The discrepancy between social isolation and loneliness as a clinically meaningful metric: findings from the Irish and English longitudinal studies of ageing (TILDA and ELSA).

OBJECTIVE: Scant evidence is available on the discordance between loneliness and social isolation among older adults. We aimed to investigate this discordance and any health implications that it may have. METHOD: Using nationally representative datasets from ageing cohorts in Ireland (TILDA) and England (ELSA), we created a metric of discordance between loneliness and social isolation, to which we refer as Social Asymmetry. This metric was the categorised difference between standardised scores on a scale of loneliness and a scale of social isolation, giving categories of: Concordantly Lonely and Isolated, Discordant: Robust to Loneliness, or Discordant: Susceptible to Loneliness. We used regression and multilevel modelling to identify potential relationships between Social Asymmetry and cognitive outcomes. RESULTS: Social Asymmetry predicted cognitive outcomes cross-sectionally and at a two-year follow-up, such that Discordant: Robust to Loneliness individuals were superior performers, but we failed to find evidence for Social Asymmetry as a predictor of cognitive trajectory over time. CONCLUSIONS: We present a new metric and preliminary evidence of a relationship with clinical outcomes. Further research validating this metric in different populations, and evaluating its relationship with other outcomes, is warranted. Copyright © 2016 John Wiley & Sons, Ltd.

Cognitive reserve and self-efficacy as moderators of the relationship between stress exposure and executive functioning among spousal dementia caregivers.

BACKGROUND: A substantial literature has reported that stress negatively impacts on cognitive processes. As dementia caregiving can be stressful, it has been hypothesized that the challenges of dementia care may increase caregivers' own vulnerability to cognitive decline. Prefrontal processes are thought to be most vulnerable to stress; however, few studies have examined whether greater caregiver stress predicts poorer executive dysfunction, and no previous research has considered potential moderators of this relationship. We examined (1) whether greater psychological stress mediated a relationship between caregiver stress exposure and executive functioning and (2) whether greater self-efficacy and cognitive reserve (CR) moderated this relationship. METHOD: Spousal dementia caregivers (n = 253) completed the Neuropsychiatric Inventory Questionnaire (stress exposure), the Perceived Stress Scale, the National Adult Reading Test (CR), the Fortinsky dementia-specific caregiver self-efficacy scale, and the Color Trails Test (executive functioning). Moderated mediation was tested using the PROCESS macro. Age, gender, and dementia risk factors were included as covariates. RESULTS: Greater stress exposure indirectly predicted executive functioning through psychological stress. Stronger relationships between greater psychological stress and poorer executive functioning were observed among caregivers with lower CR; there was no evidence that self-efficacy moderated the relationship between stress exposure and psychological stress. CONCLUSIONS: Our findings are in line with the idea that greater psychological stress in response to challenges associated with dementia care predicts poorer caregiver executive functioning, particularly among caregivers with low CR. However, these findings are cross sectional; it is also possible that poorer executive functioning contributes to greater caregiver stress.

Social support mediates the relationships between extraversion, neuroticism, and cognitive function in older adults.

OBJECTIVES: We supplement existing findings on a link between social support and cognitive function in later life by considering the role of personality as an antecedent to both, and of social support as a mediator of the link between personality and cognitive function. STUDY DESIGN: An observational cohort study. METHODS: We evaluated social support using the Lubben Social Network Scale, across 624 adults aged over 60 years, and investigated this measure as a mediator of the relationships between extraversion and neuroticism at baseline 2007-2009, and cognitive function at follow-up, 2 years later. A half-longitudinal mediation design, within a structural equation modelling framework, was used. RESULTS: There was a direct effect of extraversion, such that lower levels were related to higher scores of cognitive function. There was no significant direct effect of neuroticism on cognitive function at follow-up. Social support partially mediated the paths between both extraversion and neuroticism and cognitive function at follow-up. Decomposing the mediation effects by using social support subscales (measuring support from friends, relatives and neighbours) showed meaningful indirect effects for both predictors. CONCLUSION: Results suggest that social support may offer a target for interventions for cognitively at-risk older adults and add to the existing empirical evidence describing the link between personality and cognitive function.

Peer volunteer perspectives following a complex social cognitive intervention: a qualitative investigation.

BACKGROUND: Peer volunteers can be key to delivering effective social cognitive interventions due to increased potential for social modeling. We consulted peer volunteers who had just taken part in an 8-week social and nutritional mealtime intervention with older adults living alone, to seek their evaluation of the intervention. METHODS: Semi-structured focus groups were used with a total of 21 volunteers (17 female) and two facilitators. Thematic analysis was used to interrogate the data. RESULTS: Six themes (16 sub-themes) are discussed. Peer volunteers described the importance of the socializing aspect of the intervention, of pairing considerations and compatibility in peer interventions, of considering the needs of the participant, of benefits to the volunteers, and of the practical considerations of conducting an intervention. Volunteers also discussed considerations for future research and services for older adults living alone. CONCLUSIONS: Volunteers found their involvement in the intervention to be personally beneficial, and revealed some valuable considerations for the researchers to take forward to future research. Results are pertinent to intervention design and could inform future social cognitive and other peer-oriented interventions for older adults living alone.

Clinical Consensus Guidelines on the Application of Cerebrospinal Fluid Biomarkers for Alzheimer's Disease Diagnosis: Recommendations of the Irish Network for Biomarkers in Neurodegeneration.

It is accepted that a lumbar puncture (LP) and cerebrospinal fluid (CSF) biomarker analysis support the routine diagnostic work-up for the differential diagnosis of dementia due to Alzheimer's disease (AD) within certain patient cohorts1. These tests, which measure CSF protein concentrations of amyloid-ß42 (Aß42), total tau (t-tau) and phospho tau (p-tau), were recently validated, accredited and made available clinically for the first time in Ireland. A working group, comprising Irish clinical and scientific researchers, met to review a) the validation results; b) international consensus opinions, and c) research and clinical evidence as to the clinical utility of CSF biomarker analysis for AD dementia diagnosis. The outcome of this meeting was the formulation of a consensus statement paper for the benefit of health care professionals involved in the diagnosis and management of dementia to ensure appropriate use of these biomarker tests in clinical settings in Ireland.

Loneliness and vascular biomarkers: the Dublin Healthy Ageing Study.

BACKGROUND: Loneliness has been associated with poor physical health and a link has been suggested between the presence of loneliness, cardiovascular health and inflammatory markers. OBJECTIVE: To investigate the association between vascular disease biomarkers and loneliness in a community-dwelling non-demented elderly population. DESIGN: cross-sectional community based assessment. PARTICIPANTS: 466 subjects with mean age 75.45 (SD, 6.06) years. 208 (44.6%) were male. RESULTS: Higher levels of HbA1c, but not other vascular biomarkers were independently associated with being lonely. CONCLUSION: Loneliness was associated with raised levels of HbA1c in a community dwelling elderly population. The mechanism for this association has yet to be elucidated but may reflect an abnormal stress response in people who are lonely.

Loneliness and cognition in older people: the Dublin Healthy Ageing study.

INTRODUCTION: While several studies have found a link between impaired cognition and social isolation, few have examined the relationship between cognition and loneliness. Loneliness has been thought to increase the risk of development of Alzheimer's dementia. AIM: The aims of this study were to explore the relationship between loneliness and cognition and to determine whether specific cognitive domains are associated with loneliness. DESIGN: Cross-sectional community-based study. PARTICIPANTS: This study included 466 community-dwelling subjects with mean age 75.45 (SD 6.06) years, of which 208(44%) were males. RESULTS: Loneliness was significantly associated with impaired global cognition independent of social networks and depression. The domains of psychomotor processing speed and delayed visual memory were specifically associated with self-reported loneliness. CONCLUSION: This cross-sectional study demonstrated an association between loneliness and specific aspects of cognition independent of depression, social networks and other demographics. The mechanism for this association is unclear and warrants further investigation.

Social support differentially moderates the impact of neuroticism and extraversion on mental wellbeing among community-dwelling older adults.

BACKGROUND: Personality affects psychological wellbeing, and social support networks may mediate this effect. This may be particularly pertinent in later life, when social structures change significantly, and can lead to a decline in psychological wellbeing. AIM: To examine, in an older population, whether the relationships between neuroticism and extraversion and mental wellbeing are moderated by available social support networks. METHOD: We gathered information from 536 community-dwelling older adults, regarding personality, social support networks, depressive symptomatology, anxiety and perceived stress, as well as controlling for age and gender. RESULTS: Neuroticism and extraversion interacted with social support networks to determine psychological wellbeing (depression, stress and anxiety). High scores on the social support networks measure appear to be protective against the deleterious effects of high scores on the neuroticism scale on psychological wellbeing. Meanwhile, individuals high in extraversion appear to require large social support networks in order to maintain psychological wellbeing. CONCLUSION: Large familial and friendship social support networks are associated with good psychological wellbeing. To optimise psychological wellbeing in older adults, improving social support networks may be differentially effective for different personality types.

Demonstration of safety in Alzheimer's patients for intervention with an anti-hypertensive drug Nilvadipine: results from a 6-week open label study.

BACKGROUND: Nilvadipine may lower rates of conversion from mild-cognitive impairment to Alzheimer's disease (AD), in hypertensive patients. However, it remains to be determined whether treatment with nilvadipine is safe in AD patients, given the higher incidence of orthostatic hypotension (OH) in this population, who may be more likely to suffer from symptoms associated with the further exaggeration of a drop in BP. OBJECTIVE: The aim of this study was to investigate the safety and tolerability of nilvadipine in AD patients. METHODS: AD patients in the intervention group (n = 56) received nilvadipine 8 mg daily over 6-weeks, compared to the control group (n = 30) who received no intervention. Differences in systolic (SBP) and diastolic (DBP) blood pressure, before and after intervention, was assessed using automated sphygmomanometer readings and ambulatory BP monitors (ABP), and change in OH using a finometer. Reporting of adverse events was monitored throughout the study. RESULTS: There was a significant reduction in the SBP of treated patients compared to non-treated patients but no significant change in DBP. Individuals with higher initial blood pressure (BP) had greater reduction in BP but individuals with normal BP did not experience much change in their BP. While OH was present in 84% of the patients, there was no further drop in BP recorded on active stand studies. There were no significant differences in adverse event reporting between groups. CONCLUSION: Nilvadipine was well tolerated by patients with AD. This study supports further investigation of its efficacy as a potential treatment for AD.

Associations between holotranscobalamin, vitamin B12, homocysteine and depressive symptoms in community-dwelling elders.

BACKGROUND: Vitamin B12 and homocysteine have been shown to be associated with depression or depressive symptoms, but the relationship has not been universal. Both vitamin B12 and homocysteine may exert an effect via vascular mechanisms; it is possible that other mechanisms apply. Holotranscobalamin is a novel, more accurate measure of tissue vitamin B12. OBJECTIVES: To examine associations between vitamin B12, serum folate, holotranscobalamin, homocysteine and depressive symptoms in a sample of healthy elderly. METHODS: Cross-sectional, observational community based study. RESULTS: Lower levels of holotranscobalamin and vitamin B12 were associated with higher levels of depressive symptoms when controlled for Mini-mental state examination scores and psychosocial and cardiovascular risk factors. Homocysteine was not associated with depressive symptoms when biological and psychosocial covariates were included. CONCLUSIONS: It is possible that low levels of vitamin B12 or holotranscobalamin are associated with depressive symptoms via mechanisms other than vascular pathology.

Psychosocial correlates of aspects of sleep quality in community-dwelling Irish older adults.

OBJECTIVES: While it is known that psychosocial factors affect overall sleep quality, there is little consensus on the factors that affect different aspects of sleep. The Pittsburgh Sleep Quality Index (PSQI) provides a means of examining these separate aspects of sleep. METHOD: This study investigated whether the different components of the PSQI are affected by different psychosocial factors, or whether all aspects of sleep are associated with the same factors. 505 community-dwelling older adults took part in this study. Psychosocial status, comprising of measures of depression, anxiety, perceived stress, social and emotional loneliness and personality, was assessed for each participant. Health-related factors (pain, comorbidities, polypharmacy) as well as age and gender were also measured. RESULTS: Neuroticism, depression, anxiety and age accounted for overall sleep quality. Further analyses revealed that different psychosocial and health-related factors such as pain, loneliness and personality accounted for scores in the different components. CONCLUSION: Interventions for poor sleep quality may depend on the aspect of sleep affected in the individual, and treatment may be contingent on a number of different psychosocial variables. Future research could focus on developing personalised treatment programs for older adults with sleep complaints.

Cognitive rehabilitation for early stage Alzheimer's disease: a pilot study with an Irish population.

OBJECTIVES: Research shows that cognitive rehabilitation (CR) has the potential to improve goal performance and enhance well-being for people with early stage Alzheimer's disease (AD). This single subject, multiple baseline design (MBD) research investigated the clinical efficacy of an 8-week individualised CR intervention for individuals with early stage AD. METHODS: Three participants with early stage AD were recruited to take part in the study. The intervention consisted of eight sessions of 60-90 minutes of CR. Outcomes included goal performance and satisfaction, quality of life, cognitive and everyday functioning, mood, and memory self-efficacy for participants with AD; and carer burden, general mental health, quality of life, and mood of carers. RESULTS: Visual analysis of MBD data demonstrated a functional relationship between CR and improvements in participants' goal performance. Subjective ratings of goal performance and satisfaction increased from baseline to post-test for three participants and were maintained at follow-up for two. Baseline to post-test quality of life scores improved for three participants, whereas cognitive function and memory self-efficacy scores improved for two. CONCLUSIONS: Our findings demonstrate that CR can improve goal performance, and is a socially acceptable intervention that can be implemented by practitioners with assistance from carers between sessions. This study represents one of the promising first step towards filling a practice gap in this area. Further research and randomised-controlled trials are required.

Assessment of behavioural markers of autonoetic consciousness during episodic autobiographical memory retrieval: a preliminary analysis.

There is ongoing theoretical debate regarding episodic memory and how it can be accurately measured, in particular if the focus should be content-based recall of episodic details or something more experiential involving the subjective capacity to mentally travel back in time and "re-live" aspects of the original event. The autonoetic subscale of the Episodic Autobiographical Memory Interview (EAMI) is presented here as a new test instrument that attempts to redress theoretical and methodological shortcomings in autobiographical memory assessment. The EAMI merges a phenomenological detail-based approach with an assessment of autonoetic consciousness, departing considerably from traditional Remember/Know paradigms used within this field. We present findings from an initial pilot study investigating the potential markers of autonoetic consciousness that may accompany episodic retrieval. Key behavioural indices of autonoetic consciousness, notably those of viewer perspective, visual imagery, and emotional re-experiencing, emerged as being inextricably bound with the level of phenomenological detail recalled and the overall re-living judgment. The autonoetic subscale of the EAMI permits conceptually refined assessment of episodic personal memories and the accompanying subjective experience of mental re-living, characteristic of episodic memory.

Psychological distress and frailty transitions over time in community-dwelling older adults.

OBJECTIVES: Physical health and, in particular, frailty may be associated with psychological factors among older adults. We aimed to investigate the relationships between aspects of psychological distress and progression of frailty over time among older adults. METHODS: We used a longitudinal observational study design with 624 participants aged over 60 years (mean age=72.75, s.d.=7.21, 68% female) completing a baseline comprehensive biopsychosocial geriatric assessment, and 447 returning for a follow-up assessment 2 years later. Aspects of psychological distress, physical health, and frailty were analysed for the purposes of this study. We employed a series of logistic regression analyses to determine psychological predictors of changing states of aspects of frailty over time. RESULTS: With individual components of frailty, neuroticism and age predicted negative transitions of exhaustion and grip strength, respectively, whereas age alone was a predictor of transitions in overall frailty scores based on four components. CONCLUSION: We conclude that neuroticism and age may impact upon physical frailty and its progression over time in an ageing population. These findings may reflect the tendency for those with high levels of neuroticism to endorse negative symptoms, or alternatively, neuroticism may result in exhaustion via worry in an older population. Further research is required to further elucidate this relationship.

Sleep disturbance in mild to moderate Alzheimer's disease.

BACKGROUND AND PURPOSE: To determine the prevalence of sleep disturbance in a memory clinic population of Alzheimer's disease (AD) patients and identify its clinical correlates. PATIENTS AND METHODS: Data from 215 attendees at a memory clinic, who were diagnosed with Alzheimer's disease, were examined. This included data from cognitive, functional and neuropsychological assessments. Sleep disturbance was determined using the question about diurnal rhythm disturbance on the BEHAVE-AD questionnaire. Two groups, with and without sleep disturbance, were compared. Group differences were analysed using univariate analysis and stepwise logistic regression analysis. RESULTS: The prevalence of sleep disturbance in this sample was 24.5%. The BEHAVE-AD 'aggressiveness' (P=0.009) and 'global rating' (P=0.029) (a measure of global impact of behavioural disturbance) were found to be significant predictors of sleep disturbance in AD. CONCLUSIONS: Sleep disturbance in AD is associated with other behavioural symptoms, notably aggressiveness. Sleep disturbance in AD has significant impact on the patient and/or caregiver. Consideration of co-morbid behavioural symptoms may aid the clinician in choosing a suitable treatment for sleep disturbance in AD.

Hyperresponsivity to the serotonin agonist m-chlorophenylpiperazine in Alzheimer's disease. A controlled study.

The serotonin agonist m-chlorophenylpiperazine (mCPP) was administered intravenously to 12 patients with Alzheimer's disease and ten age-matched controls. It produced distinct behavioral effects in both treatment groups; however, significantly greater responsivity to mCPP was found in patients with Alzheimer's disease than in controls in measures of psychomotor activation, restlessness, and perceptual abnormalities. Significant and similar increases in plasma prolactin and cortisol levels were found in both patients with Alzheimer's disease and controls following the administration of mCPP vs placebo. Furthermore, blood pressure and pulse changes following mCPP were not significantly different between the groups. Elderly controls, however, did show a significantly greater temperature response following mCPP than did patients with Alzheimer's disease. The overall cognitive effects of mCPP were minimal; however, mCPP produced significantly greater worsening in recent memory and knowledge memory in patients with Alzheimer's disease than in controls. These findings could not be explained by pharmacokinetic differences across populations, because plasma concentrations of mCPP were similar in patients with Alzheimer's disease and controls. The increased behavioral responsivity but unchanged neuroendocrine or other physiologic responsivity to mCPP may be related to damaged brain serotonin neurons or other neuronal systems that interact with serotonin neurons that have been found in postmortem and biopsy studies of patients with Alzheimer's disease.

Effects of clozapine and fluphenazine treatment on responses to m-chlorophenylpiperazine infusions in schizophrenia.

OBJECTIVE: To explore serotonin function in patients with schizophrenia during typical and atypical neuroleptic treatment. We hypothesized that clinically relevant doses of the atypical neuroleptic clozapine would attenuate responses to the serotonin agonist m-chlorophenylpiperazine (m-CPP). DESIGN AND INTERVENTIONS: m-CPP or placebo was administered intravenously over 90 seconds to patients who had been receiving no medications for at least 3 weeks. m-CPP was also administered during treatment with the typical neuroleptic fluphenazine and the atypical neuroleptic clozapine. PATIENTS: Fifteen inpatients (two women and 13 men) who met DSM-III-R criteria for chronic schizophrenia (n = 13) or schizoaffective disorder (n = 2) participated in the study. Mean age (+/- SD) was 33.8 +/- 8.0 years. MAIN OUTCOME MEASURES: Measures of m-CPP effects included plasma cortisol and prolactin, body temperature, and the Brief Psychiatric Rating Scale (BPRS). The final BPRS total score at approximately 12 weeks of treatment was used to assess response to clozapine. RESULTS: m-CPP infusion significantly increased plasma cortisol and prolactin levels in drug-free patients. There was a range of behavioral responses while drug-free, but no statistically significant effects on BPRS total or BPRS factor scores. Clozapine treatment significantly blocked neuroendocrine responses to m-CPP, whereas fluphenazine had no effect. Clozapine also appeared to attenuate behavioral responses. CONCLUSIONS: These results demonstrate that clozapine treatment has potent serotonin antagonist effects in patients with schizophrenia. This may be related to clozapine's therapeutic effects since patients with greater cortisol response to m-CPP while drug-free had a better subsequent response to clozapine.

High-dose selegiline in treatment-resistant older depressive patients.

BACKGROUND: We examined the effect of high-dose selegiline in 16 treatment-resistant older depressive patients. We hypothesized that selegiline, at a dosage of 60 mg/d, would be at least partially effective but that the higher doses would not maintain the monoamine oxidase B selectivity observed with the lower doses of selegiline. METHODS: Sixteen treatment-resistant subjects (mean [+/- SD] age, 65.6 +/- 9.3 years) entered a double-blind, randomized, crossover study of placebo vs 3 weeks of selegiline at a dosage of 60 mg/d. Objective measures of mood and behavior were obtained in all subjects, and 10 of the subjects underwent repeated lumbar punctures for analysis of monoamine metabolites in the cerebrospinal fluid. RESULTS: Objective measures of mood and behavior revealed significant improvement in the Hamilton Depression Rating Scale score (37.4% decrease), the Global Depression score (22.7% decrease), and the Brief Psychiatric Rating Scale score (19.3% decrease); subjective behavioral measures, however, did not show significant improvement during the 3-week medication trial. Cerebrospinal fluid values revealed a statistically significant drop in 3-methoxy-4-hydroxyphenylglycol (51%) and 5-hydroxyindoleacetic acid (17%) levels, and there was a significant lowering of systolic blood pressure on standing (15%), but these changes were not accompanied by clinical side effects. CONCLUSIONS: Our results suggest that high-dose selegiline can be an effective antidepressant in treatment-resistant older depressive patients. While the selegiline dose required has nonselective monoamine oxidase effects and thus would not be free of possible tyramine interactions, other advantages suggest that further investigations with selegiline are warranted in this population.

Recent alcohol intake and suicidality--a neuropsychological perspective.

BACKGROUND: Alcohol use disorders and suicidal behaviours are among the most prevalent and damaging of all psychiatric phenomena in Ireland and worldwide. Furthermore, alcohol use both chronic and acute has long been identified as a potent riskfactor for suicidal behaviour. AIMS: In this paper, the authors review the observational and experimental evidence for the acute neuropsychological effects of alcohol intake on suicidal ideation and behaviour. METHODS: A selective review of the literature was conducted, using the PubMed database. Search terms employed included 'alcohol', 'suicide', 'binge' and 'acute alcohol intake'. RESULTS: Cognitive mechanisms implicated include alcohol-induced deficits in attention-allocation, prospective cognition, autobiographical memory and disinhibition. Emotional mechanisms include alcohol-induced dysphoria, depression and aggression. CONCLUSIONS: This paper serves to highlight the importance of identifying and tackling acute alcohol intake and binge drinking as a risk factor for suicidal behaviour.

Does modulation of glutamatergic function represent a viable therapeutic strategy in Alzheimer's disease?

Although glutamate dysfunction has been implicated in the pathogenesis of Alzheimer's disease (AD), it is unclear which direction a glutamatergic strategy should take in this illness. Increasing glutamate function may enhance excitotoxicity and neuronal death, whereas decreasing activity in this excitatory amino acid pathway may impair memory processes. Pharmacological modulation of the different NMDA and nonNMDA receptor sites, together with the concept of an agonist versus antagonist approach, are discussed in this review. It would appear that a glutamatergic approach may represent a new and exciting option to pursue in the experimental pharmacotherapeutics of AD.