Age-related hearing loss associated with differences in the neural correlates of feature binding in visual working memory.

The underlying neural mechanisms underpinning the association between age-related hearing loss (ARHL) and dementia remain unclear. A limitation has been the lack of functional neuroimaging studies in ARHL cohorts to help clarify this relationship. In the present study, we investigated the neural correlates of feature binding in visual working memory with ARHL (controls = 14, mild HL = 21, and moderate or greater HL = 23). Participants completed a visual change detection task assessing feature binding while their neural activity was synchronously recorded via high-density electroencephalography. There was no difference in accuracy scores for ARHL groups compared to controls. There was increased electrophysiological activity in those with ARHL, particularly in components indexing the earlier stages of visual cognitive processing. This activity was more pronounced with more severe ARHL and was associated with maintained feature binding. Source space (sLORETA) analyses indicated greater activity in networks modulated by frontoparietal and temporal regions. Our results demonstrate there may be increased involvement of neurocognitive control networks to maintain lower-order neurocognitive processing disrupted by ARHL.

Exposure to the troubles in Northern Ireland, memory functioning, and social activity engagement: results from NICOLA.

We investigated the potential impact of a cohort traumatic exposure, the Troubles in Northern Ireland, on memory functioning in later life, and the potential moderating effect of social activity engagement. Using data from 6571 participants aged 60 + in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) cohort, we used a structural equation modelling framework to explore associations between traumatic exposure during the Troubles and memory functioning. As expected, social activity engagement was positively associated with memory functioning, ß = .102. Traumatic exposure was also positively associated with memory functioning, ß = .053. This association was stronger at low levels of social activity engagement; among those with higher levels, there was little association, interaction ß = - 0.054. The positive association between traumatic exposure during the Troubles and memory functioning was not moderated by the age at which the exposures occurred (based on analysis of a subsample with available data), interaction ß = - 0.015. We conclude that superior memory functioning was associated with higher levels of traumatic exposure during the Troubles, particularly among those with lower levels of social activity engagement, and regardless of the age at which the exposures occurred. Future longitudinal analyses are required to build on these results, which potentially have implications for life-course epidemiology, in relation to critical periods for traumatising experiences. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-022-00683-5.

Structural Correlates of Overt Sentence Reading in Mild Cognitive Impairment and Mild-to-Moderate Alzheimer's Disease.

BACKGROUND: Overt sentence reading in mild cognitive impairment (MCI) and mild-tomoderate Alzheimer's disease (AD) has been associated with slowness of speech, characterized by a higher number of pauses, shorter speech units and slower speech rate and attributed to reduced working memory/ attention and language capacity. OBJECTIVE: This preliminary case-control study investigates whether the temporal organization of speech is associated with the volume of brain regions involved in overt sentence reading and explores the discriminative ability of temporal speech parameters and standard volumetric MRI measures for the classification of MCI and AD. METHODS: Individuals with MCI, mild-to-moderate AD, and healthy controls (HC) had a structural MRI scan and read aloud sentences varying in cognitive-linguistic demand (length). The association between speech features and regional brain volumes was examined by linear mixed-effect modeling. Genetic programming was used to explore the discriminative ability of temporal and MRI features. RESULTS: Longer sentences, slower speech rate, and a higher number of pauses and shorter interpausal units were associated with reduced volumes of the reading network. Speech-based classifiers performed similarly to the MRI-based classifiers for MCI-HC (67% vs. 68%) and slightly better for AD-HC (80% vs. 64%) and AD-MCI (82% vs. 59%). Adding the speech features to the MRI features slightly improved the performance of MRI-based classification for AD-HC and MCI-HC but not HC-MCI. CONCLUSION: The temporal organization of speech in overt sentence reading reflects underlying volume reductions. It may represent a sensitive marker for early assessment of structural changes and cognitive- linguistic deficits associated with healthy aging, MCI, and AD.

Cognitive and Structural Correlates of Conversational Speech Timing in Mild Cognitive Impairment and Mild-to-Moderate Alzheimer's Disease: Relevance for Early Detection Approaches.

Background: Increasing efforts have focused on the establishment of novel biomarkers for the early detection of Alzheimer's disease (AD) and prediction of Mild Cognitive Impairment (MCI)-to-AD conversion. Behavioral changes over the course of healthy ageing, at disease onset and during disease progression, have been recently put forward as promising markers for the detection of MCI and AD. The present study examines whether the temporal characteristics of speech in a collaborative referencing task are associated with cognitive function and the volumes of brain regions involved in speech production and known to be reduced in MCI and AD pathology. We then explore the discriminative ability of the temporal speech measures for the classification of MCI and AD. Method: Individuals with MCI, mild-to-moderate AD and healthy controls (HCs) underwent a structural MRI scan and a battery of neuropsychological tests. They also engaged in a collaborative referencing task with a caregiver. The associations between the conversational speech timing features, cognitive function (domain-specific) and regional brain volumes were examined by means of linear mixed-effect modeling. Genetic programming was used to explore the discriminative ability of the conversational speech features. Results: MCI and mild-to-moderate AD are characterized by a general slowness of speech, attributed to slower speech rate and slower turn-taking in conversational settings. The speech characteristics appear to be reflective of episodic, lexico-semantic, executive functioning and visuospatial deficits and underlying volume reductions in frontal, temporal and cerebellar areas. Conclusion: The implementation of conversational speech timing-based technologies in clinical and community settings may provide additional markers for the early detection of cognitive deficits and structural changes associated with MCI and AD.

Social factors may mediate the relationship between subjective age-related hearing loss and episodic memory.

Objectives: To investigate whether the relationship between subjective age-related hearing loss (SARHL) and episodic memory functioning is mediated by measures of social functioning.Methods: Using data from 8,163 adults over 50 that participated in the Irish Longitudinal Study of Ageing (three waves, each two years apart), we used a multiple mediation model within a Structural Equation Modelling framework to explore potential social mediators of the relationship between SARHL and episodic memory functioning, controlling for demographic and health covariates.Results: Neither the direct effect of self-reported hearing difficulties on memory functioning (ß = -.03), nor the total effect (ß = .01), were significant. A small inconsistent indirect effect of self-reported hearing difficulties on episodic memory via weekly social activity engagement (ß = -.002) was found.Conclusions: Self-reported hearing difficulties may exert an indirect effect on episodic memory via weekly social activity engagement. The findings may have implications for identification of individuals at risk of memory decline in later life.

Age-related hearing loss associated with altered response efficiency and variability on a visual sustained attention task.

This study investigated the association between age-related hearing loss (ARHL) and differences in response efficiency and variability on a sustained attention task. The study population comprised 32 participants in a hearing loss group (HLG) and 34 controls without hearing loss (CG). Mean reaction time (RT) and accuracy were recorded to assess response efficiency. RT variability was decomposed to examine temporal aspects of variability associated with neural arousal and top-down executive control of vigilant attention. The HLG had a significantly longer mean RT, possibly reflecting a strategic approach to maintain accuracy. The HLG also demonstrated altered variability (indicative of greater decline in neural arousal) but maintained executive control that was significantly predictive of poorer response efficiency. Adults with ARHL may rely on higher-order attention networks to compensate for decline in both peripheral sensory function and in subcortical arousal systems which mediate lower-order automatic neurocognitive processes.

The Behavioral Variant Frontotemporal Dementia Phenocopy Syndrome: A Review.

OBJECTIVES: The relatively recent identification of a subgroup of patients with apparent behavioral variant frontotemporal dementia (bvFTD) that fails to progress with time has led to a reevaluation of our understanding of bvFTD, and a growing body of research that attempts to characterize the mimic or "phenocopy" syndrome. In this article, we review the literature relating to the phenocopy syndrome, focusing in particular on distinguishing characteristics and potential etiologies. METHODS: Published articles were identified via a systematic search of PubMed and Embase. Observational and interventional studies, case reports, and case series were sought for inclusion. RESULTS: While bvFTD and the phenocopy syndrome are clinically indistinguishable at initial presentation, the presence or absence of characteristic changes on neuroimaging predicts 2 very different illness trajectories. The etiology for the phenocopy presentation remains uncertain. It is likely that the syndrome represents a heterogenous assortment of clinical frontal syndromes encompassing atypical neurodegenerative, psychiatric, psychological, and as yet unknown neuropsychiatric causes. CONCLUSIONS: Although the prognosis of the phenocopy syndrome is generally held to be more favorable than that of bvFTD, patients and families are subject to major disruption in their relationships and social and occupational functioning. Early recognition is crucial to facilitate timely interventions aimed at maintaining relationships, roles, and quality of life of those affected.

Orthostatic Blood Pressure Recovery Is Associated With the Rate of Cognitive Decline and Mortality in Clinical Alzheimer's Disease.

BACKGROUND: Impaired recovery of blood pressure (BP) after standing has been shown to be related to cognitive function and mortality in people without dementia, but its role in people with Alzheimer's disease (AD) is unknown. The aim of this study was to investigate the association of the orthostatic BP response with cognitive decline and mortality in AD. METHODS: In this post hoc analysis of a randomized controlled trial (Nilvad), we measured the beat-to-beat response of BP upon active standing in mild-to-moderate AD. This included the initial drop (nadir within 40 seconds) and recovery after 1 minute, both expressed relative to resting values. We examined the relationship between a small or large initial drop (median split) and unimpaired (≥100%) or impaired recovery (<100%) with 1.5-year change in Alzheimer's Disease Assessment-cognitive subscale (ADAS-cog) scores and all-cause mortality. RESULTS: We included 55 participants (age 73.1 ± 6.2 years). Impaired BP recovery was associated with higher increases in ADAS-cog scores (systolic: ß [95% confidence interval] = 5.6 [0.4-10.8], p = .035; diastolic: 7.6 [2.3-13.0], p = .006). During a median follow-up time of 49 months, 20 participants died. Impaired BP recovery was associated with increased mortality (systolic: HR [95% confidence interval] = 2.9 [1.1-7.8], p = .039; diastolic: HR [95% confidence interval] = 5.5 [1.9-16.1], p = .002). The initial BP drop was not associated with any outcome. Results were adjusted for age, sex, and intervention group. CONCLUSIONS: Failure to fully recover BP after 1 minute of standing is associated with cognitive decline and mortality in AD. As such, BP recovery can be regarded as an easily obtained marker of progression rate of AD.

Depressive symptoms predict increased social and emotional loneliness in older adults.

Objectives: Explorations of relationships between loneliness and depression have focused on loneliness as a uni-dimensional construct. We hypothesised that reciprocal relationships may exist between depressive symptomatology and social and emotional subtypes of loneliness.Methods: Using data from 373 adults aged over 50, who participated in an observational cohort study, we employed a cross-lagged approach within a Structural Equation Modelling framework, to investigate reciprocal links between depressive symptomatology, and social and emotional loneliness, across two waves of data collection, two years apart (controlling for age, sex, education, comorbidities, social network index, and perceived stress).Results: Both depressive symptomatology and loneliness decreased slightly between waves. Auto-regressive effects were strong for all three variables of interest. Cross-lagged pathways were evident, such that depressive symptomatology at baseline predicted both emotional (ß = 0.26, p < 0.05) and social (ß = 0.17, p < 0.05) loneliness at follow-up. Neither emotional (ß = 0.07, p > 0.05) nor social (ß = 0.05, p > 0.05) loneliness at baseline predicted depressive symptomatology at follow-up.Conclusions: Results challenge existing understanding of the associations between loneliness and depression. Further investigation of emotional and social loneliness in individuals with depressive disorders is warranted. Findings are discussed in relation to mechanisms that may explain the relationships observed, and possible implications.

Mediating the relationship between loneliness and cognitive function: the role of depressive and anxiety symptoms.

Objective: To evaluate the relationship between loneliness and cognitive functioning, and whether depressive and anxiety symptoms have intermediate roles therein.Methods: Information about 7,433 participants of the Irish Longitudinal Study on Ageing (a prospective, representative cohort study), aged over 50, was collected at three time-points two years apart, and analysed using Structural Equation Modelling to assess whether depressive and anxiety symptoms mediate the relationship between loneliness and cognitive functioning. Cognitive functioning was measured as a latent factor, with four indicators: measures of immediate and delayed word recall, verbal fluency, and a global measure (the MMSE). Loneliness was measured using the UCLA Loneliness scale, depressive symptoms using the CES-D-ML scale, and anxiety symptoms using the HADS-A scale.Results: Loneliness at time-point 1 predicted cognitive functioning at time-point 3, ß = -0.103, p < 0.001, and depressive (ß = 0.426, p < 0.001) and anxiety (ß = 0.410, p < 0.001) symptoms at time-point 2. Depressive (ß = -0.020, p = 0.001) but not anxiety (ß = -0.000, p = 0.658) symptoms mediated the relationship between loneliness and cognitive functioning, total effect: ß = -0.123, p < 0.001.Conclusion: The relationship between loneliness and cognitive functioning is in part explained by its relationship with depressive symptoms. Statistically, the mediation model helps us understand possible mechanisms through which loneliness impacts cognitive functioning. Results have implications for cognitive functioning interventions for older adults, and imply that loneliness is also a worthwhile target for intervention.

Lonely SARTs: loneliness and sustained attention in the Irish longitudinal study of aging.

Based on biologically plausible mechanisms and previous research, it is possible to hypothesize a reciprocal association between sustained attention and loneliness. We investigated this association using a cross-lagged modeling approach. Using data from 6,239 participants aged over 50 in TILDA, a nationally representative study of aging, we used structural equation models to investigate potential cross-lagged associations between sustained attention and loneliness, measured at baseline and again after four years. Sustained attention at baseline had a small association with loneliness four years later, but loneliness at baseline was not associated with sustained attention at follow-up. Auto-regressive associations were strong for both loneliness over time and sustained attention over time. Sustained attention may account for a small proportion of the variance in loneliness over time among older adults, and may constitute a risk factor in the development of loneliness. Implications for the identification of at-risk individuals and the prevention of loneliness are discussed.

Bones of Contention: A Comprehensive Literature Review of Non-SSRI Antidepressant Use and Bone Health.

Osteoporotic fractures are associated with major morbidity and mortality, particularly among older age groups. In recent decades, selective serotonin reuptake inhibitors (SSRI) antidepressants have been linked to reduced bone mineral density and increased risk of fragility fracture. However, up to one-third of antidepressant prescriptions are for classes other than SSRIs. Older patients, who are particularly vulnerable to osteoporosis and its clinical and psychosocial consequences, may be prescribed non-SSRI antidepressants preferentially because of increasing awareness of the risks SSRIs pose to bone health. However, to date, the skeletal effects of non-SSRI antidepressants have not been comprehensively reviewed. In this article, we collate and review the available data and discuss the findings. Based on the current literature, we tentatively suggest that tricyclic antidepressants may increase the risk of fracture via mechanisms other than a direct effect on bone mineral density. The risk is apparently confined to current users only and is greatest in the earliest stage of treatment, diminishing thereafter. There is, as yet, insufficient data to conclusively determine the effects of other antidepressant classes on bone. Judicious prescribing of antidepressants among higher risk groups necessitates a thorough review of the individual's risk factors for osteoporosis as well as attention to their falls risk. Further longitudinal, rigorously controlled studies are needed to answer some of the remaining questions on the effects of non-SSRI antidepressants on bone and the mechanisms by which they are exerted.

Altered verbal fluency processes in older adults with age-related hearing loss.

Epidemiological studies have linked age-related hearing loss (ARHL) with an increased risk of neurocognitive decline. Difficulties in speech perception with subsequent changes in brain morphometry, including regions important for lexical-semantic memory, are thought to be a possible mechanism for this relationship. This study investigated differences in automatic and executive lexical-semantic processes on verbal fluency tasks in individuals with acquired hearing loss. The primary outcomes were indices of automatic (clustering/word retrieval at start of task) and executive (switching/word retrieval after start of the task) processes from semantic and phonemic fluency tasks. To extract indices of clustering and switching, we used both manual and computerised methods. There were no differences between groups on indices of executive fluency processes or on any indices from the semantic fluency task. The hearing loss group demonstrated weaker automatic processes on the phonemic fluency task. Further research into differences in lexical-semantic processes with ARHL is warranted.

Blood Pressure Variability and Progression of Clinical Alzheimer Disease.

Blood pressure variability (BPV) has been shown to have predictive value over blood pressure (BP) levels alone in stroke patients. We assessed whether BPV predicts cognitive and functional decline in Alzheimer disease, using data from a randomized trial (NILVAD [A European Multicentre Double-blind Placebo-controlled Phase III Trial of Nilvadipine in Mild to Moderate Alzheimer's Disease]). Patients with mild-to-moderate Alzheimer disease were included if they had ≥3 office BP measurements available to determine visit-to-visit BPV. Day-to-day BPV was assessed using home BP measurements in a subsample. The variation independent of mean was used to calculate BPV. Outcomes were change in Alzheimer's Disease Assessment Scale-cognitive subscale-12 and Disability Assessment for Dementia after 1 and 1.5 years. A total of 460 patients aged 72.1 (SD=8.1) years, with mean BP of 134.0/75.1 (10.9/6.3) mm Hg were included. After 1 year, patients in the highest quartile of BPV had deteriorated more on Alzheimer's Disease Assessment Scale-cognitive subscale compared with patients in the lowest quartile (systolic: ß, 2.24 [95% CI, 0.11-4.38], P=0.040; diastolic: ß, 2.54 [95% CI, 0.33-4.75] P=0.024). This association was still present after 1.5 years (systolic: ß, 2.86 [95% CI, 0.35-5.36], P=0.026; diastolic: ß, 3.30 [95% CI, 0.67-5.93], P=0.014). There was no effect of visit-to-visit BPV on Disability Assessment for Dementia. Day-to-day BPV was available for 46 patients. Significant associations were observed between day-to-day BPV and deterioration on Alzheimer's Disease Assessment Scale-cognitive subscale (systolic: P=0.036) and Disability Assessment for Dementia (systolic: P=0.020; diastolic: P=0.007) after 1 year, but not after 1.5 years. All associations were adjusted for potential confounders, including intervention group. In conclusion, this post hoc analysis indicates that higher visit-to-visit and day-to-day BPV might be associated with progression of Alzheimer disease. Targeting BPV may be a future target to slow decline in patients with Alzheimer disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02017340.

Is the Quick Mild Cognitive Impairment Screen (QMCI) more accurate at detecting mild cognitive impairment than existing short cognitive screening tests? A systematic review of the current literature.

OBJECTIVES: Differentiating normal cognition, mild cognitive impairment (MCI), and dementia is important, as these conditions differ in terms of their prognosis and treatment. Existing short cognitive screening tests vary widely in their accuracy, sensitivity, and specificity at detecting MCI and dementia. The Quick Mild Cognitive Impairment Screen (QMCI) was developed in 2012 as a fast and accurate "MCI specific" screening test. The aim of the current study was to conduct a literature review to compare the accuracy, sensitivity, and specificity of the QMCI at differentiating normal cognition, MCI, and dementia to existing short cognitive screening tests at their optimal cut-off scores. METHODS: A search of the electronic journal databases EBSCO, Psych info, and Science Direct was undertaken using the keywords "Quick Mild Cognitive Impairment Screen," "QMCI," "accuracy," "sensitivity," and "specificity." Results of individual studies were examined, and 2 × 2 tables were drawn up to obtain the overall accuracy, sensitivity, and specificity of each test across the studies included. RESULTS: Results from individual studies show that the QMCI has higher accuracy at detecting MCI and dementia than these cognitive screens. Pooled analysis shows that it also has greater sensitivity and specificity at optimal cut-off points for each test. CONCLUSIONS: Based in the current review, the QMCI represents a more accurate, sensitive, and specific screening test for MCI and dementia than the SMMSE or the MoCA. This has important implications in screening for cognitive impairment.

Visual short-term memory binding deficit with age-related hearing loss in cognitively normal older adults.

Age-related hearing loss (ARHL) has been posited as a possible modifiable risk factor for neurocognitive impairment and dementia. Measures sensitive to early neurocognitive changes associated with ARHL would help to elucidate the mechanisms underpinning this relationship. We hypothesized that ARHL might be associated with decline in visual short-term memory binding (VSTMB), a potential biomarker for preclinical dementia due to Alzheimer's disease (AD). We examined differences in accuracy between older adults with hearing loss and a control group on the VSTMB task from a single feature (shapes) condition to a feature binding (shapes-colors) condition. Hearing loss was associated with a weaker capacity to process bound features which appeared to be accounted for by a weaker sensitivity for change detection (A'). Our findings give insight into the neural mechanisms underpinning neurocognitive decline with ARHL and its temporal sequence.

Effects of Nilvadipine on Cerebral Blood Flow in Patients With Alzheimer Disease.

Cerebrovascular changes, including reduced cerebral blood flow (CBF), occur early in the development of Alzheimer disease and may accelerate disease progression. This randomized, double-blind, placebo-controlled study investigated how 6 months of treatment with the calcium antagonist nilvadipine would affect CBF in patients with mild-to-moderate Alzheimer disease. CBF was measured with magnetic resonance arterial spin labeling in whole-brain gray matter and in a priori defined regions of interest including the hippocampus. Fifty-eight patients were randomly assigned (29 in each group), of whom 22 in both groups had no magnetic resonance exclusion criteria and were medication compliant over 6 months. Mean age was 72.8±6.2 years, mean mini-mental state examination was 20.4±3.4. Nilvadipine treatment lowered systolic blood pressure (Δ=-11.5 [95% CI, -19.7 to -3.2] mm Hg; P<0.01), while whole-brain gray-matter CBF remained stable (Δ=5.4 [95% CI, -6.4 to 17.2] mL/100 g per minute; P=0.36). CBF in the hippocampus increased (left: Δ=24.4 [95% CI, 4.3-44.5] mL/100 g per minute; P=0.02; right: Δ=20.1 [95% CI, -0.6 to 40.8] mL/100 g per minute; P=0.06). There was no significant change in CBF in the posterior cingulate cortex (Δ=5.2 [95% CI, -16.5 to 27.0] mL/100 g per minute; P=0.63) or other regions of interest. In conclusion, nilvadipine reduced blood pressure and increased CBF in the hippocampus, whereas other regions showed stable or small nonsignificant increases in CBF. These findings not only indicate preserved cerebral autoregulation in Alzheimer disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02017340.

Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension.

Background Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. Methods and Results Four hundred seventy-seven patients with mild-to-moderate Alzheimer disease were randomized to the calcium-channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop ≥20/≥10 mm Hg after 1 minute of standing) and OH-related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow-up visits. Mean age of the study population was 72.2±8.2 years and mean Mini-Mental State Examination score was 20.4±3.8. Baseline blood pressure was 137.8±14.0/77.0±8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by -7.8/-3.9 mm Hg for nilvadipine and by -0.4/-0.8 mm Hg for placebo ( P<0.001). Across the 78-week intervention period, there was no difference between groups in the proportion of patients with OH at a study visit (odds ratio [95% CI]=1.1 [0.8-1.5], P=0.62), nor in the proportion of visits where a patient met criteria for OH, corrected for number of visits (7.7±13.8% versus 7.3±11.6%). OH-related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. Conclusions This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild-to-moderate Alzheimer disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02017340.

Monocytes exposed to plasma from patients with Alzheimer's disease undergo metabolic reprogramming.

The search for a blood-based biomarker that identifies Alzheimer's disease (AD) and can replace current invasive and expensive diagnostic tests, continues. The most extensively-examined peripheral marker is ß-amyloid (Aß) but the results are inconsistent across studies and do not reflect the changes that take place in the brain. Several studies have assessed possible proteomic signatures but with inconsistent findings, although increases in circulating inflammatory molecules are generally observed. Here, rather than focus on identifying changes in the circulation, we evaluated the effect of plasma from patients with mild cognitive impairment (MCI) and AD on the human monocyte-like cell line, THP-1 cells, and plasma from an AD mouse model on a mouse monocyte-macrophage cell line, J774.2 cells. Plasma from AD patients and the AD mouse model increased inflammatory molecules in the cells and these changes were accompanied by an increase in glycolysis. Interestingly, plasma from MCI patients exerted no significant effect on THP-1 cells. The possibility therefore exists that evaluating the effect of plasma on IL-8 and TNFα mRNA in THP-1 cells combined with analysis of glycolysis in these cells, may be the basis of an indicator that discriminates between AD and MCI and normal controls, but is unlikely to be useful in identifying early pathological changes.

Cognitive functioning among cognitively intact dementia caregivers compared to matched self-selected and population controls.

PURPOSE OF THE STUDY: Caregiving for a person with dementia is frequently used to model the impact of chronic stress on health, including cognitive functioning. However, the prevalence of typically healthier, self-selecting non-caregiving control groups could contribute to a picture of poorer caregiver performance and overstate the negative effects of stress. We investigated differences in cognitive performance between dementia caregivers and two groups of non-caregivers recruited using different sampling methods. DESIGN AND METHODS: We compared cognitive function and psychological wellbeing among 252 spousal dementia caregivers with demographically matched non-caregiving control groups drawn from (1) a population study and (2) a self-selecting sample. Comparable cognitive measures included immediate and delayed recall, processing speed reaction time and verbal fluency. RESULTS: Caregiver and non-caregiver performance was comparable on most cognitive domains. However, caregivers outperformed both control groups on processing speed (p ≤ .05) and reaction time (p ≤ .05), despite having higher levels of stress and depression (ps < .001). Furthermore, caregivers had significantly better free recall than self-selecting controls (p < .001). IMPLICATIONS: Our results, overall, do not support the idea that caregiving is associated with stress-induced cognitive deficits. Rather, the trend toward better caregiver performance is consistent with the healthy caregiver hypothesis.