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Biomedical subjects

R D Rogers

Publications and source records attributed to R D Rogers.

At least 37 records · Page 2Linked to original sources

Stability evaluation of a cement based waste form to microbially induced degradation.

In this study the current Nuclear Regulatory Commission (NRC) protocol is used to evaluate the stability of Tuskegee cement/cobalt chloride waste form in the presence of Thiobacillus thiooxidans (T. thiooxidans). A critical examination of this protocol and identified limitations are reported also. Tuskegee cement/cobalt chloride waste forms were shown to exhibit considerable instability to microbial degradation as indicated by significant physical deterioration, and increased leaching of calcium and cobalt on exposure to T. thiooxidans. The instability was aggravated with higher levels of cobalt chloride content of the waste forms. The degradative capability of T. thiooxidans closely followed its ability to significantly decrease the pH of its environment. Inherent limitations in the NRC protocol were observed which could lead to serious result interpretation errors. The use of a T. thiooxidans culture that is significantly lower in pH in comparison to the control medium could lead to an overestimation of the degradative effect of T. thiooxidans, while the use of a culture that is substrate limited could result in an underestimation of T. thiooxidans capability.

Acidithiobacillus thiooxidans↗

Preorganized ligand arrays based on spirotetrahydrofuranyl motifs. Synthesis of the stereoisomeric 1,8,14-trioxatrispiro[4.1.4.1.4. 1]octadecanes and the contrasting conformational features and ionic binding capacities of these belted ionophores.

The cis,trans trispiro ether 4 is accessible from several synthetic directions as a consequence of a crossover in reaction selectivity when proceeding from nucleophilic attack on the cis dispiro ketone to oxygenation of the alpha,beta-unsaturated ester 17. Its cis,cis isomer 3 was obtained in 17 steps and 14.6% overall yield from 3, 5-dimethoxybenzoic acid by making use of the alicyclic side chain in N as a "conformational lock". Although 4 shows no measurable tendency to complex with alkali metal ions, 3 binds strongly to Li(+) and Na(+) ions, as well as to CH(3)NH(3)(+). Whereas the 3eq conformation is populated in the solid state and in solution, complex formation occurs readily. (13)C NMR studies have defined slow exchange limits as the 2:1 sandwich complex with lithium ion is initially formed and transformed progressively into a 1:1 species upon the addition of more LiClO(4). Only the 2:1 complex with sodium ion is formed during comparable titration with NaClO(4). Association constants, molecular mechanics calculations, and X-ray crystallographic studies provide insight into the binding capacity of this belted tridentate ionophore.

Crystallography, X-Ray↗

Coordination of lanthanide triflates and perchlorates with N,N,N',N'-tetramethylsuccinamide.

Compounds formed from the reaction of N,N,N',N'-tetramethylsuccinamide (TMSA) with trivalent lanthanide salts possessing the poorly coordinating counteranions triflate (CF3SO3-) and perchlorate (ClO4-) have been prepared and examined. Structural features of these Ln-TMSA compounds have been studied in the solid phase by thermogravimetric analysis, infrared spectroscopy, and, in selected cases, by single-crystal X-ray diffraction and in solution by infrared spectroscopy. Eight-coordinate compounds, [Ln(TMSA)4]3+, derived from coordination of four succinamide ligands to the metal ion could be formed with all lanthanides examined (Ln = La, Pr, Nd, Eu, Yb, Lu). Structural analyses by single-crystal X-ray diffraction were performed for the lanthanide triflate salts Ln(C8H16N2O2)4(CF3SO3)3: Ln = La, compound 1, monoclinic, P2(1)/n, a = 11.0952(2) A, b = 19.2672(2) A, c = 24.9759(3) A, beta = 90.637(1) degrees, Z = 4, Dcalcd = 1.586 g cm-3; Ln = Nd, compound 2, monoclinic, C2/c, a = 24.6586(10) A, b = 19.3078(7) A, c = 11.1429(4) A, beta = 90.450(1) degrees, Z = 4, Dcalcd = 1.603 g cm-3; Ln = Eu, compound 3, monoclinic, C2/c, a = 24.4934(2) A, b = 19.3702(1) A, c = 11.1542(1) A, beta = 90.229(1) degrees, Z = 4, Dcalcd = 1.617 g cm-3; Ln = Lu, compound 5, monoclinic, C2/c, a = 24.2435(4) A, b = 19.6141(2) A, c = 11.2635(1) A, beta = 90.049(1) degrees, Z = 4, Dcalcd = 1.626 g cm-3. X-ray analysis was also carried out for the perchlorate salt: Ln = Eu, compound 4, triclinic, P1, a = 10.9611(2) A, b = 14.6144(3) A, c = 15.7992(2) A, alpha = 106.594(1) degrees, beta = 91.538(1) degrees, gamma = 90.311(1) degrees, Z = 2, Dcalcd = 1.561 g cm-3. In the presence of significant amounts of water, 7-coordinate compounds with mixed aquo-TMSA cation structures [Ln(TMSA)3(H2O)]3+ (Ln = Yb) and [Ln(TMSA)2(H2O)3]3+ (Ln = La, Pr, Nd, Eu, Yb) have been isolated with structural determinations by single-crystal X-ray diffraction obtained for the following species: Yb(C8H16N2O2)3(H2O)(CF3SO3)3, compound 6, monoclinic, P2(1)/n, a = 8.9443(3) A, b = 11.1924(4) A, c = 44.2517(13) A, beta = 93.264(1) degrees, Z = 4, Dcalcd = 1.735 g cm-3; Yb(C8H16N2O2)3(H2O)(ClO4)3, compound 7, monoclinic, Cc, a = 19.2312(6) A, b = 11.1552(3) A, c = 19.8016(4) A, beta = 111.4260(1) degrees, Z = 4, Dcalcd = 1.690 g cm-3; Yb(C8H16N2O2)2(H2O)3(CF3SO3)3, compound 8, triclinic, P1, a = 8.6719(1) A, b = 12.2683(2) A, c = 19.8094(3) A, alpha = 75.815(1) degrees, beta = 86.805(1) degrees, gamma = 72.607(1) degrees, Z = 2, Dcalcd = 1.736 g cm-3. Unlike in the analogous nitrate salts, only bidentate binding of the succinamide ligand to the lanthanide metal is observed. IR spectroscopy studies in anhydrous acetonitrile suggest that the solid-state structures of these Ln-TMSA compounds are maintained in solution.

Journal Article↗

Development of a biofilm formation method for waste forms stability evaluation.

The development of an accurate assessment protocol is critical for the prediction of long-term performance of waste disposal systems under field conditions. In this study, the development of a biofilm formation method for the evaluation of waste forms stability to microbially induced degradation (MID) is reported. The development process involved significant modifications to the existing Nuclear Regulatory Commission (NRC) approach. In the biofilm formation method, the control media and fermenter broths are designed to be of similar pH to avoid overestimation of the microbe's capability to degrade the waste forms. In the NRC approach, the pH values are different. The existing one-stage process of the NRC approach is also replaced with a two-stage process in the biofilm formation method. This is to ensure full evaluation of the microbe's involvement in waste forms degradation. The first stage of the two-stage process is for biofilm formation and the second is for biofilm evaluation. The use of a two-stage process eliminates the possibility of substrate limitation, resulting in values of degradation indices that are about two times higher than those obtained using the single-stage NRC approach. Two waste forms (100% Tuskegee cement and 21% cobalt chloride/79% cement) were used in the development of the biofilm formation method. Both waste forms showed evidence of biofilm formation. The formation of biofilm on the cobalt-containing waste form indicates a lack of anti-microbial capability of cobalt.

Biodegradation, Environmental↗

Vicinal tetrahydrofuranyl substitution of alkyl chains. Tetra-, penta-, and hexafunctionalized arrays.

The tetrakis (tetrahydrofuranyl) dialdehydes 14 and 19 are accessible by oxidative cleavage of extensively substituted cyclohexenes, which have in turn been assembled in a stereocontrolled manner. Reaction of 14 with an excess of the Normant reagent followed by ring closure resulted in conversion to the hexafunctionalized polyether 15. Allylindation of the same dialdehyde gave rise to lactol 16, a reactivity pattern that was essentially duplicated when 19 was treated with the Normant reagent. Attempts to add allylmagnesium bromide to 19 resulted in operation of a Tishchenko reaction with formation of lactone 23. By means of X-ray diffraction analysis, it was possible to ascertain the conformation adopted by 20 and 23 in the solid state. In addition, 15 was shown to populate a conformation in which the oxygen are very predominantly in gauche arrangements, this structural preorganization taking place in the absence of any metal ions.

Aldehydes↗

Naphthol- and resorcinol-based azo dyes as metal ion complexants in aqueous biphasic systems.

Aqueous biphasic systems (ABS) are comprised of both a polymer-rich phase (e.g., polyethylene glycol, PEG) and a salt-rich phase [e.g., (NH4)2SO4] such that both phases are 80% water on a molar basis. ABS have demonstrated applications as environmentally-friendly methods to separate relatively hydrophobic anionic species, such as pertechnetate and mercury halide anionic complexes, from high ionic strength solutions although partitioning of hydrated metal ions, such as Fe3+ and actinides, to the PEG-rich phase is negligible without the addition of a metal ion complexant to the system. Four naphthol- or resorcinol-based dyes; 1-(2-pyridylazo)-2-naphthol (PAN), 1-(thiazolylazo)-2-naphthol (TAN), 4-(2-pyridylazo)-resorcinol (PAR) and 4-(2-thiazolylazo)-resorcinol (TAR), each incorporating a naphthol or resorcinol with an ortho azo functional group, have been studied as metal ion extractants in ABS as a function of pH. In the PEG-2000/ (NH4)2SO4 ABS, the distribution ratios of Fe3+, Co2+ and Ni2- were enhanced by several orders of magnitude at high pH in contrast to the behavior of Cs+, Cd2+ and Eu3+ whose partitioning behavior was largely unaffected by the presence of these extractants at any pH. The three extracted metal ions, Fe3+, Co2+ and Ni2+, could be stripped by contact with a fresh salt phase at low pH.

Azo Compounds↗

Investigation of aqueous biphasic systems for the separation of lignins from cellulose in the paper pulping process.

In efforts to apply a polymer-based aqueous biphasic system (ABS) extraction to the paper pulping process, the study of the distribution of various lignin and cellulosic fractions in ABS and the effects of temperature on system composition and solute partitioning have been investigated. The partitioning of three lignin species (Indulin AT, Indulin C, and Reax 85A) have been studied in ABS prepared from stock solutions of 40% (w/w) poly(ethylene glycol) (PEG)-2000 and increasing concentrations of K2CO3, (NH4)2SO4, and NaOH. The partitioning of these lignins is affected by the free energy of hydration of the salt forming the ABS, the tie line length, and the dissociation of the sulfonic acid and hydroxyl groups of the distributed solutes. The partitioning of fibrous cellulose and diethylaminoethyl cellulose have been studied in 40% (w/w) PEG-2000-(NH4)2SO4 ABS. The hydrophilic nature of these species is important in terms of their phase preference when designing a polymer-based aqueous biphasic extraction process for use in a paper pulping process. Both cellulosic samples do not dissolve, but rather report to the salt-rich phase of an ABS. In both chemical pulping and Organosolv pulping, temperatures in excess of 120 degrees C are needed to solubilize the lignin from the cellulose fraction of wood. To study the effects of temperature on the phase diagram and solute partitioning, phthalic acid and NH499TcO4 (as system probes) have been partitioned in 40% (w/w) PEG-2000-(NH4)2SO4 ABS at known tie line lengths as a function of temperature. Temperature does not appear to affect the partitioning results beyond the expected increase in phase divergence as temperature is increased. The PEG-2000 polymer itself appears to be stable to chemical pulping conditions.

Cellulose↗

Solvatochromic studies in polyethylene glycol--salt aqueous biphasic systems.

The polarities of the co-existing phases of a polyethylene glycol (PEG)-2000-K3PO4 aqueous biphasic system (ABS) have been examined using Reichardt's carboxylated pyridinium-N-phenoxybetaine dye as a probe. Using this probe, the polarities of these phases have been compared to those of conventional solvent extraction systems and micellar systems using values obtained from the literature. In general, these extraction systems are comparable in polarity to rather polar solvents. Data on the free energy of transfer of solvents suggests that this may be due to the failure of the probe to account for the real polarity of the salt-rich phase compared to the polymer-rich phase. Examination of the monophasic region of these systems suggests that the reason for this is that the probe is partitioned to a discreet solvent domain dominated by PEG, even though phase separation of the solution is not observed. The use of linear free energy relationships for the characterization of ABS is briefly discussed.

Phosphates↗

Impaired planning but intact decision making in early Huntington's disease: implications for specific fronto-striatal pathology.

Previous neuropsychological data have suggested that deficits in early Huntington's disease (HD) include executive impairments, which often are linked with frontal-lobe dysfunction. This study sought to investigate the profile of cognitive deficits using two computerised tasks whose performance is known to rely on intact functions of separate areas of the prefrontal cortex. Twenty patients with early HD and 20 matched controls were given the one-touch Tower of London, a stringent measure of visuo-spatial planning, and a decision making task, which involved selecting and gambling on outcomes on the basis of their differing probabilities. Patients were significantly less accurate than controls on the planning test, which is sensitive to frontal lobe lesions and is strongly associated with the dorsolateral prefrontal cortex in functional imaging studies. On the decision making task, patients were unimpaired on the quality of their decision making, in contrast to previous reports of impairment on this task in patients with ventromedial prefrontal cortex lesions. This dissociation of performance is discussed in terms of the usual path of progression of HD through the striatum and the resultant pattern of disruption of the functioning of the different cortico-striatal functional loops.

Adult↗

Probabilistic learning and reversal deficits in patients with Parkinson's disease or frontal or temporal lobe lesions: possible adverse effects of dopaminergic medication.

Three groups of patients with Parkinson's disease (PD) - mild, unmedicated (UPD), mild, medicated (MPD) and severe, medicated (SPD) - and patients with lesions of the frontal lobe (FLL) or temporal lobe (TLL) were compared with matched controls on the learning and reversal of probabilistic and two-pair concurrent colour discriminations. Both of the cortical lesion groups showed reversal deficits, with no increase in perseverative responding. The UPD group, although impaired on a spatial recognition task, showed intact discrimination learning and reversal; the MPD and SPD patients showed non-perseverative reversal impairments on both reversal tasks. Two hypotheses - based on disease severity and possible deleterious effects of medication - are offered to explain the reversal impairments of the PD patients and the results are discussed in terms of the role of dopamine in reward-based learning.

Adult↗

Deficits in decision-making in patients with aneurysms of the anterior communicating artery.

Patients with aneurysmal subarachnoid haemorrhage (SAH) secondary to ruptured anterior communicating artery aneurysms (ACoA) often suffer from neuropsychological sequelae including personality and behavioural changes. In this study, 31 patients with ruptured aneurysms of the ACoA resulting in SAH [mean age 50.9 years, NART (National Adult Reading Test) IQ 108.7] were compared with a group of 29 normal controls (mean age 51.9 years, NART IQ 109.7) on a specific task of decision-making. A similar task has been imaged previously and shown to activate regions involving the ventromedial prefrontal cortex. Patients with ACoA rupture showed no significant difference from controls on the task in their speed or quality of decision-making. They did, however, exhibit increased risk-taking behaviour, placing higher bets in a measure of the task which involved choices between actions associated with differing magnitudes of reward and punishment. ACoA patients demonstrated true risk-taking behaviour as opposed to simple impulsivity. Such a deficit in decision-making may be a result of direct damage to the orbital prefrontal cortex itself (as a result of micro-ischaemia or infarction after ACoA aneurysmal rupture) or to a disconnection in the ventromedial circuits from distant or generalized brain damage.

Aneurysm, Ruptured↗

Contrasting cortical and subcortical activations produced by attentional-set shifting and reversal learning in humans.

Much evidence suggests that lesions of the prefrontal cortex (PFC) produce marked impairments in the ability of subjects to shift cognitive set, as exemplified by performance of the Wisconsin Card Sorting Test (WCST). However, studies with humans and experimental primates have suggested that damage to different regions of PFC induce dissociable impairments in two forms of shift learning implicit in the WCST (that is, extradimensional (ED) shift learning and reversal shift learning), with similar deficits also being apparent after damage to basal ganglia structures, especially the caudate nucleus. In this study, we used the same visual discrimination learning paradigm over multidimensional stimuli, and the H215O positron emission tomography (PET) technique, to examine regional cerebral blood flow (rCBF) changes associated with these subcomponent processes of the WCST. In three conditions, subjects were scanned while acquiring visual discriminations involving either (i) the same stimulus dimension as preceding discriminations (intradimensional (ID) shifts); (ii) different stimulus dimensions from previous discriminations (ED shifts) or (iii) reversed stimulus-reward contingencies (reversal shifts). Additionally, subjects were scanned while responding to already learnt discriminations ('performance baseline'). ED shift learning, relative to ID shift learning, produced activations in prefrontal regions, including left anterior PFC and right dorsolateral PFC (BA 10 and 9⁄46). By contrast, reversal learning, relative to ID shift learning, produced activations of the left caudate nucleus. Additionally, compared to reversal and ID shift learning, ED shift learning was associated with relative deactivations in occipito-temporal pathways (for example, BA 17 and 37). These results confirm that, in the context of visual discrimination learning over multidimensional stimuli, the control of an acquired attentional bias or'set', and the control of previously acquired stimulus-reinforcement associations, activate distinct cortical and subcortical neural stations. Moreover, we propose that the PFC may contribute to the control of attentional-set by modulating attentional processes mediated by occipito-temporal pathways.

Adult↗

Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex.

Patients sustaining lesions of the orbital prefrontal cortex (PFC) exhibit marked impairments in the performance of laboratory-based gambling, or risk-taking, tasks, suggesting that this part of the human PFC contributes to decision-making cognition. However, to date, little is known about the particular regions of the orbital cortex that participate in this function. In the present study, eight healthy volunteers were scanned, using H(2)(15)0 PET technology, while performing a novel computerized risk-taking task. The task involved predicting which of two mutually exclusive outcomes would occur, but critically, the larger reward (and penalty) was associated with choice of the least likely outcome, whereas the smallest reward (and penalty) was associated with choice of the most likely outcome. Resolving these "conflicting" decisions was associated with three distinct foci of regional cerebral blood flow increase within the right inferior and orbital PFC: laterally, in the anterior part of the middle frontal gyrus [Brodmann area 10 (BA 10)], medially, in the orbital gyrus (BA 11), and posteriorly, in the anterior portion of the inferior frontal gyrus (BA 47). By contrast, increases in the degree of conflict inherent in these decisions was associated with only limited changes in activity within orbital PFC and the anterior cingulate cortex. These results suggest that decision making recruits neural activity from multiple regions of the inferior PFC that receive information from a diverse set of cortical and limbic inputs, and that the contribution of the orbitofrontal regions may involve processing changes in reward-related information.

Adult↗

Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour.

RATIONALE: Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking. However, little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour. OBJECTIVES AND METHODS: We compared the effects of rapid plasma tryptophan depletion, acute doses of the mixed indirect catecholamine agonist, methylphenidate (40 mg), and acute doses of the alpha(1)/alpha(2 )agonist, clonidine (1.5 microg/kg), on aspects of visual discrimination learning involving either acquisition of altered stimulus-reward associations (i.e. updating the affective valence of exteroceptive stimuli) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions. RESULTS: Relative to subjects who received placebo, subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations, but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension. By contrast, subjects who received methylphenidate were able to learn effectively about changing stimulus-reward associations, but showed an enhanced ability to shift an attentional bias, in combination with slowed response times. Subjects who received clonidine showed neither of these changes. CONCLUSIONS: These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.

Adolescent↗

Discrimination, reversal, and shift learning in Huntington's disease: mechanisms of impaired response selection.

In a series of three experiments, we investigated different aspects of response selection in early-stage clinically symptomatic Huntington's disease (HD) patients in the context of discrimination learning. A series of structurally related response selection tasks involving discrimination, reversal, and shift learning were employed. In Experiment 1, the mechanisms of our previously reported [37] finding of impaired extra-dimensional shift learning were explored. The results suggested that impaired shift learning in HD is a result of perseverative responding. In Experiment 2, performance on a concurrent-pair (CP) discrimination and reversal task was examined. HD patients showed no deficits in CP discrimination learning or reversal. In Experiment 3, the performance of HD patients on a probabilistic discrimination and reversal task was examined. HD patients were impaired in the learning of a probabilistic discrimination, and also its reversal. This reversal deficit was again the result of perseverative responding. In addition, there was a strong correlation between HD patients' activities of daily living scores and reversal errors. The result are consistent with current theories of the role of the basal ganglia in cognition, and suggest specific impairments in response selection mechanisms in HD, in particular, in overcoming selection biases based on prior reinforcement.

Adult↗

Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms.

We used a novel computerized decision-making task to compare the decision-making behavior of chronic amphetamine abusers, chronic opiate abusers, and patients with focal lesions of orbital prefrontal cortex (PFC) or dorsolateral/medial PFC. We also assessed the effects of reducing central 5-hydroxytryptamine (5-HT) activity using a tryptophan-depleting amino acid drink in normal volunteers. Chronic amphetamine abusers showed suboptimal decisions (correlated with years of abuse), and deliberated for significantly longer before making their choices. The opiate abusers exhibited only the second of these behavioral changes. Importantly, both sub-optimal choices and increased deliberation times were evident in the patients with damage to orbitofrontal PFC but not other sectors of PFC. Qualitatively, the performance of the subjects with lowered plasma tryptophan was similar to that associated with amphetamine abuse, consistent with recent reports of depleted 5-HT in the orbital regions of PFC of methamphetamine abusers. Overall, these data suggest that chronic amphetamine abusers show similar decision-making deficits to those seen after focal damage to orbitofrontal PFC. These deficits may reflect altered neuromodulation of the orbitofrontal PFC and interconnected limbic-striatal systems by both the ascending 5-HT and mesocortical dopamine (DA) projections.

Adult↗

Emotional bias and inhibitory control processes in mania and depression.

BACKGROUND: Despite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. The disinhibited behaviour characteristic of mania and evidence that subgenual prefrontal cortex is differentially activated in mania and depression both suggest that dissociable deficits will emerge on tasks that require inhibitory control and are subserved by ventromedial prefrontal cortex. METHODS: Manic patients and controls undertook computerized neuropsychological tests of memory and planning ability. In addition, manic and depressed patients were directly compared with controls on a novel affective shifting task that requires inhibitory control over different components of cognitive and emotional processing. RESULTS: Manic patients were impaired on tests of memory and planning. Importantly, affective shifting performance of manic patients differed from that of depressed patients. Manic patients were impaired in their ability to inhibit behavioural responses and focus attention, but depressed patients were impaired in their ability to shift the focus of attention. Depressed patients exhibited an affective bias for negative stimuli, and we believe this to be the first demonstration of an affective bias for positive stimuli in manic patients. CONCLUSIONS: Observed impairments on tests of memory and planning suggest a global pathology for mania consistent with previous profiles for this disorder and similar to established profiles for depression. The results on the affective shifting task demonstrate the presence of mood-congruent bias and dissociable components of inhibitory control in mania and depression. Against a background of memory and planning impairments in the two groups, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.

Adult↗

Specific cognitive deficits in mild frontal variant frontotemporal dementia.

Eight patients with relatively mild frontal variant frontotemporal dementia (fvFTD) were compared with age- and IQ-matched control volunteers on tests of executive and mnemonic function. Tests of pattern and spatial recognition memory, spatial span, spatial working memory, planning, visual discrimination learning/attentional set-shifting and decision-making were employed. Patients with fvFTD were found to have deficits in the visual discrimination learning paradigm specific to the reversal stages. Furthermore, in the decision-making paradigm, patients were found to show genuine risk-taking behaviour with increased deliberation times rather than merely impulsive behaviour. It was especially notable that these patients demonstrated virtually no deficits in other tests that have also been shown to be sensitive to frontal lobe dysfunction, such as the spatial working memory and planning tasks. These results are discussed in relation to the possible underlying neuropathology, the anatomical connectivity and the hypothesized heterogeneous functions of areas of the prefrontal cortex. In particular, given the nature of the cognitive deficits demonstrated by these patients, we postulate that, relatively early in the course of the disease, the ventromedial (or orbitofrontal) cortex is a major locus of dysfunction and that this may relate to the behavioural presentation of these patients clinically described in the individual case histories.

Adult↗