Alzheimer's disease (AD) still remains an enigma for researchers and clinicians. The onset of AD ... more Alzheimer's disease (AD) still remains an enigma for researchers and clinicians. The onset of AD is insidious, gradually progressive and multifactorial. The recent accumulated scientific evidences suggests that the pathological changes resemble the autoimmune-driven self-sustaining inflammatory process as a result of prolonged oxidative stress and immune dyshomeostasis. Apart from aging, during life span various other factors-mainly environmental, lifestyle, chronic stress, polymicrobial infections and neuroendocrine functions-affect the immune system. Here, we provide crosstalk among "trigger insults/inflammatory stimulus" i.e., polymicrobial infection, chronic stress, pro-inflammatory diet and cholinergic signaling to put forward a "Systemic Immune Dyshomeostasis" model as to connect the events leading to AD development and progression. Our model implicates altered cholinergic signaling and suggests pathological stages with various modifiable risk factors and triggers at different chronological age and stage of cognitive decline. The search of specific autoantibodies for AD which may serve as the suitable blood/CSF biomarkers should be actively pursued for the early diagnosis of AD. The preventive and therapeutic strategies should be directed towards maintaining the normal functioning of the immune system throughout the life span and specific modulation of the immune responses in the brain depending on the stage of changes in brain.
Background: Coronaviruses (CoVs) have a neuroinvasive potential, which has been discussed in vari... more Background: Coronaviruses (CoVs) have a neuroinvasive potential, which has been discussed in various research papers. During the current pandemic, the novel CoV, i.e., SARS-CoV-2, is causing a considerable number of fatalities and posing a great danger of a recurrent epidemic. COVID-19 has been labeled as a public health emergency of international concern, and the epidemic curves are on the rise. Purpose: Some studies discuss the neurological implications of SARS-CoV-2 but in light of growing number of evidences we cannot ignore the planning of mental health care settings in COVID-19. We are discussing how this novel CoV can affect the human brain directly and indirectly, including psychiatric problems, and how neurological conditions can be explored as a diagnostic tool in COVID-19 by analyzing cohort studies and review papers that discuss the recent neurological findings in COVID-19. Method: Current research and review papers were searched to find out any relation between the COVI...
Parkinson's disease (PD) is an old age disorder of basal ganglia which involves oligomerization o... more Parkinson's disease (PD) is an old age disorder of basal ganglia which involves oligomerization of asynuclein protein and formation of intercellular inclusions known as ''Lewy bodies'' in substantia nigra and caudate nuclei in brain which is progressive in nature. It is second most prevalent neurodegenerative disorder characterized by tremor at rest, muscle rigidity, slowness of movement (bradykinesia, akinesia), and changes in posture (instability). Both excess and deficiency in levels of transition metals (especially iron, copper) can be detrimental to the central nervous system. Abnormalities in iron (Fe) and copper (Cu) metabolism have been reported to produce oxidative stress which is one of the major cause in pathogenesis of PD. In the present study 35 PD patients and 33 controls of Northern Indian population were included and serum levels of Fe, Cu and ceruloplasmin (Cp) were measured. Serum Fe (p \ 0.01) and Cu (p \ 0.01) levels were found to be significantly decreased in PD, whereas there was no significant change in Cp levels in PD patients as compared to controls. These results suggest the existence of a defect in iron which over the time, may hasten the entry of iron into the brain and decrease iron in the extracellular compartment in PD patients.
Funding Information We also thank agencies ICMR and CSIR for fellowships and projects GAP0091 (IC... more Funding Information We also thank agencies ICMR and CSIR for fellowships and projects GAP0091 (ICMR) and BSC0123 (CSIR) for financial assistance.
The present study aimed to evaluate association of genetic variants on drug response and therapy ... more The present study aimed to evaluate association of genetic variants on drug response and therapy optimization parameters in patients treated with first-line antiepileptic drugs (AEDs). Genetic variants from ion channels, their functionally related genes, and synaptic vesicle cycle (SVC) genes with a potential role in epilepsy pathophysiology were thus prioritized. A total of 12 genes from ion channels and related gene set and seven genes from SVC comprising 155 SNPs were genotyped and evaluated with drug response, dose levels, and drug levels in 408 patients with epilepsy. Both GABRA1 and SCN1A variants showed haplotypic and diplotypic associations in response to phenytoin (PHT). Diplotype analysis of GABRA1 variants revealed association of rs12658835|rs7735530 (AG/AG) (P-valuecorrected = 0.034, OR = 3.75, 95% CI = 1.36-11.05) and rs12658835|rs7735530|rs7732641|rs2279020 (AGCA/AGCA) (P-valuecorrected = 0.035, OR = 2.48, 95% CI = 0.96-6.41) with recurrent seizures. SCN1A haplotype ...
Laboratory error is defined as any defect from ordering tests to reporting and interpretation of ... more Laboratory error is defined as any defect from ordering tests to reporting and interpretation of results. Laboratory errors have a reported frequency of 0.012-0.6% of all test results which in turn has huge impact on diagnosis and patient management as 60-70% of all diagnosis are made on the basis of laboratory tests. Total testing process in the laboratory is a cyclical process divided into three phases: preanalytical, analytical and postanalytical. First, preanalytical phase in which requirement for a test is determined, the test is ordered and the patient is identified. It is followed by specimen collection and transport to the laboratory. The specimen is prepared and tested in the analytical phase. During the postanalytical phase, the results are reported to the individual who ordered the test and any action or intervention is undertaken. Initially, the policies and procedures developed by the laboratory were more concerned on analytical phase to reduce errors during laboratory testing and emphasis was in ensuring proper calibration and testing. The last few decades have seen a significant decrease in the rates of analytical errors in clinical laboratories. Currently, available evidences demonstrate that the pre-and postanalytical steps are more error prone.
American journal of Alzheimer's disease and other dementias, 2014
Dementia is an age-related disorder associated with elderly population, resulting from interactio... more Dementia is an age-related disorder associated with elderly population, resulting from interaction of lifestyle risk factors with genetic, vascular, and other risk factors to affect risk of disease. Alzheimer's disease (AD) is the most common form of dementia, estimated to be affecting 4.4% of the population older than 65 years of age. Apolipoprotein E (ApoE) ε4 allele is a known genetic risk factor for AD, which not only predisposes and influences the severity of pathological changes in the brain, thereby modifying the age at onset, but also promotes cognitive decline early in nondemented older people. To review the published evidence on ApoE polymorphism with the susceptibility to AD and frequency of ApoE ε4 genotype (ε4/-) and homozygotes (ε4/4) among patients diagnosed with AD as compared to controls in Indian Population. In the present study, MEDLINE was reviewed for articles published till June 2013 supplemented by citation analysis from retrieved articles to select case-c...
Mouse peritoneal macrophages (MPM) when elicited by the antioxidant ascorbic acid have been found... more Mouse peritoneal macrophages (MPM) when elicited by the antioxidant ascorbic acid have been found to be significantly stimulatory, exhibiting marked alteration at the cellular and enzyme levels. Alterations recorded were as follows--cellular yield per mouse, their protein content, lysosomal acid hydrolase levels and capability to phagocyte, all were significantly enhanced. The new stimulant was observed to produce no synergistic action on MPM when thioglycollate, BCG or endotoxin along with the same stimulated the latter. Levels of antioxidants like ascorbic acid and glutathione were found to be enhanced in elicited macrophages whereas superoxide dismutase levels varied when the three above stimulators were administered. However, the ascorbic acid elicited cells showed an increase in glutathione levels and a decrease in SOD levels but no change in total intracellular ascorbic acid levels. Further, though ascorbic acid interaction enhanced the phagocytic capability of MPM as compared...
During post-analytical phase, critical value notification to responsible caregiver in a timely ma... more During post-analytical phase, critical value notification to responsible caregiver in a timely manner has potential to improve patient safety which requires cooperative efforts between laboratory personnel and caregivers. It is widely accepted by hospital accreditors that ineffective notification can lead to diagnostic errors that potentially harm patients and are preventable. The objective of the study was to assess the variables affecting critical value notification, their role in affecting it's quality and approaches to improve it. In the present study 1,187 critical values were analysed in the Clinical Chemistry Laboratory catering to tertiary care hospital for neuropsychiatric diseases. During 25 months of study period, we evaluated critical value notification with respect to clinical care area, caregiver to whom it was notified and timeliness of notification. During the study period (25 months), the laboratory obtained 1,279 critical values in clinical chemistry. The analytes most commonly notified were sodium and potassium (20.97 & 20.8 % of total critical results). Analysis of critical value notification versus area of care showed that critical value notification was high in ICU and emergency area followed by inpatients and 64.61 % critical values were notified between 30 and 120 min after receiving the samples. It was found that failure to notify the responsible caregiver in timely manner represent an important patient safety issue and may lead to diagnostic errors. The major area of concern are notification of critical value for outpatient samples, incompleteness of test requisition forms regarding illegible writing, lack of information of treating physician and location of test ordering and difficulty in contacting the responsible caregiver.
Alzheimer's disease International (ADI) estimates that there are currently 30 million people with... more Alzheimer's disease International (ADI) estimates that there are currently 30 million people with dementia in the world. The main objective was to perform meta-analysis of studies of CSF tau and Amyloid β 42 (Aβ 42) levels in Alzheimer's disease (AD) patients and controls. In the present study MEDLINE was reviewed from 1995 to 2009, supplemented by citation analysis from retrieved articles to select case control studies. Descriptive statistics showed that median effect size (raw mean difference) of CSF tau and Aβ 42 levels were 301 pg/ml (Range: 22 to 614 pg/ml) and-352 pg/ml (Range:-969 to 203 pg/ml) respectively. The pooled effect size CSF tau and Aβ 42 was 289.14 pg/ml (95% CI 253.278 to 325.013 pg/ml) and-329.02 pg/ml (95% CI-387.740 to-270.445 pg/ml) respectively. Heterogeneity in effect size of selected studies was present for both parameters (CSF tau: Q statistics = 1816.596, DF = 40, P = 0.000 and CSF Aβ 42 : Q-statistics = 1259.358, DF = 24, p < 0.001). Based on the findings of meta-analysis in the present study, CSF tau and Aβ 42 levels in AD and controls may be considered as potential biomarker along with the clinical phenotype to perform them during high quality diagnostic testing in dementia.
Background Alzheimer’s disease (AD) is one of the leading genetically complex and heterogeneous d... more Background Alzheimer’s disease (AD) is one of the leading genetically complex and heterogeneous disorder that is influenced by both genetic and environmental factors. The underlying risk factors remain largely unclear for this heterogeneous disorder. In recent years, high throughput methodologies, such as genome-wide linkage analysis (GWL), genome-wide association (GWA) studies, and genome-wide expression profiling (GWE), have led to the identification of several candidate genes associated with AD. However, due to lack of consistency within their findings, an integrative approach is warranted. Here, we have designed a rank based gene prioritization approach involving convergent analysis of multi-dimensional data and protein-protein interaction (PPI) network modelling. Results Our approach employs integration of three different AD datasets- GWL,GWA and GWE to identify overlapping candidate genes ranked using a novel cumulative rank score (SR) based method followed by prioritization u...
International Journal of Alzheimer's Disease, 2011
CSF tau and Aβ42 are considered as important markers to diagnose Alzheimer’s disease in early sta... more CSF tau and Aβ42 are considered as important markers to diagnose Alzheimer’s disease in early stages. Hence, it is important to assess their status in different types of dementia. The main objective of this study was to assess whether these CSF biomarkers can be used to make the differential diagnosis of AD. In the present study, articles published from 1998 till 2009 were taken and meta-analysis was performed to clarify the consistency in trends of biomarkers- CSF tau and Aβ42in AD and other dementias and whether the same can be used as diagnostic biomarkers for its early diagnosis. 11 out of 60 for CSF tau and 07 out of 40 for CSF Aβ42, dementia case-control studies were selected for final analysis. Descriptive statistics shows that median effect size (raw mean difference) of CSF tau was 429 pg/mL (range: 32 to 910 pg/mL) in AD whereas in Dementia due to other causes (DOC) studies it was 69 pg/mL (range: −53 to 518 pg/mL). Similarly the median effect size of CSF Aβ42levels was −44...
Dementia and Geriatric Cognitive Disorders Extra, 2017
Background: As variability in the clinical profile of dementia subtypes had been reported with re... more Background: As variability in the clinical profile of dementia subtypes had been reported with regional differences across the world, we conducted a retrospective hospital-based study in a North Indian population. Methods: We retrieved patient records from 2007 to 2014 for details of clinical evaluation, diagnosis, neuroimaging, biochemical investigations, and follow-up of 1,876 patients with dementia (PwD), and the data were analyzed using descriptive statistics. Results: Of the total PwD, Alzheimer disease (AD) accounted for 30% followed by vascular dementia (VaD) 26%, mixed dementia (MD) 21%, Parkinson-related dementia 11%, frontotemporal dementia (FTD) 7%, and infective dementia 5%. Of all PwD excluding the infective group (n = 1,777), 63% were men, 39% were from rural areas, 87% had behavioral abnormalities along with cognitive deficits, and 73% had impaired ADLs. Among dementia subtypes, a positive family history, cardiovascular and metabolic risk factors, and behavioral abnor...
Indian journal of clinical biochemistry : IJCB, 2008
Alzheimer's disease is the most common form of dementia in the elderly and it's prevalenc... more Alzheimer's disease is the most common form of dementia in the elderly and it's prevalence is rapidly rising. Oxidative stress plays important role in the pathophysiology of Alzheimer's disease. Metals like copper, iron derived through diet can act as pro-oxidant under oxidative stress. In the present study, serum copper levels were evaluated in 50 patients with Alzheimer's disease, 24 patients with Vascular Dementia and 30 controls. All the groups were also investigated for serum ceruloplsmin levels. The mean copper levels in Alzheimer's disease and Vascular Dementia were significantly raised compared to controls. An attempt has been made to study the relationship of serum copper with ceruloplasmin. Our study found weak correlation between copper and ceruloplasmin levels in Alzheimer's disease and Vascular Dementia.
Indian journal of clinical biochemistry : IJCB, 2009
The present study was conducted to assess correlation of ammonia levels with valproate levels in ... more The present study was conducted to assess correlation of ammonia levels with valproate levels in epileptic patients presenting with valproate toxicity and also whether liver enzymes and ammonia levels could serve as biochemical marker of valproate toxicity. 100 patients with epilepsy who had received valproate therapy for more than 12 months and had presented with valproate toxicity and 100 controls were included in the study. The serum valproate, ammonia and liver enzymes were measured in these subjects. In patients with valproate toxicity, the mean level of serum valproate was 110.91 ± 28.68 mg/dL (therapeutic range 50-100 mg/dL). Serum ammonia was higher (86.37 ± 39.90 µg/dL) in patients with valproate toxicity compared to controls (68.73 ± 30.07 µg/dL). Out of 100 patients, only 37 patients had serum valproate level > 120 mg/dL and 22 patients had raised levels of valproate as well as ammonia. Age < 30 years and serum ammonia > 69 μg/dL is risk factors for valproate tox...
Advances in instrument technology and automation have simplified tasks in laboratory diagnostics ... more Advances in instrument technology and automation have simplified tasks in laboratory diagnostics reducing errors during analysis thereby improving the quality of test results. However studies show that most laboratory errors occur in the pre-analytical phase. In view of the paucity of studies examining pre-analytical errors, we examined a total of 1513 request forms received at our laboratory during a 3 month period. The forms were scrutinized for the presence of specific parameters to assess the pre-analytical errors affecting the laboratory results. No diagnosis was provided on 61.20% of forms. Type of specimen was not mentioned in 61.60% of the forms and 89.25% of all forms were illegible. Critical results were encountered in 17.30% of patients, and of these 76.60% were not communicated due to incomplete forms. Thus, by following standard operating procedures vigorously from patient preparation to sample processing the laboratory results can be significantly improved without any extra cost.
Alzheimer's disease (AD) still remains an enigma for researchers and clinicians. The onset of AD ... more Alzheimer's disease (AD) still remains an enigma for researchers and clinicians. The onset of AD is insidious, gradually progressive and multifactorial. The recent accumulated scientific evidences suggests that the pathological changes resemble the autoimmune-driven self-sustaining inflammatory process as a result of prolonged oxidative stress and immune dyshomeostasis. Apart from aging, during life span various other factors-mainly environmental, lifestyle, chronic stress, polymicrobial infections and neuroendocrine functions-affect the immune system. Here, we provide crosstalk among "trigger insults/inflammatory stimulus" i.e., polymicrobial infection, chronic stress, pro-inflammatory diet and cholinergic signaling to put forward a "Systemic Immune Dyshomeostasis" model as to connect the events leading to AD development and progression. Our model implicates altered cholinergic signaling and suggests pathological stages with various modifiable risk factors and triggers at different chronological age and stage of cognitive decline. The search of specific autoantibodies for AD which may serve as the suitable blood/CSF biomarkers should be actively pursued for the early diagnosis of AD. The preventive and therapeutic strategies should be directed towards maintaining the normal functioning of the immune system throughout the life span and specific modulation of the immune responses in the brain depending on the stage of changes in brain.
Background: Coronaviruses (CoVs) have a neuroinvasive potential, which has been discussed in vari... more Background: Coronaviruses (CoVs) have a neuroinvasive potential, which has been discussed in various research papers. During the current pandemic, the novel CoV, i.e., SARS-CoV-2, is causing a considerable number of fatalities and posing a great danger of a recurrent epidemic. COVID-19 has been labeled as a public health emergency of international concern, and the epidemic curves are on the rise. Purpose: Some studies discuss the neurological implications of SARS-CoV-2 but in light of growing number of evidences we cannot ignore the planning of mental health care settings in COVID-19. We are discussing how this novel CoV can affect the human brain directly and indirectly, including psychiatric problems, and how neurological conditions can be explored as a diagnostic tool in COVID-19 by analyzing cohort studies and review papers that discuss the recent neurological findings in COVID-19. Method: Current research and review papers were searched to find out any relation between the COVI...
Parkinson's disease (PD) is an old age disorder of basal ganglia which involves oligomerization o... more Parkinson's disease (PD) is an old age disorder of basal ganglia which involves oligomerization of asynuclein protein and formation of intercellular inclusions known as ''Lewy bodies'' in substantia nigra and caudate nuclei in brain which is progressive in nature. It is second most prevalent neurodegenerative disorder characterized by tremor at rest, muscle rigidity, slowness of movement (bradykinesia, akinesia), and changes in posture (instability). Both excess and deficiency in levels of transition metals (especially iron, copper) can be detrimental to the central nervous system. Abnormalities in iron (Fe) and copper (Cu) metabolism have been reported to produce oxidative stress which is one of the major cause in pathogenesis of PD. In the present study 35 PD patients and 33 controls of Northern Indian population were included and serum levels of Fe, Cu and ceruloplasmin (Cp) were measured. Serum Fe (p \ 0.01) and Cu (p \ 0.01) levels were found to be significantly decreased in PD, whereas there was no significant change in Cp levels in PD patients as compared to controls. These results suggest the existence of a defect in iron which over the time, may hasten the entry of iron into the brain and decrease iron in the extracellular compartment in PD patients.
Funding Information We also thank agencies ICMR and CSIR for fellowships and projects GAP0091 (IC... more Funding Information We also thank agencies ICMR and CSIR for fellowships and projects GAP0091 (ICMR) and BSC0123 (CSIR) for financial assistance.
The present study aimed to evaluate association of genetic variants on drug response and therapy ... more The present study aimed to evaluate association of genetic variants on drug response and therapy optimization parameters in patients treated with first-line antiepileptic drugs (AEDs). Genetic variants from ion channels, their functionally related genes, and synaptic vesicle cycle (SVC) genes with a potential role in epilepsy pathophysiology were thus prioritized. A total of 12 genes from ion channels and related gene set and seven genes from SVC comprising 155 SNPs were genotyped and evaluated with drug response, dose levels, and drug levels in 408 patients with epilepsy. Both GABRA1 and SCN1A variants showed haplotypic and diplotypic associations in response to phenytoin (PHT). Diplotype analysis of GABRA1 variants revealed association of rs12658835|rs7735530 (AG/AG) (P-valuecorrected = 0.034, OR = 3.75, 95% CI = 1.36-11.05) and rs12658835|rs7735530|rs7732641|rs2279020 (AGCA/AGCA) (P-valuecorrected = 0.035, OR = 2.48, 95% CI = 0.96-6.41) with recurrent seizures. SCN1A haplotype ...
Laboratory error is defined as any defect from ordering tests to reporting and interpretation of ... more Laboratory error is defined as any defect from ordering tests to reporting and interpretation of results. Laboratory errors have a reported frequency of 0.012-0.6% of all test results which in turn has huge impact on diagnosis and patient management as 60-70% of all diagnosis are made on the basis of laboratory tests. Total testing process in the laboratory is a cyclical process divided into three phases: preanalytical, analytical and postanalytical. First, preanalytical phase in which requirement for a test is determined, the test is ordered and the patient is identified. It is followed by specimen collection and transport to the laboratory. The specimen is prepared and tested in the analytical phase. During the postanalytical phase, the results are reported to the individual who ordered the test and any action or intervention is undertaken. Initially, the policies and procedures developed by the laboratory were more concerned on analytical phase to reduce errors during laboratory testing and emphasis was in ensuring proper calibration and testing. The last few decades have seen a significant decrease in the rates of analytical errors in clinical laboratories. Currently, available evidences demonstrate that the pre-and postanalytical steps are more error prone.
American journal of Alzheimer's disease and other dementias, 2014
Dementia is an age-related disorder associated with elderly population, resulting from interactio... more Dementia is an age-related disorder associated with elderly population, resulting from interaction of lifestyle risk factors with genetic, vascular, and other risk factors to affect risk of disease. Alzheimer's disease (AD) is the most common form of dementia, estimated to be affecting 4.4% of the population older than 65 years of age. Apolipoprotein E (ApoE) ε4 allele is a known genetic risk factor for AD, which not only predisposes and influences the severity of pathological changes in the brain, thereby modifying the age at onset, but also promotes cognitive decline early in nondemented older people. To review the published evidence on ApoE polymorphism with the susceptibility to AD and frequency of ApoE ε4 genotype (ε4/-) and homozygotes (ε4/4) among patients diagnosed with AD as compared to controls in Indian Population. In the present study, MEDLINE was reviewed for articles published till June 2013 supplemented by citation analysis from retrieved articles to select case-c...
Mouse peritoneal macrophages (MPM) when elicited by the antioxidant ascorbic acid have been found... more Mouse peritoneal macrophages (MPM) when elicited by the antioxidant ascorbic acid have been found to be significantly stimulatory, exhibiting marked alteration at the cellular and enzyme levels. Alterations recorded were as follows--cellular yield per mouse, their protein content, lysosomal acid hydrolase levels and capability to phagocyte, all were significantly enhanced. The new stimulant was observed to produce no synergistic action on MPM when thioglycollate, BCG or endotoxin along with the same stimulated the latter. Levels of antioxidants like ascorbic acid and glutathione were found to be enhanced in elicited macrophages whereas superoxide dismutase levels varied when the three above stimulators were administered. However, the ascorbic acid elicited cells showed an increase in glutathione levels and a decrease in SOD levels but no change in total intracellular ascorbic acid levels. Further, though ascorbic acid interaction enhanced the phagocytic capability of MPM as compared...
During post-analytical phase, critical value notification to responsible caregiver in a timely ma... more During post-analytical phase, critical value notification to responsible caregiver in a timely manner has potential to improve patient safety which requires cooperative efforts between laboratory personnel and caregivers. It is widely accepted by hospital accreditors that ineffective notification can lead to diagnostic errors that potentially harm patients and are preventable. The objective of the study was to assess the variables affecting critical value notification, their role in affecting it's quality and approaches to improve it. In the present study 1,187 critical values were analysed in the Clinical Chemistry Laboratory catering to tertiary care hospital for neuropsychiatric diseases. During 25 months of study period, we evaluated critical value notification with respect to clinical care area, caregiver to whom it was notified and timeliness of notification. During the study period (25 months), the laboratory obtained 1,279 critical values in clinical chemistry. The analytes most commonly notified were sodium and potassium (20.97 & 20.8 % of total critical results). Analysis of critical value notification versus area of care showed that critical value notification was high in ICU and emergency area followed by inpatients and 64.61 % critical values were notified between 30 and 120 min after receiving the samples. It was found that failure to notify the responsible caregiver in timely manner represent an important patient safety issue and may lead to diagnostic errors. The major area of concern are notification of critical value for outpatient samples, incompleteness of test requisition forms regarding illegible writing, lack of information of treating physician and location of test ordering and difficulty in contacting the responsible caregiver.
Alzheimer's disease International (ADI) estimates that there are currently 30 million people with... more Alzheimer's disease International (ADI) estimates that there are currently 30 million people with dementia in the world. The main objective was to perform meta-analysis of studies of CSF tau and Amyloid β 42 (Aβ 42) levels in Alzheimer's disease (AD) patients and controls. In the present study MEDLINE was reviewed from 1995 to 2009, supplemented by citation analysis from retrieved articles to select case control studies. Descriptive statistics showed that median effect size (raw mean difference) of CSF tau and Aβ 42 levels were 301 pg/ml (Range: 22 to 614 pg/ml) and-352 pg/ml (Range:-969 to 203 pg/ml) respectively. The pooled effect size CSF tau and Aβ 42 was 289.14 pg/ml (95% CI 253.278 to 325.013 pg/ml) and-329.02 pg/ml (95% CI-387.740 to-270.445 pg/ml) respectively. Heterogeneity in effect size of selected studies was present for both parameters (CSF tau: Q statistics = 1816.596, DF = 40, P = 0.000 and CSF Aβ 42 : Q-statistics = 1259.358, DF = 24, p < 0.001). Based on the findings of meta-analysis in the present study, CSF tau and Aβ 42 levels in AD and controls may be considered as potential biomarker along with the clinical phenotype to perform them during high quality diagnostic testing in dementia.
Background Alzheimer’s disease (AD) is one of the leading genetically complex and heterogeneous d... more Background Alzheimer’s disease (AD) is one of the leading genetically complex and heterogeneous disorder that is influenced by both genetic and environmental factors. The underlying risk factors remain largely unclear for this heterogeneous disorder. In recent years, high throughput methodologies, such as genome-wide linkage analysis (GWL), genome-wide association (GWA) studies, and genome-wide expression profiling (GWE), have led to the identification of several candidate genes associated with AD. However, due to lack of consistency within their findings, an integrative approach is warranted. Here, we have designed a rank based gene prioritization approach involving convergent analysis of multi-dimensional data and protein-protein interaction (PPI) network modelling. Results Our approach employs integration of three different AD datasets- GWL,GWA and GWE to identify overlapping candidate genes ranked using a novel cumulative rank score (SR) based method followed by prioritization u...
International Journal of Alzheimer's Disease, 2011
CSF tau and Aβ42 are considered as important markers to diagnose Alzheimer’s disease in early sta... more CSF tau and Aβ42 are considered as important markers to diagnose Alzheimer’s disease in early stages. Hence, it is important to assess their status in different types of dementia. The main objective of this study was to assess whether these CSF biomarkers can be used to make the differential diagnosis of AD. In the present study, articles published from 1998 till 2009 were taken and meta-analysis was performed to clarify the consistency in trends of biomarkers- CSF tau and Aβ42in AD and other dementias and whether the same can be used as diagnostic biomarkers for its early diagnosis. 11 out of 60 for CSF tau and 07 out of 40 for CSF Aβ42, dementia case-control studies were selected for final analysis. Descriptive statistics shows that median effect size (raw mean difference) of CSF tau was 429 pg/mL (range: 32 to 910 pg/mL) in AD whereas in Dementia due to other causes (DOC) studies it was 69 pg/mL (range: −53 to 518 pg/mL). Similarly the median effect size of CSF Aβ42levels was −44...
Dementia and Geriatric Cognitive Disorders Extra, 2017
Background: As variability in the clinical profile of dementia subtypes had been reported with re... more Background: As variability in the clinical profile of dementia subtypes had been reported with regional differences across the world, we conducted a retrospective hospital-based study in a North Indian population. Methods: We retrieved patient records from 2007 to 2014 for details of clinical evaluation, diagnosis, neuroimaging, biochemical investigations, and follow-up of 1,876 patients with dementia (PwD), and the data were analyzed using descriptive statistics. Results: Of the total PwD, Alzheimer disease (AD) accounted for 30% followed by vascular dementia (VaD) 26%, mixed dementia (MD) 21%, Parkinson-related dementia 11%, frontotemporal dementia (FTD) 7%, and infective dementia 5%. Of all PwD excluding the infective group (n = 1,777), 63% were men, 39% were from rural areas, 87% had behavioral abnormalities along with cognitive deficits, and 73% had impaired ADLs. Among dementia subtypes, a positive family history, cardiovascular and metabolic risk factors, and behavioral abnor...
Indian journal of clinical biochemistry : IJCB, 2008
Alzheimer's disease is the most common form of dementia in the elderly and it's prevalenc... more Alzheimer's disease is the most common form of dementia in the elderly and it's prevalence is rapidly rising. Oxidative stress plays important role in the pathophysiology of Alzheimer's disease. Metals like copper, iron derived through diet can act as pro-oxidant under oxidative stress. In the present study, serum copper levels were evaluated in 50 patients with Alzheimer's disease, 24 patients with Vascular Dementia and 30 controls. All the groups were also investigated for serum ceruloplsmin levels. The mean copper levels in Alzheimer's disease and Vascular Dementia were significantly raised compared to controls. An attempt has been made to study the relationship of serum copper with ceruloplasmin. Our study found weak correlation between copper and ceruloplasmin levels in Alzheimer's disease and Vascular Dementia.
Indian journal of clinical biochemistry : IJCB, 2009
The present study was conducted to assess correlation of ammonia levels with valproate levels in ... more The present study was conducted to assess correlation of ammonia levels with valproate levels in epileptic patients presenting with valproate toxicity and also whether liver enzymes and ammonia levels could serve as biochemical marker of valproate toxicity. 100 patients with epilepsy who had received valproate therapy for more than 12 months and had presented with valproate toxicity and 100 controls were included in the study. The serum valproate, ammonia and liver enzymes were measured in these subjects. In patients with valproate toxicity, the mean level of serum valproate was 110.91 ± 28.68 mg/dL (therapeutic range 50-100 mg/dL). Serum ammonia was higher (86.37 ± 39.90 µg/dL) in patients with valproate toxicity compared to controls (68.73 ± 30.07 µg/dL). Out of 100 patients, only 37 patients had serum valproate level > 120 mg/dL and 22 patients had raised levels of valproate as well as ammonia. Age < 30 years and serum ammonia > 69 μg/dL is risk factors for valproate tox...
Advances in instrument technology and automation have simplified tasks in laboratory diagnostics ... more Advances in instrument technology and automation have simplified tasks in laboratory diagnostics reducing errors during analysis thereby improving the quality of test results. However studies show that most laboratory errors occur in the pre-analytical phase. In view of the paucity of studies examining pre-analytical errors, we examined a total of 1513 request forms received at our laboratory during a 3 month period. The forms were scrutinized for the presence of specific parameters to assess the pre-analytical errors affecting the laboratory results. No diagnosis was provided on 61.20% of forms. Type of specimen was not mentioned in 61.60% of the forms and 89.25% of all forms were illegible. Critical results were encountered in 17.30% of patients, and of these 76.60% were not communicated due to incomplete forms. Thus, by following standard operating procedures vigorously from patient preparation to sample processing the laboratory results can be significantly improved without any extra cost.
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Papers by Rachna Agarwal