R.P.C. Kessels

Cognitive Functioning in Elderly Persons with Type 2 Diabetes and Metabolic Syndrome: the Hoorn Study

Background/Aims: Type 2 diabetes mellitus (DM2) is associated with mild decrements in cognitive functioning, particularly in the elderly. It is often preceded by a ‘prediabetic stage’, characterized by the co-occurrence of insulin resistance and vascular risk factors, usually referred to as the metabolic syndrome. Cognitive decrements may already develop in these early stages. Methods: Cognitive functioning was compared cross-sectionally between DM2 patients (n = 64), patients with metabolic syndrome but without DM2 (n = 83) and control subjects (n = 100) participating in the prospective population-based Hoorn study. Participants performed an extensive neuropsychological examination. Vascular and metabolic determinants were recorded. Results: Both the DM2 group and the metabolic syndrome group performed worse than controls on the domains of information processing speed and attention and executive functioning (mean differences in z-scores 0.2–0.3, all p < 0.05). There were no significant differences in performance between the DM2 and metabolic syndrome group. None of the individual risk factors of the metabolic syndrome, measured at either the present or the previous examination, was a key determinant of cognitive functioning. Conclusion: These results show that DM2-associated cognitive decline may develop in early stages of the disease, possibly in relation to risk factors clustered in the metabolic syndrome.

Attentionally modulated effects of cortisol and mood on memory for emotional faces in healthy young males.

Heightened cortisol levels due to stress or acute administration seem to enhance memory for emotional material, independently of emotional valence. An arousal-driven neurobiological mechanism involving the amygdala has been proposed. The relation between pre-task salivary measures of cortisol (by convention named basal levels) and emotionally modulated memory has not been investigated yet. Given the association between higher basal levels of cortisol and indices of low mood, valence-specific effects on emotionally modulated memory could be expected (e.g. mood-congruent or stimulus-specific forms of processing). This study was designed to investigate the relationship between basal levels of salivary cortisol, self-reported mood and spatial memory for neutral, happy and angry facial expressions in healthy young volunteers (N=31). Memory performance was indexed using a modified version of a computerized object-relocation task, using emotional facial expressions as stimuli. Results showed a significant relation between cortisol and depressive mood. More importantly, both the levels of cortisol and depressive mood were inversely related to the memory performance for the happy facial expressions, while a similar relationship between cortisol and memory performance on angry faces neared significance. An explanation in terms of the down-regulation of social behavior by elevated basal cortisol levels is postulated.

Early neuropsychological evaluation in patients with ischaemic stroke provides valid information

OBJECTIVESnThis study describes the feasibility and validity of neuropsychological evaluation in the early stage post-stroke. Early information on cognitive functioning in stroke patients could improve discharge decision, programming of rehabilitation strategies, and better prepare proxies for the problems they can be presented with in daily life. In this explorative study, our primary focus was on the feasibility of early neuropsychological evaluation. Furthermore, we looked at the possible prognostic relevance of early examination.nnnPATIENTS AND METHODSnFifty-seven consecutive patients (age 19-80) were enrolled within 4-20 days after their first ischaemic stroke (Modified-Rankin Scale (M-RS): 2-4). Patients were re-tested after 12-24 months, and functional outcome was assessed.nnnRESULTSnIn the early stage 44 (77%), patients could complete 82% of the administered tasks. At second evaluation, test performances improved, but a stable test profile was found with respect to abnormalities on the different tasks (P<0.0001). Moreover, initial sum scores of all composite cognitive domains including intellectual functioning (R2=0.80), language (R2=0.76), memory (R2=0.32), perception and visuospatial construction (R2=0.60), attention and psychomotor-functioning (R2=0.80) had significant predictive validity with respect to functional outcome (P<0.001).nnnCONCLUSIONnThis study supports the feasibility of early neuropsychological evaluation after ischaemic stroke onset and the prognostic validity for cognitive outcome in the long term.

Spatial and temporal order memory in Korsakoff patients

This study directly compared how well Korsakoff patients can process spatial and temporal order information in memory under conditions that included presentation of only a single feature (i.e., temporal or spatial information), combined spatiotemporal presentation, and combined spatiotemporal order recall. Korsakoff patients were found to suffer comparable spatial and temporal order recall deficits. Of interest, recall of a single feature was the same when only spatial or temporal information was presented compared to conditions that included combined spatiotemporal, presentation and recall. In contrast, control participants performed worse when they have to recall both spatial and temporal order compared to when they have to recall only one of these features. These findings together indicate that spatial and temporal information are not automatically integrated. Korsakoff patients have profound problems in coding the feature at hand. Moreover, their lower recall of both features at the same time suggests that Korsakoff patients are impaired in binding different contextual attributes together in memory.

Spatial memory impairment in patients after tumour resection: evidence for a double dissociation

Human spatial memory can be divided into multiple, partly separate cognitive processes. In this study, object location memory was studied using a set of tasks that assessed three different spatial memory aspects: positional memory, object location binding, and a combined process. Also, maze learning and spatial span memory were measured. Ten patients who had undergone intracranial tumour resection participated, and their individual results were compared with control data from 24 healthy subjects. Four patients showed selective spatial memory impairments; two patients were impaired at positional memory, and two other patients were impaired on object location binding and the combined process. This double dissociation provides further evidence for the notion that object location memory is not a unitary system, but consists of at least two separate mechanisms. In addition, spatial memory problems were predominantly present in the patients with lesions in either the right hemisphere or in the parietal lobe. These results are in agreement with previous findings on the involvement of the right hemisphere and the posterior parietal cortices in spatial processing.

The Brixton Spatial Anticipation Test as a test for executive function: validity in patient groups and norms for older adults.

Impairments in executive functioning frequently occur after acquired brain damage, in psychiatric disorders, and in relation to aging. The Brixton Spatial Anticipation Test is a relatively new measure for assessing the ability to detect and follow a rule, an important aspect of executive functioning. To date, normative data on this task are limited, particularly concerning the elderly. This study presents age- and education-adjusted regression-based norms obtained in a group of healthy older participants (n = 283; mean age 67.4 +/- 8.5 years). The applicability and validity of these norms were further examined in different groups of patients with stroke (n = 106), diabetes mellitus (n = 376), MCI/early dementia (n = 70), psychiatric disorders (n = 63), and Korsakoffs syndrome (n = 41). The results showed that patients with Korsakoffs syndrome, stroke, and psychiatric disorders performed significantly worse than healthy controls. Test-retest correlation (n = 83), learning effects, and correlations with other neuropsychological tests were also explored. Based on the present study, the Brixton test appears a useful addition to existing measures of executive functioning. Moreover, the test can be reliably applied in different groups of clinical patients.

P and M channel-specific interference in the what and where pathway.

It was the purpose of this experiment to study interference effects of colour or luminance peripheral flicker (in order to saturate either the parvocellular or the magnocellular stream) on object identity and spatial location memory. Colour flicker interfered with object identity recognition, whereas luminance flicker affected memory for spatial location. Moreover, overall performance was worse if coloured rather than grey-scaled objects were used in the stimulus display. There was no selective effect of coloured flicker affecting coloured objects and chromatic flicker affecting chromatic objects. These results provide strong evidence for the theoretical position that the what pathway relies heavily on information derived from the P stream and the where pathway on the M stream.

Applicability of the Rivermead Behavioural Memory Test - Third Edition (RBMT-3) in Korsakoff's syndrome and chronic alcoholics

Purpose To examine the applicability of the newly developed Rivermead Behavioural Memory Test – Third Edition (RBMT-3) as an ecologically-valid memory test in patients with alcohol-related cognitive disorders. Patients and methods An authorized Dutch translation of the RBMT-3 was developed, equivalent to the UK version, and administered to a total of 151 participants – 49 patients with amnesia due to alcoholic Korsakoff’s syndrome, 49 patients with cognitive impairment and a history of chronic alcoholism, not fulfilling the Korsakoff criteria, and 53 healthy controls. Between-group comparisons were made at subtest level, and the test’s diagnostic accuracy was determined. Results Korsakoff patients performed worse than controls on all RBMT-3 subtests (all P-values < 0.0005). The alcoholism group performed worse than controls on most (all P-values < 0.02), but not all RBMT-3 subtests. Largest effects were found between the Korsakoff patients and the controls after delayed testing. The RBMT-3 had good sensitivity and adequate specificity. Conclusion The RBMT-3 is a valid test battery to demonstrate everyday memory deficits in Korsakoff patients and non-Korsakoff patients with alcohol abuse disorder. Korsakoff patients showed an impaired performance on subtests relying on orientation, contextual memory and delayed testing. Our findings provide valuable information for treatment planning and adjustment in patients with alcohol-related cognitive impairments.

Blood pressure levels in pre-diabetic stages are associated with worse cognitive functioning in patients with type 2 diabetes

Type 2 diabetes mellitus (T2DM) is associated with mild decrements in cognitive functioning, but the relation of these decrements to metabolic and vascular risk factors is unclear. The present study compared the vascular risk factor profile over the preceding 16 years between T2DM patients with good cognitive functioning and those with poor cognitive functioning.

Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials

BACKGROUNDnIn women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available.nnnAIMnTo investigate the efficacy and safety of 2 novel on-demand pharmacologic treatments that have been designed to treat 2 FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition) using a personalized medicine approach using an allocation formula based on genetic, hormonal, and psychological variables developed to predict drug efficacy in the subgroups.nnnMETHODSn497 women (21-70 years old) with FSIAD were randomized to 1 of 12 8-week treatment regimens in 3 double-blinded, randomized, placebo-controlled, dose-finding studies conducted at 16 research sites in the United States. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T;xa00.5 mg), sildenafil (S; 50 mg), buspirone (B; 10 mg) and combination therapies (T 0.25 mgxa0+ S 25 mg, T 0.25 mgxa0+ S 50 mg, T 0.5 mgxa0+ S 25 mg, T 0.5 mgxa0+ S 50 mg, and T 0.25 mgxa0+ B 5 mg, T 0.25 mgxa0+ B 10 mg, T 0.5 mgxa0+ B 5 mg, T 0.5 mgxa0+ B 10 mg).nnnOUTCOMESnThe primary efficacy measure was the change in satisfying sexual events (SSEs) from the 4-week baseline to the 4-week average of the 8-week active treatment period after medication intake. For the primary end points, the combination treatments were compared with placebo and the respective monotherapies on this measure.nnnRESULTSnIn women with low sensitivity for sexual cues, 0.5 mg Txa0+ 50 mg S increased the number of SSEs from baseline compared with placebo (difference in change [Δ]xa0= 1.70, 95% CIxa0= 0.57-2.84, Pxa0= .004) and monotherapies (S: Δxa0= 1.95, 95% CIxa0= 0.44-3.45, Pxa0= .012; T: Δxa0= 1.69, 95% CIxa0= 0.58-2.80, Pxa0= .003). In women with overactive inhibition, 0.5 mg Txa0+ 10 mg B increased the number of SSEs from baseline compared with placebo (Δxa0=xa00.99, 95% CIxa0= 0.17-1.82, Pxa0= .019) and monotherapies (B: Δxa0= 1.52, 95% CIxa0= 0.57-2.46, Pxa0= .002; T:xa0Δxa0= 0.98, 95% CIxa0= 0.17-1.78, Pxa0= .018). Secondary end points followed this pattern of results. The most common drug-related side effects were flushing (Txa0+ S treatment, 3%; Txa0+ B treatment, 2%), headache (placebo treatment, 2%; Txa0+ S treatment, 9%), dizziness (Txa0+ B treatment, 3%), and nausea (Txa0+ S treatment, 3%; Txa0+ B treatment, 2%).nnnCLINICAL IMPLICATIONSnTxa0+ S and Txa0+ B are promising treatments for women with FSIAD.nnnSTRENGTHS AND LIMITATIONSnThe data were collected in 3 well-designed randomized clinical trials that tested multiple doses in a substantial number of women. The influence of Txa0+ S and Txa0+ B on distress and the potentially sustained improvements after medication cessation were not investigated.nnnCONCLUSIONSnTxa0+ S and Txa0+ B are well tolerated and safe and significantly increase the number of SSEs in different FSIAD subgroups. Tuiten A, van Rooij K, Bloemers J, etxa0al. Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomizedxa0Clinical Trials. J Sex Med 2018;15:201-216.