The risk of criminal behavior in the elderly and patients with neurodegenerative disease.

Behavioral changes are commonly observed in patients with dementia and can lead to criminal offenses, even without a history of criminal or antisocial behavior. Due to the growth of the aging population, this poses a rising problem to deal with for the criminal justice system and in general for society. Criminal behavior may include minor crimes such as theft or traffic violations, but also serious crimes such as physical abuse, sexual offense, or murder. In the assessment of criminal behavior among elderly (first-time) offenders, it is important to be aware of possible neurodegenerative diseases at the time of the crime. This book chapter provides an overview on criminal behavior in the elderly and specifically discusses existing literature on patients suffering from a neurodegenerative disease, including Alzheimer disease, vascular dementia, frontotemporal dementia, Parkinson disease, and Huntington disease. Each section is introduced by a true case to illustrate how the presence of a neurodegenerative disease may affect the criminal judgment. The chapter ends with a summary, multifactorial model of crime risk, future perspectives, and concluding remarks.

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.

The role of the orbitofrontal cortex in cognition and behavior.

The orbitofrontal cortex (OFC) plays a crucial role in behavior and is a common site for damage due to different types of injuries, e.g., closed head injuries, cerebrovascular accidents, tumors, neurosurgical interventions. Despite the (severe) behavioral changes following OFC lesions, persons with damage to the OFC appear to be cognitively intact, i.e., at least when assessed by means of standard neuropsychological tests. Meanwhile, neuropsychological tests addressing reversal learning, gambling, and social cognition show a decline in these patients. The goal of the present review is to link the performance of these latter neuropsychological tests to behavior. The results suggest that in patients with orbitofrontal lesions, reversal learning is more associated with behavioral disinhibition and that impairment in recognition of expressed emotion is more associated with social inappropriate behavior. The faux pas test (theory of mind) appears not to be sensitive to orbitofrontal lesions. Future studies should involve a larger numbers of patients with well-defined locations in the OFC and should integrate specific neuropsychological tests and quantitative behavioral measures to better understand the contribution of the OFC to cognition and behavior.

The perception of sexuality in older adults and its relationship with cognitive functioning.

OBJECTIVES: Investigating whether cognitive functioning is associated with the perception of one's sexuality in old age. DESIGN: Cross-sectional analysis, using observation cycle 2005/2006 of the population-based prospective cohort of the Longitudinal Aging Study Amsterdam. SETTING: Municipal registries in three Dutch regions. PARTICIPANTS: 1,908 older adults (mean [standard deviation] age: 71 [8.87] years; 54% women). MEASUREMENTS: Sexuality and intimacy were assessed using four questions. Four cognitive domains were assessed: general cognitive functioning (Mini-Mental State Examination), memory performance (Auditory Verbal Learning Test), processing speed (Coding Task), and fluid intelligence (Raven's Coloured Progressive Matrices). Multinomial regression analysis was used, with sexuality as outcome. The interaction effect between gender and sexuality was also tested. RESULTS: Lower fluid intelligence was associated with perceiving sexuality as unimportant; lower general cognitive functioning was associated with perceiving sexuality as unimportant; and lower immediate memory recall was associated with evaluating sexual life as unpleasant. Associations were also found between lower fluid intelligence, processing speed, and general cognitive functioning, and agreeing with sexuality no longer being important. Lower processing speed, general cognitive functioning, and delayed memory recall were associated with disagreeing with a remaining need for intimacy when getting older. Finally, the association between fluid intelligence and perceiving sexuality as important, and the association between immediate memory recall score and evaluating sexual life as pleasant, was only significant in women. The association between lower general cognitive functioning and perceiving sexuality as unimportant seemed stronger in women compared with men. CONCLUSIONS: Higher cognitive functioning was associated with the way in which older people perceive their current sexuality.

Feelings of loneliness, but not social isolation, predict dementia onset: results from the Amsterdam Study of the Elderly (AMSTEL).

BACKGROUND: Known risk factors for Alzheimer's disease and other dementias include medical conditions, genetic vulnerability, depression, demographic factors and mild cognitive impairment. The role of feelings of loneliness and social isolation in dementia is less well understood, and prospective studies including these risk factors are scarce. METHODS: We tested the association between social isolation (living alone, unmarried, without social support), feelings of loneliness and incident dementia in a cohort study among 2173 non-demented community-living older persons. Participants were followed for 3 years when a diagnosis of dementia was assessed (Geriatric Mental State (GMS) Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT)). Logistic regression analysis was used to examine the association between social isolation and feelings of loneliness and the risk of dementia, controlling for sociodemographic factors, medical conditions, depression, cognitive functioning and functional status. RESULTS: After adjustment for other risk factors, older persons with feelings of loneliness were more likely to develop dementia (OR 1.64, 95% CI 1.05 to 2.56) than people without such feelings. Social isolation was not associated with a higher dementia risk in multivariate analysis. CONCLUSIONS: Feeling lonely rather than being alone is associated with an increased risk of clinical dementia in later life and can be considered a major risk factor that, independently of vascular disease, depression and other confounding factors, deserves clinical attention. Feelings of loneliness may signal a prodromal stage of dementia. A better understanding of the background of feeling lonely may help us to identify vulnerable persons and develop interventions to improve outcome in older persons at risk of dementia.

Cognitive functioning and its influence on sexual behavior in normal aging and dementia.

OBJECTIVE: Motivational aspects, emotional factors, and cognition, all of which require intact cognitive functioning may be essential in sexual functioning. However, little is known about the association between cognitive functioning and sexual behavior. The aim of this article is to review the current evidence for the influence of cognitive functioning on sexual behavior in normal aging and dementia. METHODS: A systematic literature search was conducted in PubMed, Ovid, Cochrane, and PsycINFO databases. The databases were searched for English language papers focusing on human studies published relating cognitive functioning to sexual behavior in the aging population. Keywords included sexual behavior, sexuality, cognitive functioning, healthy elderly, elderly, aging and dementia. RESULTS: Eight studies fulfilled our inclusion criteria. Of these studies, five included dementia patients and/or their partners, whereas only three studies included healthy older persons. Although not consistently, results indicated a trend that older people who are not demented and continue to engage in sexual activity have better overall cognitive functioning. Cognitive decline and dementia seem to be associated with diminished sexual behavior in older persons. CONCLUSIONS: The association between cognitive functioning and sexual behavior in the aging population is understudied. The results found are inconclusive.

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

UNLABELLED: Inflammatory mechanisms, like microglial activation, could be involved in the pathogenesis of Alzheimer's disease (AD). (R)-[(11)C]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)-[(11)C]PK11195 binding is present in AD and mild cognitive impairment (MCI), currently also known as "prodromal AD." METHODS: Nineteen patients with probable AD, 10 patients with prodromal AD (MCI), and 21 healthy control subjects were analyzed. Parametric images of binding potential (BP(ND)) of (R)-[(11)C]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 BP(ND) and cognition were evaluated using Pearson correlation coefficients. RESULTS: Voxel-wise statistical parametric mapping (SPM) analysis showed small clusters of significantly increased (R)-[(11)C]PK11195 BP(ND) 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)-[(11)C]PK11195 BP(ND) between clinically stable prodromal AD patients and those who progressed to dementia, and BP(ND) did not correlate with cognitive function. CONCLUSION: Microglial activation is a subtle phenomenon occurring in AD.

Microglial activation in healthy aging.

Healthy brain aging is characterized by neuronal loss and decline of cognitive function. Neuronal loss is closely associated with microglial activation and postmortem studies have indeed suggested that activated microglia may be present in the aging brain. Microglial activation can be quantified in vivo using (R)-[(11)C]PK11195 and positron emission tomography. The purpose of this study was to measure specific binding of (R)-[(11)C]PK11195 in healthy subjects over a wide age range. Thirty-five healthy subjects (age range 19-79 years) were included. In all subjects 60-minute dynamic (R)-[(11)C]PK11195 scans were acquired. Specific binding of (R)-[(11)C]PK11195 was calculated using receptor parametric mapping in combination with supervised cluster analysis to extract the reference tissue input function. Increased binding of (R)-[(11)C]PK11195 with aging was found in frontal lobe, anterior and posterior cingulate cortex, medial inferior temporal lobe, insula, hippocampus, entorhinal cortex, thalamus, parietal and occipital lobes, and cerebellum. This indicates that activated microglia appear in several cortical and subcortical areas during healthy aging, suggesting widespread neuronal loss.

The role of extracerebral cholesterol homeostasis and ApoE e4 in cognitive decline.

We examined the associations between extracerebral markers of cholesterol homeostasis and cognitive decline over 6 years of follow-up, and studied the modifying effect of apolipoprotein E (ApoE) e4. Data were collected in the Longitudinal Aging Study Amsterdam (n = 967, with longitudinal data on cognition, ages ≥ 65 years) and analyzed using linear mixed models. General cognition (Mini-Mental State Examination; MMSE), memory (Auditory Verbal Learning Test), and information processing speed (Coding task) were measured. The results show that ApoE e4 was a significant effect modifier. Significant associations were found only in ApoE e4 noncarriers (n = 718). We found a nonlinear negative association between the ratio of lanosterol to cholesterol (≤ 189.96 ng/mg), a marker for cholesterol synthesis, and general cognition. Lower cholesterol absorption, i.e., lower ratios of campesterol and sitosterol to cholesterol, as well as a higher rate of cholesterol synthesis relative to absorption were associated with lower information processing speed. In ApoE e4 carriers, the negative association between the ratio of campesterol to cholesterol and memory reached borderline significance. Future research should focus on the interaction between (disturbed) cholesterol homeostasis and ApoE e4 status with respect to dementia.

Role of lipoproteins and inflammation in cognitive decline: do they interact?

The aim of this study was to examine the associations between high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, and cognition and focus on the modifying effect of inflammation. Data were collected in the population-based Longitudinal Aging Study Amsterdam and analyzed with mixed linear models. The sample comprised 1003 persons ≥ 65 years with cognitive data on at least 2 occasions over 6 years of follow-up. Cognition was measured with the Mini-Mental State Examination (general cognition), Auditory Verbal Learning Test (memory), and Coding Task (information processing speed). We found an independent association between high HDL cholesterol and better memory performance. In addition, low LDL cholesterol was predictive of worse general cognitive performance and faster decline on information processing speed. Furthermore, a significant modifying effect of inflammation (C-reactive protein, α-antichymotrypsin) was found. A negative additive effect of low LDL cholesterol and high inflammation was found on general cognition and memory performance. Also, high triglycerides were associated with lower memory performance in those with high inflammation. Thus, a combination of these factors may be used as markers of prolonged lower cognitive functioning.

Advance directives for euthanasia in dementia: how do they affect resident care in Dutch nursing homes? Experiences of physicians and relatives.

OBJECTIVES: To gain insight into how advance directives for euthanasia affect resident care in Dutch nursing homes. DESIGN: Survey of elderly care physicians and additional qualitative interviews with a selection of elderly care physicians and relatives of people with dementia who had an advance directive for euthanasia. SETTING: Dutch nursing home practice. PARTICIPANTS: Four hundred thirty-four elderly care physicians completed the general part of the questionnaire; 110 physicians provided case histories. Interviews were conducted with 11 physicians and eight relatives. MEASUREMENTS: The questionnaire contained general questions about the incidence of advance directives for euthanasia in people with dementia. A second part involved questions about the most recent case of a person with dementia and an advance directive for euthanasia who had died. The interviews with elderly care physicians and relatives focused on further exploration of the decision-making process regarding adherence to the advance directive for euthanasia. RESULTS: Despite law-based possibilities, advance directives for euthanasia of people with dementia were rarely adhered to, although they seem to have a supportive role in setting limitations on life-sustaining treatments. Elderly care physicians and relatives were found to be reluctant to adhere to advance directives for euthanasia. Not being able to engage in meaningful communication played a crucial role in this reluctance. CONCLUSION: Advance directives for euthanasia are never adhered to in the Netherlands in the case of people with advanced dementia, and their role in advance care planning and end-of-life care of people with advanced dementia is limited. Communication with the patient is essential for elderly care physicians to consider adherence to an advance directive for euthanasia of a person with dementia.

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.

User evaluation of the DEMentia-specific Digital Interactive Social Chart (DEM-DISC). A pilot study among informal carers on its impact, user friendliness and, usefulness.

OBJECTIVE: The need for information about the disease and coping with the consequences, as well as on available care and welfare services, is frequently unmet in people with dementia and their carers. To provide carers of community-dwelling people with dementia with tailored information, the DEMentia-specific dynamic interactive social chart (DEM-DISC) was developed. The impact on the daily life of people with dementia and their carers, the user friendliness and usefulness of a first prototype of DEM-DISC was evaluated. METHOD: DEM-DISC was tested among informal carers in a pretest-posttest control group design. Fourteen informal carers could access DEM-DISC at home during a two month period. Fourteen controls did not have access to DEM-DISC. Data were collected by separate interviews with people with dementia and carers at pretest and posttest, by means of digital logging, short telephone interviews, and a bottleneck checklist during the intervention period. RESULTS: People with dementia and informal carers reported more met and less unmet needs after DEM-DISC use and carers in the experimental group reported higher levels of competence than controls. Although they were not explicitly satisfied with this first prototype of DEM-DISC, carers found DEM-DISC easy to learn and relatively user friendly. Carers acknowledged the system's benefits. CONCLUSION: The positive effects might be caused by the systematic and tailored individual way of information provisioning by DEM-DISC. It would be worthwhile to continue to develop DEM-DISC and to conduct randomized trials on the impact on patients and carers as well as the impact on nursing home admission and healthcare expenditure.

Advance directives in dementia: issues of validity and effectiveness.

BACKGROUND: Although advance directives may seem useful instruments in decision-making regarding incompetent patients, their validity in cases of dementia has been a much debated subject and little is known about their effectiveness in practice. This paper assesses the contribution of advance directives to decision-making in the care of people with dementia, with a special focus on non-treatment directives and directives for euthanasia. METHODS: The relevant problems from the ethical debate on advance directives in cases of dementia are summarized and we discuss how these relate to what is known from empirical research on the validity and effectiveness of advance directives in the clinical practice of dementia care. RESULTS: The ethical debate focuses essentially on how to respond to the current wishes of a patient with dementia if these contradict the patient's wishes contained in an advance directive. The (very limited) empirical data show that the main factors in medical decision-making in such cases is not the patient's perspective but the medical judgment of the physician and the influence of relatives. Insight into the experiences and wishes of people with dementia regarding advance directives is totally lacking in empirical research. CONCLUSIONS: Ethics and actual practice are two "different worlds" when it comes to approaching advance directives in cases of dementia. It is clear, however, that the use of advance directives in practice remains problematic, above all in cases of advance euthanasia directives, but to a lesser extent also when non-treatment directives are involved. Although generally considered valid, their effectiveness seems marginal. Further empirical research into the (potential) value of advance directives in dementia care is recommended.

What do community-dwelling people with dementia need? A survey of those who are known to care and welfare services.

BACKGROUND: The aging society will bring an increase in the number of people with dementia living in the community. This will mean a greater demand on care and welfare services to deliver efficient and customized care, which requires a thorough understanding of subjective and objective care needs. This study aims to assess the needs of community-dwelling people with dementia as reported by themselves and by their informal carers. The study also aims to give insight into the service use and gaps between needs and the availability of services. METHODS: 236 community-dwelling people with dementia and 322 informal carers were interviewed separately. (Un)met needs were assessed using the Camberwell Assessment of Needs for the Elderly (CANE). RESULTS: Most unmet needs were experienced in the domains of memory, information, company, psychological distress and daytime activities. People with dementia reported fewer (unmet) needs than their carers. Type and severity of dementia, living situation and informal carer characteristics were related to the number of reported needs. CONCLUSIONS: This study showed a large number of unmet needs in dementia. Reasons for unmet needs are lack of knowledge about the existing service offer, a threshold to using services and insufficient services offer. These results provide a good starting point for improving community care for people with dementia.

Classification models for early identification of persons at risk for dementia in primary care: an evaluation in a sample aged 80 years and older.

AIM: To evaluate previously developed classification models to make implementation in primary care possible and aid early identification of persons at risk for dementia. METHODS: Data were drawn from the OCTO-Twin study. At baseline, 521 persons >or= 80 years of age were nondemented, and for 387 a blood sample was available. Predictors of dementia were collected and analyzed in initially nondemented persons using generalized estimating equations and Cox survival analyses. RESULTS: In the basic model using predictors already known or easily obtained (basic set), the mean 2-year predictive value increased from 6.9 to 28.8% in persons with memory complaints and an MMSE score

Inflammatory markers in AD and MCI patients with different biomarker profiles.

OBJECTIVE: The aim of this study was to demonstrate the involvement of the inflammatory proteins IL-6, ACT and CRP early in the pathology process of AD in patients with mild cognitive impairment (MCI) and AD. METHODS: IL-6, ACT, CRP, Abeta42, phospho-tau (p-tau) and total tau concentrations in serum and CSF of 145 patients with probable AD and 67 patients with MCI were measured by sandwich ELISA. MCI patients were characterized as high- respectively low-risk MCI according to their Abeta42/tau risk profile. RESULTS: CSF and serum CRP levels were significantly higher in MCI compared to AD patients after adjustment for age, ApoE epsilon4 genotype and cardiovascular diseases (p<0.01). This difference remained present in patients with a low-risk biomarker profile for AD after adjustment for abovementioned covariates. CSF IL-6 levels were also significantly higher in MCI patients with a low-risk CSF profile. CONCLUSIONS: These findings suggest that inflammatory processes might be involved in early stages of AD, even before Abeta and tau changes are present in CSF of MCI patients.

Somatic chronic diseases and 6-year change in cognitive functioning among older persons.

The influence of seven highly prevalent somatic chronic diseases on changes in cognitive functioning is investigated in older persons in a prospective design covering a 6-year follow-up period. The data were collected as part of the Longitudinal Aging Study Amsterdam (LASA). The associations between chronic diseases and cognitive functioning during 6 years of follow-up were analyzed among 1358 respondents (age 62-85) using generalized estimated equations (GEE). Cognitive tests were used to assess: general cognitive functioning, fluid intelligence, information processing speed and memory performance. In the fully adjusted models diabetes mellitus, stroke and peripheral artherosclerosis were associated with cognitive decline during a 6-year follow-up period in older persons. In the unadjusted models cardiac disease was negatively associated with memory function. However, after the correction for possible confounders this association became positive. Cancer was also associated with better memory function. A faster decline in especially memory function was found for diabetes mellitus, stroke, cancer, and peripheral artherosclerosis. The study shows that in older persons specific chronic diseases (diabetes mellitus, stroke, cancer, and peripheral artherosclerosis) are associated with decline in one or more domains of cognitive functioning during a 6-year follow-up period. These findings further stress that careful clinical evaluation of cognitive functioning in older persons with these diseases is required in order to provide adequate care.

Anxiety symptoms and cognitive performance in later life: results from the longitudinal aging study Amsterdam.

OBJECTIVES: This study investigates whether, and if so how, anxiety symptoms are related to cognitive decline in elderly persons and whether anxiety symptoms precede cognitive decline. METHOD: Data were obtained from the Longitudinal Aging Study Amsterdam. Anxiety symptoms were measured with the Hospital Anxiety and Depression Scale. General cognitive functioning was measured with the Mini-Mental State Examination, episodic memory with the Auditory Verbal Learning Test, fluid intelligence with the Raven's Coloured Progressive Matrices and information processing speed with the coding task. Multilevel analyses were performed to investigate the relationship between anxiety symptoms and cognitive decline over 9 years, taking into account confounding variables. RESULTS: Although not consistent across all dimensions of cognitive functioning, a curvilinear effect of anxiety on cognitive performance was found. Furthermore, we found that previous measurement of anxiety symptoms were not predictive of cognitive decline at a later time-point. CONCLUSION: This study suggests that the effect of anxiety on cognition depends on the severity of the present anxiety symptoms with mild anxiety associated with better cognition, whereas more severe anxiety is associated with worse cognition. The effect of anxiety symptoms on cognitive functioning seems to be a temporary effect, anxiety is not predictive of cognitive decline.