Brian D. Power

The syndromal validity and nosological position of apathy in Parkinson's disease†

Although apathy is among the most frequent behavioral changes in Parkinsons disease (PD), its diagnosis is still problematic, and the overlap with depression and dementia poorly studied. Aim of the study was validate specific criteria to diagnose apathy in PD, and to examine its association with subsyndromes of depression and dementia. A series of 164 patients with PD, 44 patients with “primary” depression and no PD, 23 patients with Alzheimers disease, and 26 age‐comparable healthy controls underwent a comprehensive psychiatric assessment that included a structured psychiatric interview and the Apathy Scale. A set of seven diagnostic criteria showed high sensitivity and specificity for clinically diagnosed apathy. Fifty‐two of the 164 patients with PD (32%) met diagnostic criteria for apathy. Eighty‐three percent of patients with apathy had comorbid depression and 56% had dementia. Only 5 of the 40 PD patients (13%) with neither depression nor dementia had apathy. We validated a set of standardized criteria for the diagnosis of apathy in PD. About one third of a series of patients attending a Movement Disorders Clinic showed apathy. Both depression and dementia were the most frequent comorbid conditions of apathy in PD.

Depression in Alzheimer's disease: Phenomenology, clinical correlates and treatment

Depression is one of the most frequent comorbid psychiatric disorders in Alzheimers disease and other dementias, and is associated with worse quality of life, greater disability in activities of daily living, a faster cognitive decline, a high rate of nursing home placement, relatively higher mortality, and a higher frequency of depression and burden in caregivers. Depression in Alzheimers disease is markedly under-diagnosed, and most patients with depression are either not treated or are on subclinical doses of antidepressants. This is related to the lack of validated diagnostic criteria and specific instruments to assess depression in dementia. Apathy and pathological affect-crying are the main differential diagnoses of depression in Alzheimers disease. Left untreated, major depression in Alzheimers disease may last for about 12 months. Recent randomized controlled trials demonstrated the efficacy of sertraline and moclobemide to treat depression in Alzheimers disease. Other psychoactive compounds may be useful as well, but careful consideration must be given to potentially serious side-effects.

Age at Initiation of Cannabis Use Predicts Age at Onset of Psychosis: The 7- to 8-Year Trend

We investigated the existence of a temporal association between age at initiation of cannabis use and age at onset of psychotic illness in 997 participants from the 2010 Survey of High Impact Psychosis (SHIP) in Australia. We tested for group differences in age at onset of psychotic illness and in the duration of premorbid exposure to cannabis (DPEC). Analyses were repeated in subgroups of participants with a schizophrenia-spectrum disorder (SSD), a diagnosis of lifetime cannabis dependence (LCD), and a comorbid SSD/LCD diagnosis. The association between age at initiation of cannabis use and age at onset of psychotic illness was linear and significant, F(11, 984) = 13.77, P < .001, even after adjusting for confounders. The effect of age at initiation of cannabis use on DPEC was not significant (mean duration of 7.8 years), and this effect was similar in participants with a SSD, LCD, and comorbid SSD/ LCD diagnosis although a shift toward shorter premorbid exposure to cannabis was noted in the SSD/LCD subgroup (mean duration of 7.19 years for SSD/LCD). A temporal direct relationship between age at initiation of cannabis use and age at onset of psychotic illness was detected with a premorbid exposure to cannabis trend of 7-8 years, modifiable by higher severity of premorbid cannabis use and a diagnosis of SSD. Cannabis may exert a cumulative toxic effect on individuals on the pathway to developing psychosis, the manifestation of which is delayed for approximately 7-8 years, regardless of age at which cannabis use was initiated.

Antidepressant therapy in post-stroke depression.

Background: About 40% of patients with stroke will develop depression at some stage after the acute event. Post-stroke depression (PSD) is associated with a poor prognosis. Depressed patients have more severe deficits in activities of daily living, a worse functional outcome, more severe cognitive deficits and increased mortality as compared to stroke patients without depression. Objective: This review will focus on available controlled trials of treatment for PSD. Methods: An unsystematic review of recent studies for the treatment of PSD. Results: Randomized controlled trials have demonstrated the efficacy of sertraline, citalopram and nortriptyline to treat post-stroke depression. Whether antidepressant medication may help to prevent post-stroke depression and decrease post-stroke mortality will require further controlled studies.

Body adiposity in later life and the incidence of dementia: The health in men study

Objective To determine if adiposity in later life increases dementia hazard. Methods Cohort study of 12,047 men aged 65–84 years living in Perth, Australia. Adiposity exposures were baseline body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR). We used the Western Australian Data Linkage System (WADLS) to establish the presence of new cases of dementia between 1996 and 2009 according to the International Classification of Diseases (ICD). Crude and adjusted hazard ratio (HR, 95% confidence interval, 95%CI) of dementia for each adiposity marker was calculated using Cox regression models. Other measured factors included age, marital status, education, alcohol use, smoking, diet, physical activity, and prevalent hypertension, diabetes, dyslipidaemia and cardiovascular disease. Results Compared with men with BMI<25, participants with BMI between 25–30 had lower adjusted HR of dementia (HR = 0.82, 95% CI = 0.70–0.95). The HR of dementia for men with BMI≥30 was comparable to men with BMI<25 (HR = 0.82, 95%CI = 0.67–1.01). Waist circumference showed no obvious association with dementia hazard. Men with WHR≥0.9 had lower adjusted HR of dementia than men with WHR <0.9 (HR = 0.82, 95%CI = 0.69–0.98). We found a “J” shape association between measures of obesity and the hazard of dementia, with the nadir of risk being in the overweight range of BMI and about 1 for WHR. Conclusions Higher adiposity is not associated with incident dementia in this Australian cohort of older men. Overweight men and those with WHR≥0.9 have lower hazard of dementia than men with normal weight and with WHR<0.9.

The effect of drug use on the age at onset of psychotic disorders in an Australian cohort

BACKGROUND We aimed to examine the association between illicit substance use and age at onset in psychotic disorders in an Australian cohort. METHODS Retrospectively acquired information on substance use during the year prior to illness onset was collected from 1642 participants enrolled in the Australian National 2010 Survey of High Impact Psychosis study (SHIP), with an ICD-10 diagnosis of schizophrenia spectrum or affective psychosis. Latent class analysis was performed according to illicit substance use, using age as an active covariate; identified classes were subsequently validated. Cox regression was used to examine the independent contribution of the identified substance use classes and several confounding variables to the prediction of age at onset of psychosis. RESULTS Three classes according to substance use were identified: non-users (n=803), cannabis predominant users (n=582), and polysubstance users (n=257). For participants with schizophrenia spectrum disorders, cannabis predominant users had a higher hazard of earlier age at onset than for non-users (adjusted HR=1.38, 95% CI=1.2-1.6); polysubstance users had an even higher hazard (adjusted HR=1.95, 95% CI=1.5-2.4). In contrast, for participants with affective psychosis, cannabis predominant users (adjusted HR=1.10, 95% CI=0.8-1.4) and polysubstance users (adjusted HR=0.87, 95% CI=0.6-1.3) did not have a higher hazard of earlier age at onset compared with non-users. CONCLUSIONS Illicit substance use in the 12 months prior to psychosis onset has a differential effect on age at onset in schizophrenia spectrum and affective psychotic disorders. Our findings are compatible with the notion that illicit drugs bring forward age at onset in schizophrenia spectrum disorders but not affective psychotic disorders.

Age at initiation of amphetamine use and age at onset of psychosis: The Australian Survey of High Impact Psychosis

Individuals with a psychotic disorder who had a premorbid history of amphetamine use (n=382) were analyzed in groups according to age of initiation to amphetamine (AIA) and mean number of years of duration of premorbid exposure to amphetamine (DPEA) was calculated. Univariate General Linear Models were used to test for group differences in age at onset of psychotic illness (AOI) and DPEA. Although a temporal direct relationship between AIA and AOI was detected (mean duration 5.3 years), our findings suggested this association was spurious and better explained by a later initiation to amphetamine than to cannabis (by 2-3 years).

Does accumulating exposure to illicit drugs bring forward the age at onset in schizophrenia

Objective: Whilst cannabis has been associated with an earlier age at onset in schizophrenia, the impact of amphetamine and/or cocaine plus cannabis consumption on age at onset remains unclear. The present study was designed to test the hypothesis that consumption of amphetamine and/or cocaine in addition to cannabis would lead to an earlier age at onset of schizophrenia than that seen for cannabis consumption alone. A secondary objective was to determine what kind of effect additional substance use exerted (e.g. additive, multiplicative). Method: Patients with a diagnosis of schizophrenia were recruited from consecutive admissions to the inpatient and outpatient services of a large psychiatric hospital in Perth, Australia and 167 participants were assessed using the Diagnostic Interview for Psychosis, which included detailed inquiry into illicit drug use in the 12 months prior to the onset of psychiatric symptoms. Participants were categorized into four groups: no illicit substance use (n = 65), cannabis use (n = 68), cannabis plus amphetamine use (n = 25), and cocaine plus cannabis/cocaine plus cannabis plus amphetamine use (n = 9). Analysis of variance was performed to detect trends, and linear regression used to analyze the consumption of each additional substance as a predictor of age at onset. Results: We observed a linear trend for mean age at onset: 23.34 (SD = 6.91) years for no illicit substance use, 22.51 (SD = 5.27) years for cannabis use, 20.84 (SD = 3.48) years for cannabis plus amphetamine use, and 19.56 (SD = 3.54) years for cocaine plus cannabis/cocaine plus cannabis plus amphetamine use; the variation in the means between groups was statistically significant: F(1,163) = 5.66, p = 0.008, Cohen’s d = 0.38. For the consumption of each additional substance, age at onset was earlier by 1.2 years: R2 = 0.034, F(1,165) = 5.72, p = 0.018. Conclusions: Whilst preliminary, these findings suggest that additional consumption of each substance predicted an earlier age at onset by approximately 1 additional year.

No additive effect of cannabis on cognition in schizophrenia

BACKGROUND We aimed to examine the association between lifetime cannabis use and estimates of both premorbid and current cognitive function in psychotic disorders in an Australian cohort. METHODS In an Australian multicenter cohort, 1237 participants with an established ICD-10 diagnosis of psychotic disorder were categorised according to history of lifetime cannabis use (non-users, n=354; cannabis users, n=221; cannabis dependency, n=662). Groups were analyzed according to available indices of cognitive ability: the National Adult Reading Test - Revised (NART-R) for ability prior to illness onset; and the Digit Symbol Coding Test (DSCT) for current ability. Two-way analysis of variance was conducted without any covariate, followed by a two-way analysis of covariance (using age, age at onset of psychiatric illness, premorbid IQ and the Socio-Economic Index for Areas (SEIFA) rankings). RESULTS Whilst there appeared to be a significant association between cannabis use and mean DSCT (higher DSCT scores in cannabis using groups) F(2,1080)=9.478, p<0.001, η2=0.017), once covariates were used in the analysis there were no significant differences between groups in mean DSCT scores (F(2,1011)=0.929, p=0.395, η2=0.002). Similarly there were no differences between groups in mean NART scores once, age, age at illness onset and SEIFA rankings were used as covariates (F(2,1032)=1.617, p=0.199, η2=0.003). CONCLUSIONS Confounding variables underpin the association between cannabis use and cognitive function in psychotic disorders. Taken together, it would appear that cannabis use or dependence has no additive effect on cognitive dysfunction in these disorders.

Validation of a protocol for manual segmentation of the thalamus on magnetic resonance imaging scans.

We present a validated protocol for manual segmentation of the thalamus on T1-weighted magnetic resonance imaging (MRI) scans using brain image analysis software. The MRI scans of five normal control subjects were randomly selected from a larger cohort recruited from Lund University Hospital and Landskrona Hospital, Sweden. MRIs were performed using a 3.0T Philips MR scanner, with an eight-channel head coil, and high resolution images were acquired using a T1-weighted turbo field echo (T1 TFE) pulse sequence, with resulting voxel size 1×1×1 mm3. Manual segmentation of the left and right thalami and volume measurement was performed on 28-30 contiguous coronal slices, using ANALYZE 11.0 software. Reliability of image analysis was performed by measuring intra-class correlations between initial segmentation and random repeated segmentation of the left and right thalami (in total 10 thalami for segmentation); inter-rater reliability was measured using volumes obtained by two other experienced tracers. Intra-class correlations for two independent raters were 0.95 and 0.98; inter-class correlations between the expert rater and two independent raters were 0.92 and 0.98. We anticipate that mapping thalamic morphology in various neuropsychiatric disorders may yield clinically useful disease-specific biomarkers.