Can Inconsistent Association between Hypertension and Cognition in Elders be Explained by Levels of Organochlorine Pesticides?

<div><p>The relation between hypertension and cognition in elders remains unclear, and studies on the effect of antihypertensive drugs on cognition have demonstrated conflicting results. This study was performed to evaluate if the association between hypertension and cognition in elders differed depending on serum concentrations of organochlorine (OC) pesticides, common neurotoxic chemicals. Participants were 644 elders aged 60–85 years who participated in the National Health and Nutrition Examination Survey 1999–2002 and were able to complete a cognitive test. We selected 6 OC pesticides that were commonly detected in the elderly. Cognition was assessed by the Digit Symbol Substitution Test (DSST), a relevant tool for evaluating hypertension-related cognitive function, and low cognition was defined by the DSST score < 25^th percentile. When OC pesticides were not considered in the analyses, elders with hypertension had about 1.7 times higher risk of low cognition than those without hypertension. However, in analyses stratified by serum concentrations of OC pesticides, the associations between hypertension and low cognition were stronger the higher the serum concentrations of p,p’-DDT, p,p’-DDE, β-hexachlorocyclohexane, and trans-nonachlor increased. Among elders in the 3^rd tertile of these pesticides, adjusted odds ratios were from 2.5 to 3.5. In contrast, hypertension was not clearly associated with the risk of low cognition in elders in the 1^st tertile of these pesticides. Similar patterns were observed for the continuous DSST score dependent variable. The difference in the association between hypertension and DSST scores according to the levels of OC pesticides suggest a key role of OC pesticides in the development of hypertension-related cognitive impairment and may help to identify hypertensive elders who are at a high risk of cognitive impairment.</p></div

Characteristics of study subjects by quintiles of age (n = 644).

<p>Characteristics of study subjects by quintiles of age (n = 644).</p

Adjusted^* means of Digit Symbol Substitution Test score among all subjects or stratified by tertiles of serum concentrations of organochlorine pesticides.

<p>*Adjusted for age, sex, race-ethnicity, education, poverty income ratio, cigarette smoking, and body mass index.</p><p>Adjusted^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0144205#t002fn001" target="_blank">*</a>} means of Digit Symbol Substitution Test score among all subjects or stratified by tertiles of serum concentrations of organochlorine pesticides.</p

Associations of age and 6 organochlorine (OC) pesticides on the risk of low cognitive score (<25th percentile of study subjects, 28 of 133 symbols correctly substituted).

<p>Odds ratios were estimated using logistic regression with a common reference group of elderly in the 1^st quintile of age and the combined 1st plus 2^nd tertile of each OC pesticide, adjusted for age, sex, race-ethnicity, education, poverty income ratio, cigarette smoking, body mass index, physician-diagnosed heart disease, physician-diagnosed hypertension, and physician-diagnosed diabetes. Statistically significant odds ratios were marked with *. Q1, first quintile (60–63 years); Q2, second quintile (64–67 years); Q3, third quintile (68–72 years); Q4, forth quintile (73–79 years); Q5, fifth quintile (80–85 years); T1+T1, first and second tertiles; T3, third tertile</p

Adjusted^* odds ratios (ORs) and 95% confidence intervals (CIs) between hypertension and the risk of low Digit Symbol Substitution Test score (<25^th% of study subjects) among all subjects or stratified by serum concentrations of organochlorine (OC) pesticides.

<p>*Adjusted for age, sex, race-ethnicity, education, poverty income ratio, cigarette smoking, and body mass index.</p><p>Adjusted^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0144205#t003fn001" target="_blank">*</a>} odds ratios (ORs) and 95% confidence intervals (CIs) between hypertension and the risk of low Digit Symbol Substitution Test score (<25^th% of study subjects) among all subjects or stratified by serum concentrations of organochlorine (OC) pesticides.</p

Change in EG-ISFET biosensor currents for AD and control saliva samples.

<p>The change of current generated from the AD and control groups. Data are presented as median. *<i>p</i> ≤ 0.05.</p

Top view image of the EG-ISFET sensor device.

<p>The EG-ISFET sensor consists of an independent reference and sensing region for simultaneous measurements of samples from patient and control groups. A commercially available transistor (MC14007UBCP) was used as the MOSFET part of the sensor. The gate terminal of both sensing and reference regions was segregated from the conventional ISFET device. A SnO₂ membrane was deposited on the gate terminal of the EG-ISFET sensor and used as the sensing membrane. Response currents generated were measured using a Hewlett-Packard 4156B High-Precision Semiconductor Parameter Analyzer.</p

Effect of the pH on the sensitivity of SnO₂ membrane.

<p>The reference voltage (V) is shown as a function of pH evaluated at a reference current of 100 μA.</p

Drift rate of SnO₂ membrane in a solution with pH 7.

<p>The reference voltage (V) is shown as a function of pH evaluated at a reference current of 100 μA.</p

Non-Invasive Screening for Alzheimer’s Disease by Sensing Salivary Sugar Using <i>Drosophila</i> Cells Expressing Gustatory Receptor (Gr5a) Immobilized on an Extended Gate Ion-Sensitive Field-Effect Transistor (EG-ISFET) Biosensor

<div><p>Body fluids are often used as specimens for medical diagnosis. With the advent of advanced analytical techniques in biotechnology, the diagnostic potential of saliva has been the focus of many studies. We recently reported the presence of excess salivary sugars, in patients with Alzheimer’s disease (AD). In the present study, we developed a highly sensitive, cell-based biosensor to detect trehalose levels in patient saliva. The developed biosensor relies on the overexpression of sugar sensitive gustatory receptors (Gr5a) in <i>Drosophila</i> cells to detect the salivary trehalose. The cell-based biosensor was built on the foundation of an improved extended gate ion-sensitive field-effect transistor (EG-ISFET). Using an EG-ISFET, instead of a traditional ion-sensitive field-effect transistor (ISFET), resulted in an increase in the sensitivity and reliability of detection. The biosensor was designed with the gate terminals segregated from the conventional ISFET device. This design allows the construction of an independent reference and sensing region for simultaneous and accurate measurements of samples from controls and patients respectively. To investigate the efficacy of the cell-based biosensor for AD screening, we collected 20 saliva samples from each of the following groups: participants diagnosed with AD, participants diagnosed with Parkinson’s disease (PD), and a control group composed of healthy individuals. We then studied the response generated from the interaction of the salivary trehalose of the saliva samples and the Gr5a in the immobilized cells on an EG-ISFET sensor. The cell-based biosensor significantly distinguished salivary sugar, trehalose of the AD group from the PD and control groups. Based on these findings, we propose that salivary trehalose, might be a potential biomarker for AD and could be detected using our cell-based EG-ISFET biosensor. The cell-based EG-ISFET biosensor provides a sensitive and direct approach for salivary sugar detection and may be used in the future as a screening method for AD.</p></div