Nurturing syndrome: a form of pathological bereavement with delusions in Alzheimer's disease

We report the history and neuroimaging profile of two patients, CS and KC who developed an unusual bereavement reaction with delusions following the deaths of their husbands. Their neuropsychological profiles met criteria for dementia of Alzheimer type. The delusions about their husbands' existence were persistent despite a considerable passage of time after their deaths. SPECT investigation showed reduction of blood flow in the frontal area in both patients when compared with demented controls and in particular a significant reduction in perfusion was observed in the right frontal regions. We argue that this significant reduction of blood flow in the right frontal area, in the context of severe cognitive deterioration, might be responsible for their delusional reaction to bereavement which we interpret as result of reality monitoring and episodic memory failure.     

Consent recommendations for research and international data sharing involving persons with dementia

Consent is generally required for research and sharing rich individual-level data but presents additional ethical and legal challenges where participants have diminished decision-making capacity. We formed a multi-disciplinary team to develop best practices for consent in data-intensive dementia research. We recommend that consent processes for research and data sharing support decision-making by persons with dementia, protect them from exploitation, and promote the common good. Broad consent designed to endure beyond a loss of capacity and combined with ongoing oversight can best achieve these goals. Persons with dementia should be supported to make decisions and enabled to express their will and preferences about participation in advance of a loss of capacity. Regulatory frameworks should clarify who can act as a representative for research decisions. By promoting harmonization of consent practices across institutions, sectors, and countries, we hope to facilitate data sharing to accelerate progress in dementia research, care, and prevention.     

Palliative and aggressive end-of-life care for patients with dementia

OBJECTIVES: The goals of this study were to establish the frequency of palliative and aggressive treatment measures among patients with and without dementia during the last six months of life, to identify relationships between the severity of dementia and aggressive and palliative care, and to determine whether treatment patterns have changed over time. METHODS: Antemortem data for 279 patients with dementia and 24 control patients who were brought for autopsy in chronic care facilities between 1985 and 2000 were reviewed. The severity of dementia was defined by scores on the Clinical Dementia Rating scale. Data on use of systemic antibiotics (designated as an aggressive treatment measure) and on use of narcotic and nonnarcotic pain medications and nasal oxygen (defined as palliative measures) were collected from medical charts. RESULTS: Fifty-three percent of the patients with dementia and 46 percent of those without dementia had received systemic antibiotics. Fourteen percent of the patients with dementia and 38 percent of those without dementia had received narcotic pain medications. The prevalence of aggressive and palliative measures did not vary significantly with the severity of dementia. Eleven percent of the patients with dementia who died between 1991 and 1995 and 18 percent of those who died between 1996 and 2000 had received narcotic pain medications in the last six months of their lives. CONCLUSIONS: Use of systemic antibiotics is prevalent in the treatment of patients with end-stage dementia, despite the limited utility and discomfort associated with the use of these agents. That patients with severe dementia and those with milder cognitive impairment received similar treatment may be contrary to good clinical practice, given the poor prognosis of patients with severe dementia.     

Jargon dyslexia in an individual with semantic dementia: further evidence for task-specificity in phonological output

We report a patient with semantic dementia who demonstrated a very unusual dyslexia. He had a global loss of conceptual knowledge in the context of a fluent dysphasia and intact syntax. However, he did not have the surface dyslexia which is typical of semantic dementia; rather his reading impairment was characterized by speech production errors resulting in multiple neologisms. In a series of experiments it was established that input phonological and input orthographical processing were intact as was output phonology for naming and propositional speech. We demonstrate that our patient has a task-specific phonological deficit and we argue that reading and propositional speech rely upon dissociable phonological output systems. Thus we corroborate our earlier evidence of task-specific phonological output stores (Crutch and Warrington, 2001). We also document a greater difficulty with comprehending the written than the spoken word. We account for this pattern of performance in terms of our patient's attempting to read by the indirect phonological route, as with other semantic dementia patients, but suggest that this process is overridden by the task-specific speech production deficit.     

Diagnosing and managing patients with dementia

As the number of older Americans grows, the prevalence of dementia is increasing. Older patients who present to primary care offices often have some form of dementia, but various factors can cause the diagnosis to be missed or delayed. Physicians can work to proactively assess dementia in their patients and provide a timely diagnosis. The diagnostic process for dementia includes screening for pathology and, when indicated, conducting a cognitive evaluation and performing a differential diagnosis. Several brief but reliable tools are available to aid in screening and evaluating patients for dementia.     

Preserved Knowledge of Maps of Countries: Implications for the Organization of Semantic Memory

We describe two patients with selectively preserved knowledge of the category of countries. Following a series of cerebral infarcts, patient DB presented with severe perceptual impairment, including dense apperceptive agnosia, prosopagnosia, and topographical agnosia. Despite these deficits, he could effortlessly name countries from their outline maps. Patient WH, who suffered from semantic dementia, had severe naming and comprehension difficulties, with extremely sparse residual semantic knowledge. Remarkably, the category of countries was preserved. First, we argue that, for both patients, this category preservation occurs at a semantic level. Second, we discuss our findings in the context of three current models of category-specific effects (perceptual, ontogenetic, and evolutionary models). We argue that the perceptual model (Humphreys and colleagues) cannot easily accommodate our findings. By contrast, the ontogenetic (Warrington and colleagues) and evolutionary models (Caramazza and colleagues) can explain our findings. However, some modifications to both models are required. The ontogenetic model needs to envisage a spatial channel for the development of map knowledge, which is anatomically separate from channels of other categories of knowledge. The evolutionary model needs to envisage the possibility that some categories of knowledge, such as countries, may not be prewired, but learned during ontogenetic development.     

Preserved knowledge of maps of countries: implications for the organization of semantic memory

We describe two patients with selectively preserved knowledge of the category of countries. Following a series of cerebral infarcts, patient DB presented with severe perceptual impairment, including dense apperceptive agnosia,prosopagnosia, and topographical agnosia. Despite these deficits, he could effortlessly name countries from their outline maps. Patient WH, who suffered from semantic dementia, had severe naming and comprehension difficulties, with extremely sparse residual semantic knowledge. Remarkably, the category of countries was preserved. First, we argue that, for both patients, this category preservation occurs at a semantic level. Second, we discuss our findings in the context of three current models of category-specific effects (perceptual, ontogenetic, and evolutionary models). We argue that the perceptual model (Humphreys and colleagues) cannot easily accommodate our findings. By contrast, the ontogenetic (Warrington and colleagues) and evolutionary models (Caramazza and colleagues) can explain our findings. However, some modifications to both models are required. The ontogenetic model needs to envisage a spatial channel for the development of map knowledge, which is anatomically separate from channels of other categories of knowledge. The evolutionary model needs to envisage the possibility that some categories of knowledge, such as countries, may not be prewired, but learned during ontogenetic development.     

Background of the neuropathological site in neurocognitive decline in elderly schizophrenic patients

We herein report the neuropathological findings of a schizophrenic patient who showed cognitive decline and deterioration of psychiatric symptoms in his elderly years. In the neuropathological investigation in this case, Alzheimer‐type pathology and argyrophilic grain pathology were observed. Schizophrenic patients can sometimes show cognitive decline in later life as an intrinsic symptom. However, they may also be complicated with dementia in later life, although these complications in a clinical setting have not been well examined. Few reports have investigated whether or not schizophrenic patients are likely to be complicated with dementia, and the findings remain controversial. We confirmed relatively mild ageing changes neuropathologically in the present case. How much these pathological changes influenced his psychiatric symptoms is unclear, but these changes were thought to have some degree of relevance. We also discuss the relationship between schizophrenia and dementia. We should remain alert to the fact that even schizophrenic patients can contract neurodegenerative diseases as a dual diagnosis in their clinical course and that they can show complicated symptoms. Further investigations of the clinical‐pathological relationship between schizophrenia and dementia are thus needed.     

Assessing quality of life in dementia: Preliminary psychometric testing of the Quality of Life Assessment Schedule (QOLAS)

We adapted a generic, individualised, patient-centred quality of life (QOL) assessment technique, the Quality of Life Assessment Schedule (QOLAS) for use with patients with dementia. The QOLAS was administered to a group of patients with mild to moderate dementia alongside a number of other measures of well-being to assess its psychometric properties. Each patient's main carer also completed the QOLAS, giving a proxy rating of the QOL of the patient. The patients understood the interview and were able to describe their quality of life both qualitatively and quantitatively. In this preliminary study the QOLAS was demonstrated to have good validity (content, construct, and criterion) and good internal reliability. The carers rated the patients as having a worse QOL than did the patients themselves on all subdomains of the QOLAS. The results suggest that patients with mild to moderate dementia can rate their own QOL and that the QOLAS is a promising method for assessing QOL in this patient group. The discrepancy between the patients' own views and the views of their carers raises important issues about whether the patient or a proxy is the best judge of QOL in patients with dementia.     

APOE-ε4 in age-related memory complaints and Alzheimer's disease

APOE-ε4 has been consistently found to be frequent in patients with senile dementia of the Alzheimer type (SDAT). Since forgetfulness may represent an early stage of dementia, APOE-ε4 frequency can be expected to be high in such subjects, particularly in those who later develop dementia. We examined here the proportion of ε4 alleles in patients with SDAT (n = 179), controls (n = 154) and subjects with age-related memory complaints (ARMC, n = 167); 16 of them developed dementia of Alzheimer type and three of them dementia of vascular type. We also evaluated the relative risk of dementia (of Alzheimer type) in ARMC subjects who are ε4-carriers, using a Cox proportional hazards model. The APOE-ε4 allele frequency was 27% in SDAT, 25% in ARMC patients who became demented, 15% in ARMC subjects who remained such after at least 1 year of follow-up, and 10% in controls. APOE-ε4 allele was significantly more frequent in SDAT than in controls or than in stable ARMC (OR = 3.7 [2–6.3] and OR = 2.5 (1.5–4], respectively, p > 0.01). The risk of dementia in ARMC subjects carrying an ε4 allele was three-fold that of those without (expβ = 3.1 [0.98–10], p = 0.05). Older age at onset of memory decline and lower minimental scores at initial visit were also associated with development of dementia in ARMC subjects (exp β = 1.1 [1.0–1.2], p = 0.05 and exp = 0.76 [0.6–0.9]), p = 0.008). In conclusion, the APOE-ε4 allele was found to occur frequently in ARMC who subsequently develop dementia, therefore it can indicate a predisposition for dementia in such patients.     

Caregiver burden, health-related quality of life and coping in dementia caregivers: a comparison of frontotemporal dementia and Alzheimer's disease

Frontotemporal dementia (FTD) is the second most prevalent dementia after Alzheimer's disease (AD). We compared 29 FTD and 90 AD caregivers with respect to burden, health-related quality of life (HQoL) and coping. FTD caregivers were more burdened than AD caregivers, and caregivers of patients who were demented for shorter duration had lower HQoL. We furthermore compared the 29 FTD caregivers with 34 caregivers of institutionalized FTD patients to understand their specific caregiver issues. Caregivers of FTD patients institutionalized after shorter dementia duration were most burdened and affected in their HQoL. Overall, passive coping strategies were associated with increased burden and decreased HQoL. We recommend that FTD caregivers be offered more support than AD caregivers. Furthermore, we suggest that interventions target passive coping strategies.     

Animal-assisted therapy for people suffering from severe dementia

INTRODUCTION: The elderly represent the fastest growing population group in France. The care management of people suffering from dementia has become an important problem. Demented patients manifest behavioral problems, depression, apathy, impairment in social activities and language skill disorders. The literature contains few studies investigating animal-assisted therapy for demented patients. However, there is a clear need for psychological assistance for this population. In the management of such behavioural problems associated with dementia, we propose to develop a dog-assisted therapy. Three qualitative case studies are analysed to specify the perceptions of the therapist regarding animal-assisted therapy. SUBJECTS AND METHODOLOGY: This study is a qualitative pilot study. Subjects were two female and one male patients admitted in a nursing home. They were diagnosed with severe dementia. Their mean age was 94 years. All of them agreed to attend the dog therapy activities and informed consent from their family was requested. We met these patients 15 times over nine months. The meetings always took place in the same place for 30 min, once a week. The evaluation was based on the clinical observations of the psychologist. RESULTS: This study revealed many psychological benefits for patients with dementia. The animal-assisted therapy had a calming effect on the patients. It could well be helpful as a communication link during therapy sessions. The dog, because of its unconditional acceptance, increases the self-esteem of the patient and contributes to a more secure environment. The patients, who rarely interacted socially, increased their interactions with the dog. In spite of the lack of normal verbal use of language, nonverbal communication continues including touching and posture. Furthermore, patients verbalized that the dog was affectionate and they could identify themselves with it. CONCLUSIONS: This prospective study leads up to the conclusion that pet therapy could prove to be efficient. We conducted animal-assisted therapy sessions for patients with severe dementia and found that psychological assistance could be flexible enough, to meet the special needs of institutionalized persons suffering from dementia. The pet therapy programs may provide help for many patients, but the framework and conditions of this practice should be clearly defined, until the dog itself, can become the therapist.     

The Dementia Rating Scale in Alzheimer's disease,Huntington's disease and progressive supranuclear palsy

The Dementia Rating Scale (DRS) comprises a series of five subtests which assess attention, memory, initiation/perseveration, construction, and conceptualisation. It can be delivered in full in approximately 30 min, making it a useful test for the detection and estimation of the overall level of dementia. We analysed the pattern of subscale test scores in patients with cortical and subcortical dementias, who were matched for their overall level of dementia on this scale. Patients with dementia of Alzheimer's type were more impaired than patients with Huntington's disease (HD) and progressive supranuclear palsy (PSP) on the memory subtest, whereas patients with HD and PSP were more impaired on the initiation/perseveration subtest. This is evidence in favour of the concept of cortical and subcortical dementias as separate, although overlapping, entities. Qualitative differences in the pattern of cognitive impairment in these disorders can be detected with a brief cognitive status examination.     

DSM-III-R criteria for primary degenerative dementia and multi-infarct dementia [corrected]

Primary degenerative dementia (PDD) and multi-infarct dementia (MID) are the two most common categories of cognitive decline in old age. The definitions of these two clinical entities are currently based on clinical evaluation and on the exclusion of other underlying causes, and still lack a consensus. The DSM-III-R criteria are widely used for the diagnosis of dementia. However, their role in the differentiation between PDD and MID has not been thoroughly examined. A consecutive series of 98 demented patients who met the DSM-III-R criteria for dementia were admitted to a clinical study. Upon evaluating their type of dementia according to these criteria, 53 patients could not be diagnosed either as having PDD or MID. The DSM-III-R criteria for these two types of dementia are critically reviewed. Proposed modifications, aimed at refining their differential diagnostic role, are presented, enabling better allocation of demented patients into PDD, MID, or intermediate groups.     

Vitamin B12 deficiency in dementia and cognitive impairment: the effects of treatment on neuropsychological function

BACKGROUND: Vitamin B12 assay is part of the routine investigation of dementia, although few studies have investigated the effects of treatment on cognition. We examined the effects of B12 treatment on neuropsychological function and disease progression in patients presenting with dementia or cognitive impairment. METHODS: From 1432 patients who were assessed at the Bristol Memory Disorders Clinic, 125 patients with low serum B12 were identified. Sixty-six patients presenting with dementia, and 22 with cognitive impairment were seen for a second assessment after treatment. Changes in neuropsychological test scores were compared with those of patients with normal serum B12, matched by age and diagnosis. RESULTS: The majority of patients with low serum B12 had normal Hb and MCV values. We found no cases of reversible B12 deficiency dementia. The B12 treatment patients who presented with dementia showed no significant improvement, and no less deterioration, in their neuropsychological function than their matched group. However, a treatment effect was demonstrated among the patients presenting with cognitive impairment. These improved significantly compared to matched patients on the verbal fluency test (p<0.01). CONCLUSION: All patients with cognitive impairment should be investigated for B12 deficiency. Vitamin B12 treatment may improve frontal lobe and language function in patients with cognitive impairment, but rarely reverses dementia.     

Dementia and antiphospholipid antibodies

Antiphospholipid antibodies (aPLAb) may cause both focal ischemic and diffuse brain damage and may be associated with dementia. We have examined the relationship of aPLAb to dementia in the elderly. Blood samples were obtained from 87 consecutive patients with dementia (74 +/- 11 years old) and 69 controls (78 +/- 9 years old), residents of an old age home who were not overtly demented. Levels of aPLAb were measured by a standardized ELISA, utilizing cardiolipin as antigen, and we considered levels above 20 IgG antiphospholipid units (GPLU) as significantly elevated. We found that 5 of the 87 demented patients (6%), but none of the 69 controls, had significantly elevated aPLAb levels (p = 0.03, one-tailed Fisher's exact test). All the patients with high aPLAb levels were diagnosed clinically as having dementia of the Alzheimer type, except for 1 who had mixed dementia, and none had features of an immune-mediated disease. Thus, a small but significant number of patients with dementia have high levels of aPLAb. The role of the aPLAb in these patients, with apparently diffuse brain disease, is currently unknown.     

Neuropsychological markers of dementia on visual-spatial tasks: a comparison between Alzheimer's type and vascular forms of dementia.

The incidence of the "closing-in" phenomenon and of the tendency to give "primitive answers" on the Raven's Colored Matrices was studied in 50 normal subjects and in two groups of Alzheimer's type (n = 41) and of vascular (n = 35) dementia patients, carefully matched as for the overall severity of dementia and the degree of visual-spatial impairment. The aims of this research were to determine if these patterns of behavior can be considered as neuropsychological markers of dementia and if their incidence is similar in the two dementia groups. Results show that both the closing-in phenomenon and the tendency to give globalistic and odd responses on the Raven's Colored Matrices are good markers of dementia and that, in particular, they point to a degenerative, rather than to a vascular form of dementia. From the clinical point of view, these data suggest that a qualitative analysis of the patient's behavior can increase the diagnostic efficacy of neuropsychological tests and that neuropsychological markers of dementia point more to Alzheimer's disease (considered as the most prototypic form of dementia) than to a vascular form of dementia even when the two groups of patients are well balanced in terms of visual-spatial impairment and the overall severity of dementia.     

The relative frequency of "dementia of unknown etiology" increases with age and is nearly 50% in nonagenarians

CONTEXT: With the recent change in pathological criteria for Alzheimer disease (AD), a group of patients has emerged who do not meet pathological criteria for any well-characterized degenerative dementias. Whether these unclassified patients have vascular dementia or some other form of dementia is not known. OBJECTIVE: To determine the clinical characteristics, pathological substrate, and relative frequency of dementia not caused by well-characterized degenerative dementias. DESIGN/SETTING: Clinicopathological study of a prospectively observed sample of elderly nondemented and demented subjects recruited from our urban community. METHODS: In our series of 128 subjects with prospective neuropsychological evaluations as well as neuropathology, we identified 35 clinically nondemented subjects and 20 demented patients who did not meet pathological criteria for well-characterized degenerative dementias such as AD or dementia with Lewy bodies. The 20 demented patients were grouped together under the term dementia of unknown etiology (DUE). We compared clinical, genetic, neuropsychological, pathological, and neurochemical characteristics of the nondemented group, patients with DUE, and 28 patients with AD and no other pathological abnormality. RESULTS: Mean age at death for patients with DUE was 89.1 +/- 5.8 years compared with 79.9 +/- 11.4 years for AD (P<.001). Patients with AD and DUE did not differ in sex, risk factors, apolipoprotein E genotype, neuropsychological features, or neurological features. Hippocampal sclerosis (in 11 patients with dementia and no controls) and leukoencephalopathy (in 7 patients with dementia and 1 control) were associated with cognitive impairment; other vascular markers were not. Dementia of unknown etiology accounted for 5% of all cases of dementia among patients dying in their 70s, 21% for patients dying in their 80s, and 48% for patients dying in their 90s. CONCLUSIONS: A significant percentage of demented patients older than 80 years do not meet pathological criteria for AD or dementia with Lewy bodies. Hippocampal sclerosis and leukoencephalopathy are common in these patients but rare in clinically nondemented subjects.     

Are dexamethasone suppression test nonsuppression and thyroid dysfunction related to a family history of dementia in patients with major depression? An exploratory study.

OBJECTIVE: Recent data suggest that the low thyroid function syndrome in depression is nonspecific. They also suggest that depression may constitute a risk factor for the development of dementia, especially in atypical patients who have high rates of hypothalamo-pituitary-adrenal axis disorders. This study aimed to search for correlations among Dexamethasone Suppression Test (DST) cortisol levels, thyroid indices, and family history of dementia in patients with depression. METHODS: A sample of 30 patients, aged 21 to 60 years and suffering from major depression according to DSM-IV criteria, took part in the study. Three had a family history of dementia in first-degree relatives. We measured their serum levels of free T3, free T4, thyroid-stimulating hormone, thyroid binding inhibitory immunoglobulines, thyroglobulin antibodies, and thyroid microsomal antibodies (TMAs). We applied the 1-mg DST to all patients. The statistical analysis included 1-way multivariate analysis of covariance using t tests as the post hoc tests. RESULTS: Significantly higher levels of TMAs were found in patients with a family history of dementia, compared with those who did not have this family history. CONCLUSION: The results of this study suggest that a more pronounced autoimmune process may characterize depression patients with a family history of dementia.     

The prognostic significance of abnormalities seen on magnetic resonance imaging in late life depression: clinical outcome, mortality and progression to dementia at three years

OBJECTIVE. To study the course of depressive symptoms over 3 years, rate of dementia and mortality in relation to baseline neuroradiological abnormalities. DESIGN. Retrospective casenote analysis of 38 patients (of 44) who had a Magnetic Resonance Imaging (MRI) scan 3 years earlier. Twenty-two patients also received a detailed interview. RESULTS. Overall outcome was good for around two-thirds of the sample. Poorer clinical course was associated with lesions in pons and more than five Virchow Robins spaces in the corona radiata. Pontine raphe lesions and confluent periventricular lesions were associated with later dementia and with reduced survival from cardiovascular death. Males had more recurrences and a reduced survival. CONCLUSIONS. MRI lesions influence outcome, mortality and the onset of dementia. However, because they are quite common in elderly depressed patients they have limited utility on their own as predictors of outcome. The association of periventricular lesions with dementia is a new finding, and suggests that the site and type of lesions may be as important than the quality of them.