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Perminder S Sachdev

Publications and source records attributed to Perminder S Sachdev.

At least 19 recordsLinked to original sources
PubMed2006

A sham-controlled trial of the efficacy and safety of twice-daily rTMS in major depression.

BACKGROUND: Studies of repetitive transcranial magnetic stimulation (rTMS) in depression have mostly involved once-daily treatment, with positive but modest clinical results. This study tested the efficacy and safety of twice-daily rTMS over 2 weeks. METHOD: Thirty-eight depressed subjects enrolled in a double-blind, sham-controlled trial of twice-daily rTMS (left prefrontal cortex, 10 Hz, 110% intensity, 1500 stimuli per session) over 2 weeks. Mood and neuropsychological functioning were assessed weekly by blind raters, using the Montgomery-Asberg Depression Rating Scale (MADRS) as the primary outcome measure, plus the Hamilton Rating Scale for Depression (HRSD) and self-report measures. After the blind period, 22 subjects continued with once-daily rTMS to receive a total of 6 weeks of active rTMS. RESULTS: Subjects were moderately treatment resistant. Active treatment resulted in significantly greater improvement than sham over the 2-week blind period on one outcome measure only (MADRS p<0.05). Subjects showed further improvement over the 6 weeks of active rTMS. Neuropsychological test scores did not change significantly. CONCLUSIONS: rTMS given twice daily was effective and safe, with no adverse neuropsychological effects.

Adult↗
PubMed2006

Prediction of cognitive decline after stroke using proton magnetic resonance spectroscopy.

Structural MRI measures have been used to predict cognitive decline in elderly subjects, but few studies have used proton magnetic resonance spectroscopy ((1)H-MRS) for this purpose, particularly after stroke. We studied the potential of (1)H-MRS to predict cognitive decline in patients with stroke or TIA and healthy ageing controls over 12 months and 3 years. Structural MRI and single-voxel (1)H-MRS in the frontal white matter and the occipito-parietal gray matter were performed at the index assessment (3-6 months post-stroke) in 49 stroke/TIA patients and 60 controls. Neuropsychological testing was performed at the index assessment and repeated at 12 months in 30 stroke/TIA patients and 49 controls, and at 3 years in 25 patients and 48 controls. In stroke/TIA patients, frontal NAA/Cr predicted cognitive decline over 12 months and 3 years, and in elderly control subjects frontal NAA predicted cognitive decline over 12 months only. In stroke/TIA patients, the (1)H-MRS measures were better predictors of cognitive decline than structural measures. (1)H-MRS may be useful in assessing early cognitive impairment after stroke/TIA and in normal ageing.

Aged↗
PubMed2006

Effects of cerebrovascular risk factors on gray matter volume in adults aged 60-64 years: a voxel-based morphometric study.

The effect of putative cerebrovascular risk factors on gray matter volume in a community-dwelling, non-demented 60- to 64-year-old cohort was investigated. Cranial T1-weighted MRI scans were obtained in 337 adults and voxel-based morphometric analyses were applied to detect regional gray matter volume differences related to hypertension, diabetes, smoking, and hyperlipidemia in men and women, respectively. Hypertension-related gray matter volume reduction was found in right superior, bilateral medial frontal, left superior temporal and left precentral gyri in men. No regional differences in gray matter related to hypertension were seen in women. Conversely, female but not male smokers had more gray matter volume in right fusiform gyrus and right temporal subgyral gray matter. No differences were observed in gray matter volume in association with diabetes or hyperlipidemia for men or women. Our results suggest that there are different patterns of regional effects in gray matter volume in relation to different cerebrovascular risk factors, and sex differences for the same risk factors.

Brain↗
PubMed2006

A high-resolution single photon emission computed tomography study of verbal recognition memory in Alzheimer's disease.

BACKGROUND: In view of the recent technological advances and its ease of availability, we used single photon emission computed tomography (SPECT) to examine the performance of early Alzheimer's disease (AD) subjects on a verbal recognition memory task. METHODS: Eighteen early AD and 10 matched healthy control subjects underwent split-dose (99m)Tc-HMPAO (Ceretec) SPECT using a verbal recognition memory and control task. SPECT images co-registered with MRI scans were used to determine relative regional cerebral blood flow (rCBF) changes in regions of interest. RESULTS: In healthy control subjects, verbal recognition increased rCBF in the right occipital region, thalamus, left prefrontal pole, posterior parietal region and cerebellum, and decreased rCBF in the right hippocampus. AD subjects showed bilateral prefrontal, posterior parietal and occipital increases, unilateral increase in the left posterior temporal region, and bilateral reductions in the hippocampus. Although activation was significantly different between the two groups in the right thalamus and left medial prefrontal region, the verbal recognition task did not enhance discrimination between groups. CONCLUSIONS: Compared with controls, AD subjects activate a similar but more extensive bilateral network during verbal recognition, possibly reflecting an attempt to compensate for impaired processing.

Aged↗
PubMed2006

Depression in mild cognitive impairment in a community sample of individuals 60-64 years old.

OBJECTIVE: This cross-sectional study examined the prevalence and characteristics of depression in subjects with mild cognitive impairment (MCI). The data presented here are from the first wave of the longitudinal Personality and Total Health Through Life 60+ (PATH 60+) Project. METHOD: A total of 2551 community-dwelling individuals in the age range 60-64 years were recruited randomly through the electoral roll. They were screened using a short cognitive battery and those who screened positive underwent detailed medical and neuropsychological assessments. There were 29 subjects who fulfilled the Mayo Clinic criteria for MCI and these were compared to 520 controls. Subjects were evaluated for depression symptoms and DSM-IV major and minor depression syndromes. RESULTS: Subjects with MCI had more minor depression and higher scores on a symptom scale. However, a multivariate examination of specific symptoms showed that the differences were confined to only two motivation-related symptoms ("felt slowed up" and "little interest or pleasure"). CONCLUSION: Motivation-related depressive symptoms are more relevant in subjects with MCI than mood-related symptoms.

Australia↗
PubMed2006

Differential effects of transcranial magnetic stimulation of left and right posterior parietal cortex on mental rotation tasks.

A recently published study used the interference strategy of transcranial magnetic stimulation (TMS) to demonstrate the role of the right posterior parietal cortex (PPC) in the mental rotation of alphanumeric stimuli. We used similar stimulation parameters over the same left and right PPC regions, and examined the ability to rotate more complex 3D Shepard and Metzler (1971) images. There was reduced accuracy of performance with both right and left PPC stimulation for different angles of rotation of the visual stimuli. Right PPC stimulation led to reduced accuracy to rotate stimuli by 1200, whereas left PPC stimulation affected 180 degrees C rotation. We hypothesise that the two hemispheres make different contributions to the processing underlying visuospatial mental imagery: the right PPC is important for spatial rotations through smaller angles; the left hemisphere has a unique role when the stimuli to be compared are rotated through 180 degrees C, a task that engages verbal strategies due to the well-documented special nature of enantiomorphs.

Adult↗
PubMed2006

Longitudinal changes during aging using proton magnetic resonance spectroscopy.

OBJECTIVE: We aimed to examine the longitudinal change in proton magnetic resonance spectroscopy ((1)H-MRS) visible metabolites (N-acetyl aspartate [NAA], creatine [Cr], choline [Cho], and myo-Inositol [mI]) in brains of elderly individuals over 3 years and relate them to cognitive function. METHODS: Neurologically and psychiatrically normal volunteers (n = 40) were examined at baseline and 3 years later with (1)H-MRS in two voxels (frontal white matter n = 29, and occipitoparietal gray matter n = 36) and with detailed neuropsychological assessments. Longitudinal analyses were performed with age, educational level, sex, and white matter hyperintensities (WMH) in voxels as covariates. RESULTS: Frontal mI was significantly increased over time in male participants, but all other metabolites were stable over time. Neuropsychological performance was not significantly changed over 3 years, and there was no relationship between change in metabolite levels and change in neuropsychological function. CONCLUSIONS: MRS-visible metabolites are stable in elderly persons over 3 years, with the exception of mI which shows an increase. Increasing mI may be a marker of aging or a preclinical neurodegenerative process. MRS changes do not correlate with change in neurocognitive function during aging.

Aged↗
PubMed2006

Combined cerebral blood flow effects of a cholinergic agonist (milameline) and a verbal recognition task in early Alzheimer's disease.

RU 35926/CI-979 (milameline) is a partial muscarinic agonist with promnestic effects in animal models. Preliminary animal studies suggest that this agent has the capacity to reverse cholinergic dysfunction and that it may impact on regional cerebral blood flow (rCBF). A total of 10 subjects with Alzheimer's disease (AD) of mild severity underwent high resolution split-dose single photon emission computed tomography (SPECT) during performance of a verbal recognition and control task, both before and after 18 weeks treatment with melameline or placebo. SPECT images were coregistered with individual's magnetic resonance imaging scans allowing extraction of rCBF values from multiple anatomical regions of interest (ROI). The effect of milameline was examined in eight individuals who were found after unblinding to be taking active drug. Effects of milameline were most apparent in the frontal regions, basal ganglia and thalamus. In the group as a whole, the greatest increase in rCBF due to milameline treatment was observed in the left globus pallidus. Response to milameline treatment was associated with increases in rCBF in the cingulate gyrus bilaterally, and less so for the left thalamus. Milameline-related increases in rCBF values were exaggerated by the verbal recognition task. Milameline has a demonstrable effect on cerebral blood flow in mild AD. Consistent with emerging animal data, the effects on rCBF appear most prominent in frontal and subcortical regions in AD subjects. The effects on rCBF appear to be augmented by the performance of a cognitively demanding task, raising the possibility that such tasks could assist in building an awareness of the functional neuropsychopharmacology of drugs designed for cognitive enhancement.

Alzheimer Disease↗
PubMed2005

Gray matter reduction is correlated with white matter hyperintensity volume: a voxel-based morphometric study in a large epidemiological sample.

Both brain atrophy and T2-weighted white matter hyperintensities (WMH) are common findings in the brains of asymptomatic elderly individuals as well as in disease-specific brains. The study of the relationship between these two salient features is therefore important. To investigate such a relationship, we performed a brain magnetic resonance imaging (MRI) study on 397 asymptomatic individuals aged between 60 and 64 years, who were recruited randomly from a large community sample. WMH were delineated on T2-weighted fluid attenuation inversion recovery (FLAIR) whole brain scans using an automated procedure. The results showed that gray matter reduction, subarachnoid CSF (SA-CSF) increase and lateral ventricular dilation were significantly correlated with WMH load. Deep white matter hyperintensity (DWMH) had significant correlation with all three global atrophy indices, but periventricular white matter hyperintensity (PVWMH) was correlated only with gray matter volume. Voxel-based morphometric (VBM) analysis showed that regional gray matter reduction correlated more closely with WMH load of the proximate region than with WMH elsewhere. The results suggest that WMH have a relationship with brain atrophy in middle age, although the study cannot determine which process, i.e. the development of WMH or atrophy, is primary. The study also demonstrates that DWMH has a more significant relationship with structural brain changes, and may therefore be more functionally relevant than PVWMH. Further delineation of this relationship needs a longitudinal study of the changes in both WMH and indices of brain atrophy.

Age Factors↗
PubMed2005

Clinical and neuroimaging correlates of mild cognitive impairment in a middle-aged community sample: the personality and total health through life 60+ study.

This cross-sectional study aimed at determining the clinical and structural brain magnetic resonance imaging correlates of mild cognitive impairment (MCI). The data presented here are from the first wave of the longitudinal Personality and Total Health through Life 60+ project. 2,551 community-dwelling individuals in the age range of 60-64 years were recruited randomly through the electoral roll. They were screened using Mini-Mental State Examination and a short cognitive battery. Those who screened positive underwent detailed medical and neuropsychological assessments. Of the 224 subjects who screened positive, 117 underwent a detailed assessment. Twenty-nine subjects fulfilled the Mayo Clinic criteria for MCI. Magnetic resonance imaging scans were analyzed for 26 subjects with MCI as well as normal controls. Subjects were clinically evaluated for depressive symptoms and major and minor depression syndromes. Logistic regression analysis was performed predicting MCI from anterior and mid-ventricular brain ratios, cortical atrophy measures, hippocampal volumes, volumes of amygdala and white matter hyperintensities after adjusting for age, gender, years of education, depression and physical disability. None of the neuroanatomical substrates appeared as predictors of MCI. The only predictors were higher depression scores and fewer years of education. Structural neuroimaging may not have an added advantage in the detection of MCI in middle-aged community-dwelling subjects. It may be that this age group is too young for such brain changes to be identified.

Amygdala↗
PubMed2005

Chronic repetitive transcranial magnetic stimulation is antidepressant but not anxiolytic in rat models of anxiety and depression.

Transcranial magnetic stimulation (TMS) has been proposed as a treatment for depression and anxiety disorders. While the antidepressant effect has been modelled in animals, there have been few attempts to examine a possible anxiolytic effect of repetitive TMS (rTMS) in animal models. We administered 18 days of rTMS to male Sprague-Dawley rats. On days 10 through 18, rats were tested in several anxiety models (social interaction, emergence, elevated plus-maze, and predator odor avoidance) and in the forced swim test. No group differences were apparent on any of the anxiety models, while TMS produced an antidepressant effect in the forced swim test. Interestingly, on day 1 of the forced swim test, the home cage control group displayed increased swimming behaviour compared with sham-treated animals, suggesting an observable level of stress may have accompanied sham treatment. The results from the forced swim test suggested that TMS had modest antidepressant properties, but it did not show anxiolytic properties in the models examined. The study also suggested that stress associated with handling should be taken into account in the interpretation of TMS studies in animals.

Agonistic Behavior↗
PubMed2005

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.

Aged↗
PubMed2005

A rating scale for neuroleptic malignant syndrome.

The development of a rating scale for neuroleptic malignant syndrome (NMS) is described. The clinical and laboratory features of NMS were categorised into six domains after a thorough literature review and examination of patients. The reliability of this scale was established on 25 NMS patients and 50 control subjects based on chart reviews. A factor analysis supported a six-factor solution. The validity of the scale was indicated by the relationship of the severity rating to duration of illness and outcome. The inter-rater reliability of the scale was established prospectively in 10 subjects. The scale offers a measure of severity of NMS in the clinical setting so as to support the clinical diagnosis, monitor patients and determine their progress. The scale may be applicable not only to NMS or suspected NMS but also to NMS-like syndromes such as lethal catatonia.

Adult↗
PubMed2005

Cognitive correlates of 1H MRS measures in the healthy elderly brain.

Ageing is associated with cognitive decline, with some studies indicating that this decline can be mostly accounted for by slowing of information processing speed. Whilst it is likely that this is associated with age-related changes in fronto-subcortical neuronal circuits, such changes are not visible on routine neuroimaging. We examined the integrity of this brain region using proton magnetic resonance spectroscopy (1H MRS) and hypothesised that functional changes measured by 1H MRS would be associated with cognitive performance. Fifty-nine healthy elderly subjects (age 58-85 years) underwent single-voxel 1H MRS in frontal white matter and occipito-parietal gray matter, and a comprehensive neuropsychological battery. The results showed a significant correlation between frontal white matter NAA/H2O and a composite measure of neuropsychological performance representing speed of information processing, attentional function and visual memory, controlling for age and sex. This research highlights the importance of the relationship between regional brain changes and cognitive function in the ageing brain, and suggests that MRS may be a sensitive marker of subclinical change in cognition.

Aged↗
PubMed2005

Homocysteine and brain atrophy.

Homocysteine (Hcy) has been implicated as a risk factor for vascular disease as well as brain atrophy. There is evidence to implicate Hcy in increased oxidative stress, DNA damage, the triggering of apoptosis and excitotoxicity, all important mechanisms in neurodegeneration. Hcy is also prothrombotic and proatherogenic, and causes damage to the vessel wall. It is related to brain atrophy in older individuals, and possibly to white matter hyperintensities (WMH) in the brain. Epidemiological evidence and longitudinal data support Hcy as a risk factor for cognitive impairment and Alzheimer's Disease (AD). This may be due to cerebrovascular as well as direct neurotoxic mechanisms. Its role in Parkinson Disease (PD) is less well supported. High Hcy has been suggested as a mediating factor in alcohol-related brain atrophy. The high prevalence of hyperhomocysteinemia in the population and its easy treatability make Hcy an interesting amino acid for future intervention studies in the prevention of degenerative brain disorders. Intervention studies are necessary to confirm its aetiological role.

Alcoholism↗
PubMed2005

Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample.

BACKGROUND: Case control studies have supported a relationship between low folic acid and vitamin B112 and high homocysteine levels as possible predictors of depression. The results from epidemiological studies are mixed and largely from elderly populations. METHOD: A random subsample of 412 persons aged 60-64 years from a larger community sample underwent psychiatric and physical assessments, and brain MRI scans. Subjects were assessed using the PRIME-MD Patient Health Questionnaire for syndromal depression and severity of depressive symptoms. Blood measures included serum folic acid, vitamin B12, homocysteine and creatinine levels, and total antioxidant capacity. MRI scans were quantified for brain atrophy, subcortical atrophy, and periventricular and deep white-matter hyperintensity on T2-weighted imaging. RESULTS: Being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables. CONCLUSIONS: Low folic acid and high homocysteine, but not low vitamin B12 levels, are correlates of depressive symptoms in community-dwelling middle-aged individuals. The effects of folic acid and homocysteine are overlapping but distinct.

Aged↗
PubMed2005

The differentiation of mild frontotemporal dementia from Alzheimer's disease and healthy aging by neuropsychological tests.

BACKGROUND: Frontotemporal dementia (FTD) is difficult to diagnose in the early stages and may be misdiagnosed as Alzheimer's disease (AD) or as a psychiatric disorder. This study aimed to investigate neuropsychological function in FTD of mild severity and compare it to that of mild AD and healthy control participants. METHODS: The study comprised 11 individuals with FTD, 29 with AD and 27 healthy controls. Participants completed a comprehensive neuropsychological assessment in which each area of cognitive function was examined with several widely used clinical tests. Test scores were converted to age-corrected scaled scores and combined to form indices for six areas of cognitive function. These indices were attention, psychomotor speed, memory acquisition, memory recall, executive function and constructional ability. RESULTS: The FTD group performed below the level of the controls in all areas except constructional ability. FTD and AD groups showed distinct patterns of neuropsychological performance. The FTD group showed predominantly executive dysfunction with less impaired memory function, while the AD group showed the opposite pattern. The capacity of the tests to discriminate between groups was good overall, with 90% of the total sample correctly classified. Predictive success for the FTD group was 64%, given a base rate of 16%. CONCLUSION: Administration of a comprehensive neuropsychological protocol including several tests of executive function allows increased certainty about accurate clinical diagnosis of mild FTD.

Aged↗