Time Of Dementia Research Articles

Love in a Time of Dementia

Love in a Time of Dementia

Evolution of prodromal Parkinson's disease and dementia with Lewy bodies: a prospective study.

Parkinson's disease has a long prodromal stage with various subclinical motor and non-motor manifestations; however, their evolution in the years before Parkinson's disease is diagnosed is unclear. We traced the evolution of early motor and non-motor manifestations of synucleinopathy from the stage of idiopathic rapid eye movement (REM) sleep behaviour disorder until defined neurodegenerative disease. During 2004-16, we recruited and then annually followed 154 polysomnography-proven patients with idiopathic REM sleep behaviour disorder, of whom 55 phenoconverted to defined parkinsonism or dementia. Longitudinal data on multiple prodromal features, including the Unified Parkinson's Disease Rating Scale parts I-III, quantitative motor tests, olfaction, colour vision, cognition, and autonomic functions were gathered annually (average = five follow-up visits, range: 2-12 years). The same measures were also assessed in 102 age- and sex-matched healthy control subjects. By looking backward from the time of dementia or parkinsonism diagnosis, we examined trajectories of each prodromal feature using mixed effect models. Based on analysis, olfactory loss was first to develop, with predicted onset >20 years before phenoconversion. This was followed by impaired colour vision, constipation, and erectile dysfunction, starting 10-16 years prior to phenoconversion. At 7-9 years before phenoconversion, slight urinary dysfunction and subtle cognitive decline could be detected. Among motor symptoms altered handwriting, turning in bed, walking, salivation, speech, and facial expression began to be disrupted starting 7-11 years prior to parkinsonism diagnosis, but remained mild until soon before phenoconversion. Motor examination abnormalities began 5-7 years before phenoconversion, with the alternate tap test having the longest interval (8 years before phenoconversion). Among cardinal motor phenotypes, bradykinesia appeared first, ∼5-6 years prior to phenoconversion, followed by rigidity (Year -3) and tremor (Year -2). With direct prospective evaluation of an idiopathic REM sleep behaviour disorder cohort during phenoconversion, we documented an evolution of prodromal manifestations similar to that predicted by pathological staging models, with predicted prodromal intervals as long as 20 years.

Review: Clinical, neuropathological and genetic features of Lewy body dementias.

Lewy body dementias are the second most common neurodegenerative dementias after Alzheimer's disease and include dementia with Lewy bodies and Parkinson's disease dementia. They share similar clinical and neuropathological features but differ in the time of dementia and parkinsonism onset. Although Lewy bodies are their main pathological hallmark, several studies have shown the emerging importance of Alzheimer's disease pathology. Clinical amyloid-β imaging using Pittsburgh Compound B (PiB) supports neuropathological studies which found that amyloid-β pathology is more common in dementia with Lewy bodies than in Parkinson's disease dementia. Nevertheless, other co-occurring pathologies, such as cerebral amyloid angiopathy, TDP-43 pathology and synaptic pathology may also influence the development of neurodegeneration and dementia. Recent genetic studies demonstrated an important role of APOE genotype and other genes such as GBA and SNCA which seem to be involved in the pathophysiology of Lewy body dementias. The aim of this article is to review the main clinical, neuropathological and genetic aspects of dementia with Lewy bodies and Parkinson's disease dementia. This is particularly relevant as future management for these two conditions may differ.

Involving people with dementia and their carers in dementia education for undergraduate healthcare professionals: a qualitative study of motivation to participate and experience.

A topic guide was developed to understand factors influencing motivation and retention. A purposeful sample of participant families, who had at least 12 months of involvement in the program, were selected from a cohort of 282 families and were invited to take part in an in-depth qualitative interview. Interviews were audio recorded, transcribed verbatim, and analyzed using thematic analysis. This was subsequently refined in an on-going process of analysis aided by the use of Nvivo 11. Interviewing stopped when thematic saturation was reached. Eighteen families took part in an in-depth qualitative interviews. Four themes were identified from the analysis. These themes were motivators, value to family, value to the person with dementia, and student factors. This study identifies underpinning factors that motivate families to join dementia education programs and the impact of such programs upon them. We found that engagement in such programs can have therapeutic benefits to participants, and do not cause harm. These findings can be used to strengthen recruitment and enhance family involvement in similar programs.

The effectiveness of creating an online life story book on persons with early dementia and their informal caregivers: a protocol of a randomized controlled trial

BackgroundDementia has a high burden for patients, informal caregivers and society. Given changes in care systems, more persons with dementia will live longer at home. However, living at home (with dementia) with a good quality of life is not easy to achieve. Dementia is often accompanied by neuropsychiatric symptoms like apathy, agitation, depression, and anxiety, which have a negative impact on quality of life. Whereas cognitive deterioration can hardly be influenced, it is possible to reduce neuropsychiatric symptoms. As autobiographical memories remain intact for a relatively long time in dementia, reminiscence interventions can promote feelings of pleasure and trust. The Online Life Story Book (OLSB) allows to digitally share memories (stories, pictures, video or audio fragments). The main objective is to study the effects of the OLSB on neuropsychiatric symptoms. The study has four secondary objectives: 1) to study the effectiveness of the intervention on the burden and quality of life of the primary informal caregiver; 2) to provide a preliminary health-economic evaluation; 3) to study the (time to) nursing home admittance as a longer term effect; 4) to provide a process evaluation.Methods and designA randomized controlled trial with individual randomization to one of two conditions is conducted: 1) intervention “Online Life Story Book”; 2) control condition (care as usual). Participants are persons with early dementia and their primary caregivers. In the intervention OLSB, a trained volunteer guides the participants through the process of putting together a timeline of their lives during 5 meetings within a period of 8-10 weeks. To assess the effects of the intervention on the primary outcome, neuropsychiatric symptoms, the Neuropsychiatric Inventory (NPI) will be assessed at three time points: before the intervention (baseline, T0), 3 months (T1) and 6 months (T2) post baseline.DiscussionWhen proven effective, the Online Life Story Book can be a valuable addition to the existing provision of care for persons with dementia and their informal caregivers.Trial registrationThis study has been approved by the Twente Medical Ethics Committee under the file number p16-04 (Dutch Trial Register: NTR5939, date of registration: 14 March 2016).

Distribution and Load of Amyloid-β Pathology in Parkinson Disease and Dementia with Lewy Bodies.

Parkinson disease (PD), Parkinson disease with dementia (PDD), and Dementia with Lewy bodies (DLB) differ clinically with regard to the presence and timing of dementia. In this postmortem study, we evaluated whether the burden and distribution pattern of amyloid-β (Aβ) pathology differs among these disease entities. We assessed Aβ phases and neuritic plaque scores in 133 patients fulfilling clinical diagnostic criteria for PD, PDD, and DLB, and determined the presence and load of Aβ pathology in 5 cortical and 4 subcortical regions in a subset of patients (n = 89) using a multispectral imaging system. Aβ phases and neuritic plaque scores were higher in DLB versus PDD (both p < 0.001) and in PDD vs PD patients (p = 0.020 and 0.022, respectively). Aβ pathology was more often observed in the entorhinal cortex, amygdala and putamen in DLB versus PDD patients; Aβ load was higher in both cortical and subcortical regions. PDD patients had more frequent Aβ pathology in temporal cortex and higher Aβ load in cortical regions and striatum versus PD patients. Our findings suggest that the load and extent of Aβ pathology may contribute to cognitive dysfunction in PDD and the early-stage severe dementia in DLB.

What do we know about eye movements in Alzheimer's disease? The past 37 years and future directions.

What do we know about eye movements in Alzheimer's disease? The past 37 years and future directions.

Cortical Lewy bodies and Aβ burden are associated with prevalence and timing of dementia in Lewy body diseases.

Our main objective was to determine the neuropathological correlates of dementia in patients with Lewy body disease (LBD). Furthermore, we used data derived from clinical, neuropathological and genetic studies to investigate boundary issues between Dementia with Lewy bodies (DLB) and Parkinson's disease with (PDD) and without (PDND) dementia. One hundred and twenty-one cases with a neuropathological diagnosis of LBD and clinical information on dementia status were included in the analysis (55 PDD, 17 DLB and 49 PDND). We carried out topographical and semi-quantitative assessment of Lewy bodies (LB), Aβ plaques and tau-positive neuropil threads (NT). The APOE genotype and MAPT haplotype status were also determined. The cortical LB (CLB) burden was the only independent predictor of dementia (OR: 4.12, P < 0.001). The total cortical Aβ plaque burden was an independent predictor of a shorter latency to dementia from onset of motor signs (P = 0.001). DLB cases had a higher LB burden in the parietal and temporal cortex, compared to PDD. Carrying at least one APOE ϵ4 allele was associated with a higher cortical LB burden (P = 0.02), particularly in the neocortical frontal, parietal and temporal regions. High CLB burden is a key neuropathological substrate of dementia in LBD. Elevated cortical LB pathology and Aβ plaque deposition are both correlated with a faster progression to dementia. The higher CLB load in the temporal and parietal regions, which seems to be a distinguishing feature of DLB, may account for the shorter latency to dementia and could be mediated by the APOE ϵ4 allele.

The pattern of cortical atrophy in Parkinson’s disease with mild cognitive impairment according to the timing of cognitive dysfunction

The density of Lewy bodies or the concurrent β-amyloid pathology would act as modulators in the relative timing of dementia during the course of Parkinson's disease. Depending on the temporal relationship between the onset of parkinsonism and that of cognitive impairment, patients with Parkinson's disease with mild cognitive impairment were divided into two groups of earlier (<1 year) and later (≥1 year) cognitive decline, and cortical atrophy patterns and correlation of gray matter and timing of cognitive decline were analyzed using voxel-based morphometry. The morphometric analysis showed that patients with earlier cognitive decline demonstrated greater cortical atrophy in the inferior parietal and orbitofrontal areas than did those with later cognitive decline. Additionally, the anatomical bases of the timing of their cognitive decline differed in terms of correlation patterns. These data suggest that the pathological burden in Parkinson's disease with mild cognitive impairment may be more severe in patients with earlier cognitive decline than in those with later cognitive decline, and that the neural basis corresponding to the timing of cognitive decline may differ in these patients.

HOLDING ONE ANOTHER (WELL, WRONGLY, CLUMSILY) IN A TIME OF DEMENTIA

Abstract: This essay takes a close look at a species of care that is particularly needed by people with progressive dementias but that has not been much discussed in the bioethics literature: the activity of holding the person in her or his identity. It presses the claim that close family members have a special responsibility to hold on to the demented person's identity for her or him, and offers some criteria for doing this morally well or badly. Finally, it considers how even those with dementia can hold others in their identities, and suggests that this kind of holding too can have great moral worth.

P-148: The resource utilization in dementia (RUD) instrument is valid to assess informal care time in dementia

P-148: The resource utilization in dementia (RUD) instrument is valid to assess informal care time in dementia

CHOLINESTERASE INHIBITORS AND ALZHEIMER'S DISEASE OUTCOMES

To the Editor: In their article, ‘‘Outcome of Alzheimer’s Disease: Potential Impact of Cholinesterase Inhibitors,’’ Gillette-Guyonnet and colleagues investigated the impact of cholinesterase inhibitors (CEIs) on the natural history of Alzheimer’s disease (AD) using rapid deterioration of cognitive function, institutionalization, and weight loss as outcomes (1). They found that the risk of all three outcomes was significantly decreased after one year’s use of CEIs. These results support the role of CEIs in improving AD outcomes. The authors excluded patients whose follow-up was discontinued for any reason, including death, and no information is provided about whether mortality rates varied significantly between treated and untreated groups. Previous studies of mortality in dementia have found that it is reduced (2) or unchanged (3) by CEI use. Trials investigating the use of galantamine in mild cognitive impairment were terminated due to a nonstatistically significant higher mortality rate in the treated arm (4). Given these varied findings, mortality is an important outcome to consider in the postmarket analysis of CEIs. We have conducted a retrospective mortality review of all patients seen at our Memory Clinics since their commencement in October 1999 to May 2005. Charts were systematically reviewed to obtain the cognitive diagnosis, the treatment given and its duration, past medical history, medication use including over-the-counter supplements, physical examination findings, and imaging results. Patient status (dead or alive) was assessed by direct contact with the patients, their families, their family doctors, and by searches of local obituary columns. Of the 440 patients seen, 248 were eligible for treatment with CEIs, based on a diagnosis of Alzheimer’s disease, Lewy body dementia, or mixed dementia. Of these, 22 patients were lost to follow-up. The remaining 226 were divided into two groups based on whether they had been treated with any CEI for a period longer than 3 months, with 26 who had declined treatment (group 1) and 200 who had received it (group 2). Group 1 (untreated) patients were significantly older at referral than those in group 2 (81.4 6 4.7 vs 75.9 6 8.0, t 5 3.049, p , .05), and group 1 contained a higher proportion of female participants than group 2 (p , .05). There were no differences in MiniMental State Exam score or comorbidities at baseline. There were 8/26 (30.8%) deaths in group 1, and 35/200 (17.6%) in group 2, a difference that was not significant. Within group 1, only high blood pressure was significantly more frequent among dead patients (p , .05). Group 2 was further subdivided based on the last medication taken: donepezil (n 5 97), rivastigmine (n 5 43), or galantamine (n 5 60). The mortality rates between the three subgroups were not significantly different. The size of our sample does not allow us to analyze the extent to which the age or sex difference between groups 1 and 2 accounted for our results. Schaufele (5) cites previous estimates of survival time in dementia from 5 to 10 years. The average time of follow-up in our population (from diagnosis to last in-clinic contact) was 25.7 months in group 1 and 26.9 in group 2. Our analysis shows no increased mortality in patients treated with CEIs compared with those who were not, or between patients receiving different CEIs. However, the number of untreated patients was small and prevents us from drawing firm conclusions. It is important to continue the postmarket evaluation of these drugs. Similar research in a larger population would be desirable to clarify the possible impact of CEIs on mortality in patients with dementia.

O1-05-02: Cognitive factors of dementia associated with Parkinson’s disease and Alzheimer’s disease

Background: Declines in executive function and visuospatial abilities have been suggested as specific cognitive features of dementia associated with Parkinson’s disease (PDD); however, characterization of cognitive deficits during transition between Parkinson’s disease (PD) and PDD have not been fully explored. Objective(s): To investigate different rates of cognitive decline in PDD compared to 1) nondemented PD and 2) Alzheimer’s disease (AD). Dementia groups were matched on dementia severity. Preclinical (prior to dementia diagnosis) versus post diagnosis epochs were determined from archival data. We hypothesized differential cognitive decline would reflect disease specific onset and progression as measured by Clinical Dementia Rating (CDR). Methods: 338 participants enrolled in a longitudinal study of aging and dementia and followed with annual clinical and cognitive assessments were studied (PD 66, PDD 136, AD 136). Dementia was rated using the CDR. A ninety-minute psychometric battery was administered annually. Factor analyses were used to characterize a 3-factor solution (verbal, visuospatial and working memory), indicating cross-sectional and longitudinal strengths and weaknesses by domain. Results/Conclusions: Compared to PD, patients with PDD begin with significantly lower scores on all cognitive indices and their rate of progression was significantly steeper throughout the study. Compared to AD, patients with PDD experienced similar rates of verbal memory decline, although AD performance was significantly worse at all points of assessment. Visuospatial and working memory abilities in AD patients were relatively preserved until time of dementia onset/diagnosis. In contrast, PDD visuospatial and working memory declines were steeper than AD prior to dementia diagnosis and then paralleled AD after diagnosis. PDD visuospatial and working memory performance were significantly worse than AD at all times or assessment. Further, variability in the preclinical phase of PDD, an index of disease severity, was significantly greater than in the AD group. It appears that visuospatial and working memory impairments are prominent features of preclinical PDD. After dementia onset, however, these features progress in a similar manner to AD. Controlling for motor slowing and depression did not change the overall pattern of results. These data support using domain specific testing strategies to diagnose early stage PDD.

Indices of neuropsychological functioning and decline over time in dementia

Analysis of performance on 22 neuropsychological tests in 58 patients with presumed dementia of the Alzheimer type and 58 with presumed multi-infarct dementia, and in subgroups reassessed 10 months later, provided useful indications of relative levels of success of various types of test as indices of neuropsychological functioning and decline over time in dementia. Short versions of the Token test were found to be amongst the best indices, and either can be recommended for inclusion in collections of tests used for clinical or research purposes in studies of dementia.

Awareness of time in dementia of the Alzheimer type.

A prospective study of 35 patients with moderate or mild dementia of the Alzheimer type was performed to assess and compare their awareness of time. A Mini-Mental Status Examination score was used to separate those 16 patients with mild dementia (range, 15 to 24) from those 19 with moderate dementia (range, 7 to 15). Each patient was scored on awareness of time. Those classified as moderate but not those with mild dementia showed significant loss of awareness of time.

Hospital survival time in dementia: A controlled study of the effect of marital status on the interval between first admission and death

AbstractThe influence of marital status on ‘hospital survival time’ (the interval between first admission and death) was investigated in a controlled study of hospital dementia patients. There was no evidence of a significant relationship between marital status and hospital survival time after controlling for age and sex differences. The presence of a supporting spouse did not apparently shorten hospital survival time or postpone admission. Mortality following admission was analysed during the period of the study 1971–86. The probability of death during the six months following first admission was 45% for males and 32% for female patients (patients of all marital status combined), and the respective 12‐month figures were 59% and 44%. The median hospital survival time for married male and female patients was 0.6 years and 1.8 years, which suggests that first admission to hospital occurred as a late event. It follows that additional community support to families may not be effective in further reducing the demand for hospital care during the terminal stages of dementia.

Simple and choice reaction time in dementia: Clinical implications

The present study investigated differences between normal elderly subjects matched for age and education and patients with dementia of the Alzheimer's type (DAT) on two measures of reaction time (RT). Statistically significant group differences clearly demonstrate that normal elderly subjects have faster RT than subjects with senile dementia on all RT tasks. The DAT patients were most clearly differentiated in terms of overall group means and clinical classification from their age-matched counterparts on the choice RT task. Eleven of 12 (92%) DAT patients displayed choice RT's 2 or more standard deviations above those of age-matched normals. While both RT measures were discriminative between patients and normals, the overall results argue for increased sensitivity when choice is required in RT in accessing the cognitive deficits in DAT.