Judith Aharon-Peretz

Detection of Alzheimer’s and Parkinson’s disease from exhaled breath using nanomaterial-based sensors

AIM To study the feasibility of a novel method in nanomedicine that is based on breath testing for identifying Alzheimers disease (AD) and Parkinsons disease (PD), as representative examples of neurodegenerative conditions. PATIENTS & METHODS Alveolar breath was collected from 57 volunteers (AD patients, PD patients and healthy controls) and analyzed using combinations of nanomaterial-based sensors (organically functionalized carbon nanotubes and gold nanoparticles). Discriminant factor analysis was applied to detect statistically significant differences between study groups and classification success was estimated using cross-validation. The pattern identification was supported by chemical analysis of the breath samples using gas chromatography combined with mass spectrometry. RESULTS The combinations of sensors could clearly distinguish AD from healthy states, PD from healthy states, and AD from PD states, with a classification accuracy of 85, 78 and 84%, respectively. Gas chromatography combined with mass spectrometry analysis showed statistically significant differences in the average abundance of several volatile organic compounds in the breath of AD, PD and healthy subjects, thus supporting the breath prints observed with the sensors. CONCLUSION The breath prints that were identified with combinations of nanomaterial-based sensors have future potential as cost-effective, fast and reliable biomarkers for AD and PD.

Behavioral Differences between White Matter Lacunar Dementia and Alzheimer’s Disease: A Comparison on the Neuropsychiatric Inventory

Background and Purpose: Behavioral abnormalities account for much of the morbidity of vascular dementia (VaD) and Alzheimer’s disease (AD). The goals of the study were to compare the behavioral changes in patients with VaD associated with ischemic white matter subcortical changes and lacunar infarctions (VaD-WSI) to those in patients with AD. Methods: Thirty outpatients with VaD and multiple lacunar infarctions in the periventricular white matter and 30 AD patients, matched for age and severity of dementia, were enrolled in this prospective study. The behavioral abnormalities of these patients were assessed by interviewing their caregivers with the Neuropsychiatric Inventory. Results: A similar spectrum of noncognitive behavioral changes was found in AD and WSI patients. In VaD-WSI, the severity of delusions, hallucinations, aggression, irritability, aberrant motor behavior, nighttime behavior and appetite changes was correlated with cognitive decline, whereas depression, apathy, anxiety and euphoria were unrelated to the severity of dementia. In AD, none of the behavioral changes correlated with the severity of dementia. Conclusion: Behavioral changes are frequent in VaD-WSI and are present regardless of the severity of the cognitive decline. It is therefore important to assess behavioral as well as cognitive changes at early stages of the illness, to ensure appropriate treatment.

Posterior Cortical Atrophy Variants of Alzheimer’s Disease

Posterior cortical atrophy (PCA) was first described by Benson in 1988 and, since then, has been regarded as a variant of Alzheimer’s disease. We present 2 patients with symptoms suggestive of PCA and 2 patients with apraxia as the initial manifestation. Primary motor and sensory modalities were intact. Mild memory impairment was present early in the course of the disease and gradually worsened. Parieto-occipital atrophy was evident on brain MRI. HMPAO-SPECT demonstrated parieto-occipital hypoperfusion significantly different from the temporoparietal hypoperfusion usually described in senile dementia of the Alzheimer type. These findings suggest that HMPAO-SPECT can help in diagnosing atypical variants of Alzheimer’s disease. We suggest that PCA represents two clinically related behavioral phenotypes: PCA with predominantly apraxia manifestations and PCA with predominantly visuospatial disturbances.

Gaucher disease associated with parkinsonism: four further case reports.

Type 1 Gaucher disease is considered the non‐neuronopathic form of this autosomal recessively inherited lysosomal storage disease. We report the simultaneous occurrence of Gaucher disease with parkinsonian in four adult patients. The patients had a relatively early onset of parkinsonian manifestations, and their disease was rapidly progressive and refractory to therapy. Each had a different Gaucher genotype, although four alleles carried the common N370S mutation. No mutations were identified in the genes for parkin or α‐synuclein. The concurrence of these two phenotypes, both in this series of patients and in others in the literature, suggests a shared pathway, modifier, or other genetic etiology. Published 2003 Wiley‐Liss, Inc.

Androgen replacement therapy in Turner syndrome: a pilot study.

CONTEXT Women with Turner syndrome (TS) have reduced levels of androgens due to ovarian failure. HYPOTHESES Morbidity associated with TS, such as bone fragility, metabolic changes, obesity, neurocognitive profile, and sexual problems may partly relate to androgen insufficiency and improve on androgen replacement therapy (ART). OBJECTIVES The objective of the study was to determine the effect of androgens on morbidity in TS. DESIGN Fourteen TS women (aged 17-27 yr) participated in a randomized, double-blind, placebo-controlled crossover pilot. The study was conducted in a hospital outpatient clinic between December 2001 and July 2004. INTERVENTION TS patients were on estrogen/progestin replacement therapy. Subjects received oral 1.5 mg methyl testosterone (ART) or placebo for 1 yr and the alternative for another year. MAIN OUTCOME MEASURES The study compared body composition as a primary outcome, and physiology, biochemistry, visceral fat, cognition, and quality of life (QOL) as secondary outcomes. RESULTS ART as compared with placebo reduced total cholesterol, triglycerides, and high-density lipoprotein cholesterol. It improved bone mineral density, increased lean body mass, and decreased fat mass. ART improved attention, reaction time, and verbal memory and had no effect on executive functions and spatial cognition. Patients reported improved QOL, including general health, coping with stress, and sexual desire. CONCLUSIONS Androgen insufficiency plays a role in TS-impaired body composition, neurocognition, and QOL, and these aspects improve with ART, which was safe and effective when given for 1 yr.

Dopamine asymmetry interacts with medication to affect cognition in Parkinson's disease

Contradictory evidence exists regarding the nature and degree of impaired cognitive flexibility in PD. Dopaminergic medication may be expected to ameliorate such cognitive deficits, yet both medicated and unmedicated patients have been reported to perform more poorly than control subjects on tasks of cognitive flexibility, suggesting that such deficits may also be affected by other disease-related variables. The present study examined whether asymmetric dopamine deficiency (revealed by unilateral symptom onset) is related to the performance of spontaneous and reactive flexibility in PD, and the possible interaction of dopaminergic medication with such asymmetry. Thirty-five PD patients with mild motor symptoms and unilateral onset of PD (left-onset=14; right-onset=21) performed the Alternate Uses (AU) and intradimensional/extradimensional shift (IED) tasks. Interaction between side of onset and medication was observed for the number of errors in the AU task and number of reversal errors in the IED task. Significantly more AU errors were made by medicated patients with left-onset, as compared to all other participants. Conversely, medicated patients with right-onset made the most reversal errors. These results suggest that relatively early in the disease process when dopamine deficit in the less-affected hemisphere is mild, optimal dopaminergic medication (with respect to motor function) may involve over-medication of the less-affected hemisphere. Thus, AU errors may be the consequence of hyperdopaminergic state leading to impaired functioning of the left hemisphere, whereas increased reversal errors in right-onset PD patients receiving dopaminergic medication is related to impaired dopamine function in the right hemisphere.

Walking on Virtual Tiles

This paper examines the application of virtual reality cues, generating the biofeedback effects of a real tiled floor, reported in [8], for gait improvement in Parkinsons Disease (PD) patients. A portable apparatus, comprising head and body-mounted 3-axis accelerometers, a wearable computer and see-through head-mounted display, creates a virtual tiled floor, responding to the patients own dynamics. Performance of PD patients using the device improved (higher speed, longer stride) by about 30% on average.

Natural history of dementia associated with lacunar infarctions.

BACKGROUND Lacunar stroke (VaD-L) is the most common stroke subtype associated with vascular dementia (VaD). OBJECTIVE To evaluate the rate of cognitive and behavioral changes in patients with probable VaD-L. METHODS We measured rates of change on the Mini-Mental State Examination (MMSE), Digit Span, Logical Memory, Controlled Oral Word Association Test, CERAD battery and the Neuropsychiatric Inventory (NPI) of 77 [age at entry 65.9+/-8.1 (mean+/-standard deviation) years] patients with probable VaD, periventricular white matter and basal ganglia lacunae, longitudinally studied for 25.7+/-11 months. RESULTS Mean number of follow-up visits was 2.6. Overall annual vascular event rate was 0.25. VaD-L in mildly and moderately impaired patients is characterized by progressive cognitive and behavioral decline. The rate of cognitive and behavioral progression depends on the occurrence of vascular episodes (VE) during the course of the illness [(-1.1) MMSE and (+4.0) NPI points annually without VE vs. (-2.0) and (+10.3) points following VE]. The rates of progression are a function of the severity of the cognitive and behavioral impairment. Impaired cognition is associated with impaired behavior. A subgroup of VaD-L patients runs a progressively deteriorating course despite the absence of clinically apparent new vascular episodes. CONCLUSION VaD-L is characterized by cognitive and behavioral decline in 83% of the patients. The rate of decline is determined mainly by the severity of the cognitive and behavioral impairment at baseline and by the occurrence of new vascular episodes.

Blood-Borne Activity-Dependent Neuroprotective Protein (ADNP) is Correlated with Premorbid Intelligence, Clinical Stage, and Alzheimer’s Disease Biomarkers

Biomarkers for Alzheimers disease (AD) are vital for disease detection in the clinical setting. Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) is essential for brain formation and linked to cognitive functions. Here, we revealed that blood borne expression of ADNP and its paralog ADNP2 is correlated with premorbid intelligence, AD pathology, and clinical stage. Age adjustment showed significant associations between: 1) higher premorbid intelligence and greater serum ADNP, and 2) greater cortical amyloid and lower ADNP and ADNP2 mRNAs. Significant increases in ADNP mRNA levels were observed in patients ranging from mild cognitive impairment (MCI) to AD dementia. ADNP2 transcripts showed high correlation with ADNP transcripts, especially in AD dementia lymphocytes. ADNP plasma/serum and lymphocyte mRNA levels discriminated well between cognitively normal elderly, MCI, and AD dementia participants. Measuring ADNP blood-borne levels could bring us a step closer to effectively screening and tracking AD.

Progression of Dementia Associated with Lacunar Infarctions

Background: Lacunar stroke (L) is the most common stroke subtype associated with vascular dementia (VaD-L). Objective: To evaluate the cognitive and behavioral course in patients with probable VaD-L. Methods: We longitudinally measured rates of change on MMSE, digit span, logical memory, Controlled Oral Word Association, CERAD battery and neuropsychiatric inventory (NPI) in 77 patients (age at entry 69 ± 8.1 years) with probable VaD-L for 25.75 ± 11 months. Results: The mean number of follow-up visits was 2.6 ± 0.67 (range 2–4). Time interval between any two consecutive visits was at least 5 months (range 5–41). MMSE deteriorated by 1.44± 1.8 points annually and NPI increased by 6.01 ± 13.7 points annually (p < 0.0001). The rates of cognitive and behavioral decline were predominantly influenced by the cognitive state at entry into the study and the occurrence of new vascular episodes during follow-up [(–0.95 ± 1.7) MMSE and (+2.02 ± 14.1) NPI points annually without vascular episodes vs. (–2.09 ± 1.6) and (+11.3 ± 11.4) points following vascular episodes (p < 0.0001)]. Impaired cognition was associated with impaired behavior (p < 0.001). VaD-L patients without additional vascular episodes at follow-up have a progressively deteriorating course as well (p < 0.0001). Conclusion: VaD-L is characterized by cognitive and behavioral decline. The rate of decline is determined mainly by the severity of the cognitive and behavioral impairment at baseline and by the occurrence of new vascular episodes.