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1.  Test of variables of attention (TOVA) as a predictor of early attention complaints, an antecedent to dementia 
The goal of this study was to determine if impairments detected by the test of variables of attention (TOVA) may be used to predict early attention complaints and memory impairments accurately in a clinical setting. We performed a statistical analysis of outcomes in a patient population screened for attention deficit hyperactivity disorder or attention complaints, processing errors as measured by TOVA and the Wechsler Memory Scale (WMS-III) results. Attention deficit disorder (ADD) checklists, constructed using the Diagnostic and Statistical Manual of Mental Disorders 4th Edition criteria, which were completed by patients at PATH Medical, revealed that 72.8% of the patients had more than one attention complaint out of a total of 16 complaints, and 41.5% had more than five complaints. For the 128 males with a significant number of ADD complaints, individuals whose scores were significantly deviant or borderline (SDB) on TOVA, had a significantly greater number of attention complaints compared with normals for omissions (P < 0.02), response time (P < 0.015), and variability (P < 0.005), but not commissions (P > 0.50). For males, the mean scores for auditory, visual, immediate, and working memory scores as measured by the WMS-III were significantly greater for normals versus SDBs on the TOVA subtest, ie, omission (P < 0.01) and response time (P < 0.05), but not variability or commissions. The means for auditory, visual, and immediate memory scores were significantly greater for normals versus SDBs for variability (P < 0.045) only. In females, the mean scores for visual and working memory scores were significantly greater for normals versus SDBs for omissions (P < 0.025). The number of SDB TOVA quarters was a significant predictor for “impaired” or “normal” group membership for visual memory (P < 0.015), but not for the other three WMS-III components. For males, the partial correlation between the number of attention complaints and the number of SDB TOVA quarters was also significant (r = 0.251, P < 0.005). For the 152 females with a significant number of attention complaints, no significant differences between SDBs and normals were observed (P > 0.15). This is the first report, to our knowledge, which provides evidence that TOVA is an accurate predictor of early attention complaints and memory impairments in a clinical setting. This finding is more robust for males than for females between the ages of 40 and 90 years.
PMCID: PMC2987500  PMID: 21127685
attention complaints; dementia; TOVA; Wechsler Memory Scale
2.  Age-related increases in parathyroid hormone may be antecedent to both osteoporosis and dementia 
Numerous studies have reported that age-induced increased parathyroid hormone plasma levels are associated with cognitive decline and dementia. Little is known about the correlation that may exist between neurological processing speed, cognition and bone density in cases of hyperparathyroidism. Thus, we decided to determine if parathyroid hormone levels correlate to processing speed and/or bone density.
The recruited subjects that met the inclusion criteria (n = 92, age-matched, age 18-90 years, mean = 58.85, SD = 15.47) were evaluated for plasma parathyroid hormone levels and these levels were statistically correlated with event-related P300 potentials. Groups were compared for age, bone density and P300 latency. One-tailed tests were used to ascertain the statistical significance of the correlations. The study groups were categorized and analyzed for differences of parathyroid hormone levels: parathyroid hormone levels <30 (n = 30, mean = 22.7 ± 5.6 SD) and PTH levels >30 (n = 62, mean = 62.4 ± 28.3 SD, p ≤ 02).
Patients with parathyroid hormone levels <30 showed statistically significantly less P300 latency (P300 = 332.7 ± 4.8 SE) relative to those with parathyroid hormone levels >30, which demonstrated greater P300 latency (P300 = 345.7 ± 3.6 SE, p = .02). Participants with parathyroid hormone values <30 (n = 26) were found to have statistically significantly higher bone density (M = -1.25 ± .31 SE) than those with parathyroid hormone values >30 (n = 48, M = -1.85 ± .19 SE, p = .04).
Our findings of a statistically lower bone density and prolonged P300 in patients with high parathyroid hormone levels may suggest that increased parathyroid hormone levels coupled with prolonged P300 latency may become putative biological markers of both dementia and osteoporosis and warrant intensive investigation.
PMCID: PMC2768728  PMID: 19825157
3.  Attention-deficit-hyperactivity disorder and reward deficiency syndrome 
Molecular genetic studies have identified several genes that may mediate susceptibility to attention deficit hyperactivity disorder (ADHD). A consensus of the literature suggests that when there is a dysfunction in the “brain reward cascade,” especially in the dopamine system, causing a low or hypo-dopaminergic trait, the brain may require dopamine for individuals to avoid unpleasant feelings. This high-risk genetic trait leads to multiple drug-seeking behaviors, because the drugs activate release of dopamine, which can diminish abnormal cravings. Moreover, this genetic trait is due in part to a form of a gene (DRD2 A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites. This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with deficient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities. It has been proposed that genetic variants of dopaminergic genes and other “reward genes” are important common determinants of reward deficiency syndrome (RDS), which we hypothesize includes ADHD as a behavioral subtype. We further hypothesize that early diagnosis through genetic polymorphic identification in combination with DNA-based customized nutraceutical administration to young children may attenuate behavioral symptoms associated with ADHD. Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions.
PMCID: PMC2626918  PMID: 19183781
attention deficit hyperactivity disorder (ADHD); genes; reward dependence; reward deficiency syndrome; treatment; neuropsychological deficits
4.  Plasma growth hormones, P300 event-related potential and test of variables of attention (TOVA) are important neuroendocrinological predictors of early cognitive decline in a clinical setting: Evidence supported by structural equation modeling (SEM) parameter estimates 
Age  2007;29(2-3):55-67.
A review of the literature in both animals and humans reveals that changes in sex hormone have often been associated with changes in behavioral and mental abilities. Previously published research from our laboratory, and others, provides strong evidence that P300 (latency) event-related potential (ERP), a marker of neuronal processing speed, is an accurate predictor of early memory impairment in both males and females across a wide age range. It is our hypothesis, given the vast literature on the subject, that coupling growth hormones (insulin-like growth factor-I, (IGF-I) and insulin-like growth factor binding protein 3 (IGF-BP3)), P300 event-related potential and test of variables of attention (TOVA) are important neuroendocrinological predictors of early cognitive decline in a clinical setting. To support this hypothesis, we utilized structural equation modeling (SEM) parameter estimates to determine the relationship between aging and memory, as mediated by growth hormone (GH) levels (indirectly measured through the insulin-like growth factor system), P300 latency and TOVA, putative neurocognitive predictors tested in this study. An SEM was developed hypothesizing a causal directive path, leading from age to memory, mediated by IGF-1 and IGF-BP3, P300 latency (speed), and TOVA decrements. An increase in age was accompanied by a decrease in IGF-1 and IGF-BP3, an increase in P300 latency, a prolongation in TOVA response time, and a decrease in memory functioning. Moreover, independent of age, decreases in IGF-1 and IGF-BP3, were accompanied by increases in P300 latency, and were accompanied by increases in TOVA response time. Finally, increases in P300 latency were accompanied by decreased memory function, both directly and indirectly through mediation of TOVA response time. In summary, this is the first report utilizing SEM to reveal the finding that aging affects memory function negatively through mediation of decreased IGF-1 and IGF-BP3, and increased P300 latency (delayed attention and processing speed).
PMCID: PMC2267660  PMID: 19424831
Structural equation modeling (SEM); P300 latency; TOVA;  IGF-1; IGF-BP3; Age and memory

Results 1-4 (4)