A comparison of white matter microstructure and correlates with neuropsychological measures in younger and older adults.

OBJECTIVE: With a globally aging population, there is a need to better understand how brain structure relates to function in healthy older and younger adults. METHODS: 34 healthy participants divided into older (17; Mean = 70.9, SD = 5.4) and younger adults (17; Mean = 28.1, SD = 2.8) underwent diffusion-weighted imaging and neuropsychological assessment, including the California Verbal Learning Test 2nd Edition and the Trail Making Test (TMT-A and TMT-B). Differences in white matter microstructure for older and younger adults and the association between DTI metrics (fractional anisotropy, FA; mean diffusivity, MD) and cognitive performance were analyzed using tract-based spatial statistics (p < 0.05, corrected). RESULTS: Older adults had significantly lower FA and higher MD than younger adults in widespread brain regions. There was a significant negative correlation between executive function (TMT-B) and MD for older adults in the right superior/anterior corona radiata and the corpus callosum. No significant relationship was detected between DTI metrics and executive function in younger adults or with memory performance in either group. CONCLUSIONS: The findings underscore the need to examine brain-behaviour relationships as a function of age. Future studies should include comprehensive assessments in larger lifespan samples to better understand the aging brain.

A Systematic Review of Neuroimaging Studies Comparing Individuals with Subjective Cognitive Decline to Healthy Controls.

BACKGROUND: Individuals with subjective cognitive decline (SCD) are hypothesized to be the earliest along the cognitive continuum between healthy aging and Alzheimer's disease (AD), although more research is needed on this topic. Given that treatment approaches may be most effective pre-clinically, a primary objective of emerging research is to identify biological markers of SCD using neuroimaging methods. OBJECTIVE: The current review aimed to comprehensively present the neuroimaging studies on SCD to date. METHODS: PubMed and PsycINFO databases were searched for neuroimaging studies of individuals with SCD. Quality assessments were completed using the Appraisal tool for Cross-Sectional Studies. RESULTS: In total, 62 neuroimaging studies investigating differences between participants with SCD and healthy controls were identified. Specifically, the number of studies were as follows: 36 MRI, 6 PET, 8 MRI/PET, 4 EEG, 7 MEG, and 1 SPECT. Across neuroimaging modalities, 48 of the 62 included studies revealed significant differences in brain structure and/or function between groups. CONCLUSION: Neuroimaging methods can identify differences between healthy controls and individuals with SCD. However, inconsistent results were found within and between neuroimaging modalities. Discrepancies across studies may be best accounted for by methodological differences, notably variable criteria for SCD, and differences in participant characteristics and risk factors for AD. Clinic based recruitment and cross-sectional study design were common and may bias the literature. Future neuroimaging investigations of SCD should consistently incorporate the standardized research criteria for SCD (as recommended by the SCD-Initiative), include more details of their SCD sample and their symptoms, and examine groups longitudinally.

Functional near infrared spectroscopy activation during an executive function task differs between healthy older and younger adults.

Background: Healthy aging can include declines in processing speed and executive function. Further research is needed to characterize the neurobiological underpinnings of these cognitive changes in older adulthood. The current study used functional near infrared spectroscopy (fNIRS), an optical neuroimaging technique, to examine differences in cerebral oxygenation between healthy older adults (OA) and younger adults (YA) during a measure of cognitive interference. Methods: Thirty-four participants were sampled from two age groups: YA (mean age = 28.1 years, SD = 2.8, F = 9) and OA (mean age = 70.9 years, SD = 5.4, F = 9). Participants completed the Multi-Source Interference Task (MSIT), a measure of executive function with high and low-demand conditions, while undergoing fNIRS recordings using a TechEn CW6 system with 34-source-detector channels, situated over the prefrontal cortex. Functional activation patterns, accuracy, and reaction time were compared between and within groups for each condition. Results: Behaviourally, during the control condition, OA and YA had comparable accuracy, although OA had significantly slower reaction times than YA. During the interference condition, OA had significantly lower accuracy and slower reaction times than YA. Results demonstrated a significant difference between groups with an age-related increase in HbO for OA in both conditions (p < 0.05). Within groups, OA showed greater activation during the control condition, while YA demonstrated greater activation during the interference condition. Conclusions: The findings suggest that OA recruit additional neural resources to achieve similar behavioural performance during low-level cognitive interference, but that compensation in OA may be insufficient to support behavioural performance at higher levels of interference.

The relationship between cardiovascular risk and lifestyle activities on hippocampal volumes in normative aging.

Background: Despite the life-course perspective of popular aging models, few studies on healthy aging to date have examined both younger and older adulthood. The current study examined how cumulative vascular risk factors and self-reported levels of physical, social, and cognitive activity are associated with differences in hippocampal volumes in healthy younger and older adults. Methods: 34 neurologically healthy participants were separated into two age cohorts: a younger adult group (age 25-35, n = 17) and an older adult group (age 65-82, n = 17). Participants underwent a 3 T T1 MRI and completed a series of questionnaires. Voxel-based morphometry examined whole-brain grey matter density differences between groups. Hippocampal volumes were computed. Analyses examined the association between hippocampal volumes, cumulative vascular risk, and self-reported levels of physical, social, and cognitive activity, both within and across groups. Results: Between-group comparisons revealed greater cortical atrophy in older relative to young adults in regions including the left and right hippocampus and temporal fusiform cortex. Across-group analyses revealed a significant negative association between cardiovascular risk scores and bilateral hippocampal volumes across age groups. A significant negative association was identified between frequency of social activities and bilateral hippocampal volumes in older adults only. No significant associations were found between left or right hippocampal volumes and total, cognitive, or physical activities in both within- and across-group analyses. Conclusion: Greater cumulative vascular risk is associated with smaller hippocampal volumes across age cohorts. Findings suggest that social activities with low cognitive load may not be beneficial to structural brain outcomes in older age.

Aging in Place: Challenges of Older Adults with Self-Reported Cognitive Decline.

BACKGROUND: An emergent concern related to the aging and the increased risk of cognitive decline is the institutionalization of older adults. Evidence has shown that aging in place leads to many benefits, including higher quality of life. In order to support older adults, it is imperative that we understand the challenges people with changes in cognition face while aging in place. METHODS: A total of sixteen older adults with self-reported cognitive decline and six informal caregivers of individuals reporting cognitive decline, all of whom are living in independent residences, participated. Focus group sessions with semi-structured interviews were conducted, followed by thematic qualitative data analyses. RESULTS: Thematic analyses led to the identification of six challenges to aging in place, including: 1) memory decline, 2) emotional challenges/low mood, 3) social isolation/loneliness, 4) difficulty with mobility and physical tasks, 5) difficulties with activities of daily living/instrumental activities of daily living, and 6) lack of educational resources on cognitive change. CONCLUSION: The themes identified in the current study represent common challenges in aging in place for older adults with self-reported cognitive decline. Identification of these themes allows for important next steps, which can focus on supports through targeted interventions.

Spectral dynamic causal modelling of resting-state fMRI: an exploratory study relating effective brain connectivity in the default mode network to genetics.

We conduct an imaging genetics study to explore how effective brain connectivity in the default mode network (DMN) may be related to genetics within the context of Alzheimer's disease and mild cognitive impairment. We develop an analysis of longitudinal resting-state functional magnetic resonance imaging (rs-fMRI) and genetic data obtained from a sample of 111 subjects with a total of 319 rs-fMRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. A Dynamic Causal Model (DCM) is fit to the rs-fMRI scans to estimate effective brain connectivity within the DMN and related to a set of single nucleotide polymorphisms (SNPs) contained in an empirical disease-constrained set which is obtained out-of-sample from 663 ADNI subjects having only genome-wide data. We relate longitudinal effective brain connectivity estimated using spectral DCM to SNPs using both linear mixed effect (LME) models as well as function-on-scalar regression (FSR). In both cases we implement a parametric bootstrap for testing SNP coefficients and make comparisons with p-values obtained from asymptotic null distributions. In both networks at an initial q-value threshold of 0.1 no effects are found. We report on exploratory patterns of associations with relatively high ranks that exhibit stability to the differing assumptions made by both FSR and LME.

Identification of Earlier Biomarkers for Alzheimer's Disease: A Multimodal Neuroimaging Study of Individuals with Subjective Cognitive Decline.

BACKGROUND: Individuals with subjective cognitive decline (SCD) are thought to be the earliest along the cognitive continuum between healthy aging and Alzheimer's disease (AD). OBJECTIVE: The current study used a multi-modal neuroimaging approach to examine differences in brain structure and function between individuals with SCD and healthy controls (HC). METHODS: 3T high-resolution anatomical images and resting-state functional MRI scans were retrieved for 23 individuals with SCD and 23 HC from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. RESULTS: The SCD and HC groups were not significantly different in age or education level. Voxel-based morphometry results did not show significant differences in grey matter volume between the groups. Functional MRI results revealed significantly greater functional connectivity in the default mode network in regions including the bilateral precuneus cortex, bilateral thalamus, and right hippocampal regions in individuals with SCD relative to controls. Conversely, those with SCD showed decreased functional connectivity in the bilateral frontal pole, caudate, angular gyrus, and lingual gyrus, compared to HC. CONCLUSION: Findings revealed differences in brain function but not structure between individuals with SCD and HC. Overall, this study represents a crucial step in characterizing individuals with SCD, a group recognized to be at increased risk for AD. It is imperative to identify biomarkers of AD prior to significant decline on clinical assessment, so that disease-delaying interventions may be delivered at the earliest possible time point.

Neuropsychological assessment of traumatic brain injury: Current ethical challenges and recommendations for future practice.

Numerous ethical challenges may arise over the course of neuropsychological assessment. This paper highlights the ethical considerations associated with neuropsychological assessment of individuals with traumatic brain injury. Issues regarding professional competency, providing and obtaining informed consent, neuropsychological test selection and administration, effectively communicating assessment results, and working as part of a multidisciplinary team are discussed with practical recommendations. Ultimately, a comprehensive understanding of these issues as well as an integration of resources to guide clinical practice will contribute to ethical decision-making and strong professional practice.

Resting State BOLD Variability Is Linked to White Matter Vascular Burden in Healthy Aging but Not in Older Adults With Subjective Cognitive Decline.

Background: Alzheimer's disease (AD) is the leading cause of dementia. A lack of curative treatments and a rapidly aging global population have amplified the need for early biomarkers of the disease process. Recent advances suggest that subjective cognitive decline (SCD) may be one of the earliest symptomatic markers of the AD cascade. Previous studies have identified changes in variability in the blood-oxygen-level-dependent (BOLD) signal in patients with AD, with a possible association between BOLD variability and cerebrovascular factors in the aging brain. The objective of the current study was to determine whether changes in BOLD variability can be identified in individuals with SCD, and whether this signal may be associated with markers of cerebrovascular integrity in SCD and older adults without memory complaints. Method: Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database from 19 participants with SCD and 19 similarly-aged controls. For each participant, a map of BOLD signal variability (SDBOLD) was computed as the standard deviation of the BOLD time-series at each voxel. Group comparisons were performed to examine differences in resting-state SDBOLD in SCD vs. healthy controls. Relationships were then examined between participant SDBOLD maps and neuroimaging markers of white matter vascular infarcts in each group separately. Results: Between-group comparisons showed no significant differences in whole-brain SDBOLD in individuals with SCD and controls. In the healthy aging group, higher white matter hyperintensity (WMH) burden was associated with greater SDBOLD in right temporal regions (p < 0.05), and lower scores on a measure of global executive functioning. These associations were not identified in individuals with SCD. Conclusion: The current study underscores previous evidence for a relationship between SDBOLD and white matter vascular infarcts in the healthy aging brain. The findings also provide evidence for a dissociable relationship between healthy aging and SCD, such that in healthy controls, increased WMH is associated with declines in executive function that is not observed in older adults who present with memory complaints. Further multimodal work is needed to better understand the contributions of vascular pathology to the BOLD signal, and its potential relationship with pathological aging.

Resting State BOLD Variability in Alzheimer's Disease: A Marker of Cognitive Decline or Cerebrovascular Status?

Background: Alzheimer's disease (AD) is a neurodegenerative disorder that may benefit from early diagnosis and intervention. Therefore, there is a need to identify early biomarkers of AD using non-invasive techniques such as functional magnetic resonance imaging (fMRI). Recently, novel approaches to the analysis of resting-state fMRI data have been developed that focus on the moment-to-moment variability in the blood oxygen level dependent (BOLD) signal. The objective of the current study was to investigate BOLD variability as a novel early biomarker of AD and its associated psychophysiological correlates. Method: Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) 2 database from 19 participants with AD and 19 similarly aged controls. For each participant, a map of BOLD signal variability (SDBOLD) was computed as the standard deviation of the BOLD timeseries at each voxel. Group comparisons were performed to examine global differences in resting state SDBOLD in AD versus healthy controls. Correlations were then examined between participant SDBOLD maps and (1) ADNI-derived composite scores of memory and executive function and (2) neuroimaging markers of cerebrovascular status. Results: Between-group comparisons revealed significant (p < 0.05) increases in SDBOLD in patients with AD relative to healthy controls in right-lateralized frontal regions. Lower memory scores and higher WMH burden were associated with greater SDBOLD in the healthy control group (p < 0.1), but not individuals with AD. Conclusion: The current study provides proof of concept of a novel resting state fMRI analysis technique that is non-invasive, easily accessible, and clinically compatible. To further explore the potential of SDBOLD as a biomarker of AD, additional studies in larger, longitudinal samples are needed to better understand the changes in SDBOLD that characterize earlier stages of disease progression and their underlying psychophysiological correlates.

Functional Magnetic Resonance Imaging and Functional Near-Infrared Spectroscopy: Insights from Combined Recording Studies.

Although blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a widely available, non-invasive technique that offers excellent spatial resolution, it remains limited by practical constraints imposed by the scanner environment. More recently, functional near infrared spectroscopy (fNIRS) has emerged as an alternative hemodynamic-based approach that possesses a number of strengths where fMRI is limited, most notably in portability and higher tolerance for motion. To date, fNIRS has shown promise in its ability to shed light on the functioning of the human brain in populations and contexts previously inaccessible to fMRI. Notable contributions include infant neuroimaging studies and studies examining full-body behaviors, such as exercise. However, much like fMRI, fNIRS has technical constraints that have limited its application to clinical settings, including a lower spatial resolution and limited depth of recording. Thus, by combining fMRI and fNIRS in such a way that the two methods complement each other, a multimodal imaging approach may allow for more complex research paradigms than is feasible with either technique alone. In light of these issues, the purpose of the current review is to: (1) provide an overview of fMRI and fNIRS and their associated strengths and limitations; (2) review existing combined fMRI-fNIRS recording studies; and (3) discuss how their combined use in future research practices may aid in advancing modern investigations of human brain function.

Neuroleptic Malignant Syndrome: A Review from a Clinically Oriented Perspective.

Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening side-effect that can occur in response to treatment with antipsychotic drugs. Symptoms commonly include hyperpyrexia, muscle rigidity, autonomic dysfunction and altered mental status. In the current review we provide an overview on past and current developments in understanding the causes and treatment of NMS. Studies on the epidemiological incidence of NMS are evaluated, and we provide new data from the Canada Vigilance Adverse Reaction Online database to elaborate on drug-specific and antipsychotic drug polypharmacy instances of NMS reported between 1965 and 2012. Established risk factors are summarized with an emphasis on pharmacological and environmental causes. Leading theories about the etiopathology of NMS are discussed, including the potential contribution of the impact of dopamine receptor blockade and musculoskeletal fiber toxicity. A clinical perspective is provided whereby the clinical presentation and phenomenology of NMS is detailed, while the diagnosis of NMS and its differential is expounded. Current therapeutic strategies are outlined and the role for both pharmacological and non-pharmacological treatment strategies in alleviating the symptoms of NMS are discussed.