Sharon Erzinçlioğlu

Perception, attention, and working memory are disproportionately impaired in dementia with Lewy bodies compared with Alzheimer's disease

OBJECTIVE To test the hypotheses that visuoperceptual and attentional ability are disproportionately impaired in patients having dementia with Lewy Bodies (DLB) compared with Alzheimers disease (AD). METHODS A comprehensive battery of neuropsychological tasks designed to assess working, episodic, and semantic memory, and visuoperceptual and attentional functions was given to groups of patients with DLB (n=10) and AD (n=9), matched for age, education, and mini mental state examination (MMSE), and to normal controls (n=17). RESULTS Both patient groups performed equally poorly on tests of episodic and semantic memory with the exception of immediate and delayed story recall, which was worse in the AD group. Digit span was by contrast spared in AD. The most striking differences were on tests of visuoperceptual/spatial ability and attention. Whereas patients with AD performed normally on several subtests of the visual object and space perception battery, the DLB group showed substantial impairments. In keeping with previous studies, the AD group showed deficits in selective attention and set shifting, but patients with DLB were more impaired on virtually every test of attention with deficits in sustained, selective, and divided attention. CONCLUSIONS Patients with DLB have substantially greater impairment of attention, working memory, and visuoperceptual ability than patients with AD matched for overall dementia severity. Semantic memory seems to be equally affected in DLB and AD, unlike episodic memory, which is worse in AD. These findings may have relevance for our understanding of the genesis of visual hallucinations, and the differential diagnosis of AD and DLB.

Ventilatory function and winter fresh fruit consumption in a random sample of British adults.

The relation between ventilatory function and the reported frequency of consumption of fresh fruit and fruit juice was studied among 1502 lifelong non-smokers and 1357 current smokers aged 18-69 with no history of chronic respiratory disease. Forced expiratory volume in one second (FEV1) was assessed by turbine spirometry. As winter fruit consumption was more widely dispersed than summer consumption and few subjects ate fruit more frequently in the winter, winter fruit consumption was taken as an indicator of habitual (year round) consumption. After adjustment for sex, age, height, cigarette consumption, region of residence, and household socioeconomic group, FEV1 was associated with winter fruit consumption. The mean adjusted FEV1 among those who never drank fresh fruit juice and ate fresh fruit less than once a week during the winter was 78 ml lower (95% confidence interval 24-132 ml) than the mean for the other subjects. A similar difference was found in all age-sex groups and among both current smokers and lifelong non-smokers. Antioxidant and other actions of vitamin C may protect against pulmonary emphysema, or reduce bronchoconstrictor responses to environmental pollutants.

Evolution of Cognitive Deficits and Conversion to Dementia in Patients with Mild Cognitive Impairment: A Very-Long-Term Follow-Up Study

Ten patients with mild cognitive impairment (MCI) underwent extensive neuropsychological evaluation at 12-monthly intervals for a minimum of 6 years. All 10 patients declined and 5 have now died. The onset of dementia, as defined by a fall in global cognitive function (MMSE <24) or activities of daily living (Clinical Dementia Rating Scale; CDR) ranged from 1 to 8 years with generally good concordance between these measures. The rate of decline on the MMSE was highly variable ranging from 0.86 to 2.83 points per year. Other than a consistent impairment on tests of episodic memory and category fluency (8 out of 10), other early cognitive deficits were difficult to define and tended to be unstable in the early stages. Impairment of semantic memory, visuo-spatial and attentional abilities eventually developed but the sequence of deficit acquisition was heterogeneous. These findings are discussed in the light of current views of MCI. Amnestic MCI may not be an accurate concept unless semantic memory impairment is also considered as an integral core deficit. Full-blown dementia may take many years to develop in patients with MCI but was a universal feature in this study.

Patterns of Frontal Lobe Atrophy in Frontotemporal Dementia: A Volumetric MRI Study

Objectives: Frontotemporal dementia (FTD), the second commonest degenerative cause of dementia under the age of 65, often presents with striking changes in behaviour and personality in association with frontal lobe atrophy. Based on the behavioural changes observed in FTD, it is commonly assumed that the orbitofrontal cortex is the earliest and most severely affected frontal sub-region. However, evidence to support this assumption has to date been largely lacking. Methods: Using a novel volumetric MRI method, we performed a detailed volumetric analysis of six frontal regions in 12 subjects with the frontal or behavioural variant of FTD (fvFTD) and 12 age-, education- and sex-matched normal controls. The regions studied were: the orbitofrontal and insula regions (representing the orbitobasal cortex); the inferior and middle frontal regions (representing the dorsolateral prefrontal areas); and the superior frontal and anterior cingulate regions (representing the medial prefrontal areas). Results: As a group, the fvFTD patients showed atrophy involving all six regions. We then segregated the 12 patients into three sub-groups according to their overall degree of atrophy. In the mildest group (n = 3) all regions fell within 2 standard deviations of normal. In the intermediate group (n = 6) only the orbitofrontal region (bilaterally) fell clearly outside the control range (>2 z scores below the control mean); the next most atrophic region in this group was the right insular region. The severe group (n = 3) had generalized atrophy throughout the frontal regions measured. Conclusions: In conclusion, patients with the earliest stages of fvFTD show no significant loss of volume in any frontal lobe area as measured by a novel MRI volumetric technique. When volume loss does occur, changes are initially seen in the orbitofrontal cortex before atrophy becomes more widespread. These results provide some partial support for the often-quoted assumption that the orbitofrontal cortex is the locus of earliest pathology in fvFTD, although these findings must be regarded as preliminary in view of the small numbers of patients involved.

A Comparison of the Addenbrooke's Cognitive Examination (ACE), Conventional Neuropsychological Assessment, and Simple MRI-Based Medial Temporal Lobe Evaluation in the Early Diagnosis of Alzheimer's Disease

Objective:To examine the contribution of the Addenbrookes Cognitive Examination (ACE), neuropsychological assessment, and a magnetic resonance imaging (MRI)-based temporal lobe rating scale to the prediction of which patients with questionable dementia will progress to Alzheimers disease (AD). Methods:Fifty subjects (19 early AD, 31 questionable dementia [QD]) underwent the ACE, a neuropsychological evaluation, and a volumetric MRI. The degree of atrophy of hippocampal, parahippocampal, and other temporal lobe structures was assessed using a validated visual rating scale. Subjects were followed 8 monthly for an average of 19.1 months. Results:Of the 31 QD subjects, 11 converted to AD within 24 months of follow-up (another 2 developed dementia with Lewy bodies) and 18 were nonconverters. Converters were impaired relative to nonconverters at baseline on measures of episodic and semantic memory (category fluency and naming) and the ACE. Converters also had a greater degree of hippocampal and parahippocampal atrophy. Discriminant analysis demonstrated that the best single test for distinguishing converters was the ACE. In combination, the hippocampal rating and category fluency were also contributory. Conclusions:Progression to AD in patients with QD is best predicted by neuropsychological measures, particularly those that assess episodic and semantic memory, although simple rating methods based on MRI may have an adjunctive role.

Stress, distress and mucosal immunity in carers of a partner with fronto-temporal dementia.

Objectives: This study investigates the psychological and physiological impact of caring for a partner with fronto-temporal dementia (FTD). Carers were expected to exhibit greater stress and poorer psychological well-being in comparison with non-carers, and suppressed mucosal immunity. Method: Twenty-five carers and 36 non-carers completed standardised psychological assessments of perceived stress, psychological well-being, coping and social support. Levels of mucosal immunity were assessed in saliva samples collected over the 3 days of the study, alongside daily assessments of stress, arousal and mood. Results: Informal carers as a group reported greater stress and poorer psychological well-being, but there was considerable variation, with some carers reporting better psychological functioning than non-carers. Immune levels were not suppressed in carers compared with non-carers; counter to hypothesis, there was a positive correlation between immunity and poorer psychological well-being. Conclusions: This research suggests that caring for a partner with FTD increases distress and carers might benefit from psychological intervention. However, the variation in psychological well-being requires explanation. Furthermore, this first examination of mucosal immunity employing participants experiencing enduring stress suggests that, in contrast to previous research, enduring stress does not lead to suppression of mucosal immunity and may actually enhance it.

The Effects of Hippocampal Lesions on MRI Measures of Structural and Functional Connectivity

Focal lesions can affect connectivity between distal brain regions (connectional diaschisis) and impact the graph‐theoretic properties of major brain networks (connectomic diaschisis). Given its unique anatomy and diverse range of functions, the hippocampus has been claimed to be a critical “hub” in brain networks. We investigated the effects of hippocampal lesions on structural and functional connectivity in six patients with amnesia, using a range of magnetic resonance imaging (MRI) analyses. Neuropsychological assessment revealed marked episodic memory impairment and generally intact performance across other cognitive domains. The hippocampus was the only brain structure exhibiting reduced grey‐matter volume that was consistent across patients, and the fornix was the only major white‐matter tract to show altered structural connectivity according to both diffusion metrics. Nonetheless, functional MRI revealed both increases and decreases in functional connectivity. Analysis at the level of regions within the default‐mode network revealed reduced functional connectivity, including between nonhippocampal regions (connectional diaschisis). Analysis at the level of functional networks revealed reduced connectivity between thalamic and precuneus networks, but increased connectivity between the default‐mode network and frontal executive network. The overall functional connectome showed evidence of increased functional segregation in patients (connectomic diaschisis). Together, these results point to dynamic reorganization following hippocampal lesions, with both decreased and increased functional connectivity involving limbic‐diencephalic structures and larger‐scale networks.

Multiple determinants of lifespan memory differences

Memory problems are among the most common complaints as people grow older. Using structural equation modeling of commensurate scores of anterograde memory from a large (N = 315), population-derived sample (www.cam-can.org), we provide evidence for three memory factors that are supported by distinct brain regions and show differential sensitivity to age. Associative memory and item memory are dramatically affected by age, even after adjusting for education level and fluid intelligence, whereas visual priming is not. Associative memory and item memory are differentially affected by emotional valence, and the age-related decline in associative memory is faster for negative than for positive or neutral stimuli. Gray-matter volume in the hippocampus, parahippocampus and fusiform cortex, and a white-matter index for the fornix, uncinate fasciculus and inferior longitudinal fasciculus, show differential contributions to the three memory factors. Together, these data demonstrate the extent to which differential ageing of the brain leads to differential patterns of memory loss.

No effect of hippocampal lesions on stimulus-response bindings

&NA; The hippocampus is believed to be important for rapid learning of arbitrary stimulus‐response contingencies, or S‐R bindings. In support of this, Schnyer et al. (2006) (Experiment 2) measured priming of reaction times (RTs) to categorise visual objects, and found that patients with medial temporal lobe damage, unlike healthy controls, failed to show evidence of reduced priming when response contingencies were reversed between initial and repeated categorisation of objects (a signature of S‐R bindings). We ran a similar though extended object classification task on 6 patients who appear to have selective hippocampal lesions, together with 24 age‐matched controls. Unlike Schnyer et al. (2006), we found that reversing response contingencies abolished priming in both controls and patients. Bayes Factors provided no reason to believe that response reversal had less effect on patients than controls. We therefore conclude that it is unlikely that the hippocampus is needed for S‐R bindings. HighlightsHippocampus is thought important for rapid binding of stimuli (S) and responses (R).Six patients with hippocampal damage showed evidence of normal S‐R bindings.Both patients and controls showed priming of object size judgments.Patients and controls showed equivalent priming reductions when responses reversed.The hippocampus is not necessary for this type of S‐R binding.