Mala Naik

A Novel Blood Test for the Early Detection of Alzheimer's Disease

Despite a variety of testing approaches, it is often difficult to make an accurate diagnosis of Alzheimers disease (AD), especially at an early stage of the disease. Diagnosis is based on clinical criteria as well as exclusion of other causes of dementia but a definitive diagnosis can only be made at autopsy. We have investigated the diagnostic value of a 96-gene expression array for detection of early AD. Gene expression analysis was performed on blood RNA from a cohort of 203 probable AD and 209 cognitively healthy age matched controls. A disease classification algorithm was developed on samples from 208 individuals (AD = 103; controls = 105) and was validated in two steps using an independent initial test set (n = 74; AD = 32; controls = 42) and another second test set (n = 130; AD = 68; controls = 62). In the initial analysis, diagnostic accuracy was 71.6 ± 10.3%, with sensitivity 71.9 ± 15.6% and specificity 71.4 ± 13.7%. Essentially the same level of agreement was achieved in the two independent test sets. High agreement (24/30; 80%) between algorithm prediction and subjects with available cerebrospinal fluid biomarker was found. Assuming a clinical accuracy of 80%, calculations indicate that the agreement with underlying true pathology is in the range 85%-90%. These findings suggest that the gene expression blood test can aid in the diagnosis of mild to moderate AD, but further studies are needed to confirm these findings.

Clinically important renal impairment in various groups of old persons

Objective – To assess renal function in various groups of elderly persons, and to determine the proportion of patients with clinically important renal impairment. Design – Cross-sectional study. Participants – Three geriatric populations aged 70 years and over, representing increasing levels of care/treatment: community-dwelling elderly referred to a geriatric outpatient department, inpatients on a geriatric ward, and nursing home patients. Main outcome measures – Cockroft and Gaults formula was applied to calculate glomerular filtration rate (GFR). Differences in GFR between age groups and between care levels were explored. Results – Altogether 288 elderly persons were included in the study. We observed a general age-related decline of renal function. Only 2% of the participants had normal renal function (GFR >90 ml/min), 13% had light (GFR 60–89 ml/min), 68% moderate (GFR 30–59 ml/min), and 17% severe (GFR 15–29 ml/min) impairment in GFR. Moderate or severely decreased GFR was observed in 75% of the outpatients, 78% of the patients from the geriatric ward, and 91% of the nursing home patients. Altogether 99% of patients aged 85+ had renal impairment necessitating dosing adjustment for drugs that are mainly eliminated through renal excretion. Conclusion – Clinically important renal impairment is common in old age, especially in the frailest elderly living in nursing homes. This finding underlines the necessity for close supervision of drug treatment based on renal function in old age.

Not less but different: psychotropic drug utilization trends in Norwegian nursing homes during a 12-year period. The Bergen District Nursing Home (BEDNURS) Study

Background and aims: The use of psychotropic drugs in nursing homes is generally considered to be inappropriately high. The aim of the present survey was to compare psychotropic drug use in nursing homes (NHs) in 1985 relative to 1996/97, and to explore predictors for this drug use. Methods: Cross-sectional study. Mental capacity was assessed by means of the Clinical DementiaRating scale (CDR), and behavior registered by trained nurses. Scheduled, daily use of psychotropic drugs among long-term care residents in 1985 (N=1247) and 1996/97 (N=1035) was recorded. Bivariate analyses and logistic regression analyses were applied to establish predictors for psychoactive drug use. Results: From 1985 to 1996/97, the proportion of residents using any psychotropic drug increased from 52 to 57%. Antipsy-chotic drug use decreased from 33 to 22%, while anxiolytics increased from 11 to 16%, hypnotics from 11 to 14%, and antidepressants from 12 to 31%. Psychotropic drug use was predominantly associated with behavioral symptoms and not with mental impairment. Concurrent use of two or more psychotropic drugs increased from 23 to 32% of all psychotropic users. Conclusions: During the study period, a substantial decline in the use of antipsychotics was observed, but a generally increased overall use of psychotropic drugs, particularly antidepressants. Psychotropic drug treatment was mainly associated with behavioral symptoms.

Quantitative EEG Applying the Statistical Recognition Pattern Method: A Useful Tool in Dementia Diagnostic Workup

Background/Aim: The aim of this study was to examine the discriminatory power of quantitative EEG (qEEG) applying the statistical pattern recognition (SPR) method to separate Alzheimers disease (AD) patients from elderly individuals without dementia and from other dementia patients. Methods: The participants were recruited from 6 Nordic memory clinics: 372 unselected patients [mean age 71.7 years (SD 8.6), 54% women] and 146 healthy elderly individuals [mean age 66.5 years (SD 7.7), 60% women]. After a standardized and comprehensive assessment, clinical diagnoses were made according to internationally accepted criteria by at least 2 clinicians. EEGs were recorded in a standardized way and analyzed independently of the clinical diagnoses, using the SPR method. Results: In receiver operating characteristic curve analyses, the qEEGs separated AD patients from healthy elderly individuals with an area under the curve (AUC) of 0.90, representing a sensitivity of 84% and a specificity of 81%. The qEEGs further separated patients with Lewy body dementia or Parkinsons disease dementia from AD patients with an AUC of 0.9, a sensitivity of 85% and a specificity of 87%. Conclusion: qEEG using the SPR method could be a useful tool in dementia diagnostic workup.

Diffusion tensor imaging (DTI) in dementia patients with frontal lobe symptoms

Background: Diffusion tensor imaging (DTI) is a recent MRI technique demonstrating white matter tracts in the brain. Dementia is a neurodegenerative disease and this method has been used to demonstrate the loss of axonal fibers and myelin and decrease of fiber density in this condition. Purpose: To study a possible correlation between frontal lobe symptoms in patients with dementia and reduced fractional anisotropy (FA) in white matter/fascicles in the frontal lobes. Material and Methods: The study included 23 patients with dementia and frontal lobe symptoms and 20 controls (10 Alzheimer patients without frontal lobe symptoms and 10 normal controls). Clinical tests and MRI with DTI were performed. FA in subcortical white matter of both the frontal lobes was analyzed and correlated with clinical frontal score tests. Results: We found a significant correlation between frontal score results and reduction in FA in the frontal lobes. The FA in the study group was significantly lower than the FA in the control group. Conclusion: The present study reveals that there is a probable correlation between the extent of frontal lobe symptoms and FA in fascicles/white matter tissue in the frontal lobes.

Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers

Background/Aims: Dementia biomarkers that are accessible and easily applicable in nonspecialized clinical settings are urgently needed. Quantitative electroencephalography (qEEG) is a good candidate, and the statistical pattern recognition (SPR) method has recently provided promising results. We tested the diagnostic value of qEEG-SPR in comparison to cognition, structural imaging, and cerebrospinal fluid (CSF) biomarkers. Methods: A total of 511 individuals were recruited from the multicenter NORD EEG study [141 healthy controls, 64 subjective cognitive decline, 124 mild cognitive impairment, 135 Alzheimers disease (AD), 15 dementia with Lewy bodies/Parkinsons disease with dementia (DLB/PDD), 32 other dementias]. The EEG data were recorded in a standardized way. Structural imaging data were visually rated using scales of atrophy in the medial temporal, frontal, and posterior cortex. Results: qEEG-SPR outperformed structural imaging, cognition, and CSF biomarkers in DLB/PDD diagnosis, outperformed structural imaging in AD diagnosis, and improved the differential diagnosis of AD. In addition, qEEG-SPR allowed differentiation of two clinically different AD subtypes. Conclusion: Adding qEEG to the diagnostic workup substantially increases the detection of AD pathology even in pre-dementia stages and improves differential diagnosis. EEG could serve as a good complement to currently established dementia biomarkers since it is cheap, noninvasive, and extensively applied outside academic centers.

DRUG USE IN HOMES FOR THE AGED. A COMPARISON BETWEEN MENTALLY INTACT AND MENTALLY IMPAIRED RESIDENTS

The aim of this study was to analyze drug use in 347 residents in homes for the aged in Bergen, Norway. All drugs prescribed on a regular schedule were assessed, the prevalence of potentially harmful drug combinations, and inappropriately prescribed drugs were studied and related to mental capacity of the residents. Mental capacity was assessed by means of the Clinical Dementia Rating scale (CDR). The median number of drugs used was 4.0 (range 0–11, 95% CI 3.0–4.0). Mentally impaired residents consumed fewer drugs than mentally intact ones. In a logistic regression analysis the use of NSAIDS, beta-blockers and anxiolytics was significantly lower in mentally impaired residents (OR 0.37, 95% CI 0.17–0.80, OR 0.35, 95% CI 0.13–0.95, and OR 0.45, 95% CI 0.21–0.94, respectively), and the use of laxatives and vitamin B-12 higher (OR 2.19, 95% CI 1.04–4.62, and OR 5.08, 95% CI 1.11–23.25, respectively). Twenty percent of mentally intact and 21% of mentally impaired residents have potentially harmful two-by-two drug combinations, and drugs augmenting sedating properties were dominating. The prevalence of inappropriately used drugs was significantly lower in mentally impaired residents (20%) than in mentally intact ones (33%)). Antidepressants with anticholinergic properties, benzodiazepines with long half-life and phenothiazines were the most frequent.

Identifying patients at risk of acute symptomatic seizure after ischemic stroke

Contributors to post‐stroke seizure research have advocated the need for prospective studies of acute symptomatic seizures after stroke. Identification of the patient at risk of seizure and the impact of the event on outcome is a prerequisite for this kind of research. The aim of this study was to identify risk factors, make an outline for a risk score, and look at consequences of seizure on short‐time clinical outcomes.

EEG Theta Power Is an Early Marker of Cognitive Decline in Dementia due to Alzheimer’s Disease

BACKGROUND Quantitative EEG (qEEG) power could potentially be used as a diagnostic tool for Alzheimers disease (AD) and may further our understanding of the pathophysiology. However, the early qEEG power changes of AD are not well understood. OBJECTIVE To investigate the early changes in qEEG power and the possible correlation with memory function and cerebrospinal fluid biomarkers. In addition, whether qEEG power could discriminate between AD, mild cognitive impairment (MCI), and older healthy controls (HC) at the individual level. METHODS Standard EEGs from 138 HC, 117 MCI, and 117 AD patients were included from six Nordic memory clinics. All EEGs were recorded consecutively before the diagnosis and were not used for the consensus diagnosis. Absolute and relative power was calculated for both eyes closed and open condition. RESULTS At group level using relative power, we found significant increases globally in the theta band and decreases in high frequency power in the temporal regions for eyes closed for AD and, to a lesser extent, for MCI compared to HC. Relative theta power was significantly correlated with multiple neuropsychological measures and had the largest correlation coefficient with total tau. At the individual level, the classification rate for AD and HC was 72.9% for relative power with eyes closed. CONCLUSION Our findings suggest that the increase in relative theta power may be the first change in patients with dementia due to AD. At the individual level, we found a moderate classification rate for AD and HC when using EEGs alone.