINS, 2009, 15, 915–923.)