Neural correlates of episodic memory in healthy aging and Alzheimer's disease.

Contains fulltext : 83219.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 20 december 2010Promotores : Fernandez, G.S.E., Olde Rikkert, M.G.M., Kessels, R.P.C. Co-promotor : Rijpkema, M.J.P.173 p

Cholinesterase inhibitors and add-on nutritional supplements in Alzheimer's disease: A systematic review of randomized controlled trials

Item does not contain fulltextTo date, single drug and nutrient-based interventions have failed to show a clinically relevant effect on Alzheimer's disease (AD). Multidomain interventions may alleviate symptoms and alter the disease course in a synergistic manner. This systematic review examines the effect of adding nutritional supplementation to cholinesterase inhibitors. A systematic PubMed and Cochrane search resulted in nine high quality studies. The studies had low to moderate risk of bias and focused on oxidative stress, homocysteine levels, membrane fluidity, inflammation and acetylcholine levels. Only the use of vitamin E supplements could reduce the rate of functional decline when combined with cholinesterase inhibitors in one study, whereas cognition was not affected in both this and other studies. None of the other nutritional supplements showed convincing evidence of a beneficial effect when combined with cholinesterase inhibitors. This shows that cognitive and functional improvement is difficult to achieve in patients with AD, despite epidemiological data and evidence of biological effects of nutritional supplements. Addressing one disease pathway in addition to cholinesterase inhibitor therapy is probably insufficient to alter the course of the disease. Personalized, multifactorial interventions may be more successful in improving cognition and daily functioning

De (gewenste) toekomst van de wetenschap in Nederland: een analyse van de Nationale Wetenschapsagenda met betrekking tot dementie en veroudering.

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How does additional diagnostic testing influence the initial diagnosis in patients with cognitive complaints in a memory clinic setting?

Contains fulltext : 150589.pdf (publisher's version ) (Open Access)BACKGROUND: patients suspected of dementia frequently undergo additional diagnostic testing (e.g. brain imaging or neuropsychological assessment) after standard clinical assessment at a memory clinic. This study investigates the use of additional testing in an academic outpatient memory clinic and how it influences the initial diagnosis. METHODS: the initial diagnosis after standard clinical assessment (history, laboratory tests, cognitive screening and physical and neurological examination) and the final diagnosis after additional testing of 752 memory clinic patients were collected. We specifically registered if, and what type of, additional testing was requested. RESULTS: additional testing was performed in 518 patients (69%), 67% of whom underwent magnetic resonance imaging, 45% had neuropsychological assessment, 14% had cerebrospinal fluid analysis and 49% had (combinations of) other tests. This led to a modification of the initial diagnosis in 17% of the patients. The frequency of change was highest in patients with an initial non-Alzheimer's disease (AD) dementia diagnosis (54%, compared with 11 and 14% in patients with AD and 'no dementia'; P < 0.01). Finally, after additional testing 44% was diagnosed with AD, 9% with non-AD dementia and 47% with 'no dementia'. CONCLUSION: additional testing should especially be considered in non-AD patients. In the large group of patients with an initial AD or 'no dementia' diagnosis, additional tests have little diagnostic impact and may perhaps be used with more restraint.6 p

Spatial working memory in normal aging and midl cognitive impairment (MCI)

Contains fulltext : 73475.pdf (publisher's version ) (Closed access)1 p

Neural underpinnings of autobiographical memory in aging, MCI and AD

Contains fulltext : 73606.pdf (publisher's version ) (Closed access)1 p

Spatial working memory in aging and mild cognitive impairment: Effects of task load and contextual cueing

Contains fulltext : 89194.pdf (publisher's version ) (Closed access)Mild Cognitive Impairment (MCI) is characterized by episodic memory deficits, while aspects of working memory may also be implicated, but studies into this latter domain are scarce and results are inconclusive. Using a computerized search paradigm, this study compares 25 young adults, 25 typically aging older adults and 15 amnestic MCI patients as to their working-memory capacities for object-location information and potential differential effects of memory load and additional context cues. An age-related deficit in visuospatial working-memory maintenance was found that became more pronounced with increasing task demands. The MCI group additionally showed reduced maintenance of bound information, i.e., object-location associations, again especially at elevated memory load. No effects of contextual cueing were found. The current findings indicate that working memory should be considered when screening patients for suspected MCI and monitoring its progression.19 p

Age differences in neural correlates of route encoding and route recognition.

Contains fulltext : 57971.pdf (publisher's version ) (Closed access)Spatial memory deficits are core features of aging-related changes in cognitive abilities. The neural correlates of these deficits are largely unknown. In the present study, we investigated the neural underpinnings of age-related differences in spatial memory by functional MRI using a navigational memory task with route encoding and route recognition conditions. We investigated 20 healthy young (18-29 years old) and 20 healthy old adults (53-78 years old) in a random effects analysis. Old subjects showed slightly poorer performance than young subjects. Compared to the control condition, route encoding and route recognition showed activation of the dorsal and ventral visual processing streams and the frontal eye fields in both groups of subjects. Compared to old adults, young subjects showed during route encoding stronger activations in the dorsal and the ventral visual processing stream (supramarginal gyrus and posterior fusiform/parahippocampal areas). In addition, young subjects showed weaker anterior parahippocampal activity during route recognition compared to the old group. In contrast, old compared to young subjects showed less suppressed activity in the left perisylvian region and the anterior cingulate cortex during route encoding. Our findings suggest that age-related navigational memory deficits might be caused by less effective route encoding based on reduced posterior fusiform/parahippocampal and parietal functionality combined with diminished inhibition of perisylvian and anterior cingulate cortices correlated with less effective suppression of task-irrelevant information. In contrast, age differences in neural correlates of route recognition seem to be rather subtle. Old subjects might show a diminished familiarity signal during route recognition in the anterior parahippocampal region

Neural underpinnings of autobiographical memory retrieval in Alzheimer's disease

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Autobiographical memory retrieval in patients with Alzheimer's disease

Item does not contain fulltextWith aging, the content of self-reported autobiographical memories shifts from episodic to semantic. Onset of Alzheimer's disease enhances this pattern, but the neural underpinnings of this change in Autobiographical Memory (AM), in particular the role of hippocampal degradation, are unknown. We employed fMRI contrasting autobiographical and semantic retrieval, in 22 healthy elderly and 21 Alzheimer's patients. The shift towards semantic characteristics in AM retrieval was indeed enhanced in patients. Both groups activated brain regions commonly involved in AM retrieval, including occipital association areas, medial temporal lobes, lateral temporal and midline prefrontal areas. When compared to controls, Alzheimer's patients showed enhanced activity in the left inferior frontal gyms (LIFG), ventromedial prefrontal cortex (vmPFC), right precuneus and left lingual gyrus. Activation of LIFG and vmPFC was significantly negatively correlated with hippocampal volume in patients only. Thus, we speculate that the linking function of the degraded hippocampus is taken over by the vmPFC: a shift recently observed during normal consolidation. This potentially compensatory process may support early Alzheimer's detection or prognosis