Adrienne Withall

Frequency and clinical, neuropsychological and neuroimaging correlates of apathy following stroke -the Sydney Stroke Study

BACKGROUND The frequency and clinical, neuropsychological and neuroimaging correlates of apathy in patients who have had a stroke are inadequately defined. METHOD A total of 167 consecutive patients admitted to the stroke units of two university hospitals after an ischaemic stroke and 109 controls received extensive medical, psychiatric and neuropsychological assessments; a subset received a magnetic resonance imaging (MRI) scan. The groups were matched for sex and age. Patients were assessed 3-6 months after their stroke. The sample for this study comprised 135 patients and 92 controls who completed the Apathy Evaluation Scale (AES). RESULTS Apathy was present in 26.7% of stroke patients compared to 5.4% of controls. Apathetic stroke patients were older, more functionally dependent and had lower Mini-Mental State Examination (MMSE) scores than those without apathy. Apathy was not associated with risk factors for cerebrovascular disease or stroke severity. There was a weak but significant correlation between apathy and self-reported depression but not with clinician-rated depression. Neuropsychologically, after correction for age, premorbid intelligence (IQ) and depression, apathy was associated with reduced attention and speed of information processing. On neuroimaging there were trends for associations of apathy with the extent of hyperintensities in the right hemisphere and right fronto-subcortical circuit, but not with total stroke volume or number of strokes. CONCLUSIONS Apathy is common following a cerebrovascular event. Presence of apathy may be related to older age and right fronto-subcortical pathway pathology, rather than stroke severity. It is associated with functional impairment and cognitive deficits.

Do people become more apathetic as they grow older? A longitudinal study in healthy individuals.

BACKGROUND The aim of this study was to determine levels, rates and progression of apathy in healthy older persons and to investigate factors associated with its progression. METHODS Seventy-six healthy elderly subjects, aged 58-85 years (mean 69.9), who were recruited by general advertisement and through local community groups, participated as a control group for a longitudinal study of stroke patients. Data were collected on demographic, psychological, neuropsychological and neuroimaging (MRI) variables and apathy was rated by informants on the Apathy Evaluation Scale (AES). RESULTS Apathy scores and rates increased over 5 years, especially in men. Change of apathy was associated with informant ratings of cognitive decline in the years prior to baseline assessment but not to subsequent neuropsychological, neuroimaging or functional changes. CONCLUSIONS Apathy increases with age in otherwise healthy community-dwelling individuals, particularly in men.

Prospective memory function in mild cognitive impairment and early dementia

When compared with controls, both mild cognitive impairment (MCI) and dementia are each associated with impaired memory for future intentions, or prospective memory (PM). However, prior studies have failed to agree on whether there are group differences in PM function between those with MCI and dementia. Furthermore, the degree and nature of the impairment remains to be clarified, as does the degree to which this impairment is secondary to deficits in other aspects of cognition. In the present study, MCI (n = 48), dementia (n = 39), and control participants (n = 53) were compared on Virtual Week, a measure that closely represents the types of PM tasks that occur in everyday life. Both clinical groups exhibited impairment irrespective of the specific task demands, but the magnitude of this deficit was greater for those with dementia. After covarying for other key cognitive parameters, although the absolute magnitude of the deficit was reduced, significant impairment remained. These results indicate that individuals with MCI, and to a greater extent dementia, experience generalized difficulties with PM. It is suggested that, while other cognitive deficits contribute to these difficulties, there is something unique to prospective remembering that may be additionally disrupted in these groups.

Pharmacologic Treatment of Apathy in Dementia

Apathy in patients with dementia is common, underrecognized, and undertreated. We sought to improve understanding of the pharmacologic treatment of apathy in dementia by performing a systematic literature review of studies that used apathy outcome scales to document results of pharmacologic treatments for apathy. There is limited evidence of efficiency of pharmacotherapy for treatment of apathy in dementia. The best results were found for acetylcholinesterase inhibitors. There was some evidence of efficacy for memantine, but less evidence of efficacy for stimulants, calcium antagonists, and antipsychotics. There was no evidence to support the use of antidepressants or anticonvulsants. The research quality of studies was modest. Recommendations for standardizing research and for holistic evaluation and treatment are provided.

A longitudinal study examining the independence of apathy and depression after stroke: the Sydney Stroke Study.

BACKGROUND There is growing recognition that apathy is not only a symptom of depression but may be an independent syndrome. This is the first study to investigate the relationship of apathy and depression longitudinally following stroke and to examine the association with dementia. METHOD 106 consecutive eligible participants following stroke received extensive medical, psychiatric and neuropsychological assessments at three to six months (index assessment) and 15 months (follow-up assessment) after their stroke. A subset of participants received magnetic resonance imaging (MRI) scans at index assessment. Ratings were made for DSM-IV major or minor depression and for apathy using the Apathy Evaluation Scale (AES). RESULTS While there was no significant overlap between apathy and depression at index assessment (OR = 1.79, 95% CI 0.48, 6.66), the overlap was significant a year later (OR = 7.75, 95% CI 2.60, 23.13). Dementia at index assessment was a common risk factor for both apathy and depression at follow-up (OR = 12.45, 95% CI 2.98, 52.02 and OR = 10.35, 95% CI 2.84, 37.72, respectively). CONCLUSIONS Apathy and depression after stroke have a common predictor and overlap longitudinally. The overlap might be due to cumulative vascular pathology and because of the relationship of each of these syndromes to dementia, which was an important, possibly causal, predictor for both.

The relationship between cognitive function and clinical and functional outcomes in major depressive disorder

BACKGROUND Although cognitive variables have been shown to be useful in predicting outcomes in late-life depression, there has not yet been a comprehensive study in younger persons with depression. METHOD The clinical symptoms and cognitive performance of participants were evaluated at admission to one of two university teaching hospitals and again at 3 months after remission and discharge. A total of 52 participants with a DSM-IV diagnosis of major depressive disorder, aged between 20 and 60 years and with a Hamilton Depression Rating Scale score 17 > or = entered the study. The sample for this paper comprises the 48 subjects (mean age 37.9 years, s.d.=10.7) who received admission and follow-up assessments; an attrition rate of 7.7%. RESULTS More perseverative errors on the shortened Wisconsin Card Sorting Test at admission predicted a worse clinical outcome at follow-up. Poor event-based prospective memory and more perseverative errors on the shortened Wisconsin Card Sorting Test at admission predicted worse social and occupational outcome at follow-up. CONCLUSIONS These results suggest that a brief cognitive screen at hospital admission, focusing on executive function, would have a useful prognostic value in depression. Determining early predictors of individuals at risk of poorer outcomes is important for identifying those who may need altered or additional treatment approaches.

A longitudinal study of cognitive function in melancholic and non-melancholic subtypes of Major Depressive Disorder

BACKGROUND Research concerning cognition in depression has often yielded inconsistent findings. The presence of mixed melancholic and non-melancholic subtypes of major depressive disorder (MDD) in most previous research may explain some of the contradictory results (Hickie, 1996). METHODS This longitudinal study compared the cognitive performance of people with melancholic (n=17) and non-melancholic (n=17) MDD admitted to one of two university hospitals. Participants received an extensive clinical and cognitive assessment at admission and again 3 months after recovery and discharge. RESULTS Overall, participants with melancholia had selective memory deficits with broader impairment of executive control skills. Specifically, after correcting for depression severity, they performed more poorly on tests requiring memory acquisition, mental flexibility, set-shifting, selective attention, concept-formation and multi-tasking compared to those with non-melancholic depression. These deficits were present at both assessments suggesting that the increased initial severity of cognitive deficits for those with melancholia mean that they require a longer time to recovery. LIMITATIONS The clinical homogeneity of the study sample may underestimate the extent of cognitive impairment for those presenting with comorbid illness and/or significant drug/alcohol histories. CONCLUSIONS These findings indicate that the depressed group with melancholia have a distinctly different and more impaired cognitive profile to those without melancholic features and suggest that these clinical subtypes should be considered separately in future research concerning MDD. Furthermore, the melancholic group appears to require longer periods for cognitive recovery and this has implications for return to work and daily functioning following clinical discharge.

The prevalence and causes of younger onset dementia in Eastern Sydney, Australia

BACKGROUND Service planning for people with younger onset dementia (YOD; an onset of symptoms before the age of 65 years) relies on prevalence estimates, with existing models based upon older people. This pilot study investigated the prevalence and causes of YOD in a defined catchment area of Eastern Sydney, Australia. METHODS The study was conducted in three stages: publicity building, case finding, and case validation. A brief structured questionnaire was sent to health professionals in the catchment area asking how many patients with YOD they had seen over the previous 12 months. Memory clinics and hospital records were also searched for YOD patients. Clinicians assigned a Statistical Linkage Key to each patient to prevent double counting, and indicated the cause of dementia. The majority of patients were validated by a review of medical case notes. Prevalence data were calculated for the following age groups: 30-64, 30-44, and 45-64 years. RESULTS Two hundred and four potential patients were identified, of which 141 met inclusion criteria. The primary clinical subtypes were alcohol-related dementia (18.4%), Alzheimers disease (17.7%), vascular dementia (12.8%), and frontotemporal dementia (11.3%). Eighty-eight patients were aged 30 to 64 years on census date and were therefore included in the prevalence calculations. The overall prevalence was 68.2 per 100,000 population at risk for the 30-64-year age group (95% Confidence Interval (CI): 54.9-83.4); 11.6 per 100,000 for the 30-44-year age group (95% CI: 5.3-21.7); and 132.9 per 100,000 for the 45-64 age group (95% CI: 105.8-164.2). CONCLUSIONS Younger onset dementia affects a significant number of people in Eastern Sydney with a diverse range of clinical types. This prevalence rate is higher than previous reports from the United Kingdom and Japan, with a different distribution of etiologies, which have important implications for service planning for this group.

Threat Perception in Mild Cognitive Impairment and Early Dementia

Mild cognitive impairment (MCI) and dementia affect many aspects of emotion processing. Even though the ability to detect threat is a particularly important aspect of emotion processing, no study to date has assessed threat perception in either of these groups. The purpose of the present study was to test whether individuals with MCI (n = 38) and mild dementia (n = 34) have difficulty differentiating between faces and situations normatively judged to be either high or low in threat relative to age-matched controls (n = 34). To achieve this aim, all participants completed 2 danger rating tasks that involved viewing and rating high- and low-danger images. It was also assessed whether threat perception was related to cognitive functioning and emotion recognition. The results indicated that all 3 groups were accurately, and comparably, able to differentiate high from low-danger faces. However, the dementia group had difficulties differentiating high from low-danger situations, which reflected a bias to overattribute the level of threat posed by normatively judged nonthreatening situations. This difficulty was related to more general cognitive decline.

Mortality and institutionalization in early survivors of stroke: the effects of cognition, vascular mild cognitive impairment, and vascular dementia.

We explored th effects of vascular mild cognitive impairment (VaMCI), vascular dementia (VaD), and other predictors on mortality and institutionalization in early survivors of ischemic stroke without previous dementia who had been admitted to a stroke unit. A total of 202 consecutive consenting eligible ischemic stroke survivors and a matched sample of 97 community controls were followed for up to 10 years. Data for 167 patients who underwent detailed assessment 3-6 months after stroke were analyzed to determine predictors of outcomes. Cumulative mortality rates for patients (and controls) were 27% (4%) for the first 5 years and rose to 83% (10%) by 10 years. Predictors of mortality were older age, any cognitive impairment, less independent function, and less education. Nursing home admission rates were 24% at 5 years and 32% at 10 years for patients and 0 for controls over 8.9 years. Predictors of institutionalization were less independent function and older age. Patients with ischemic stroke who survive the first week have moderate, lower-than-expected mortality rates in the first 5 years that increase thereafter. VaMCI, VaD, and functional decline are predictors of mortality, while functional decline and older age predict institutionalization.