Microglial activation in Alzheimer's disease: an (R)-[11C]PK11195 positron emission tomography study

AbstractInflammatory mechanisms, like microglial activation, could be involved in the pathogenesis of Alzheimer's disease (AD). (R)-[11C]PK11195 (1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl)-3-isoquinolinecarboxamide), a positron emission tomography (PET) ligand, can be used to quantify microglial activation in vivo. The purpose of this study was to assess whether increased (R)-[11C]PK11195 binding is present in AD and mild cognitive impairment (MCI), currently also known as “prodromal AD.”MethodsNineteen patients with probable AD, 10 patients with prodromal AD (MCI), and 21 healthy control subjects were analyzed. Parametric images of binding potential (BPND) of (R)-[11C]PK11195 scans were generated using receptor parametric mapping (RPM) with supervised cluster analysis. Differences between subject groups were tested using mixed model analysis, and associations between BPND and cognition were evaluated using Pearson correlation coefficients.ResultsVoxel-wise statistical parametric mapping (SPM) analysis showed small clusters of significantly increased (R)-[11C]PK11195 BPND in occipital lobe in AD dementia patients compared with healthy control subjects. Regions of interest (ROI)-based analyses showed no differences, with large overlap between groups. There were no differences in (R)-[11C]PK11195 BPND between clinically stable prodromal AD patients and those who progressed to dementia, and BPND did not correlate with cognitive function.ConclusionMicroglial activation is a subtle phenomenon occurring in AD

Diagnostic accuracy of consensus diagnostic criteria for frontotemporal dementia in a memory clinic population

Background/Aims: The goal of the present study was to evaluate the diagnostic accuracy of the core diagnostic criteria for frontotemporal dementia (FTD) [Neary D, et al: Neurology 1998;51:1546-1554] within a memory clinic population. Methods: The 5 core diagnostic criteria for FTD were operationalised in an informant-based written questionnaire. For a diagnosis of FTD the total clinical picture was weighted with findings on additional investigations and possible exclusion criteria, with follow-up of at least 1 year. Results: The operationalised core criteria for FTD had a sensitivity of 79% (95% CI = 57-92) and a specificity of 90% (95% CI = 85-94). Conclusion: The core diagnostic criteria for FTD applied in a caregiver questionnaire have good diagnostic accuracy among subjects without advanced dementia attending a memory clinic. This stresses the importance of the informant-based history in the differential diagnosis of dementia. Copyrigh

Early assessment of dementia: the contribution of different memory components

A broad memory test battery (reflecting explicit and implicit memory functioning) was administered to a heterogeneous sample of initially nondemented, community-dwelling elderly subjects. To examine the profile of preclinical dementia, subjects were tested twice: At baseline, all subjects were nondemented according to Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) criteria; 2 years later, a subgroup had developed dementia. Performance of the preclinically demented subjects was best characterized, relative to that of cognitively impaired subjects who did not develop dementia 2 years later, by an inability to benefit at recall from semantic relations and by absent repetition priming effects. The authors conclude that in addition to testing episodic memory functioning, it is important to be aware of semantic and implicit memory deficits in the early assessment of dementia. Copyright 2005 by the American Psychological Association

A right amygdalohippocampectomy: A diagnostic challenge

Objective Amygdalohippocampectomy (AHE) is the resective surgery for medically intractable mesial temporal lobe epilepsy. To date no study has investigated a wide range of neuropsychiatric symptoms in right AHE outpatients. Patients and methods Three patients with right AHE participated in this study. The control group are patients with cognitive complaints with no history of epilepsy or neurological impairment and no structural abnormalities on the MRI/CT. We expected no difference in verbal memory compared to the controls. Concerning affective Theory of Mind (ToM) we expect a difference between controls and AHE patients. In terms of behavior it is expected that coping and behavioral questionnaires do not significantly differ between AHE and controls, but that proxies of AHE patients do report more behavioral/psychiatric symptoms. Results No significant difference was found between groups concerning the cognitive functions. For affective ToM we did find a significant difference (p = 0.044). A significant difference for the use of more reassuring thoughts (p = 0.006) and a trend for less passive reactions on the coping questionnaire, suggesting an ‘active coping style’. Overall, AHE patients report fewer problems the self- reported questionnaires. Proxies of the AHE patients reported a trend for more behavioral disinhibition compared to proxy ratings of the control group. Conclusion Right AHE patients underestimate their behavioral and emotional changes due to self-awareness deficits. Ratings of significant others are of immense importance for the detection of psychiatric and behavioral problems. Lesions in the amygdala- orbitofrontal cortex connection disrupt the emotional network, which might explain our results

Initial complaints in frontotemporal lobar degeneration

Aims: Frontotemporal lobar degeneration (FTLD) is probably underrecognized. The goal of this study was to investigate initial complaints of both patients and their caregivers at first specialist referral. Also, we tried to assess whether misrecognition of symptoms contributed to diagnostic delay. Methods: The case notes of all patients diagnosed with FTLD at the VU University Medical Center, Alzheimer Center of Amsterdam, The Netherlands, since 1998 were retrospectively reviewed. Only patients of whom detailed information of first specialist referral was available were included. The diagnosis of FTLD was based on the clinical diagnostic criteria of Neary and Snowden, supported by ancillary investigations. Results: Forty-six patients with FTLD were included. Twenty-one patients had frontotemporal dementia (FTD), 17 semantic dementia (SD) and 8 progressive nonfluent aphasia (PA). The majority of the FTD patients presented without complaints or with somatic complaints and nearly a quarter of them expressed memory complaints. The presenting complaints of most of their caregivers differed from the patients' complaints and often consisted of cognitive complaints. In SD and PA, language problems but also forgetfulness were presented. Misrecognition of the initial symptoms in some cases seemed to have contributed to diagnostic delay. Conclusion: Presenting complaints in FTLD can be misleading. In our cohort, memory complaints occurred relatively often. A multidisciplinary approach, including a structured behavioral interview, is important to recognize symptoms of FTLD

Early life physical activity and cognition at old age

Physical activity has shown to be inversely associated with cognitive decline in older people. Whether this association is already present in early life has not been investigated previously. The association between early life physical activity and cognition was studied in 1,241 subjects aged 62-85 years, in a prospective population-based study. Physical activity between ages 15 and 25 years was asked retrospectively. The findings suggest a positive association between regular physical activity early in life and level of information processing speed at older age in men, not in women. The association could not be explained by current physical activity or other lifestyle factors. This finding supports the cognitive reserve hypothesis, and might suggest that early life physical activity may delay late-life cognitive deficits

Advance directives for euthanasia in dementia: Do law-based opportunities lead to more euthanasia?

Objective To obtain insight into current practices regarding compliance with advance directives for euthanasia (ADEs) in cases of incompetent patients with dementia in Dutch nursing homes, in light of the legal possibility offered by the new euthanasia law to perform euthanasia in these cases.Methods A written questionnaire was completed by 434 elderly care physicians (ECPs).Findings Over the years 2005-2006, many ECPs took care of patients with dementia and an ADE, actual life termination of these patients took place very rarely and never in incompetent patients. ECPs reported practical difficulties in determining the 'unbearableness' of the suffering and choosing the right moment of carrying out the ADE.Conclusions Although the enactment of the Dutch euthanasia law in theory provided a window of opportunity for euthanasia in incompetent patients with dementia and an ADE, it has not led to obvious changes in compliance with ADEs of this patient group in practice. Crucial in the reticent attitudes of ECPs appears to be the impossibility of patient-physician communication. This raises questions on the feasibility of the law on this point. In our opinion, the role of ADEs in end-of-life care of patients with advanced dementia in the Netherlands deserves serious reconsideration.Advance directives Dementia Euthanasia Nursing homes Questionnaires

The association between depressive symptoms and cognitive decline in community-dwelling elderly persons

Objective: To investigate whether depressive symptoms predict specific types of cognitive decline in order to elucidate the association between late life depression and cognitive decline. Background: Mechanisms underlying the association between late life depression and cognitive decline are still unclear. Method: Six hundred and forty-one elderly persons of the Longitudinal Aging Study Amsterdam (LASA) aged 70-85 were examined by means of two measurement occasions over a period of 3 years. Depressive symptoms were assessed by means of the CES-D. Various cognitive functions were examined using neuropsychological tests. Results: Depressive symptoms were associated with decline in speed of information processing over a 3-year period, whereas there was no association between depression and increasing memory impairment of global mental deterioration. Conclusion: These findings suggest that depressive symptoms are associated with subcortical pathology, most probable white matter lesions

Suffering from dementia - The patient's perspective: A review of the literature

Background: Among the general public there is a deep fear of developing dementia, which has led to an increasing number of people "at risk" seeking ways (such as advance directives) to avoid undergoing progressive mental decline. The views of people with dementia are vital in obtaining a real answer to the question of how the disease affects people's lives and whether it actually involves the suffering that so many fear. Method: A review of the international literature is provided on what is known about living through dementia from the patient's perspective. Results: A total of 50 papers met the inclusion criteria. The findings of these reviewed papers give insight into the impact of dementia and the ways that those who have it deal with its effects by using different coping strategies. The literature on the perspective of the patient gives no solid support to the widespread assumption that dementia is necessarily a state of dreadful suffering. Although the impact of dementia and the experiences of loss resulting in multiple "negative" emotions cannot be denied, our findings also indicate that people do not undergo the disease passively and use both emotion-oriented and problem-oriented coping strategies to deal with its challenges. The experiences of living through dementia as told by the sufferers appear to yield a more subtle picture than the assumptions made by the general public. Conclusion: The overview provides a good starting point for improving the adjustment of care to the experience and wishes of people with dementia