Altered fornix integrity is associated with sleep apnea-related hypoxemia in mild cognitive impairment.

INTRODUCTION: The limbic system is critical for memory function and degenerates early in the Alzheimer's disease continuum. Whether obstructive sleep apnea (OSA) is associated with alterations in the limbic white matter tracts remains understudied. METHODS: Polysomnography, neurocognitive assessment, and brain magnetic resonance imaging (MRI) were performed in 126 individuals aged 55-86 years, including 70 cognitively unimpaired participants and 56 participants with mild cognitive impairment (MCI). OSA measures of interest were the apnea-hypopnea index and composite variables of sleep fragmentation and hypoxemia. Microstructural properties of the cingulum, fornix, and uncinate fasciculus were estimated using free water-corrected diffusion tensor imaging. RESULTS: Higher levels of OSA-related hypoxemia were associated with higher left fornix diffusivities only in participants with MCI. Microstructure of the other white matter tracts was not associated with OSA measures. Higher left fornix diffusivities correlated with poorer episodic verbal memory. DISCUSSION: OSA may contribute to fornix damage and memory dysfunction in MCI. HIGHLIGHTS: Sleep apnea-related hypoxemia was associated with altered fornix integrity in MCI. Altered fornix integrity correlated with poorer memory function. Sleep apnea may contribute to fornix damage and memory dysfunction in MCI.

Alterations in Monocyte Phenotypes and Functions after a Hip Fracture in Elderly Individuals: A 6-Month Longitudinal Study.

BACKGROUND: Healthy elderly individuals are particularly prone to catastrophic events at any moment of their lives. One stressful event for individuals aged 65 and older is a fall that results in a fracture of the hip (HF). HF causes a state of inflammation that may affect immune responses. In this connection, we have reported that HF induced alterations in neutrophil functions. OBJECTIVE: To assess the impact of HF on classical (cM), intermediate (iM) and non-classical (ncM) monocyte subsets. METHODS: Distribution, functions (chemotaxis, phagocytosis, superoxide production and cytokine production), phenotype and activation (NF-x03BA;B and PI3K) were evaluated in monocyte subsets before surgery and 6 weeks and 6 months after the event. RESULTS: The distribution of cM and ncM was unchanged, but iM transiently increased before surgery. Sustained increases (iM response to CCL2 and CX3CL1) and decreases (cM and ncM response to CCL2) in chemotaxis were observed. Phagocytosis and superoxide production were impaired in cM but not in iM or ncM. Sustained expression of HLA-DR occurred in cM but not in iM and ncM. Sustained decreased expression of CD11b occurred only in ncM. Sustained decreases (cM and ncM) and increases (iM) in CCR2 expression were observed. An elevated expression of CX3CR1 was found only in iM. cM produced elevated quantities of TNFα. There was a transient oxidative burst of production before surgery in iM and a sustained decrease in ncM. IL-10 production was severely impaired in cM and decreased in iM prior to surgery. Sustained activation (cM), inhibition (ncM) and transient activation (iM) of NF-x03BA;B were observed. Activation of PI3K was severely impaired in cM and ncM but was sustained in iM. CONCLUSION: HF had more impact on cM and ncM functions than on iM. HF triggered a switch in cM functions from phagocytic to inflammatory elevated TNFα-producing cells. These changes may impact clinical outcomes of HF with respect to inflammation, opportunistic infections and physical recovery.

Guided self-help for generalized anxiety disorder in older adults.

OBJECTIVE: The main objective of this study was to examine the efficacy of a guided self-help treatment based on cognitive behavioral principles (CBT-GSH) for generalized anxiety disorder (GAD) in older adults. METHODS: Three older adults aged from 66 to 70 and diagnosed with GAD were included in a single-case experimental multiple-baseline protocol. Data were collected using daily self-monitoring, standardized clinician ratings, and self-report questionnaires at pretest, posttest, and 6-month and 12-month follow-ups. Treatment consisted of awareness training, worry interventions, relaxation training, pleasant activities scheduling, and relapse prevention. Participants used a manual presenting weekly readings and at-home practice exercises. They also received weekly supportive phone calls from a therapist. RESULTS: At posttest, participants showed improvement on worries and GAD severity, on psychological process variables targeted by treatment (intolerance of uncertainty, negative problem orientation, cognitive avoidance, and perceived usefulness of worry), and on secondary variables associated with GAD (anxiety, depression, sleep difficulties, cognitive functioning, and disability). These results were generally maintained at 12 months after the end of treatment. Participants had favorable opinions toward the treatment. CONCLUSION: The results of this study suggest that CBT-GSH is both feasible and effective for the treatment of GAD in older adults.

Significance of Non-phase Locked Oscillatory Brain Activity in Response to Noxious Stimuli.

BACKGROUND: Although current pain-evoked electroencephalographic (EEG) studies provide valuable information regarding human brain regions involved in pain, they have mostly considered neuronal responses which oscillate in phase following a painful event. In many instances, cortical neurons respond by generating bursts of activity that are slightly out of phase from trial-to-trial. These types of activity bursts are known as induced brain responses. The significance of induced brain responses to pain is still unknown. METHODS: In this study, 23 healthy subjects were given both non-painful and painful transcutaneous electrical stimulations in separate testing blocks (stimulation strength was kept constant within blocks). Subjective intensity was rated using a numerical rating scale, while cerebral activity tied to each stimulation was measured using EEG recordings. Induced brain responses were identified using a time frequency wavelet transform applied to average-removed single trials. RESULTS: Results showed a pain-specific burst of induced theta activity occurring between 180 and 500 ms post-shock onset. Source current density estimations located this activity within the dorsolateral prefrontal cortex (DLPFC, bilaterally), however, only right DLPFC activity predicted a decrease in subjective pain as testing progressed. CONCLUSION: This finding suggests that non-phase locked neuronal responses in the right DLPFC contribute to the endogenous attenuation of pain through time. PERSPECTIVE: This article presents neuroimaging findings demonstrating that, in response to pain, non-phase locked bursts of theta activity located in the right dorsolateral prefrontal cortex are associated with a progressive decrease in subjective pain intensity, which has potentially important implications regarding how humans endogenously control their experiences of pain.

Subjective sleep characteristics associated with anxiety and depression in older adults: a population-based study.

OBJECTIVE: Sleep complaints are often associated with anxiety and depression, but the specific complaints related to each syndrome are poorly characterized, especially in older adults. The objective was to identify subjective sleep characteristics specific to anxiety and depression in this population. METHODS: A random sample of 2393 individuals aged 65 years or older was used. Anxiety and depression were categorized using DSM-V criteria for phobias, panic disorder, generalized anxiety disorder, unspecified anxiety disorder, major depressive episode, and depressive episode with insufficient symptoms. Subjective sleep characteristics were measured using the Pittsburgh Sleep Quality Index. Logistic regression models predicting anxiety or depression were used to determine the independent sleep characteristics associated with each syndrome adjusting for age, sex, education level, cognitive functioning, anxiolytic/sedative/hypnotic use, antidepressants use, subjective health, chronic diseases, cardiovascular conditions, and anxiety or depression (as appropriate). RESULTS: Nearly all Pittsburgh Sleep Quality Index subscales were significantly associated with anxiety, but these subscales shared variance and only sleep duration in hours, sleep disturbance score, and daytime functioning score were independently related to anxiety. Within these significant subscales, the main specific sleep complaints associated with anxiety were daytime sleepiness and sleep disturbances related to coughing/snoring, feeling cold, and bad dreams. The use of sleeping medication was the only specific sleep characteristic associated with depression. CONCLUSIONS: These results suggest that in older adults, symptoms of short sleep duration, daytime sleepiness and sleep disturbances are independently related to anxiety while the use of sleep medication is independently associated to depression.

Subjective sleep quality in non-demented older adults with and without cognitive impairment.

OBJECTIVE: Sleep problems are prevalent among older adults who are at risk of developing dementia. Until now, there have been relatively few studies investigating subjective sleep quality in these individuals. The first objective of this study was to compare seniors with cognitive impairment no dementia (CIND) and older adults without cognitive impairment (non-CIND) on several subjective sleep measures. The second objective was to verify whether sleep parameters associated with CIND differ between men and women. METHODS: The population sample consisted of 2287 French-speaking older adults from Québec (Canada) aged between 65 and 96 years. Participants were classified as CIND or non-CIND on the basis of their mini mental state examination score using sex, age, and education-stratified normative data. All participants completed the Pittsburgh Sleep Quality Index, and responses of CIND and non-CIND individuals were compared. A series of confounding variables (age, education, chronic diseases, mood disorders, anxiety disorders, and use of psychotropic drugs) were statistically controlled for. Student's t-tests were performed to compare characteristics of CIND and non-CIND individuals; data from male and female participants were analyzed separately. Moreover, the association between each sleep variable and CIND was measured by odds ratios based on logistic regression. RESULTS: On the whole, analyses revealed no significant association between subjective sleep parameters and CIND. Moreover, no difference was observed between men and women regarding subjective sleep quality. CONCLUSIONS: Overall, these results suggest that subjective measures of sleep do not allow differentiating cognitively impaired older individuals from those with normal cognition.

Reduced rapid eye movement sleep in late middle-aged and older apolipoprotein E ɛ4 allele carriers.

STUDY OBJECTIVES: Apolipoprotein E ɛ4 (APOE4) is the strongest genetic risk factor for Alzheimer's disease (AD). In addition, APOE4 carriers may exhibit sleep disturbances, but conflicting results have been reported, such that there is no clear consensus regarding which aspects of sleep are impacted. Our objective was to compare objective sleep architecture between APOE4 carriers and non-carriers, and to investigate the modulating impact of age, sex, cognitive status, and obstructive sleep apnea (OSA). METHODS: A total of 198 dementia-free participants aged >55 years old (mean age: 68.7 ± 8.08 years old, 40.91% women, 41 APOE4 carriers) were recruited in this cross-sectional study. They underwent polysomnography, APOE4 genotyping, and a neuropsychological evaluation. ANCOVAs assessed the effect of APOE4 status on sleep architecture, controlling for age, sex, cognitive status, and the apnea-hypopnea index. Interaction terms were added between APOE4 status and covariates. RESULTS: Rapid eye movement (REM) sleep percentage (F = 9.95, p = .002, ηp2 = 0.049) and duration (F = 9.23, p = .003, ηp2 = 0.047) were lower in APOE4 carriers. The results were replicated in a subsample of 112 participants without moderate-to-severe OSA. There were no significant interactions between APOE4 status and age, sex, cognitive status, and OSA in the whole sample. CONCLUSIONS: Our results show that APOE4 carriers exhibit lower REM sleep duration, including in cognitively unimpaired individuals, possibly resulting from early neurodegenerative processes in regions involved in REM sleep generation and maintenance.

REM sleep is associated with the volume of the cholinergic basal forebrain in aMCI individuals.

BACKGROUND: Rapid-eye movement (REM) sleep highly depends on the activity of cholinergic basal forebrain (BF) neurons and is reduced in Alzheimer's disease. Here, we investigated the associations between the volume of BF nuclei and REM sleep characteristics, and the impact of cognitive status on these links, in late middle-aged and older participants. METHODS: Thirty-one cognitively healthy controls (66.8 ± 7.2 years old, 13 women) and 31 participants with amnestic Mild Cognitive Impairment (aMCI) (68.3 ± 8.8 years old, 7 women) were included in this cross-sectional study. All participants underwent polysomnography, a comprehensive neuropsychological assessment and Magnetic Resonance Imaging examination. REM sleep characteristics (i.e., percentage, latency and efficiency) were derived from polysomnographic recordings. T1-weighted images were preprocessed using CAT12 and the DARTEL algorithm, and we extracted the gray matter volume of BF regions of interest using a probabilistic atlas implemented in the JuBrain Anatomy Toolbox. Multiple linear regressions were performed between the volume of BF nuclei and REM sleep characteristics controlling for age, sex and total intracranial volume, in the whole cohort and in subgroups stratified by cognitive status. RESULTS: In the whole sample, lower REM sleep percentage was significantly associated to lower nucleus basalis of Meynert (Ch4) volume (ß = 0.32, p = 0.009). When stratifying the cohort according to cognitive status, lower REM sleep percentage was significantly associated to both lower Ch4 (ß = 0.48, p = 0.012) and total BF volumes (ß = 0.44, p = 0.014) in aMCI individuals, but not in cognitively unimpaired participants. No significant associations were observed between the volume of the BF and wake after sleep onset or non-REM sleep variables. DISCUSSION: These results suggest that REM sleep disturbances may be an early manifestation of the degeneration of the BF cholinergic system before the onset of dementia, especially in participants with mild memory deficits.

Daily hassles, physical illness, and sleep problems in older adults with wishes to die.

BACKGROUND: Factors associated with the wish to die should be investigated in order to gain more opportunities for preventive interventions targeting older adults at risk for suicide. The goal of the research was to study the prevalence and associated factors of wishes to die in older adults living in the community using the data from a survey on the prevalence of mental disorders in this population. METHODS: With a representative sample of community living older adults aged 65 years and over (N = 2777), we compared individuals with the wish to die (n = 163) to those without the wish to die on the basis of the presence and severity of daily hassles, physical illness, and sleep quality. RESULTS: Logistic regression revealed that when depression and sociodemographic variables were held constant, self-rated physical health, number of chronic illnesses, number and intensity of daily hassles, as well as sleep problems were significantly associated with the wish to die in older adults. Painful illnesses and daytime dysfunction due to sleep problems were also associated factors with the wish to die. CONCLUSION: Since desire for death is the first step into the suicidal process, health professionals should seriously consider the important and unique contribution of these variables in order to have more opportunities for detection and intervention.

Prevalence of psychiatric disorders in community-dwelling older men and women with cognitive impairment no dementia: results from the ESA study.

OBJECTIVES: To assess the prevalence rate of mood disorders, anxiety disorders, benzodiazepine dependence, and insomnia in older men and women with probable cognitive impairment no dementia (CIND) and to examine the independent associations between each disorder and CIND. METHOD: Participants were a random sample of community-dwelling individuals aged 65-96 (N = 2414). Semi-structured in-home interviews based on DSM-IV-TR (DSM, Diagnostic and Statistical Manual of Mental Disorders) criteria evaluated the prevalence rates of mood disorders, anxiety disorders, benzodiazepine dependence, and insomnia. Participants were classified as probable CIND based on their Mini-Mental State Examination score using sex, age, and education-stratified cut-offs (lower than the 15th percentile). RESULTS: In men, 22.7% of individuals with probable CIND and 12.1% of those with normal cognition had at least one psychiatric disorder (crude odds ratio (OR): 2.13, 95% confidence interval (CI): 1.23-3.69). More specifically, mood disorders (3.43, 1.74-6.75), benzodiazepine dependence (5.10, 1.23-21.11), and comorbid anxiety and mood disorders (8.67, 2.00-37.68) were significantly associated with probable CIND, but not anxiety disorders alone and insomnia. The prevalence rate of psychiatric disorders was similar in women with probable CIND (23.1%) and in women without CIND (23.9%; 0.95, 0.64-1.42). No specific psychiatric disorder was significantly associated with probable CIND in women. All associations remained unchanged after adjustments for potential confounders. CONCLUSIONS: The association between psychiatric disorders and probable CIND appears to be sex-specific. In clinical practice, mood disorders, and benzodiazepine dependence should receive particular attention since these disorders are associated with a condition increasing the risk of dementia.

Long-chain Omega-3 fatty acids supplementation and cognitive performance throughout adulthood: A 6-month randomized controlled trial.

OBJECTIVE: To investigate whether omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation improve cognitive performance and if apolipoprotein E (APOE) genotype or age were effect modifiers. METHODS: Healthy adults of 20 to 80 years old (n = 193) were completed a 6-month double-blind randomized controlled trial with two groups: 2.5 g/day of n-3 PUFA or a placebo. Primary outcomes were visuospatial ability and working memory and secondary outcomes were episodic memory and executive function, measured at baseline and 6 months. RESULTS: Cognitive performances did not significantly differ between groups on primary or secondary outcomes after 6 months of treatment. APOE carriers and age were not effect modifiers for any outcomes. Those with low episodic memory scores and taking the n-3 PUFA supplement, significantly improved their scores (p = 0.043). CONCLUSIONS: A 6-month n-3 PUFA supplementation did not improve cognitive performance in cognitively healthy adults and APOE status or age were not effect modifiers.

A portrait of obstructive sleep apnea risk factors in 27,210 middle-aged and older adults in the Canadian Longitudinal Study on Aging.

Determining the prevalence and characteristics of individuals susceptible to present with obstructive sleep apnea (OSA) is essential for developing targeted and efficient prevention and screening strategies. We included 27,210 participants aged ≥45 years old (50.3% women) from the Canadian Longitudinal Study on Aging. Using the STOP questionnaire combined to the percentage of body fat (%BF), we estimated the prevalence of individuals at high-risk for OSA in a sex and age-specific manner, and tested the relation with comorbidities, menopause and systemic inflammation. The prevalence was 17.5%, and was lower in women (13.1%) than in men (21.9%). A high level of high-sensitivity C-reactive protein was the strongest factor associated with OSA risk and this association was 1.3-2.3 times higher in women than in men. OSA risk increased with age, cardiovascular diseases, diabetes mellitus, anxio-depressive symptoms, asthma and arthritis. In women, post-menopausal status was associated with a high OSA risk. Nearly 1 adult out of 5 older than 45 is at risk for OSA in Canada. Comorbidities, menopause and systemic inflammation, more than age, explain increased OSA prevalence. Considering this high prevalence and associations with medical and mental comorbidities, health care practitioners should incorporate systematic OSA screening in their clinical procedures.

Association between risk of obstructive sleep apnea, inflammation and cognition after 45 years old in the Canadian Longitudinal Study on Aging.

BACKGROUND: The association between obstructive sleep apnea and cognitive functioning is not yet fully understood and could be influenced by factors such as sex, age and systemic inflammation. We determined the sex- and age-specific association between obstructive sleep apnea risk and cognitive performance, and the influence of systemic inflammation on this association. METHODS: We included 25,899 participants from the Canadian Longitudinal Study of Aging comprehensive cohort, aged 45-85 years (51% women). We conducted sex- and age-specific (45-59; 60-69; ≥70) general linear models between obstructive sleep apnea risk and cognitive scores, and tested the moderating and mediating effects of high-sensitivity C-reactive protein levels. Obstructive sleep apnea risk was estimated by combining the STOP and whole-body fat percentage. Cognitive tests assessed episodic verbal memory, executive functions and psychomotor speed. Levels of high-sensitivity C-reactive protein were obtained through blood samples. RESULTS: Higher obstructive sleep apnea risk was associated with poorer episodic memory in women aged 45-59 years, and poorer executive function (p < 0.05 on multiple tests) in women aged 45-59 and 60-69 years. No such association was found in men. High-sensitivity C-reactive protein levels mediated some associations between obstructive sleep apnea risk and executive function in women and men aged <70 years. CONCLUSIONS: Being at high-risk for obstructive sleep apnea is associated with poorer cognition in women aged <70 years. These associations were partly mediated by systemic inflammation. These results underscore the importance of obstructive sleep apnea diagnosis, treatment and appropriate follow-up, particularly in middle-aged women who might already show signs of early cognitive impairments.

Medial temporal lobe and obstructive sleep apnea: Effect of sex, age, cognitive status and free-water.

Medial temporal structures, namely the hippocampus, the entorhinal cortex and the parahippocampal gyrus, are particularly vulnerable to Alzheimer's disease and hypoxemia. Here, we tested the associations between obstructive sleep apnea (OSA) severity and medial temporal lobe volumes in 114 participants aged 55-86 years (35 % women). We also investigated the impact of sex, age, cognitive status, and free-water fraction correction on these associations. Increased OSA severity was associated with larger hippocampal and entorhinal cortex volumes in women, but not in men. Greater OSA severity also correlated with increased hippocampal volumes in participants with amnestic mild cognitive impairment, but not in cognitively unimpaired participants, regardless of sex. Using free-water corrected volumes eliminated all significant associations with OSA severity. Therefore, the increase in medial temporal subregion volumes may possibly be due to edema. Whether these structural manifestations further progress to neuronal death in non-treated OSA patients should be investigated.

The association between length of benzodiazepine use and sleep quality in older population.

BACKGROUND: Sleep disturbances are frequently reported in the older adult population and benzodiazepines are the drugs most often prescribed to treat these problems. Nearly 25% of the older adult population uses these drugs and 83% of benzodiazepine users report sleep problems. Although the Collège des Médecins du Québec suggests a maximum length of use of 3 months, according to most studies the mean length of benzodiazepine use is longer. The goal of this study was to document the association between length of benzodiazepine use and sleep quality as reported by adults 65 years older and over. METHODS: Data used in this study came from the Seniors' Health Survey (ESA) conducted in a representative sample of the community-dwelling older population in Quebec, Canada. Inclusion criteria included the ability to speak and understand French. Data were analyzed using a structural equation modeling strategy. RESULTS: Long-term benzodiazepine users were more likely to report poor sleep quality. Sleep quality of initial probable problematic sleepers tended to increase over 1 year but sleep quality in benzodiazepines users increased less rapidly than in non-users. Also, women were more likely to report using benzodiazepines and having poorer sleep quality. CONCLUSION: Longitudinal studies using incident cases of benzodiazepine use should be conducted to better determine the causal relationship between sleep quality and benzodiazepine use in the older population.

Bezafibrate mildly stimulates ketogenesis and fatty acid metabolism in hypertriglyceridemic subjects.

Our objective was to determine whether bezafibrate, a hypotriglyceridemic drug and peroxisome proliferator-activated receptor (PPAR)-alpha agonist, is ketogenic and increases fatty acid oxidation in humans. We measured fatty acid metabolism and ketone levels in 13 mildly hypertriglycemic adults (67 +/- 11 years old) during 2 metabolic study days lasting 6 h, 1 day before and 1 day after bezafibrate (400 mg of bezafibrate per day for 12 weeks). beta-Hydroxybutyrate, triglycerides, free fatty acids, fatty acid profiles, insulin, and glucose were measured in plasma, and fatty acid beta-oxidation was measured in breath after an oral 50-mg dose of the fatty acid tracer [U-(13)C]linoleic acid. As expected, 12 weeks on bezafibrate decreased plasma triglycerides by 35%. Bezafibrate tended to raise postprandial beta-hydroxybutyrate, an effect that was significant after normalization to the fasting baseline values (p = 0.03). beta-Oxidation of [U-(13)C]linoleic acid increased by 30% (p = 0.03) after treatment. On the metabolic study day after bezafibrate treatment, postprandial insulin decreased by 26% (p = 0.01), and glucose concentrations were lower 2 to 5 h postprandially. Thus, in hypertriglyceridemic individuals, bezafibrate is mildly ketogenic and significantly changes fatty acid metabolism, effects that may be linked to PPARalpha stimulation and to moderately improved glucose metabolism.

Benzodiazepine use and quality of sleep in the community-dwelling elderly population.

BACKGROUND: About 50% of the elderly population report being dissatisfied with their sleep. Although benzodiazepines are the most prescribed drugs to treat sleep complaints, the effectiveness of their use on the quality of sleep is not well documented. OBJECTIVES: This study aimed to assess the association between benzodiazepine use and global sleep quality, as well as six components of sleep quality. METHODS: Data from the cross-sectional Quebec Survey on Seniors' Health (n = 2798) conducted in 2005-2006 were used. Quality of sleep was self-reported and use of benzodiazepines was assessed during the previous year. RESULTS: Benzodiazepine users reported poorer quality of sleep than non-users. The association between benzodiazepine use and each of the six quality of sleep components studied were similar except for the daytime dysfunction component. CONCLUSION: The results suggest that there is no evidence that using benzodiazepines is associated with better quality of sleep than non-users in the elderly population. Future longitudinal population-based studies are needed to assess improvements in quality of sleep in the elderly associated with the use of benzodiazepines.

Context awareness architecture for ambient-assisted living applications: Case study of nighttime wandering.

OBJECTIVES: This work presents an ambient-assisted living application that encourages seniors during nocturnal wandering episodes to return to bed in calm and comfort reassurance. METHODS: Structuring knowledge by designing a software architecture capable of delivering high-level analysis and processing. A senior's home has been upgraded into a smart home enabling the gathering of habits for two weeks and set up for personalized assistance over four weeks. Home automation devices associated with Actigraph monitors and self-reported sleep were used for more accuracy. RESULTS: The architectural model can be used in ambient-assisted living applications for which data collection is permanent and continuous. Its layered organization facilitates the management of specific and general activities of daily life. The results of the home experience show that the system gave a notification whenever the need arose. On the other hand, it allowed the caregiver to get more information about the lifestyle of the senior. CONCLUSIONS: Future work should focus on providing more services to contextualize assistance. Ontology is used to structure all the ambient knowledge of the smart home. We also plan to do more home experiments.

Evidence of a Relation Between Hippocampal Volume, White Matter Hyperintensities, and Cognition in Subjective Cognitive Decline and Mild Cognitive Impairment.

OBJECTIVE: The concepts of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) have been proposed to identify individuals in the early stages of Alzheimer's disease (AD), or other neurodegenerative diseases. One approach to validate these concepts is to investigate the relationship between pathological brain markers and cognition in those individuals. METHOD: We included 126 participants from the Consortium for the Early Identification of Alzheimer's disease-Quebec (CIMA-Q) cohort (67 SCD, 29 MCI, and 30 cognitively healthy controls [CH]). All participants underwent a complete cognitive assessment and structural magnetic resonance imaging. Group comparisons were done using cognitive data, and then correlated with hippocampal volumes and white matter hyperintensities (WMHs). RESULTS: Significant differences were found between participants with MCI and CH on episodic and executive tasks, but no differences were found when comparing SCD and CH. Scores on episodic memory tests correlated with hippocampal volumes in both MCI and SCD, whereas performance on executive tests correlated with WMH in all of our groups. DISCUSSION: As expected, the SCD group was shown to be cognitively healthy on tasks where MCI participants showed impairment. However, SCD's hippocampal volume related to episodic memory performances, and WMH to executive functions. Thus, SCD represents a valid research concept and should be used, alongside MCI, to better understand the preclinical/prodromal phase of AD.

Tractography of the external capsule and cognition: A diffusion MRI study of cholinergic fibers.

INTRODUCTION: White matter changes (WMC) in the cholinergic tracts contribute to executive dysfunction in the context of cognitive aging. WMC in the external capsule have been associated with executive dysfunction. The objectives of this study were to: 1) Characterize the lateral cholinergic tracts (LCT) and the superior longitudinal fasciculus (SLF). 2) Evaluate the association between diffusion measures within those tracts and cognitive performance. METHODS: Neuropsychological testing and high angular resolution diffusion imaging (HARDI) of 34 healthy elderly participants was done, followed by anatomically constrained probabilistic tractography reconstruction robust to crossing fibers. The external capsule was manually segmented on a mean T1 image then merged with an atlas, allowing extraction of the LCT. Diffusion tensor imaging (DTI) and HARDI-based measures were obtained. RESULTS: Correlations between diffusion measures in the LCT and the time of completion of Stroop (left LCT radial and medial diffusivity), the Symbol Search score (right LCT apparent fiber density) and the motor part of Trail-B (left LCT axial and radial diffusivity) were observed. Correlations were also found with diffusion measures in the SLF. WMC burden was low, and no correlation was found with diffusion measures or cognitive performance. DISCUSSION: DTI and HARDI, with isolation of strategic white matter tracts for cognitive functions, represent complimentary tools to better understand the complex process of brain aging.