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P S Sachdev

Publications and source records attributed to P S Sachdev.

At least 19 recordsLinked to original sources
PubMed2006

Clinical determinants of dementia and mild cognitive impairment following ischaemic stroke: the Sydney Stroke Study.

BACKGROUND: Dementia following stroke is common but its determinants are still incompletely understood. METHODS: In the Sydney Stroke Study, we performed detailed neuropsychological and medical-psychiatric assessments on 169 patients aged 50-85 years, 3-6 months after a stroke, and 103 controls with a majority of both groups undergoing MRI brain scans. Stroke subjects were diagnosed as having vascular mild cognitive impairment (VaMCI) or vascular dementia (VaD) or no cognitive impairment by consensus. Demographic, functional, cerebrovascular risk factors and neuroimaging parameters were examined as determinants of dementia using planned logistic regression. RESULTS: 21.3% of subjects were diagnosed with VaD, with one case in those aged 50-59 years, 24% in those aged 60-69 years and 23% in those 70-79 years. There was no difference by sex. The prevalence of VaMCI was 36.7%. VaD subjects had lower premorbid intellectual functioning and had 0.9 years less education than controls. The VaD and VaMCI groups did not differ from the no cognitive impairment group on any specific cerebrovascular risk factor, however overall those with impairment had a greater number of risk factors. They did not differ consistently on depression severity, homocysteine levels and neuroimaging parameters (atrophy, infarct volume and number of infarcts) except for an excess of white matter lesions on MRI and greater number of infarcts in the VaD and VaMCI groups. On a series of logistic regression analyses, stroke volume and premorbid function were significant determinants of cognitive impairment in stroke patients. CONCLUSION: Post-stroke dementia and MCI are common, especially in older individuals. Cerebrovascular risk factors are not independent risk factors for VaD, but stroke volume is a significant determinant of dementia. Premorbid functioning is a determinant of post- stroke impairment.

Aged↗
PubMed2006

Pulmonary function, cognitive impairment and brain atrophy in a middle-aged community sample.

OBJECTIVE: To determine the relationship of lung function to brain anatomical parameters and cognitive function and to examine the mediating factors for any relationships. METHODS: A random sub-sample of 469 persons (men = 252) aged 60-64 years from a larger community sample underwent brain magnetic resonance imaging scans and pulmonary function tests (forced vital capacity, FVC, forced expiratory volume in the first second, FEV(1)). Subjects were assessed for global cognitive function, episodic memory, working memory, information processing speed, fine motor dexterity and grip strength. The magnetic resonance imaging scans were analysed for overall brain atrophy, subcortical atrophy (ventricle-to-brain ratio, VBR), hippocampal volume, and white matter hyperintensity (WMH) volume. RESULTS: FEV(1) had a significant negative correlation with overall brain atrophy and VBR in men. The FEV(1)/FVC ratio had a significant correlation with WMHs in both men and women. In regression models that controlled for sex, age, height, level of activity, smoking, chronic respiratory disease and education, FEV(1) and FVC were significant predictors of VBR but no other structural brain measure. Pulmonary function was also significantly related to information processing speed and fine motor dexterity. Male subjects with chronic respiratory disease had more deep WMHs. Path analyses to examine if structural measures mediated between lung function and cognition, and whether markers of inflammation and oxidative stress or cortisol mediated between lung function and brain measures were negative. CONCLUSIONS: Decreased lung function is related to poorer cognitive function and increased subcortical atrophy in mid-adult life. Presence of chronic respiratory disease may be related to deep WMHs in men.

Atrophy↗
PubMed2005

1H MRS in stroke patients with and without cognitive impairment.

The pathophysiological basis of cognitive impairment in patients with cerebrovascular disease (CVD) is not well understood, particularly in relation to the role of non-infarction ischemic change and associated Alzheimer-type pathology. We used single voxel 1H MRS to determine the differences in brain neurometabolites in non-infarcted frontal white matter and occipito-parietal gray matter of 48 stroke patients with or without cognitive impairment and 60 elderly controls. The results showed that there were no significant neurometabolite differences between the stroke cohort and healthy elderly controls, but there was a difference in NAA/H2O between the stroke patients that had cognitive impairment (vascular dementia (VaD) and vascular cognitive impairment (VCI)) compared with those patients with no impairment. This was significant in the occipito-parietal gray matter, but not in the frontal white matter, although the results were in the same direction for the latter. This suggests that cognitive impairment in stroke patients may be related to cortical neuronal dysfunction rather than purely subcortical change. Moreover, cortical regions not obviously infarcted may have dysfunctional neurons, the pathophysiological basis for which needs further study.

Aged↗
PubMed2005

White matter hyperintensities are related to physical disability and poor motor function.

OBJECTIVE: To determine the impact of white matter hyperintensities (WMHs) on physical health and cognitive function in 60-64 year old individuals residing in the community. METHODS: A subsample of 478 persons aged 60-64 from a larger community sample underwent brain magnetic resonance imaging (MRI) scans. WMHs on T2 weighted FLAIR (fluid attenuated inversion recovery) MRI scans were assessed using an automated procedure. Subjects were assessed for global cognitive function, episodic memory, working memory (digit span), information processing speed (Symbol Digit Modalities Test; SDMT), fine motor dexterity (Purdue Pegboard), and grip strength, and completed the Physical Component Summary of the Short Form Health Survey (SF-12). Regression analyses were used to examine the effect of WMHs on physical and cognitive function. RESULTS: Deep and periventricular WMHs were present in all subjects, with women having slightly more lesions than men. WMHs were significantly associated with poorer reported physical health on the SF-12 scale, after adjusting for depression, cognitive function, and brain atrophy. WMHs were also related to lower scores on the Purdue Pegboard test, grip strength, choice reaction time, and SDMT, but not on tests of episodic memory, working memory, general intellectual function, and global cognitive function. On regression analyses, the Purdue Pegboard test and grip strength were related to physical disability. CONCLUSION: WMHs are common, albeit mild, in middle adult life. They are associated with physical disability, possibly through reduced speed, fine motor coordination, and muscular strength. They are also related to slowed information processing speed but not other cognitive functions.

Automation↗
PubMed2004

Progression of cognitive impairment in stroke patients.

OBJECTIVE: To examine the progression of neuropsychological deficits in stroke patients with and without cognitive impairment. METHODS: The authors assessed the Sydney Stroke Study cohort 1 year after index assessment with detailed neuropsychological and medical-psychiatric assessments. The neuropsychological tests were classified into cognitive domains, and composite z-scores adjusted for age and education. Changes in cognitive test scores were compared between groups and predictors of cognitive change examined. RESULTS: Patients (n = 128) had a mean decline of 0.83 (SD 2.2) points on the Mini-Mental State Examination (MMSE) compared to an increase of 0.76 (1.3) in controls (n = 78) (p < 0.0001), and a small but significant decline in informant ratings of function and cognition. The decline on a composite index of cognitive function was not significantly different in the groups after correction for age, education, and index assessment cognitive function. Stroke/transient ischemic attack patients, however, had greater decline in verbal memory and visuoconstructive function. The occurrence of an interval stroke (n = 14) significantly increased the cognitive decline to a mean 2.0 points on the MMSE. The rate of change had a significant correlation (r = 0.24) with white matter hyperintensity volume at index assessment. On regression analysis the only predictor of cognitive change was years of education, which had a protective function. CONCLUSIONS: Subjects with cerebrovascular disease have a slow decline in cognitive functioning in the absence of further cerebrovascular events, although the occurrence of such an event accentuates the dysfunction. Education plays a protective role.

Aged↗
PubMed2004

The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients.

OBJECTIVE: To characterize the neuropsychological profile of vascular cognitive impairment (VCI) and vascular dementia (VaD). METHODS: The authors examined 170 patients with stroke or TIA at 3 to 6 months after the vascular event, and 96 age-matched healthy controls, with detailed neuropsychological and medical-psychiatric assessments, with a majority (66.7%) undergoing MRI brain scans. The subjects were diagnosed as having VaD, VCI, or no cognitive impairment by consensus. The neuropsychological tests were classified into cognitive domains, and composite z-scores adjusted for age and education. RESULTS: VaD subjects had disturbance in all cognitive domains, with verbal memory, especially retention, being less affected. VCI subjects had similar but less severe disturbance. The domains that best discriminated cognitively impaired from unimpaired patients were abstraction, mental flexibility, information processing speed, and working memory. Cognitive impairment had a significant correlation with deep white matter hyperintensities, but not with volume and number of infarctions, even though the VaD subjects had larger infarct volumes than VCI subjects. The MRI variables did not provide additional discrimination between subgroups. CONCLUSIONS: The cognitive deficits in VaD and VCI are characterized by disturbance of frontal functions, with less verbal memory impairment. VaD and VCI differ in severity but not pattern of disturbance. The brain lesions that best account for these deficits are noninfarct subcortical white matter and gray matter changes due to ischemia. The picture of VaD/VCI presented shows subcortical deficits embellished by cognitive deficits from cortical infarctions.

Aged↗
PubMed2003

Double-blind controlled investigation of bilateral prefrontal transcranial magnetic stimulation for the treatment of resistant major depression.

BACKGROUND: The efficacy and safety of bilateral prefrontal repetitive transcranial magnetic stimulation (rTMS) for treating resistant major depression were examined in a double-blind, placebo-controlled study. METHOD: Nineteen medication-resistant depressed subjects were randomly assigned to 3 weeks of active or sham rTMS. Effects on mood and neuropsychological function were assessed. RESULTS: Both groups improved significantly in mood over the 3 weeks, but there was no significant difference between active and sham treatments. There were no significant neuropsychological effects. CONCLUSIONS: Bilateral rTMS was not superior to sham in treating resistant depression in this pilot study, but caused no neuropsychological impairment.

Adult↗
PubMed2003

High (15 Hz) and low (1 Hz) frequency transcranial magnetic stimulation have different acute effects on regional cerebral blood flow in depressed patients.

BACKGROUND: High and low frequency repetititve transcranial magnetic stimulation (rTMS) are both effective in treating depression but have contrary effects on motor cortical activity. This study aimed to understand further the mechanisms of action of high and low frequency rTMS by examining their acute effects on regional cerebral blood flow (rCBF) in depressed patients. METHOD: Eighteen depressed subjects underwent brain single photon emission computerized tomography (SPECT) scanning using split-dose 99mTc-HMPAO, and were examined during sham and active rTMS to the left prefrontal cortex, at 15 Hz or 1 Hz (N=9 each). Relative rCBF changes were examined by statistical parametric mapping and by regions of interest analysis. RESULTS: High (15 Hz) frequency rTMS resulted in relative rCBF increases in the inferior frontal cortices, right dorsomedial frontal cortex, posterior cingulate and parahippocampus. Decreases occurred in the right orbital cortex and subcallosal gyrus, and left uncus. Low (1 Hz) frequency rTMS led to increased relative rCBF in the right anterior cingulate, bilateral parietal cortices and insula and left cerebellum. High frequency rTMS led to an overall increase, whereas low frequency rTMS produced a slight decrease, in the mean relative rCBF in the left dorsolateral prefrontal cortex. CONCLUSIONS: High (15 Hz) and low (1 Hz) frequency rTMS led to different frontal and remote relative rCBF changes, which suggests different neurophysiological and possibly neuropsychiatric consequences of a change in frequency of rTMS.

Adult↗
PubMed2002

Relationship between plasma homocysteine levels and brain atrophy in healthy elderly individuals.

The authors examined the association of total plasma homocysteine (Hcy) levels with measures of atrophy and white matter disease on MRI scans in 36 healthy elderly individuals. Hcy had a significant positive relationship with lateral ventricle-brain ratios in the anterior (r = 0.49) and middle (r = 0.43) ventricular regions as measures of central atrophy, but not with cortical atrophy or white matter hyperintensities. In a logistic regression analysis, elevated Hcy was a significant determinant of increased anterior ventricle-brain ratio (> or =0.34) after controlling for age, folate, B12, creatinine, and white matter disease (OR = 2.3; CI, 1.03-5.09).

Aged↗
PubMed2001

Right versus left prefrontal transcranial magnetic stimulation for obsessive-compulsive disorder: a preliminary investigation.

BACKGROUND: There is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) may be useful for the treatment of obsessive-compulsive disorder (OCD), but no definitive study has been published, and the effect of laterality of stimulation is uncertain. METHOD: Subjects (N = 12) with resistant OCD were allocated randomly to either right or left prefrontal rTMS daily for 2 weeks and were assessed by an independent rater at 1 and 2 weeks and 1 month later. RESULTS: Subjects had an overall significant improvement in the obsessions (p < .01), compulsions (p < .01), and total (p < .01) scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after 2 weeks and at 1-month follow-up. This improvement was significant for obsessions (p < .05) and tended to significance for total Y-BOCS scores (p = .06) after correction for changes in depression scores on the Montgomery-Asberg Depression Rating Scale. There was no significant difference between right- and left-sided rTMS on any of the parameters examined. Two subjects (33%) in each group showed a clinically significant improvement that persisted at I month but with relapse later in I subject. CONCLUSION: A proportion (about one quarter) of patients with resistant OCD appear to respond to rTMS to either prefrontal lobe, although in the absence of a sham treatment group in this study, we cannot rule out the possibility of this being a placebo response. This treatment warrants further investigation to better establish its efficacy and examine the best parameters for response.

Adult↗
PubMed2000

Transcranial magnetic stimulation (TMS) in controlled treatment studies: are some "sham" forms active?

BACKGROUND: Carefully designed controlled studies are essential in further evaluating the therapeutic efficacy of transcranial magnetic stimulation (TMS) in psychiatric disorders. A major methodological concern is the design of the "sham" control for TMS. An ideal sham would produce negligible cortical stimulation in conjunction with a scalp sensation akin to real treatment. Strategies employed so far include alterations in the position of the stimulating coil, but there has been little systematic study of their validity. In this study, we investigated the effects of different coil positions on cortical activation and scalp sensation. METHODS: In nine normal subjects, single TMS pulses were administered at a range of intensities with a "figure eight" coil held in various positions over the left primary motor cortex. Responses were measured as motor-evoked potentials in the right first dorsal interosseus muscle. Scalp sensation to TMS with the coil in various positions over the prefrontal area was also assessed. RESULTS: None of the coil positions studied met the criteria for an ideal sham. Arrangements associated with a higher likelihood of scalp sensation were also more likely to stimulate the cortex. CONCLUSIONS: The choice of a sham for TMS involves a trade-off between effective blinding and truly inactive "stimulation." Further research is needed to develop the best sham condition for a range of applications.

Adult↗
PubMed2000

Dual voxel proton magnetic resonance spectroscopy in the healthy elderly: subcortical-frontal axonal N-acetylaspartate levels are correlated with fluid cognitive abilities independent of structural brain changes.

The published literature suggests that degeneration of the subcorticofrontal networks may underlie cognitive ageing, but appropriate methods to examine this in vivo have been lacking. Proton Magnetic Resonance Spectroscopy ((1)H-MRS) has now been used in a number of clinical studies to assess cerebral pathophysicochemistry and recently has been utilized to examine the relationship between neurochemical markers and cognitive functioning in normal individuals. Results have been somewhat conflicting and difficult to interpret. To further clarify the role of the cognitive spectroscopy technique, we measured N-acetylaspartate (NAA) levels in the frontal subcortical white matter and the occipitoparietal grey matter and correlated them with performance in different cognitive domains in a group of twenty healthy elderly individuals. Subjects underwent whole brain T(1)- and T(2)-weighted magnetic resonance imaging (MRI), dual voxel short echo-time (1)H-MRS, and a comprehensive neuropsychological assessment. Individual tests of executive and attentional abilities, and a principal components composite score reflecting these skills, but not measures of memory or verbal abilities, were correlated with NAA concentration in the frontal white matter only. These relationships were independent of other neurocognitive predictors of executive impairment such as age, midventricular dilation, frontal white matter disease, and presenescent verbal proficiency. This study suggests the ability of (1)H-MRS to differentiate anatomically distinct neurochemical markers related to specific cognitive abilities. In particular, neurometabolic fitness of the frontal subcortical-cortical axonal fibers may be important in mediating fluid intellectual processing. Longitudinal MRS studies are required to determine if the present results reflect different rates of neurocellular degeneration or preexisting individual differences in neuronal density.

Aged↗
PubMed2000

Animal models of acute drug-induced akathisia - a review.

Akathisia is a complex neurobehavioural side effect of neuroleptics and some other drugs which is characterised by subjective report and objective manifestations of restlessness. Its pathophysiology is poorly understood and there are many limitations to its investigation in humans. This paper reviews the various attempts that have been made in modelling acute akathisia in animals. Homologous as well as isomorphic models have been attempted, but most models are partial as they reproduce either the subjective or the objective features of the syndrome. None of the available models has been fully validated. Neuroleptic-induced defecation in the rat, even though constrained by a lack of symptom similarity and thereby face validity, has been most studied as a model of subjective akathisia. Rat models of restlessness, in particular those involving the use of serotonergic drugs or lesions of the ventral tegmentum or medial prefrontal cortex, are interesting partial models that should be further investigated. Neuroleptic-induced akathisia is observed in primates and has been modelled in dogs, and these should be studied further for their validation. It is also necessary to consider the subtypes of akathisia in the attempts to develop these models.

Akathisia, Drug-Induced↗
PubMed2000

Neuropsychological functioning of adults with attention deficit hyperactivity disorder.

The neuropsychological functioning of adults with Attention Deficit Hyperactivity Disorder (ADHD) was compared to that of healthy controls and individuals with mild psychiatric disorders including attentional complaints. Thirty adults in each group were examined on the Conners' Continuous Performance Test (CPT) and measures of attention, executive function, psychomotor speed, and arithmetic skills. The ADHD group performed lower than healthy controls on most measures. However when compared to the psychiatric group, the performances of the ADHD group were not significantly lower on any of the measures. The predictive power of the tests was poor in discriminating ADHD from psychiatric disorder. Implications for the clinical diagnosis of ADHD are discussed.

Adolescent↗
PubMed2000

How high a dose of stimulant medication in adult attention deficit hyperactivity disorder?

OBJECTIVE: This paper examines clinical and neuroscientific evidence to address the question whether high doses of stimulant drugs offer additional advantages in the treatment of adult attention deficit hyperactivity disorder (ADHD) and at what cost. It attempts to arrive at a reasonable upper limit of dosage for clinical purposes. METHOD: The study involves a selective review of the treatment studies of ADHD in children and adults and an examination of the pharmacokinetic and pharmacodynamic data on psychostimulants in humans and animals. RESULTS AND CONCLUSIONS: The clinical and experimental data justify the use of chronic low-dose stimulant treatment of ADHD in adults, with the recommended upper limit of dose being 1 mg/kg for methylphenidate and 0.5 mg/kg for dexamphetamine. There is no empirical evidence of greater improvement with higher doses and any beneficial effect is likely to be compromised by the adverse effects, some of which can be very serious. The recommended doses should be exceeded only after careful consideration and objective documentation of beneficial and adverse consequences. Monitoring of drug levels in blood may be of some value for compliance or pharmacokinetic considerations, as there is a direct relationship between blood and brain levels as well as dopamine transporter occupancy. These recommendations are tentative and further clinical research is warranted.

Adult↗