Alzheimer Disease: Sachdev PS

Sachdev PS. · No affiliation provided · Am J Geriatr Psychiatry. · Pubmed #17545445 No free full text.

This publication has no abstract.

Chua TC, Wen W, Slavin MJ, Sachdev PS. · Neuropsychiatric Institute, Euroa Centre, Prince of Wales Hospital, Randwick, NSW, Australia. · Curr Opin Neurol. · Pubmed #18180656 No free full text.

Abstract: PURPOSE OF REVIEW: To provide a comprehensive review of diffusion tensor imaging in evaluating microstructural changes in the spectrum of cognitive decline from ageing to Alzheimer's disease, in particular focusing on mild cognitive impairment. RECENT FINDINGS: Mild cognitive impairment represents a transition phase between normal ageing and early Alzheimer's disease. Diffusion tensor imaging has emerged as a useful imaging modality that provides information about the structural integrity of tissue. In healthy ageing, diffusion tensor imaging abnormalities occur in the frontal regions, specifically the frontal white matter, anterior cingulum and the genu of the corpus callosum. Some studies report an anterior-posterior gradient change with greater abnormalities in the genu than the splenium of the corpus callosum and in the frontal than parietal white matter. In Alzheimer's disease, diffusion tensor imaging abnormalities are concentrated in the posterior regions: the parahippocampal gyrus, temporal white matter, splenium of corpus callosum and posterior cingulum. In mild cognitive impairment, changes seem to parallel those in Alzheimer's disease, with similar posterior regions showing abnormalities. SUMMARY: Due to the similarities in diffusion tensor imaging findings in both mild cognitive impairment and Alzheimer's disease, it is likely that diffusion tensor imaging has the potential to emerge as a useful clinical tool for early detection and monitoring of disease progression and treatment response in mild cognitive impairment/Alzheimer's disease patients.

Desmond DW, Erkinjuntti T, Sano M, Cummings JL, Bowler JV, Pasquier F, Moroney JT, Ferris SH, Stern Y, Sachdev PS, Hachinski VC. · Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, New York, USA. · Alzheimer Dis Assoc Disord. · Pubmed #10609678 No free full text.

Abstract: Dementia is common among patients with cerebrovascular disease, particularly in a setting of one or more clinically evident strokes. Prior cohort and case studies have suggested that the cognitive syndrome of vascular dementia is characterized by predominant executive dysfunction, in contrast to the deficits in memory and language function that are typical of patients with Alzheimer disease. The course of cognitive decline may also differ between those dementia subtypes, with many, but not all, patients with vascular dementia exhibiting a stepwise course of decline caused by recurrent stroke and most patients with Alzheimer disease exhibiting a gradually progressive course of decline. The findings of prior studies of the cognitive syndrome of vascular dementia must be interpreted with caution, however, because of (1) possible inaccuracies in the determination of the dementia subtype and the loss of precision that might result from pooling heterogeneous subgroups of patients with vascular dementia, (2) difficulties inherent in identifying a pattern of strengths and weaknesses in patients who are required to have memory impairment and other deficits to meet operationalized criteria for dementia, and (3) the use of limited test batteries whose psychometric properties are incompletely understood. Specific questions that should be addressed by future studies are discussed.

Looi JC, Sachdev PS. · Neuropsychiatric Institute, Prince of Wales Hospital, Romwick, Australia. · Neurology. · Pubmed #10489025 No free full text.

Abstract: BACKGROUND: The concept of vascular dementia (VaD) is currently in a state of evolution. Memory impairment is emphasized as a primary criterion, reflecting the influence of AD on the concept of dementia. We have systematically reviewed whether the nature of neuropsychological dysfunction is distinct in AD and VaD, and whether similar defining criteria for the concept of dementia in both disorders can be supported. METHODS: We searched five bibliographic databases (Medline, Biological Abstracts, EMBASE, PsychINFO, PsychLIT) for research articles in which VaD and AD had been compared using neuropsychological tests and that met criteria for scientific merit. RESULTS: Of the 45 studies, 18 were excluded because of inadequacies, and the remaining 27 were analyzed. There were a number of similarities of dysfunction between VaD and AD. However, when matched for age, education, and severity of dementia, VaD patients had relatively superior function in verbal long-term memory and more impairment in frontal executive functioning compared with AD patients. Interpretation of the results is limited by uncertainty in diagnostic criteria for VaD, possible inclusion bias due to use of clinical diagnosis alone, possible overlap of AD and VaD, and the methodologic shortcomings of some studies. CONCLUSIONS: The neuropsychological differentiation of VaD from AD was consistent with the different neuroimaging findings in the two disorders, and argues for differential criteria for the definition of the syndromes. The simple application of Alzheimer's dementia criteria to VaD, with the inclusion of cerebrovascular disease etiology, may not be sufficient to capture the uniqueness of VaD.

Ross AJ, Sachdev PS, Wen W, Valenzuela MJ, Brodaty H. · School of Psychiatry, University of New South Wales, Sydney, Australia. · Neurobiol Aging. · Pubmed #15718046 No free full text.

Abstract: 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.

Christensen H, Batterham PJ, Mackinnon AJ, Jorm AF, Mack HA, Mather KA, Anstey KJ, Sachdev PS, Easteal S. · The Australian National University, Canberra, Australia. · BMC Geriatr. · Pubmed #18620605 links to  free full text

Abstract: BACKGROUND: While the evidence of an association between the apolipoprotein E (APOE) *E4 allele and Alzheimer's disease is very strong, the effect of the *E4 allele on cognitive decline in the general population is more equivocal. A cross-sectional study on the lifespan effects of the *E4 allele 1 failed to find any effect of the *E4 allele on cognitive performance at ages 20-24, 40-44 or 60-64 years. METHODS: In this four year follow-up study, we reexamine the effect of *E4 in the sample of 2,021 individuals, now aged 65-69 years. RESULTS: Performance on the Mini-Mental State Examination (MMSE) was significantly poorer for *E4 homozygotes than heterozygotes or non-carriers. The effects of the *E4 genotype on cognitive decline over four years were found on the MMSE and Symbol-Digit Modalities test but only when controlling for risk factors such as head injury and education. Analyses were repeated with the exclusion of participants diagnosed with a mild cognitive disorder, with little change. CONCLUSION: It is possible that *E4 carriers become vulnerable to greater cognitive decline in the presence of other risk factors at 65-69 years of age.

Anderson TM, Sachdev PS, Brodaty H, Trollor JN, Andrews G. · School of Psychiatry, University of New South Wales, the Clinical Research Unit for Anxiety and Depression, Darlinghurst, New South Wales, Australia. · Am J Geriatr Psychiatry. · Pubmed #17545447 No free full text.

Abstract: OBJECTIVE: This article examines the influence of sociodemographic, biological, and health variables on Mini-Mental State Exam (MMSE) performance, and assesses how the diversity of the population should be reflected in the MMSE cutoff scores used for screening. METHODS: The sociodemographic profiles and MMSE scores of adults aged 65-years and over who participated in the Australian National Mental Health and Well-being Survey were assessed (N = 1,792). RESULTS: The regression models showed that older age, education levels, language spoken at home and in country of birth, socioeconomic status (SES), occupation, sex, and presence of a mood disorder made significant and unique contributions to performance on the MMSE. The individual (univariate) influence of each factor ranged from -2.61 to 0.09 points, with non-English speaking background (NESB) making the biggest impact. Based on a MMSE score of < or =23 points, 7.7% of the Australian elderly population screened positive for cognitive impairment that may be indicative of dementia. In those scoring < or =23 points, the multivariate model accounted for 24.61% of the variance. CONCLUSION: Many sociodemographic variables and the presence of a mood disorder influence MMSE performance. Using conventional cutoff scores for screening will lead to a high rate of false positives in older adults (75+ years), those with NESB, and those with low SES, and is insensitive for those with high education. The authors suggest simple rules for the correction of the impact of these variables.

Sachdev PS, Chen X, Joscelyne A, Wen W, Altendorf A, Brodaty H. · School of Psychiatry, University of New South Wales, Sydney, Australia; Neuropsychiatric Institute, The Prince of Wales Hospital, Sydney, Australia. · J Neurol Sci. · Pubmed #17482210 No free full text.

Abstract: BACKGROUND: Hippocampal atrophy is an early feature of Alzheimer's disease (AD) but it has also been reported in vascular dementia (VaD). It is uncertain whether hippocampal size can help differentiate the two disorders. METHODS: We assessed 90 stroke/TIA patients 3-6 months after the event, and 75 control subjects, with neuropsychological tests, medical and psychiatric examination and brain MRI scans. A diagnosis of VaD, vascular mild cognitive impairment (VaMCI) or no cognitive impairment (NCI) was reached by consensus on agreed criteria. T1-weighted MRI was used to obtain total intracranial volume (TICV), gray and white matter volume, CSF volume, hippocampus and amygdala volumes, and T2-weighted scans for white matter hyperintensity (WMH) ratings. RESULTS: Stroke/TIA patients had more white matter hyperintensities (WMHs), larger ventricle-to-brain ratios and smaller amygdalae than controls, but hippocampus size and gray and white matter volumes were not different. WMHs and amygdala but not hippocampal volume distinguished stroke/TIA patients with VaD and VaMCI and without NCI and amygdala volumes. Right hippocampus volume significantly correlated with new visual learning. CONCLUSIONS: Stroke/TIA patients and patients with post-stroke VaMCI or mild VaD do not have hippocampal atrophy. The amygdala is smaller in stroke/TIA patients, especially in those with cognitive impairment, and this may be accounted for by white matter lesions. The hippocampus volume relates to episodic memory, especially right hippocampus and new visual learning. A longitudinal study of these subjects will determine whether hippocampal atrophy is a late development in VaD.

Trollor JN, Sachdev PS, Haindl W, Brodaty H, Wen W, Walker BM. · School of Psychiatry, University of New South Wales, Sydney, Australia. · Psychiatry Clin Neurosci. · Pubmed #16958947 No free full text.

Abstract: 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.

Trollor JN, Sachdev PS, Haindl W, Brodaty H, Wen W, Walker BM. · School of Psychiatry, University of New South Wales, Randwick, Australia. · Dement Geriatr Cogn Disord. · Pubmed #16479105 No free full text.

Abstract: 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.

Walker AJ, Meares S, Sachdev PS, Brodaty H. · Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia. · Int Psychogeriatr. · Pubmed #15945591 No free full text.

Abstract: 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.

Trollor JN, Sachdev PS, Haindl W, Brodaty H, Wen W, Walker BM. · School of Psychiatry, University of New South Wales, Sydney, Australia. · Psychiatry Clin Neurosci. · Pubmed #15896221 No free full text.

Abstract: In spite of its wide availability, single photon emission computerized tomography (SPECT) scanning is uncommonly used in the assessment of Alzheimer's disease (AD) and related dementias. In light of recent advances in scanning protocols and image analysis, SPECT needs to be re-examined as a tool in the diagnosis of dementia. A total of 18 subjects with early AD and 10 healthy elderly control subjects were examined with high resolution SPECT during the performance of a simple word discrimination task. SPECT images were coregistered with individual magnetic resonance imaging scans, allowing delineation of predetermined neuroanatomical Regions of Interest (ROI). There was a gradation of regional cerebral blood flow (rCBF) values in both groups, with the lowest values being in the hippocampus and the highest in the striatum, thalamus and cerebellum. Compared to healthy controls, AD subjects demonstrated lower relative rCBF in parietal and prefrontal cortices. Analysis of individual ROI demonstrated bilateral reduction of rCBF in prefrontal poles, posterior temporal and anterior parietal cortex, and unilateral reduction of rCBF in left dorsolateral prefrontal cortex, right posterior parietal cortex and the left cingulate body. There were no significant differences for hippocampal, occipital or basal ganglia rCBF. Discriminant function analysis indicated that rCBF in the prefrontal polar regions achieved the best classification of cases. SPECT has utility in the diagnostic assessment of AD if standardized and semiquantitative techniques are used.