BACKGROUND:Auditory naming tests are superior to visual confrontation naming tests in revealing word-finding difficulties in many neuropathological conditions.OBJECTIVE:To delineate characteristics of auditory naming most likely to reveal anomia in patients with dementia, and possibly improve diagnostic utility, we evaluated a large sample of patients referred with memory impairment complaints.METHODS:Patients with dementia (N = 733) or other cognitive impairments and normal individuals (N = 69) were evaluated for frequency of impairment on variables of the Auditory Naming Test (ANT) of Hamberger & Seidel versus the Boston Naming Test (BNT).RESULTS:Naming impairment occurred more frequently using the ANT total score (φ= 0.41) or ANT tip-of-the tongue score (TOT; φ= 0.19) but not ANT mean response time compared to the BNT in patients with dementia (p < 0.001). Significantly more patients were impaired on ANT variables than on the BNT in Alzheimer's disease (AD), vascular dementia (VaD), mixed AD/VaD, and multiple domain mild cognitive impairment (mMCI) but not in other dementias or amnestic MCI (aMCI). This differential performance of patients on auditory versus visual naming tasks was most pronounced in older, well-educated, male patients with the least cognitive impairment. Impaired verbal comprehension was not contributory. Inclusion of an ANT index score increased sensitivity in the dementia sample (92%). Poor specificity (41%) may be secondary to the inherent limitation of using the BNT as a control variable.CONCLUSION:The ANT index score adds diagnostic utility to the assessment of naming difficulties in patients with suspected dementia.

BACKGROUND:In preclinical models, benfotiamine efficiently ameliorates the clinical and biological pathologies that define Alzheimer's disease (AD) including impaired cognition, amyloid-β plaques, neurofibrillary tangles, diminished glucose metabolism, oxidative stress, increased advanced glycation end products (AGE), and inflammation.OBJECTIVE:To collect preliminary data on feasibility, safety, and efficacy in individuals with amnestic mild cognitive impairment (aMCI) or mild dementia due to AD in a placebo-controlled trial of benfotiamine.METHODS:A twelve-month treatment with benfotiamine tested whether clinical decline would be delayed in the benfotiamine group compared to the placebo group. The primary clinical outcome was the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Secondary outcomes were the clinical dementia rating (CDR) score and fluorodeoxyglucose (FDG) uptake, measured with brain positron emission tomography (PET). Blood AGE were examined as an exploratory outcome.RESULTS:Participants were treated with benfotiamine (34) or placebo (36). Benfotiamine treatment was safe. The increase in ADAS-Cog was 43% lower in the benfotiamine group than in the placebo group, indicating less cognitive decline, and this effect was nearly statistically significant (p = 0.125). Worsening in CDR was 77% lower (p = 0.034) in the benfotiamine group compared to the placebo group, and this effect was stronger in the APOEɛ4 non-carriers. Benfotiamine significantly reduced increases in AGE (p = 0.044), and this effect was stronger in the APOEɛ4 non-carriers. Exploratory analysis derivation of an FDG PET pattern score showed a treatment effect at one year (p = 0.002).CONCLUSION:Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD.

There is a high prevalence of anxiety disorders including specific phobias and panic disorder in the United States and Europe. A variety of therapeutic modalities including pharmacotherapy, cognitive behavioral therapy, systematic desensitization, hypnosis, in vivo exposure, and virtual reality exposure therapy have been applied. No one modality has been entirely successful. There has been only a limited attempt to combine psychological therapies in the treatment of specific phobias and panic disorder and what has been done has been primarily with systematic desensitization or cognitive behavioral therapy along with hypnotherapy. I present two cases of multiple specific phobias that were successfully treated with hypnotherapy combined with virtual reality exposure therapy or in vivo exposure therapy. The rationale for this integrative therapy and the neurobiological constructs are considered.

Psychotherapies for anxiety and depression: benefits and costs is an important position paper that advocates for the research and treatment of these two devastating disorders that are highly prevalent not only in Italy but throughout the world. The emphasis here is on evidencebased treatment and economics. This takes into consideration the preference, at least in Italy for psychological treatments over pharmacologic, as well as the importance of marshaling scarce financial resources through the national healthcare system. As noted, the economic burden of untreated anxiety and depression including, for example, absences from work, needs to be factored in. Cited was the Improving Access to Psychological Therapies (IAPT) program which draws much of its rationale from the Depression Report of Great Britain. I would like to address these concerns with considerations given to cultural differences, alternative psychological treatments, and efficacy and effectiveness as determined by randomized double-blind studies and meta-analyses. Economics

Reduced brain glucose metabolism is a consistent feature of Alzheimer's disease (AD), and predicts progression from amnestic mild cognitive impairment (aMCI) to AD dementia. Greater decreases in F18fluorodeoxyglucose uptake with positron emission tomography (FDG-PET) correlate with greater cognitive impairment along the continuum from normal cognitive status to aMCI to AD dementia. In spite of the tight linkage of glucose metabolism to brain function and the decline in AD, only a very limited number of studies have tried to understand why glucose utilization is diminished or tried to reverse this AD-related deficit. Thiamine-dependent enzymes are critical components of glucose metabolism and are reduced in brains of AD patients. Increasing thiamine in humans or animals increases glucose utilization, improves brain metabolism and cognition, including memory. The most effective way to increase blood and brain thiamine is with benfotiamine because of superior pharmacokinetics. Our aim is to test the effect of administering benfotiamine on brain glucose metabolism (FDG-PET) and clinical impact as measured by changes in Assessment Scale-Cognitive subscale (ADAS-Cog) over time in patients with aMCI or AD. A randomized, double-blind, placebo-controlled clinical trial with benfotiamine in patients with aMCI or mild AD was initiated. The primary objective is to determine whether increasing thiamine availability with benfotiamine can slow cognitive decline compared to placebo, as measured by a change in the ADAS Cog score over the twelve-month trial. The secondary objective is to test whether benfotiamine will slow the decline in glucose utilization in patients as measured by FDG-PET. Using blocked, stratified randomization, 76 patients will be assigned to the treatment or placebo group. Stratification is based on Mini Mental Status Exam score (>21) to better understand if treatment responses differ according to initial cognitive impairment. Of the 464 patients screened, 45 patients have been enrolled. Patient characteristics will be detailed in the poster. The trial will determine whether benfotiamine provides clinical or underlying biological benefit for aMCI/AD patients and if this correlates with changes in glucose utilization.

Many patients with presumptive Alzheimer’s disease (AD) or other dementias may show minimal impairment on the Boston Naming Test (BNT), a visual confrontation naming measure. We sought to determine whether a semantic naming test, the Auditory Naming Test (ANT), would improve accuracy for identifying naming deficits in patients diagnosed with dementia ( N = 458) at an outpatient memory disorders clinic. Factor analysis revealed that both tests measured the same broad construct. Frequency of naming impairment with the ANT was significantly greater than with the BNT for patients with AD, regardless of dementia severity or levels of education ( p < .01). Effect size was moderate (φ = 0.45). BNT but not ANT performance declined with age in patients with AD. Sex differences were found for the BNT, but not the ANT, in the AD population. Accuracy rate of naming impairment diagnosis with the ANT in patients with AD was good (72%). Specificity (81%) and positive predictive value (PPV) (89%) with the ANT in AD were excellent, whereas sensitivity (69%) and negative predictive value (NPV) (58%) were modest. Receiver operating characteristic with area under the curve (ROC AUC) was excellent (0.958). A similar pattern was seen in patients with vascular dementia (VaD) or mixed AD/VaD. There was no significant effect in patients with amnestic mild cognitive impairment (aMCI). It is concluded that the ANT substantially improves the ability to diagnose naming impairment in patients with AD, VaD, and mixed AD/VaD dementia, and should be included in a neuropsychological battery administered to elderly patients with suspected dementia.

The earliest and perhaps best example of an interaction between nutrition and dementia is related to thiamine (vitamin B1). Throughout the last century, research showed that thiamine deficiency is associated with neurological problems, including cognitive deficits and encephalopathy. Multiple similarities exist between classical thiamine deficiency and Alzheimer's disease (AD) in that both are associated with cognitive deficits and reductions in brain glucose metabolism. Thiamine-dependent enzymes are critical components of glucose metabolism that are reduced in the brains of AD patients and by thiamine decline, and a decrease in their levels could account for the reduction in glucose metabolism. In preclinical models, reduced thiamine can drive AD-like abnormalities, including memory deficits, neuritic plaques, and hyperphosphorylation of tau. Furthermore, excess thiamine diminishes AD-like pathologies. In addition to dietary deficits, drugs or other manipulations that interfere with thiamine absorption can cause thiamine deficiency. Elucidating the reasons why the brains of AD patients are functionally thiamine deficient and determining the effects of thiamine restoration may provide critical information to help treat patients with AD.

The earliest and perhaps best example of an interaction between nutrition and dementia is related to thiamine (vitamin B1). Throughout the last century, research showed that thiamine deficiency is associated with neurological problems, including cognitive deficits and encephalopathy. Multiple similarities exist between classical thiamine deficiency and Alzheimer's disease (AD) in that both are associated with cognitive deficits and reductions in brain glucose metabolism. Thiamine‐dependent enzymes are critical components of glucose metabolism that are reduced in the brains of AD patients and by thiamine decline, and a decrease in their levels could account for the reduction in glucose metabolism. In preclinical models, reduced thiamine can drive AD‐like abnormalities, including memory deficits, neuritic plaques, and hyperphosphorylation of tau. Furthermore, excess thiamine diminishes AD‐like pathologies. In addition to dietary deficits, drugs or other manipulations that interfere with thiamine absorption can cause thiamine deficiency. Elucidating the reasons why the brains of AD patients are functionally thiamine deficient and determining the effects of thiamine restoration may provide critical information to help treat patients with AD.

The earliest and perhaps best example of an interaction between nutrition and dementia is related to thiamine (vitamin B1). Throughout the last century, research showed that thiamine deficiency is associated with neurological problems, including cognitive deficits and encephalopathy. Multiple similarities exist between classical thiamine deficiency and Alzheimer’s disease (AD) in that both are associated with cognitive deficits and reductions in brain glucose metabolism. Thiamine-dependent enzymes are critical components of glucose metabolism that are reduced in the brains of AD patients and by thiamine decline, and a decrease in their levels could account for the reduction in glucose metabolism. In preclinical models, reduced thiamine can drive AD-like abnormalities, including memory deficits, neuritic plaques, and hyperphosphorylation of tau. Furthermore, excess thiamine diminishes AD-like pathologies. In addition to dietary deficits, drugs or other manipulations that interfere with thiamine absorption can cause thiamine deficiency. Elucidating the reasons why the brains of AD patients are functionally thiamine deficient and determining the effects of thiamine restoration may provide critical information to help treat patients with AD.

Reduced glucose metabolism is an invariant feature of Alzheimer's Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear. Thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models, thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the thiamine derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in diabetic humans and animals. In diabetes, benfotiamine induces key thiamine-dependent enzymes of the pentose shunt to reduce accumulation of toxic metabolites including advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by benfotiamine in animals. If so, the use of benfotiamine could provide a safe intervention to reverse biological and clinical processes of AD progression. This article is part of a Special Issue entitled ‘Mitochondrial function and dysfunction in neurodegeneration’.

Although there have been studies of individual professional disciplines and their attitudes toward children with emotional, behavioral, or educational problems, there has been no systematic determination using a single, psychometrically sound measure that compared different professional groups. The goal was to assess the biases toward children with emotional and behavioral difficulties in samples of professionals who are most likely to have contact with them (86 teachers, 83 psychologists, 47 social workers), as well as other adults (75 undergraduate students). After development from an item pool, the provisional Biases toward Children with Psychological and Behavioral Disorders scale consisted of 21 items in one factor which experts also had assigned to a Biases category. The scale had good internal consistency reliability (alpha = .84). Validity was supported by a team of experts, factor structure, and known-groups comparisons. Psychologists and social workers scored lower than did teachers and students.

Flying phobia is a problem that affects a significant portion of the population. There are a number of therapeutic approaches but no one is universally accepted as the gold standard. One therapy is hypnosis. A recent addition to the armamentarium is virtual reality exposure (VRE) therapy. Both therapies are short-term and compare favorably to in vivo desensitization. Heretofore a combination of both approaches has not been reported. This article presents a case of a 50-year phobia to flying that was refractory to traditional methods including pharmacotherapy, systematic desensitization, and cognitive behavioral therapy but was successfully treated using VRE therapy and hypnosis as the primary modalities. This treatment was supplemented by other approaches. The rationale for this multimodal therapy and possible mechanisms involved are discussed.

Background: A nonmetabolic role for thiamine in cholinergic neurotransmission has long been suggested. The mechanism remains unclear. We sought to extend our previous research to elucidate the effect of the thiamine metabolic antagonist, oxythiamine, on the release of acetylcholine from the brain. Methods: The potassium-stimulated release of acetylcholine from superfused rat brain slices was determined. Hand-cut slices of cerebral cortex were preincubated with tritiated choline to label acetylcholine stores. Two periods of stimulation (S1, S2) with 50 mmol/l solution for 3.5 min were performed as superfusate was collected. During S1, only 50 mmol/l potassium-containing Krebs-bicarbonate buffer with 2 mmol/l calcium was used. Using a two-by-two design, S2 consisted of exposure to 50 mmol/l potassium with or without 10–4 mol/l oxythiamine, with or without calcium. The S2/S1 ratio was calculated. Results: Oxythiamine enhanced the potassium-evoked release of acetylcholine by 60% but only when calcium was present in the superfusing medium. Conclusion: These data confirm earlier findings with oxythiamine on the calcium-mediated synaptic transmission of acetylcholine and support a possible neuromodulatory role for thiamine distinct from its actions as a cofactor during metabolic processes.

Reports in the clinical literature indicate that low levels of vitamin D are associated with cognitive impairment and dementia. Furthermore, Vitamin D is being considered for clinical trials in the treatment of Alzheimer's disease (AD) and cognitive impairment. The following investigation was conducted to determine if low vitamin D levels correlated with impaired cognitive function in a cohort of patients who were referred to a memory disorders clinic. One hundred and eight consecutive patients referred to a memory disorders clinic who had vitamin D levels obtained underwent a neurocognitive assessment. This cognitive and behavioral evaluation included the Mini-Mental Status Examination (MMSE), the Standardized Assessment of Concussion (SAC), and the Neuropsychiatric Inventory (NPI). Vitamin D levels were classified as follows: deficiency (<20 ng/ml), insufficiency (20-29 ng/ml) and optimal (30-80 ng/ml). The mean vitamin D level in this cohort was 28 ng/ml. There were 23 (21%) patients who were deficient, 45 (42%) who were insufficient and 40 (37%) who were optimal. Vitamin D levels did not correlate with age (p = 0.57), MMSE (P = 0.81), SAC (P = 0.26) or NPI (P = 0.69). The mean scores for the MMSE by group were 19.1 in the deficient, 22 in the insufficient, and 20.9 in the optimal groups. Similarly there was no significant difference in the mean SAC scores by group (deficient = 13.4; insufficient = 15.7; and optimal = 15.6). The mean NPI scores also did not differ according to vitamin D level (deficient = 14.6; insufficient = 20.3; and optimal = 17.5). Low vitamin D levels were observed in 63% of this cohort referred to a memory disorders clinic. Vitamin D levels did not correlate with measures of cognitive or behavioral impairment. It is postulated that the underlying disease process has more of an influence on cognitive and behavioral function than vitamin D levels. This concept should be considered before undertaking clinical trials utilizing vitamin D as a therapeutic agent for dementia or cognitive impairment.

The potassium-stimulated release of acetylcholine, norepinephrine, serotonin, glutamate, and 4-aminobutyrate from superfused rat cortical slices was studied during hypoxia. A reduction in oxygen tensions from 603±6 to 22±2 mm Hg selectively altered the calcium-dependent efflux of these neurotransmitters, but did not change their calcium-independent release. The calcium-dependent release of [14C]acetylcholine decreased (39%), while that of glutamate increased (66%) and 4-aminobutyrate, [3H]norepinephrine, and [3H]serotonin were unaffected. Thus, low oxygen reveals variations in the calcium-dependent release mechanisms of several neurotransmitters. These differences may have important implications for pharmacological intervention of neurotransmitter release.