Subjective cognitive decline predicts lower cingulo-opercular network functional connectivity in individuals with lower neurite density in the forceps minor.

Cognitive complaints of attention/concentration problems are highly frequent in older adults with subjective cognitive decline (SCD). Functional connectivity in the cingulo-opercular network (CON-FC) supports cognitive control, tonic alertness, and visual processing speed. Thus, those complaints in SCD may reflect a decrease in CON-FC. Frontal white-matter tracts such as the forceps minor exhibit age- and SCD-related alterations and, therefore, might influence the CON-FC decrease in SCD. Here, we aimed to determine whether SCD predicts an impairment in CON-FC and whether neurite density in the forceps minor modulates that effect. To do so, we integrated cross-sectional and longitudinal analyses of multimodal data in a latent growth curve modeling approach. Sixty-nine healthy older adults (13 males; 68.33 ± 7.95 years old) underwent resting-state functional and diffusion-weighted magnetic resonance imaging, and the degree of SCD was assessed at baseline with the memory functioning questionnaire (greater score indicating more SCD). Forty-nine of the participants were further enrolled in two follow-ups, each about 18 months apart. Baseline SCD did not predict CON-FC after three years or its rate of change (p-values > 0.092). Notably, however, the forceps minor neurite density did modulate the relation between SCD and CON-FC (intercept; b = 0.21, 95% confidence interval, CI, [0.03, 0.39], p = 0.021), so that SCD predicted a greater CON-FC decrease in older adults with relatively lower neurite density in the forceps minor. The neurite density of the forceps minor, in turn, negatively correlated with age. These results suggest that CON-FC alterations in SCD are dependent upon the forceps minor neurite density. Accordingly, these results imply modifiable age-related factors that could help delay or mitigate both age and SCD-related effects on brain connectivity.

White Matter Hyperintensities and Apolipoprotein E Affect the Association Between Mean Arterial Pressure and Objective and Subjective Cognitive Functioning in Older Adults.

BACKGROUND: White matter hyperintensities (WMH) show a robust relationship with arterial pressure as well as objective and subjective cognitive functioning. In addition, APOE ɛ4 carriership may influence how arterial pressure affects cognitive functioning. OBJECTIVE: To determine the role of region-specific WMH burden and APOE ɛ4 carriership on the relationship between mean arterial pressure (MAP) and cognitive function as well as subjective cognitive decline (SCD). METHODS: The sample consisted of 87 cognitively unimpaired middle-aged to older adults aged 50-85. We measured WMH volume for the whole brain, anterior thalamic radiation (ATR), forceps minor, and superior longitudinal fasciculus (SLF). We examined whether WMH burden mediated the relationship between MAP and cognition (i.e., TMT-A score for processing speed; Stroop performance for executive function) as well as SCD (i.e., Frequency of Forgetting (FoF)), and whether APOE ɛ4 carriership moderated that mediation. RESULTS: WMH burden within SLF mediated the effect of MAP on Stroop performance. Both whole brain and ATR WMH burden mediated the effect of MAP on FoF score. In the MAP-WMH-Stroop relationship, the mediation effect of SLF WMH and the effect of MAP on SLF WMH were significant only in APOE ɛ4 carriers. In the MAP-WMH-FoF relationship, the effect of MAP on whole brain WMH burden was significant only in ɛ4 carriers. CONCLUSION: WMH burden and APOE genotype explain the link between blood pressure and cognitive function and may enable a more accurate assessment of the effect of high blood pressure on cognitive decline and risk for dementia.

Longitudinal change in hippocampal and dorsal anterior insulae functional connectivity in subjective cognitive decline.

BACKGROUND: Subjective cognitive decline, perceived worsening of cognitive ability without apparent performance issues on clinical assessment, may be an important precursor to dementia. While previous cross-sectional research has demonstrated aberrant brain functional connectivity in subjective cognitive decline, longitudinal evaluation remains limited. METHODS: Here, we examined trajectories of functional connectivity over three measurement occasions ~18 months apart, using voxelwise latent growth models in cognitively unimpaired older adults with varying self-report of subjective cognitive decline (N = 69). RESULTS: We found that individuals who reported a greater degree of subjective cognitive decline showed a larger subsequent decrease in connectivity between components of the default mode network and increase in connectivity between salience and default mode network components. The change in functional connectivity was observed in the absence of change in cognitive performance. CONCLUSION: The results indicate that functional brain changes may underly the experience of cognitive decline before deterioration reaches a level detected by formal cognitive assessment.

Hearing Sensitivity, Cardiovascular Risk, and Neurocognitive Function: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Importance: Both cardiovascular disease risk and hearing impairment are associated with cognitive dysfunction. However, the combined influence of the 2 risk factors on cognition is not well characterized. Objective: To examine associations between hearing impairment, cardiovascular disease risk, and cognitive function. Design, Setting, and Participants: This population-based, prospective cohort, multisite cross-sectional analysis of baseline data collected between 2008 and 2011 as part of the Hispanic Community Health Study/Study of Latinos included 9623 Hispanic or Latino adults aged 45 to 74 years in New York, Chicago, Miami, and San Diego. Exposures: Hearing impairment of at least mild severity was defined as the pure tone average of 500, 1000, 2000, and 4000 Hz greater than 25 dB hearing level (dB HL) in the better ear. Our measure of cardiovascular disease risk was a latent class variable derived from body mass index, ankle-brachial index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, fasting blood glucose, and the Framingham Cardiovascular Risk score. Main Outcomes and Measures: Results on Brief-Spanish English Verbal Learning Test (episodic learning and memory), and Word Fluency (verbal fluency), and Digit Symbol Subtest (processing speed/executive functioning), and a cognitive composite of the mentioned tests (overall cognition). Results: Participants (N = 9180) were 54.4% female and age 56.5 years on average. Hearing impairment was associated with poorer performance on all cognitive measures (global cognition: unstandardized ß, -0.11; 95% CI, -0.16 to 0.07). Cardiovascular grouping (healthy, typical, high cardiovascular disease risk, and hyperglycemia) did not attenuate the associations between hearing impairment and cognition (global cognition: unstandardized ß, -0.11; 95% CI, -0.15 to -0.06). However, cardiovascular grouping interacted with hearing impairment such that hyperglycemia in the context of hearing impairment exacerbated poor performance on learning and memory tasks (F3 = 3.70 and F3 = 2.92, respectively). Conclusions and Relevance: The findings of this cohort study suggest that hearing impairment increases the likelihood that individuals with excessively high glucose perform poorly on learning and memory tasks. Further research is needed to specify the mechanisms by which cardiovascular disease risk and hearing impairment are collectively associated with cognition.

Resting-state functional brain connectivity in a predominantly African-American sample of older adults: exploring links among personality traits, cognitive performance, and the default mode network.

The personality traits of neuroticism, openness, and conscientiousness are relevant factors for cognitive aging outcomes. The present study examined how these traits were associated with cognitive abilities and corresponding resting-state functional connectivity (RSFC) of the default mode network (DMN) in an older and predominantly minority sample. A sample of 58 cognitively unimpaired, largely African-American, older adults (M age = 68.28 ± 8.33) completed a standard RSFC magnetic resonance imaging sequence, a Big Five measure of personality, and delayed memory, Stroop, and verbal fluency tasks. Personality trait associations of within-network connectivity of the posterior cingulate cortex (PCC), a hub of the DMN, were examined using a seed-based approach. Trait scores were regressed on cognitive performance (delayed memory for neuroticism, Stroop for conscientiousness, and verbal fluency for openness). Greater openness predicted greater verbal fluency and greater RSFC between the PCC and eight clusters, including the medial prefrontal cortex, left middle frontal gyrus, and precuneus. Greater PCC-precuneus connectivity predicted greater verbal fluency. Neuroticism and conscientiousness did not significantly predict either cognitive performance or RSFC. Although requiring replication and elaboration, the results implicate openness as a contributing factor to cognitive aging via concomitant cognitive performance and connectivity within cortical hubs of the DMN and add to the sparse literature on these variables in a diverse group of older adults.

Functional neuroimaging in subjective cognitive decline: current status and a research path forward.

Subjective cognitive decline is a putative precursor to dementia marked by perceived worsening of cognitive function without overt performance issues on neuropsychological assessment. Although healthy older adults with subjective cognitive decline may function normally, perceived worsening may indicate incipient dementia and predict future deterioration. Therefore, the experience of decline represents a possible entry point for clinical intervention. However, intervention requires a physical manifestation of neuroabnormality to both corroborate incipient dementia and to target clinically. While some individuals with subjective cognitive decline may harbor pathophysiology for specific neurodegenerative disorders, many do not display clear indicators. Thus, disorder-agnostic brain measures could be useful to track the trajectory of decline, and functional neuroimaging in particular may be sensitive to detect incipient dementia and have the ability to track disease-related change when the underlying disease etiology remains unclear. Therefore, in this review, we discuss functional neuroimaging studies of subjective cognitive decline and possible reconciliations to inconsistent findings. We conclude by proposing a functional model where noisy signal propagation and inefficient signal processing across whole-brain networks may lead to the subjective experience of decline and discuss future research directions guided by this model.

Aberrant memory system connectivity and working memory performance in subjective cognitive decline.

Subjective cognitive decline, a perceived worsening of cognitive functioning without objective deficit on assessment, could indicate incipient dementia. However, the neural correlates of subjective cognitive decline as assessed by magnetic resonance imaging remain somewhat unclear. Here, we evaluated differences in functional connectivity across memory regions, and cognitive performance, between healthy older adults aged 50 to 85 with (n = 35, Age = 68.5 ±â€¯7.7, 22 female), and without (n = 48, Age = 67.0 ±â€¯8.8, 29 female) subjective cognitive decline. We also evaluated neurite density, fractional anisotropy, and mean diffusivity of the parahippocampal cingulum, cingulate gyrus cingulum, and uncinate fiber bundles in a subsample of participants (n = 37). Participants with subjective cognitive decline displayed lower average functional connectivity across regions of a putative posterior memory system, and lower retrosplenial-precuneus functional connectivity specifically, than those without memory complaints. Furthermore, participants with subjective cognitive decline performed poorer than controls on visual working memory. However, groups did not differ in cingulum or uncinate diffusion measures. Our results show differences in functional connectivity and visual working memory in participants with subjective cognitive decline that could indicate potential incipient dementia.

Associations between dynamic functional connectivity and age, metabolic risk, and cognitive performance.

Advanced age is associated with reduced within-network functional connectivity, particularly within the default mode network. Most studies to date have examined age differences in functional connectivity via static indices that are computed over the entire blood-oxygen-level dependent time series. Little is known about the effects of age on short-term temporal dynamics of functional connectivity. Here, we examined age differences in dynamic connectivity as well as associations between connectivity, metabolic risk, and cognitive performance in healthy adults (N = 168; age, 18-83 years). A sliding-window k-means clustering approach was used to assess dynamic connectivity from resting-state functional magnetic resonance imaging data. Three out of 8 dynamic connectivity profiles were associated with age. Furthermore, metabolic risk was associated with the relative amount of time allocated to 2 of these profiles. Finally, the relative amount of time allocated to a dynamic connectivity profile marked by heightened connectivity between default mode and medial temporal regions was positively associated with executive functions. Thus, dynamic connectivity analyses can enrich understanding of age-related differences beyond what is revealed by static analyses.

Subjective memory complaints are associated with brain activation supporting successful memory encoding.

Subjective memory complaints, the perceived decline in cognitive abilities in the absence of clinical deficits, may precede Alzheimer's disease. Individuals with subjective memory complaints show differential brain activation during memory encoding; however, whether such differences contribute to successful memory formation remains unclear. Here, we investigated how subsequent memory effects, activation which is greater for hits than misses during an encoding task, differed between healthy older adults aged 50 to 85 years with (n = 23) and without (n = 41) memory complaints. Older adults with memory complaints, compared to those without, showed lower subsequent memory effects in the occipital lobe, superior parietal lobe, and posterior cingulate cortex. In addition, older adults with more memory complaints showed a more negative subsequent memory effects in areas of the default mode network, including the posterior cingulate cortex, precuneus, and ventromedial prefrontal cortex. Our findings suggest that for successful memory formation, older adults with subjective memory complaints rely on distinct neural mechanisms which may reflect an overall decreased task-directed attention.

Differential effect of age on posterior and anterior hippocampal functional connectivity.

Aging is associated with declines in cognitive performance and multiple changes in the brain, including reduced default mode functional connectivity (FC). However, conflicting results have been reported regarding age differences in FC between hippocampal and default mode regions. This discrepancy may stem from the variation in selection of hippocampal regions. We therefore examined the effect of age on resting state FC of anterior and posterior hippocampal regions in an adult life-span sample. Advanced age was associated with lower FC between the posterior hippocampus and three regions: the posterior cingulate cortex, medial prefrontal cortex, and lateral parietal cortex. In addition, age-related reductions of FC between the left and right posterior hippocampus, and bilaterally along the posterior to anterior hippocampal axis were noted. Age differences in medial prefrontal and inter-hemispheric FC significantly differed between anterior and posterior hippocampus. Older age was associated with lower performance in all cognitive domains, but we observed no associations between FC and cognitive performance after controlling for age. We observed a significant effect of gender and a linear effect of COMT val158met polymorphism on hippocampal FC. Females showed higher FC of anterior and posterior hippocampus and medial prefrontal cortex than males, and the dose of val allele was associated with lower posterior hippocampus - posterior cingulate FC, independent of age. Vascular and metabolic factors showed no significant effects on FC. These results suggest differential age-related reduction in the posterior hippocampal FC compared to the anterior hippocampus, and an age-independent effect of gender and COMT on hippocampal FC.