Systemic inflammation and delirium – important co-factors in the progression of dementia

PubMed Central

Cunningham, Colm

2014-01-01

It is widely accepted that inflammation plays some role in the progression of chronic neurodegenerative diseases such as Alzheimer’s disease but its precise role remains elusive. It has been known for many years that systemic inflammatory insults can signal to the brain to induce changes in CNS function, typically grouped under the syndrome of sickness behaviour. These changes are mediated via systemic and CNS cytokine and prostaglandin synthesis. When patients with dementia suffer similar systemic inflammatory insults, delirium is a frequent consequence. This profound and acute exacerbation of cognitive dysfunction is associated with poor prognosis: accelerating cognitive decline and shortening time to permanent institutionalization and death. Therefore a better understanding of how delirium occurs during dementia and how these episodes impact on existing neurodegeneration are now important priorities. The current review summarises the relationship between dementia, systemic inflammation and episodes of delirium and addresses the basic scientific approaches currently being pursued with respect to understanding acute cognitive dysfunction during aging and dementia. In addition, though there are limited studies on this subject, it is becoming increasingly clear that infections and other systemic inflammatory conditions do increase the risk of Alzheimer’s disease and accelerate the progression of established dementia. These data suggest that systemic inflammation is a major contributor to the progression of dementia and constitutes an important clinical target. PMID:21787328

Trajectories of depressive symptoms and their relationship to the progression of dementia.

PubMed

Barca, Maria Lage; Persson, Karin; Eldholm, Rannveig; Benth, Jūratė Šaltytė; Kersten, Hege; Knapskog, Anne-Brita; Saltvedt, Ingvild; Selbaek, Geir; Engedal, Knut

2017-11-01

The relationship between progression of Alzheimer's disease and depression and its underlying mechanisms has scarcely been studied. A sample of 282 outpatients with Alzheimer's disease (AD; 105 with amnestic AD and 177 with Alzheimer's dementia) from Norway were followed up for an average of two years. Assessment included Cornell Scale for Depression in Dementia and Clinical Dementia Rating Scale (CDR) at baseline and follow-up to examine the relationship between AD and depression. Additionally, MRI of the brain, CSF dementia biomarkers and APOE status were assessed at baseline. Progression of dementia was defined as the difference between CDR sum of boxes at follow-up and baseline (CDR-SB change). Trajectories of depressive symptoms on the Cornell Scale were identified using growth mixture modeling. Differences between the trajectories in regard to patients' characteristics were investigated. Three distinct trajectories of depressive symptoms were identified: 231 (82.8%) of the patients had stable low-average scores on the Cornell Scale (Class 1); 11 (3.9%) had high and decreasing scores (Class 2); and 37 (13.3%) had moderate and increasing scores (Class 3). All classes had average probabilities over 80%, and confidence intervals were non-overlapping. The only significant characteristic associated with membership in class 3 was CDR-SB change. Not all patients screened for participation were included in the study, but the included and non-included patients did not differ significantly. Some patients with amnestic MCI might have been misdiagnosed. A more rapid progression of dementia was found in a group of patients with increasing depressive symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

Measuring Family System Characteristics in Families Caring for Dementia Patients.

ERIC Educational Resources Information Center

Niederehe, George; And Others

This paper describes an ongoing study evaluating families that provide in-home care to elderly relatives wth dementia. Characteristics of the study, which include a focus on progressive senile dementia, use of a clinical approach, longitudinal design, descriptive nature, focus on the dyad of patient and primary caregiver, and use of videotaping…

Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease.

PubMed

Li, J; Wang, Y J; Zhang, M; Xu, Z Q; Gao, C Y; Fang, C Q; Yan, J C; Zhou, H D

2011-04-26

Growing evidence suggests that vascular risk factors (VRF) contribute to cognitive decline. The aim of this study was to investigate the impact of VRF on the conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD) dementia. A total of 837 subjects with MCI were enrolled at baseline and followed up annually for 5 years. The incidence of AD dementia was investigated. A mixed random effects regression model was used to analyze the association between VRF and the progression of MCI assessed with Mini-Mental State Examination and instrumental Activities of Daily Living. Cox proportional hazard models were used to identify the association between VRF and dementia conversion, and to examine whether treatment of VRF can prevent dementia conversion. At the end of the follow-up, 298 subjects converted to AD dementia, while 352 remained MCI. Subjects with VRF had a faster progression in cognition and function relative to subjects without. VRF including hypertension, diabetes, cerebrovascular diseases, and hypercholesterolemia increased the risk of dementia conversion. Those subjects with MCI in whom all VRF were treated had a lower risk of dementia than those who had some VRF treated. Treatment of individual VRF including hypertension, diabetes, and hypercholesterolemia was associated with the reduced risk of AD conversion. VRF increased the risk of incident AD dementia. Treatment of VRF was associated with a reduced risk of incident AD dementia. Although our findings are observational, they suggest active intervention for VRF might reduce progression in MCI to AD dementia.

Beyond the temporal pole: limbic memory circuit in the semantic variant of primary progressive aphasia.

PubMed

Tan, Rachel H; Wong, Stephanie; Kril, Jillian J; Piguet, Olivier; Hornberger, Michael; Hodges, John R; Halliday, Glenda M

2014-07-01

Despite accruing evidence for relative preservation of episodic memory in the semantic variant of primary progressive aphasia (previously semantic dementia), the neural basis for this remains unclear, particularly in light of their well-established hippocampal involvement. We recently investigated the Papez network of memory structures across pathological subtypes of behavioural variant frontotemporal dementia and demonstrated severe degeneration of all relay nodes, with the anterior thalamus in particular emerging as crucial for intact episodic memory. The present study investigated the status of key components of Papez circuit (hippocampus, mammillary bodies, anterior thalamus, cingulate cortex) and anterior temporal cortex using volumetric and quantitative cell counting methods in pathologically-confirmed cases with semantic variant of primary progressive aphasia (n = 8; 61-83 years; three males), behavioural variant frontotemporal dementia with TDP pathology (n = 9; 53-82 years; six males) and healthy controls (n = 8, 50-86 years; four males). Behavioural variant frontotemporal dementia cases with TDP pathology were selected because of the association between the semantic variant of primary progressive aphasia and TDP pathology. Our findings revealed that the semantic variant of primary progressive aphasia and behavioural variant frontotemporal dementia show similar degrees of anterior thalamic atrophy. The mammillary bodies and hippocampal body and tail were preserved in the semantic variant of primary progressive aphasia but were significantly atrophic in behavioural variant frontotemporal dementia. Importantly, atrophy in the anterior thalamus and mild progressive atrophy in the body of the hippocampus emerged as the main memory circuit regions correlated with increasing dementia severity in the semantic variant of primary progressive aphasia. Quantitation of neuronal populations in the cingulate cortices confirmed the selective loss of anterior cingulate von Economo neurons in behavioural variant frontotemporal dementia. We also show that by end-stage these neurons selectively degenerate in the semantic variant of primary progressive aphasia with preservation of neurons in the posterior cingulate cortex. Overall, our findings demonstrate for the first time, severe atrophy, although not necessarily neuronal loss, across all relay nodes of Papez circuit with the exception of the mammillary bodies and hippocampal body and tail in the semantic variant of primary progressive aphasia. Despite the longer disease course in the semantic variant of primary progressive aphasia compared with behavioural variant frontotemporal dementia, we suggest here that the neural preservation of crucial memory relays (hippocampal→mammillary bodies and posterior cingulate→hippocampus) likely reflects the conservation of specific episodic memory components observed in most patients with semantic variant of primary progressive aphasia. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Cache County Study on Memory in Aging: Factors Affecting Risk of Alzheimer's disease and its Progression after Onset

PubMed Central

Tschanz, JoAnn T.; Norton, Maria C.; Zandi, Peter P.; Lyketsos, Constantine G.

2014-01-01

The Cache County Study on Memory in Aging is a longitudinal, population-based study of Alzheimer's disease (AD) and other dementias. Initiated in 1995 and extending to 2013, the study has followed over 5,000 elderly residents of Cache County, Utah (USA) for over twelve years. Achieving a 90% participation rate at enrollment, and spawning two ancillary projects, the study has contributed to the literature on genetic, psychosocial and environmental risk factors for AD, late life cognitive decline, and the clinical progression of dementia after its onset. This paper describes the major study contributions to the literature on AD and dementia. PMID:24423221

The Cache County Study on Memory in Aging: factors affecting risk of Alzheimer's disease and its progression after onset.

PubMed

Tschanz, Joann T; Norton, Maria C; Zandi, Peter P; Lyketsos, Constantine G

2013-12-01

The Cache County Study on Memory in Aging is a longitudinal, population-based study of Alzheimer's disease (AD) and other dementias. Initiated in 1995 and extending to 2013, the study has followed over 5,000 elderly residents of Cache County, Utah (USA) for over twelve years. Achieving a 90% participation rate at enrolment, and spawning two ancillary projects, the study has contributed to the literature on genetic, psychosocial and environmental risk factors for AD, late-life cognitive decline, and the clinical progression of dementia after its onset. This paper describes the major study contributions to the literature on AD and dementia.

Cardiorespiratory Fitness is Associated with Atrophy in Alzheimer’s and Aging Over Two Years

PubMed Central

Vidoni, Eric D.; Honea, Robyn A.; Billinger, Sandra A.; Swerdlow, Russel H.; Burns, Jeffrey M.

2011-01-01

We sought to describe change in cardiorespiratory (CR) fitness over 2 years in those with early–stage Alzheimer’s disease (AD) and nondemented aging and assess the relationship of CR fitness with cognitive decline, brain atrophy and dementia progression. Individuals with early-stage AD (n=37) and without dementia (n=53) attended clinical evaluations, cognitive and exercise tests, and MRI at baseline and 2 years later. CR fitness was lower in those with AD over the study period. Lower baseline CR fitness was associated with progression of dementia severity in AD. Declining CR fitness over 2 years was associated with brain atrophy in AD, especially in the parahippocampus. In nondemented participants, there was a trend for lower baseline fitness to be related to cognitive decline. Both lower baseline CR fitness and declining CR fitness over 2 years were associated with regional brain atrophy. We conclude that CR fitness is chronically reduced in those with AD. Further in those with AD, CR fitness is associated with progression of dementia severity and brain atrophy in AD, suggesting a link between progression of dementia severity and cardiorespiratory health. PMID:21531480

Dementia Care at End of Life: Current Approaches.

PubMed

Bartley, Mairead M; Suarez, Laura; Shafi, Reem M A; Baruth, Joshua M; Benarroch, Amanda J M; Lapid, Maria I

2018-06-23

Dementia is a progressive and life-limiting condition that can be described in three stages: early, middle, and late. This article reviews current literature on late-stage dementia. Survival times may vary across dementia subtypes. Yet, the overall trajectory is characterized by progressive decline until death. Ideally, as people with dementia approach the end of life, care should focus on comfort, dignity, and quality of life. However, barriers prevent optimal end-of-life care in the final stages of dementia. Improved and earlier advanced care planning for persons with dementia and their caregivers can help delineate goals of care and prepare for the inevitable complications of end-stage dementia. This allows for timely access to palliative and hospice care, which ultimately improves dementia end-of-life care.

18F PET with flutemetamol for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).

PubMed

Martínez, Gabriel; Vernooij, Robin Wm; Fuentes Padilla, Paulina; Zamora, Javier; Flicker, Leon; Bonfill Cosp, Xavier

2017-11-22

18 F-flutemetamol uptake by brain tissue, measured by positron emission tomography (PET), is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and the confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using some amyloid biomarkers tests like 18 F-flutemetamol. These tests, added to the MCI core clinical criteria, might increase the diagnostic test accuracy (DTA) of a testing strategy. However, the DTA of 18 F-flutemetamol to predict the progression from MCI to Alzheimer's disease dementia (ADD) or other dementias has not yet been systematically evaluated. To determine the DTA of the 18 F-flutemetamol PET scan for detecting people with MCI at time of performing the test who will clinically progress to ADD, other forms of dementia (non-ADD) or any form of dementia at follow-up. The most recent search for this review was performed in May 2017. We searched MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), BIOSIS Citation Index (Thomson Reuters Web of Science), Web of Science Core Collection, including the Science Citation Index (Thomson Reuters Web of Science) and the Conference Proceedings Citation Index (Thomson Reuters Web of Science), LILACS (BIREME), CINAHL (EBSCOhost), ClinicalTrials.gov (https://clinicaltrials.gov), and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (http://www.who.int/ictrp/search/en/). We also searched ALOIS, the Cochrane Dementia & Cognitive Improvement Group's specialised register of dementia studies (http://www.medicine.ox.ac.uk/alois/). We checked the reference lists of any relevant studies and systematic reviews, and performed citation tracking using the Science Citation Index to identify any additional relevant studies. No language or date restrictions were applied to the electronic searches. We included studies that had prospectively defined cohorts with any accepted definition of MCI at time of performing the test and the use of 18 F-flutemetamol scan to evaluate the DTA of the progression from MCI to ADD or other forms of dementia. In addition, we only selected studies that applied a reference standard for Alzheimer's dementia diagnosis, for example, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. We screened all titles and abstracts identified in electronic-database searches. Two review authors independently selected studies for inclusion and extracted data to create two-by-two tables, showing the binary test results cross-classified with the binary reference standard. We used these data to calculate sensitivities, specificities, and their 95% confidence intervals. Two independent assessors performed quality assessment using the QUADAS-2 tool plus some additional items to assess the methodological quality of the included studies. Progression from MCI to ADD was evaluated in 243 participants from two studies. The studies reported data on 19 participants with two years of follow-up and on 224 participants with three years of follow-up. Nine (47.4%) participants converted at two years follow-up and 81 (36.2%) converted at three years of follow-up.There were concerns about participant selection and sampling in both studies. The index test domain in one study was considered unclear and in the second study it was considered at low risk of bias. For the reference standard domain, one study was considered at low risk and the second study was considered to have an unclear risk of bias. Regarding the domains of flow and timing, both studies were considered at high risk of bias. MCI to ADD;Progression from MCI to ADD at two years of follow-up had a sensitivity of 89% (95% CI 52 to 100) and a specificity of 80% (95% CI 44 to 97) by quantitative assessment by SUVR (n = 19, 1 study).Progression from MCI to ADD at three years of follow-up had a sensitivity of 64% (95% CI 53 to 75) and a specificity of 69% (95% CI 60 to 76) by visual assessment (n = 224, 1 study).There was no information regarding the other two objectives in this systematic review (SR): progression from MCI to other forms of dementia and progression to any form of dementia at follow-up. Due to the varying sensitivity and specificity for predicting the progression from MCI to ADD and the limited data available, we cannot recommend routine use of 18 F-flutemetamol in clinical practice. 18 F-flutemetamol has high financial costs; therefore, clearly demonstrating its DTA and standardising the process of the 18 F-flutemetamol modality is important prior to its wider use.

The ROSAS Cohort: A Prospective, Longitudinal Study of Biomarkers for Alzheimer's Disease. Strategy, Methods and Initial Results.

PubMed

de Mauléon, A; Soto, M; Kiyasova, V; Delrieu, J; Guignot, I; Galtier, S; Lilamand, M; Cantet, C; Lala, F; Sastre, N; Andrieu, S; Pueyo, M; Ousset, P J; Vellas, B

2017-01-01

The aims of the Research Of biomarkers in Alzheimer's diseaSe (ROSAS) study were to determine the biofluid and imaging biomarkers permitting an early diagnosis of Alzheimer's disease and better characterisation of cognitive and behavioural course of the pathology. This paper outlines the overall strategy, methodology of the study, baseline characteristics of the population and first longitudinal results from the ROSAS cohort. Longitudinal prospective monocentric observational study performed at the Alzheimer's disease Research centre in Toulouse. A total of 387 patients were studied and analyzed in 3 groups: 184 patients with dementia of Alzheimer's type, 96 patients with memory disorders without dementia (Mild Cognitive Impairment) and 107 patients without abnormal memory tests (control group), and were followed up during 4 years. Patient's sociodemographic characteristics, risk factors, medical conditions, previous and current medications, neuropsychological assessment and overall cognitive status were recorded. Blood and urine samples were collected at every year, Magnetic Resonance Imaging were performed at inclusion, after one year of follow-up and at the end of the study. At baseline, three different groups of the cohort differed interestingly in age, level of education, and in percentage of ApoEε4 carriers whereas the history of cardiovascular and endocrine pathologies were similar among the groups. During the follow-up period (3-4 years) 42 mild cognitive impairment patients (43.8%) progressed to dementia, 7 controls progressed into mild cognitive impairment and 1 patient in the control group converted from mild cognitive impairment group to dementia of Alzheimer's type group. During the first year of follow up, the incidence of progression from mild cognitive impairment to dementia of Alzheimer's type was 12.7 per 100, during the second year 33.9 per 100 and 46.7 per 100 for the third year. This paper presents the baseline characteristics of the unique French prospective monocenter study in which the natural course of dementia of Alzheimer's type was evaluated. Future analysis of blood and urine samples collection from the ROSAS study will permit to identify possible biofluid biomarkers predicting the early stages of the dementia of Alzheimer's type and risk of progression from Mild Cognitive Impairment to Alzheimer's disease.

Cycle Checkpoint Abnormalities during Dementia: A Plausible Association with the Loss of Protection against Oxidative Stress in Alzheimer’s Disease

PubMed Central

Katsel, Pavel; Tan, Weilun; Fam, Peter; Purohit, Dushyant P.; Haroutunian, Vahram

2013-01-01

Background Increasing evidence suggests an association between neuronal cell cycle (CCL) events and the processes that underlie neurodegeneration in Alzheimer’s disease (AD). Elevated levels of oxidative stress markers and mitochondrial dysfunction are also among early events in AD. Recent studies have reported the role of CCL checkpoint proteins and tumor suppressors, such as ATM and p53 in the control of glycolysis and oxidative metabolism in cancer, but their involvement in AD remains uncertain. Methods and Findings In this postmortem study, we measured gene expression levels of eight CCL checkpoint proteins in the superior temporal cortex (STC) of persons with varying severities of AD dementia and compare them to those of cognitively normal controls. To assess whether the CCL changes associated with cognitive impairment in AD are specific to dementia, gene expression of the same proteins was also measured in STC of persons with schizophrenia (SZ), which is also characterized by mitochondrial dysfunction. The expression of CCL-checkpoint and DNA damage response genes: MDM4, ATM and ATR was strongly upregulated and associated with progression of dementia (cognitive dementia rating, CDR), appearing as early as questionable or mild dementia (CDRs 0.5–1). In addition to gene expression changes, the downstream target of ATM-p53 signaling - TIGAR, a p53-inducible protein, the activation of which can regulate energy metabolism and protect against oxidative stress was progressively decreased as severity of dementia evolved, but it was unaffected in subjects with SZ. In contrast to AD, different CCL checkpoint proteins, which include p53, CHEK1 and BRCA1 were significantly downregulated in SZ. Conclusions These results support the activation of an ATM signaling and DNA damage response network during the progression of AD dementia, while the progressive decrease in the levels of TIGAR suggests loss of protection initiated by ATM-p53 signaling against intensifying oxidative stress in AD. PMID:23861893

Dementias show differential physiological responses to salient sounds.

PubMed

Fletcher, Phillip D; Nicholas, Jennifer M; Shakespeare, Timothy J; Downey, Laura E; Golden, Hannah L; Agustus, Jennifer L; Clark, Camilla N; Mummery, Catherine J; Schott, Jonathan M; Crutch, Sebastian J; Warren, Jason D

2015-01-01

Abnormal responsiveness to salient sensory signals is often a prominent feature of dementia diseases, particularly the frontotemporal lobar degenerations, but has been little studied. Here we assessed processing of one important class of salient signals, looming sounds, in canonical dementia syndromes. We manipulated tones using intensity cues to create percepts of salient approaching ("looming") or less salient withdrawing sounds. Pupil dilatation responses and behavioral rating responses to these stimuli were compared in patients fulfilling consensus criteria for dementia syndromes (semantic dementia, n = 10; behavioral variant frontotemporal dementia, n = 16, progressive nonfluent aphasia, n = 12; amnestic Alzheimer's disease, n = 10) and a cohort of 26 healthy age-matched individuals. Approaching sounds were rated as more salient than withdrawing sounds by healthy older individuals but this behavioral response to salience did not differentiate healthy individuals from patients with dementia syndromes. Pupil responses to approaching sounds were greater than responses to withdrawing sounds in healthy older individuals and in patients with semantic dementia: this differential pupil response was reduced in patients with progressive nonfluent aphasia and Alzheimer's disease relative both to the healthy control and semantic dementia groups, and did not correlate with nonverbal auditory semantic function. Autonomic responses to auditory salience are differentially affected by dementias and may constitute a novel biomarker of these diseases.

Dementias show differential physiological responses to salient sounds

PubMed Central

Fletcher, Phillip D.; Nicholas, Jennifer M.; Shakespeare, Timothy J.; Downey, Laura E.; Golden, Hannah L.; Agustus, Jennifer L.; Clark, Camilla N.; Mummery, Catherine J.; Schott, Jonathan M.; Crutch, Sebastian J.; Warren, Jason D.

2015-01-01

Abnormal responsiveness to salient sensory signals is often a prominent feature of dementia diseases, particularly the frontotemporal lobar degenerations, but has been little studied. Here we assessed processing of one important class of salient signals, looming sounds, in canonical dementia syndromes. We manipulated tones using intensity cues to create percepts of salient approaching (“looming”) or less salient withdrawing sounds. Pupil dilatation responses and behavioral rating responses to these stimuli were compared in patients fulfilling consensus criteria for dementia syndromes (semantic dementia, n = 10; behavioral variant frontotemporal dementia, n = 16, progressive nonfluent aphasia, n = 12; amnestic Alzheimer's disease, n = 10) and a cohort of 26 healthy age-matched individuals. Approaching sounds were rated as more salient than withdrawing sounds by healthy older individuals but this behavioral response to salience did not differentiate healthy individuals from patients with dementia syndromes. Pupil responses to approaching sounds were greater than responses to withdrawing sounds in healthy older individuals and in patients with semantic dementia: this differential pupil response was reduced in patients with progressive nonfluent aphasia and Alzheimer's disease relative both to the healthy control and semantic dementia groups, and did not correlate with nonverbal auditory semantic function. Autonomic responses to auditory salience are differentially affected by dementias and may constitute a novel biomarker of these diseases. PMID:25859194

The Impact of Anticipatory Grief on Caregiver Burden in Dementia Caregivers

ERIC Educational Resources Information Center

Holley, Caitlin K.; Mast, Benjamin T.

2009-01-01

Purpose: Interest in anticipatory grief (AG) has typically focused on terminal diseases such as cancer. However, the issues involved in AG are unique in the context of dementia due to the progressive deterioration of both cognitive and physical abilities. The current study investigated the nature of AG in a sample of dementia caregivers and…

Language and Dementia: Neuropsychological Aspects.

PubMed

Kempler, Daniel; Goral, Mira

2008-01-01

This article reviews recent evidence for the relationship between extralinguistic cognitive and language abilities in dementia. A survey of data from investigations of three dementia syndromes (Alzheimer's disease, semantic dementia and progressive nonfluent aphasia) reveals that, more often than not, deterioration of conceptual organization appears associated with lexical impairments, whereas impairments in executive function are associated with sentence- and discourse-level deficits. These connections between extralinguistic functions and language ability also emerge from the literature on cognitive reserve and bilingualism that investigates factors that delay the onset and possibly the progression of neuropsychological manifestation of dementia.

Mild Cognitive Impairment and Progession to Dementia: New Findings

MedlinePlus

... MD Mild cognitive impairment and progression to dementia New findings John C.S. Breitner, MD, MPH WHAT WERE ... how different they are. This article offers important new information to answer that question. The study is ...

When dementia progresses quickly: a practical approach to the diagnosis and management of rapidly progressive dementia.

PubMed

Day, Gregory S; Tang-Wai, David F

2014-01-01

Making a diagnosis of rapidly progressive dementia requires practical adaptation of the skills used to assess patients with chronic causes of cognitive impairment. An expedited assessment, commensurate with the accelerated pace of the disease, is required to identify the cause of symptoms amidst a myriad of possibilities. Features upon history, physical examination and cognitive assessment that support specific diagnoses are reviewed, and a stratified approach to testing is presented. The use of readily-accessible investigations is prioritized, acknowledging the implications and applications of novel diagnostic tests. The coordinated use of clinical and laboratory measures are promoted as a means of facilitating rapid evaluation, with the ultimate goal of identifying patients with potentially reversible causes of rapidly progressive dementia.

Carotid intima-media thickness is associated with the progression of cognitive impairment in older adults.

PubMed

Moon, Jae Hoon; Lim, Soo; Han, Ji Won; Kim, Kyoung Min; Choi, Sung Hee; Park, Kyong Soo; Kim, Ki Woong; Jang, Hak Chul

2015-04-01

We investigated the association between cardiovascular risk factors, including carotid intima-media thickness (CIMT), and future risk of mild cognitive impairment (MCI) and dementia in elderly subjects. We conducted a population-based prospective study as a part of the Korean Longitudinal Study on Health and Aging. Our study included 348 participants who were nondemented at the baseline (mean age, 71.7±6.3 years) and underwent cognitive evaluation at the 5-year follow-up. Baseline cardiovascular risk factors were compared according to the development of MCI or dementia during the study period. At the baseline evaluation, 278 subjects were cognitively normal and 70 subjects had MCI. Diagnoses of cognitive function either remained unchanged or improved during the study period in 292 subjects (nonprogression group), whereas 56 subjects showed progression of cognitive impairment to MCI or dementia (progression group). The progression group exhibited a higher prevalence of hypertension and greater CIMT compared with the nonprogression group. Other baseline cardiovascular risk factors, including sex, body mass index, diabetes mellitus, insulin resistance, total cholesterol, waist-to-hip ratio, visceral fat, pulse wave velocity, and ankle-brachial index, were not significantly different between 2 groups. The association between greater baseline CIMT and the progression of cognitive impairment was maintained after adjustment for conventional baseline risk factors of cognitive impairment. Greater baseline CIMT was also independently associated with the development of MCI in the subjects whose baseline cognitive function was normal. Greater baseline CIMT was independently associated with the risk of cognitive impairment, such as MCI and dementia in elderly subjects. © 2015 American Heart Association, Inc.

Comorbid Mild Cognitive Impairment and Depressive Symptoms Predict Future Dementia in Community Older Adults: A 24-Month Follow-Up Longitudinal Study.

PubMed

Makizako, Hyuma; Shimada, Hiroyuki; Doi, Takehiko; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Makino, Keitaro; Suzuki, Takao

2016-10-18

Older adults with mild cognitive impairment (MCI) are non-demented, but demonstrate cognitive dysfunction, and have significantly higher risk of progressing to dementia. A better understanding of more sensitive risk factors, such as combination of cognitive and psychological status, for progression of MCI to dementia may be crucial for prevention of development of dementia. To examine MCI, depressive symptoms, and comorbid MCI and depressive symptoms as risk factors for development of dementia. A total of 3,663 community-dwelling older people were included in this prospective longitudinal study. MCI was determined by age- and education-adjusted objective cognitive impairment using computerized comprehensive cognitive measures including memory, attention/executive function, and processing speed. Depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS) and defined by a GDS score of 6 or more. During the 24-month follow-up period, 72 participants (2.0%) developed dementia. Baseline MCI was significantly associated with an increased risk of incident dementia (hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.8-5.5) but depressive symptoms were not (2.0; 1.0-4.2) after adjusting for age, sex, education, prescribed medications, and walking speed. Participants with comorbid MCI and depressive symptoms at baseline had a higher risk of developing dementia (HR, 4.8; 2.3-10.5). Although MCI and depressive symptoms may be associated with increased risk for incident dementia independently, comorbid MCI and depressive symptoms have a significantly greater impact on dementia development among community-dwelling older adults.

An Italian family with inclusion-body myopathy and frontotemporal dementia due to mutation in the VCP gene.

PubMed

Gidaro, Teresa; Modoni, Anna; Sabatelli, Mario; Tasca, Giorgio; Broccolini, Aldobrando; Mirabella, Massimiliano

2008-01-01

Mutations of the valosin-containing protein gene (VCP) are responsible for autosomal-dominant hereditary inclusion-body myopathy associated with frontotemporal dementia and Paget's disease of bone. We identified the p.R155C missense mutation in the VCP gene segregating in an Italian family with three affected siblings, two of whom had a progressive myopathy associated with dementia, whereas one exhibited a progressive myopathy and preclinical signs of Paget's disease of bone. Our study demonstrates that VCP mutations are found in patients of Italian background and may lead to a variable clinical phenotype even within the same kinship.

Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification

PubMed Central

Korolev, Igor O.; Symonds, Laura L.; Bozoki, Andrea C.

2016-01-01

Background Individuals with mild cognitive impairment (MCI) have a substantially increased risk of developing dementia due to Alzheimer's disease (AD). In this study, we developed a multivariate prognostic model for predicting MCI-to-dementia progression at the individual patient level. Methods Using baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139) and those who did not (n = 120) during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI) data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework. Results Cognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87). Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex). Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions. Conclusions We developed an accurate prognostic model for predicting MCI-to-dementia progression over a three-year period. The model utilizes widely available, cost-effective, non-invasive markers and can be used to improve patient selection in clinical trials and identify high-risk MCI patients for early treatment. PMID:26901338

Motor Speech Phenotypes of Frontotemporal Dementia, Primary Progressive Aphasia, and Progressive Apraxia of Speech

ERIC Educational Resources Information Center

Poole, Matthew L.; Brodtmann, Amy; Darby, David; Vogel, Adam P.

2017-01-01

Purpose: Our purpose was to create a comprehensive review of speech impairment in frontotemporal dementia (FTD), primary progressive aphasia (PPA), and progressive apraxia of speech in order to identify the most effective measures for diagnosis and monitoring, and to elucidate associations between speech and neuroimaging. Method: Speech and…

The impact of anxiety on the progression of mild cognitive impairment to dementia in Chinese and English data bases: a systematic review and meta-analysis.

PubMed

Li, Xiao-Xue; Li, Zheng

2018-01-01

It remains unclear whether or not anxiety increases the risk of dementia in people with mild cognitive impairment (MCI). The aim of this systematic review and meta-analysis was to investigate the risk of dementia among people with MCI and anxiety compared with those with MCI and no anxiety. The hazard ratio of conversion to dementia in people with anxiety and MCI was compared with those without anxiety and was calculated using a generic inverse variance method with fixed effect models. Eleven studies from the English and Chinese databases were included, seven of which were included in the meta-analysis. The pooled hazard ratio of conversion to dementia was 1.18 95% CI [1.07, 1.31] (p = 0.002) in the group of MCI plus anxiety compared with those without anxiety. The results suggest that anxiety increases the risk of progression to dementia in people with MCI. Future interventions targeting anxiety management in vulnerable people with MCI may reduce the risk of dementia. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

18F PET with florbetaben for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).

PubMed

Martínez, Gabriel; Vernooij, Robin Wm; Fuentes Padilla, Paulina; Zamora, Javier; Flicker, Leon; Bonfill Cosp, Xavier

2017-11-22

18 F-florbetaben uptake by brain tissue, measured by positron emission tomography (PET), is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using some amyloid biomarkers tests like 18 F-florbetaben. These tests, added to the MCI core clinical criteria, might increase the diagnostic test accuracy (DTA) of a testing strategy. However, the DTA of 18 F-florbetaben to predict the progression from MCI to Alzheimer's disease dementia (ADD) or other dementias has not yet been systematically evaluated. To determine the DTA of the 18 F-florbetaben PET scan for detecting people with MCI at time of performing the test who will clinically progress to ADD, other forms of dementia (non-ADD), or any form of dementia at follow-up. The most recent search for this review was performed in May 2017. We searched MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), BIOSIS Citation Index (Thomson Reuters Web of Science), Web of Science Core Collection, including the Science Citation Index (Thomson Reuters Web of Science) and the Conference Proceedings Citation Index (Thomson Reuters Web of Science), LILACS (BIREME), CINAHL (EBSCOhost), ClinicalTrials.gov (https://clinicaltrials.gov), and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (http://www.who.int/ictrp/search/en/). We also searched ALOIS, the Cochrane Dementia & Cognitive Improvement Group's specialised register of dementia studies (http://www.medicine.ox.ac.uk/alois/). We checked the reference lists of any relevant studies and systematic reviews, and performed citation tracking using the Science Citation Index to identify any additional relevant studies. No language or date restrictions were applied to electronic searches. We included studies that had prospectively defined cohorts with any accepted definition of MCI at time of performing the test and the use of 18 F-florbetaben scan to evaluate the DTA of the progression from MCI to ADD or other forms of dementia. In addition, we only selected studies that applied a reference standard for Alzheimer's dementia diagnosis, for example, the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. We screened all titles and abstracts identified in electronic-database searches. Two review authors independently selected studies for inclusion and extracted data to create two-by-two tables, showing the binary test results cross-classified with the binary reference standard. We used these data to calculate sensitivities, specificities, and their 95% confidence intervals. Two independent assessors performed quality assessment using the QUADAS-2 tool plus some additional items to assess the methodological quality of the included studies. Progression from MCI to ADD, any other form of dementia, and any form of dementia was evaluated in one study (Ong 2015). It reported data on 45 participants at four years of follow-up; 21 participants met NINCDS-ADRDA criteria for Alzheimer's disease dementia at four years of follow-up, the proportion converting to ADD was 47% of the 45 participants, and 11% of the 45 participants met criteria for other types of dementias (three cases of FrontoTemporal Dementia (FTD), one of Dementia with Lewy body (DLB), and one of Progressive Supranuclear Palsy (PSP)). We considered the study to be at high risk of bias in the domains of the reference standard, flow, and timing (QUADAS-2). MCI to ADD; 18 F-florbetaben PET scan analysed visually: the sensitivity was 100% (95% confidence interval (CI) 84% to 100%) and the specificity was 83% (95% CI 63% to 98%) (n = 45, 1 study). Analysed quantitatively: the sensitivity was 100% (95% CI 84% to 100%) and the specificity was 88% (95% CI 68% to 97%) for the diagnosis of ADD at follow-up (n = 45, 1 study). MCI to any other form of dementia (non-ADD); 18 F-florbetaben PET scan analysed visually: the sensitivity was 0% (95% CI 0% to 52%) and the specificity was 38% (95% CI 23% to 54%) (n = 45, 1 study). Analysed quantitatively: the sensitivity was 0% (95% CI 0% to 52%) and the specificity was 40% (95% CI 25% to 57%) for the diagnosis of any other form of dementia at follow-up (n = 45, 1 study). MCI to any form of dementia; 18 F-florbetaben PET scan analysed visually: the sensitivity was 81% (95% CI 61% to 93%) and the specificity was 79% (95% CI 54% to 94%) (n = 45, 1 study). Analysed quantitatively: the sensitivity was 81% (95% CI 61% to 93%) and the specificity was 84% (95% CI 60% to 97%) for the diagnosis of any form of dementia at follow-up (n = 45, 1 study). Although we were able to calculate one estimation of DTA in, especially, the prediction of progression from MCI to ADD at four years follow-up, the small number of participants implies imprecision of sensitivity and specificity estimates. We cannot make any recommendation regarding the routine use of 18 F-florbetaben in clinical practice based on one single study with 45 participants. 18 F-florbetaben has high financial costs, therefore, clearly demonstrating its DTA and standardising the process of the 18 F-florbetaben modality are important prior to its wider use.

Predicting progression to dementia in persons with mild cognitive impairment using cerebrospinal fluid markers.

PubMed

Handels, Ron L H; Vos, Stephanie J B; Kramberger, Milica G; Jelic, Vesna; Blennow, Kaj; van Buchem, Mark; van der Flier, Wiesje; Freund-Levi, Yvonne; Hampel, Harald; Olde Rikkert, Marcel; Oleksik, Ania; Pirtosek, Zvezdan; Scheltens, Philip; Soininen, Hilkka; Teunissen, Charlotte; Tsolaki, Magda; Wallin, Asa K; Winblad, Bengt; Verhey, Frans R J; Visser, Pieter Jelle

2017-08-01

We aimed to determine the added value of cerebrospinal fluid (CSF) to clinical and imaging tests to predict progression from mild cognitive impairment (MCI) to any type of dementia. The risk of progression to dementia was estimated using two logistic regression models based on 250 MCI participants: the first included standard clinical measures (demographic, clinical, and imaging test information) without CSF biomarkers, and the second included standard clinical measures with CSF biomarkers. Adding CSF improved predictive accuracy with 0.11 (scale from 0-1). Of all participants, 136 (54%) had a change in risk score of 0.10 or higher (which was considered clinically relevant), of whom in 101, it was in agreement with their dementia status at follow-up. An individual person's risk of progression from MCI to dementia can be improved by relying on CSF biomarkers in addition to recommended clinical and imaging tests for usual care. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

'This is my story, how I remember it': In-depth analysis of Dignity Therapy documents from a study of Dignity Therapy for people with early stage dementia.

PubMed

Johnston, Bridget; Lawton, Sally; Pringle, Jan

2017-07-01

Dementia is a progressive condition that impacts on individuals, families and care professionals. Maintaining quality of life through engagement with the person with dementia is an important part of their care. Dignity Therapy is an interactive, psychotherapeutic intervention that uses a trained dignity therapist to guide the person with dementia through an interview that then creates a written legacy called a generativity document. This can provide knowledge to inform care, as the condition progresses. Generativity documents were analysed using framework analysis. Main themes from the analysis were origin of values, essence and affirmation of self, forgiveness and resolution and existentialism/ meaning of life. These themes provide evidence of the type, scope and contribution that information generated from Dignity Therapy can make to the care and support of people with dementia. They provide information about the values, self-identity and the people and events that have been important to them and influenced their lives.

Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses.

PubMed

Bisenius, S; Neumann, J; Schroeter, M L

2016-04-01

Recently, diagnostic clinical and imaging criteria for primary progressive aphasia (PPA) have been revised by an international consortium (Gorno-Tempini et al. Neurology 2011;76:1006-14). The aim of this study was to validate the specificity of the new imaging criteria and investigate whether different imaging modalities [magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET)] require different diagnostic subtype-specific imaging criteria. Anatomical likelihood estimation meta-analyses were conducted for PPA subtypes across a large cohort of 396 patients: firstly, across MRI studies for each of the three PPA subtypes followed by conjunction and subtraction analyses to investigate the specificity, and, secondly, by comparing results across MRI vs. FDG-PET studies in semantic dementia and progressive nonfluent aphasia. Semantic dementia showed atrophy in temporal, fusiform, parahippocampal gyri, hippocampus, and amygdala, progressive nonfluent aphasia in left putamen, insula, middle/superior temporal, precentral, and frontal gyri, logopenic progressive aphasia in middle/superior temporal, supramarginal, and dorsal posterior cingulate gyri. Results of the disease-specific meta-analyses across MRI studies were disjunct. Similarly, atrophic and hypometabolic brain networks were regionally dissociated in both semantic dementia and progressive nonfluent aphasia. In conclusion, meta-analyses support the specificity of new diagnostic imaging criteria for PPA and suggest that they should be specified for each imaging modality separately. © 2016 EAN.

Longitudinal decline in structural networks predicts dementia in cerebral small vessel disease

PubMed Central

Lawrence, Andrew J.; Zeestraten, Eva A.; Benjamin, Philip; Lambert, Christian P.; Morris, Robin G.; Barrick, Thomas R.

2018-01-01

Objective To determine whether longitudinal change in white matter structural network integrity predicts dementia and future cognitive decline in cerebral small vessel disease (SVD). To investigate whether network disruption has a causal role in cognitive decline and mediates the association between conventional MRI markers of SVD with both cognitive decline and dementia. Methods In the prospective longitudinal SCANS (St George's Cognition and Neuroimaging in Stroke) Study, 97 dementia-free individuals with symptomatic lacunar stroke were followed with annual MRI for 3 years and annual cognitive assessment for 5 years. Conversion to dementia was recorded. Structural networks were constructed from diffusion tractography using a longitudinal registration pipeline, and network global efficiency was calculated. Linear mixed-effects regression was used to assess change over time. Results Seventeen individuals (17.5%) converted to dementia, and significant decline in global cognition occurred (p = 0.0016). Structural network measures declined over the 3-year MRI follow-up, but the degree of change varied markedly between individuals. The degree of reductions in network global efficiency was associated with conversion to dementia (B = −2.35, odds ratio = 0.095, p = 0.00056). Change in network global efficiency mediated much of the association of conventional MRI markers of SVD with cognitive decline and progression to dementia. Conclusions Network disruption has a central role in the pathogenesis of cognitive decline and dementia in SVD. It may be a useful disease marker to identify that subgroup of patients with SVD who progress to dementia. PMID:29695593

Art and the brain: the influence of frontotemporal dementia on an accomplished artist.

PubMed

Mell, Joshua Chang; Howard, Sara M; Miller, Bruce L

2003-05-27

A talented artist developed a progressive aphasia syndrome associated with frontotemporal dementia (FTD). As her disease progressed, language and executive skills declined, but her paintings became freer and more original. She demonstrates that artistic development can occur in the setting of language-dominant types of FTD. The study of artistic development in the setting of FTD suggests that language is not required for, and may even inhibit, certain types of visual creativity.

Societal and Family Lifetime Cost of Dementia: Implications for Policy.

PubMed

Jutkowitz, Eric; Kane, Robert L; Gaugler, Joseph E; MacLehose, Richard F; Dowd, Bryan; Kuntz, Karen M

2017-10-01

To estimate the cost of dementia and the extra cost of caring for someone with dementia over the cost of caring for someone without dementia. We developed an evidence-based mathematical model to simulate disease progression for newly diagnosed individuals with dementia. Data-driven trajectories of cognition, function, and behavioral and psychological symptoms were used to model disease progression and predict costs. Using modeling, we evaluated lifetime and annual costs of individuals with dementia, compared costs of those with and without clinical features of dementia, and evaluated the effect of reducing functional decline or behavioral and psychological symptoms by 10% for 12 months (implemented when Mini-Mental State Examination score ≤21). Mathematical model. Representative simulated U.S. incident dementia cases. Value of informal care, out-of-pocket expenditures, Medicaid expenditures, and Medicare expenditures. From time of diagnosis (mean age 83), discounted total lifetime cost of care for a person with dementia was $321,780 (2015 dollars). Families incurred 70% of the total cost burden ($225,140), Medicaid accounted for 14% ($44,090), and Medicare accounted for 16% ($52,540). Costs for a person with dementia over a lifetime were $184,500 greater (86% incurred by families) than for someone without dementia. Total annual cost peaked at $89,000, and net cost peaked at $72,400. Reducing functional decline or behavioral and psychological symptoms by 10% resulted in $3,880 and $680 lower lifetime costs than natural disease progression. Dementia substantially increases lifetime costs of care. Long-lasting, effective interventions are needed to support families because they incur the most dementia cost. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Semantic Dementia and Persisting Wernicke's Aphasia: Linguistic and Anatomical Profiles

ERIC Educational Resources Information Center

Ogar, J. M.; Baldo, J. V.; Wilson, S. M.; Brambati, S. M.; Miller, B. L.; Dronkers, N. F.; Gorno-Tempini, M. L.

2011-01-01

Few studies have directly compared the clinical and anatomical characteristics of patients with progressive aphasia to those of patients with aphasia caused by stroke. In the current study we examined fluent forms of aphasia in these two groups, specifically semantic dementia (SD) and persisting Wernicke's aphasia (WA) due to stroke. We compared…

Dementia Pugilistica Revisited

PubMed Central

Castellani, Rudy J.; Perry, George

2017-01-01

 Extensive exposure of boxers to neurotrauma in the early 20th century led to the so-called punch drunk syndrome, which was formally recognized in the medical literature in 1928. “Punch drunk” terminology was replaced by the less derisive ‘dementia pugilistica’ in 1937. In the early case material, the diagnosis of dementia pugilistica required neurological deficits, including slurring dysarthria, ataxia, pyramidal signs, extrapyramidal signs, memory impairment, and personality changes, although the specific clinical substrate has assumed lesser importance in recent years with a shift in focus on molecular pathogenesis. The postmortem neuropathology of dementia pugilistica has also evolved substantially over the past 90 years, from suspected concussion-related hemorrhages to diverse structural and neurofibrillary changes to geographic tauopathy. Progressive neurodegenerative tauopathy is among the prevailing theories for disease pathogenesis currently, although this may be overly simplistic. Careful examination of historical cases reveals both misdiagnoses and a likelihood that dementia pugilistica at that time was caused by cumulative structural brain injury. More recent neuropathological studies indicate subclinical and possibly static tauopathy in some athletes and non-athletes. Indeed, it is unclear from the literature whether retired boxers reach the inflection point that tends toward progressive neurodegeneration in the manner of Alzheimer’s disease due to boxing. Even among historical cases with extreme levels of exposure, progressive disease was exceptional. PMID:29036831

Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)

ClinicalTrials.gov

2018-05-01

FTLD; Progressive Supranuclear Palsy (PSP); Frontotemporal Dementia (FTD); Corticobasal Degeneration (CBD); PPA Syndrome; Behavioral Variant Frontotemporal Dementia (bvFTD); Semantic Variant Primary Progressive Aphasia (svPPA); Nonfluent Variant Primary Progressive Aphasia (nfvPPA); FTD With Amyotrophic Lateral Sclerosis (FTD/ALS); Amyotrophic Lateral Sclerosis (ALS); Oligosymptomatic PSP (oPSP); Corticobasal Syndrome (CBS)

Constructing togetherness throughout the phases of dementia: a qualitative study exploring how spouses maintain relationships with partners with dementia who live in institutional care.

PubMed

Førsund, Linn Hege; Kiik, Riina; Skovdahl, Kirsti; Ytrehus, Siri

2016-10-01

To explore and describe how spouses involve themselves in the relationship with their partners with dementia who live in institutional care. Positive reciprocity between partners has been proven to be significant for spouses with partners living with dementia at home. However, little is known about spousal involvement after placement of a partner in an institutional setting. This subject was therefore the focus of this study. Constructivist grounded theory was used to develop meaningful concepts considering the relational processes experienced and described by the spouses. Interviews were conducted with 15 spouses (eight women and seven men ranging in age from 64-90 years) of dementia-afflicted persons living in institutional care. Theoretical sampling, constant comparison and memo-writing guided the data collection and analysis. The analysis showed how the spouses adopted different visiting routines to preserve continuity in their relationship throughout the phases of dementia. Three categories described how these visiting routines were used and adapted along with their partners' dementia progressions in the process of constructing togetherness: 'maintaining involvement and intimacy to preserve continuity in their relationship,' 'structuring visits to facilitate interaction and communication' and 'pursuing moments of mutuality to preserve continuity in a deteriorating relationship.' Being involved and experiencing continuity in the relationship seemed important to the spouses after their partners' placement in institutional care. In the process of constructing togetherness, visiting routines were used to facilitate situations in which they could connect with their partners. These routines were continuously adjusted throughout the phases of dementia. There is a need for a systematic approach to provide sufficient support to spouses throughout their partners' dementia progressions to assist their ongoing involvement. © 2016 John Wiley & Sons Ltd.

Memory performance on the story recall test and prediction of cognitive dysfunction progression in mild cognitive impairment and Alzheimer's dementia.

PubMed

Park, Jong-Hwan; Park, Hyuntae; Sohn, Sang Wuk; Kim, Sungjae; Park, Kyung Won

2017-10-01

To determine the factors that influence diagnosis and differentiation of patients with mild cognitive impairment (MCI) and Alzheimer's dementia (AD) by comparing memory test results at baseline with those at 1-2-year follow up. We consecutively recruited 23 healthy participants, 44 MCI patients and 27 patients with very mild AD according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorder Association criteria for probable Alzheimer's disease and Petersen's clinical diagnostic criteria. We carried out detailed neuropsychological tests, including the Story Recall Test (SRT) and the Seoul Verbal Learning Test, for all participants. We defined study participants as the "progression group" as follows: (i) participants who showed conversion to dementia from the MCI state; and (ii) those with dementia who showed more than a three-point decrement in their Mini-Mental State Examination scores with accompanying functional decline from baseline status, which were ascertained by physician's clinical judgment. The SRT delayed recall scores were significantly lower in the patients with mild AD than in those with MCI and after progression. Lower (relative risk 1.1, 95% confidence interval 0.1-1.6) and higher SRT delayed recall scores (relative risk 2.1, confidence interval 1.0-2.8), and two-test combined immediate and delayed recall scores (relative risk 2.0, confidence interval 0.9-2.3; and relative risk 2.8, confidence interval 1.1-4.2, respectively) were independent predictors of progression in a stepwise multiple adjusted Cox proportional hazards model, with age, sex, depression and educational level forced into the model. The present study suggests that the SRT delayed recall score independently predicts progression to dementia in patients with MCI. Geriatr Gerontol Int 2017; 17: 1603-1609. © 2016 Japan Geriatrics Society.

Economic Impact of Dementia by Disease Severity: Exploring the Relationship between Stage of Dementia and Cost of Care in Taiwan.

PubMed

Ku, Li-Jung Elizabeth; Pai, Ming-Chyi; Shih, Pei-Yu

2016-01-01

Given the shortage of cost-of-illness studies in dementia outside of the Western population, the current study estimated the annual cost of dementia in Taiwan and assessed whether different categories of care costs vary by severity using multiple disease-severity measures. This study included 231 dementia patient-caregiver dyads in a dementia clinic at a national university hospital in southern Taiwan. Three disease measures including cognitive, functional, and behavioral disturbances were obtained from patients based on medical history. A societal perspective was used to estimate the total costs of dementia according to three cost sub-categories. The association between dementia severity and cost of care was examined through bivariate and multivariate analyses. Total costs of care for moderate dementia patient were 1.4 times the costs for mild dementia and doubled from mild to severe dementia among our community-dwelling dementia sample. Multivariate analysis indicated that functional declines had a greater impact on all cost outcomes as compared to behavioral disturbance, which showed no impact on any costs. Informal care costs accounted for the greatest share in total cost of care for both mild (42%) and severe (43%) dementia patients. Since the total costs of dementia increased with severity, providing care to delay disease progression, with a focus on maintaining patient physical function, may reduce the overall cost of dementia. The greater contribution of informal care to total costs as opposed to social care also suggests a need for more publicly-funded long-term care services to assist family caregivers of dementia patients in Taiwan.

Progression of Alzheimer disease as measured by Clinical Dementia Rating sum of boxes scores

PubMed Central

Williams, Monique M.; Storandt, Martha; Roe, Catherine M.; Morris, John C.

2013-01-01

Background This study examined rates of dementia progression as ascertained by the Clinical Dementia Rating sum of boxes (CDR-SB) for symptomatic Alzheimer disease (sAD) and assessed participant characteristics as predictors of CDR-SB progression. Methods Participants (n = 792) were enrolled in longitudinal studies at an Alzheimer’s Disease Research Center, received a diagnosis of sAD with a global CDR of 0.5 (n = 466) or 1 (n = 326), and had at least one follow-up assessment. Progression in CDR-SB over time as a function of baseline global CDR was examined. Results A longitudinal increase (p<.0001) in CDR-SB was observed. The annual rate of change in CDR-SB scores was 1.43 (SE=.05) in the CDR 0.5 sample and 1.91 (SE=.07) in the CDR 1 sample. For participants followed from the beginning of the CDR stage, time to progression to a higher global CDR was longer for individuals who were CDR 0.5 (3.75 years; 95% CI 3.18-4.33) than those who were CDR 1 at baseline (2.98 years; 95%CI 2.75-3.22). In the total CDR 0.5 sample, the significant predictors of progression to the next global CDR stage (p<.01) were age at first sAD diagnosis and apolipoprotein E4 genotype. Conclusions The study findings are relevant to sAD clinical trial design and accurate, reliable ascertainment of the effect of disease-modifying treatments. PMID:22858530

Costs of care for dementia patients in community setting: an analysis for mild and moderate disease stage.

PubMed

Schwarzkopf, Larissa; Menn, Petra; Kunz, Simone; Holle, Rolf; Lauterberg, Jörg; Marx, Peter; Mehlig, Hilmar; Wunder, Sonja; Leidl, Reiner; Donath, Carolin; Graessel, Elmar

2011-01-01

Rising life expectancy is associated with higher prevalence rates of dementia disorders. When disease progresses the patients' call on formal health care services and on social support grows which imposes increasing costs of care. The aim of this study was to investigate the costs for patients with mild and moderate dementia in community setting in Germany. We assessed total costs of care and individual cost components for 383 community-living dementia patients alongside a cluster-randomized trial from societal and health insurance perspective. Utilization of formal health care services was based on insurance claims data and time dedicated to informal care was assessed within caregiver interviews. We estimated costs using a two-part regression model adjusting for age, gender and cluster-effects. Costs of care equal €47,747 (Euros) from societal perspective which is almost the 4.7-fold of health insurance expenditures. Valued informal care covers 80.2% of societal costs and increases disproportionally when disease progresses. In moderate dementia the corresponding amount exceeds the one in mild dementia by 69.9%, whereas costs for formal health care services differ by 14.3%. Due to valued informal care, costs of care for community-living patients with moderate dementia are significantly higher than for patients with mild dementia. Informal care is a non-cash item saving expenditures for professional care. To relieve social security system and family caregivers as well as to allow dementia patients to stay at home as long as possible, concepts fostering community-based dementia care and support to family caregivers need to be further developed. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Alzheimer's Dementia from a Bilingual/Bicultural Perspective: A Case Study

ERIC Educational Resources Information Center

Brice, Alejandro E.; Wallace, Sarah E.; Brice, Roanne G.

2014-01-01

Alzheimer's dementia (AD) is a progressive, degenerative disease that occurs in the cerebral cortex due to increased levels of glutamate, the proliferation of plaque-forming amyloid beta proteins, and reactive gliosis. Establishing behavioral indicators of the disease (e.g., impairments of episodic memory) and use of neuroimaging technology…

Case Study: Delirium in an Adolescent Girl with Human Immunodeficiency Virus-Associated Dementia

ERIC Educational Resources Information Center

Scharko, Alexander M.; Baker, Eva H.; Kothari, Priti; Khattak, Hina; Lancaster, Duniya

2006-01-01

Delirium and human immunodeficiency virus (HIV)-associated dementia are well recognized neuropsychiatric consequences of HIV infection in adults. Almost nothing is known regarding the management of delirium in HIV-infected children and adolescents. HIV-related progressive encephalopathy is thought to represent the pediatric form of HIV-associated…

Epidemiology of early-onset dementia: a review of the literature

PubMed Central

Vieira, Renata Teles; Caixeta, Leonardo; Machado, Sergio; Silva, Adriana Cardoso; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Carta, Mauro Giovanni

2013-01-01

Presenile Dementia or Early Onset Dementia (EOD) is a public health problem, it differs from Senile Dementia, and encloses a significant number of cases; nevertheless, it is still poorly understood and underdiagnosed. This study aims to review the prevalence and etiology of EOD, comparing EOD with Senile Dementia, as well as to show the main causes of EOD and their prevalence in population and non-population based studies. The computer-supported search used the following databases: Pubmed/Medline, ISI Web of Knowledge and Scielo. The search terms were alcohol-associated dementia, Alzheimer’s disease, dementia, Creutzfeldt-jakob disease, dementia with lewy bodies, early onset dementia, frontotemporal lobar degeneration, Huntington’s disease, mixed dementia, neurodegenerative disorders, Parkinson’s disease dementia, presenile dementia, traumatic brain injury, vascular dementia. Only papers published in English and conducted from 1985 up to 2012 were preferentially reviewed. Neurodegenerative diseases are the most common etiologies seen in EOD. Among the general population, the prevalence of EOD was found to range between 0 to 700 per 100.000 habitants in groups of 25-64 years old, with an increasing incidence with age. The progression of EOD was found to range between 8.3 to 22.8 new cases per 100.000 in those aged under 65 years. Alzheimer's disease (AD) is the major etiology, followed by Vascular Dementia (VaD) and Frontotemporal Lobar Degeneration (FTLD). A larger number of epidemiological studies to elucidate how environmental issues contribute to EOD are necessary, thus, we can collaborate in the planning and prevention of services toward dementia patients. PMID:23878613

The Reality of Well-Being-Focused Design in Dementia Care: A Case Study of Acute Dementia Wards in the United Kingdom.

PubMed

Catt, Megan; Giridharan, Renganathan

2018-01-01

The study explored design for well-being within dementia care by investigating the adoption of well-being-focused design in real-world practice, through observing National Health Service (NHS) wards. Design for well-being is an approach that considers the psychological and physiological effects of architecture to improve health and well-being. The high psychological care requirement for dementia patients makes them a significant group to study in the evaluation of current hospital facilities. A literature review was conducted to frame the current theoretical perception of the key characteristics of a good environment for dementia care. A framework was generated to summarize and used as an assessment tool in a series of observational visits to NHS wards. Interviews with clinical staff focused on care outcomes and practicalities of implementing well-being-focused design, considering the historical and economical context. Key findings from the observations and interviews were analyzed for recurring themes. The ward observations and interviews provided insight into the current progression of well-being-led design in NHS hospitals in England. The research highlights key areas of success and factors that inhibit further progression. The case studies showed a good degree of ambition to utilize well-being-focused design, with belief among staff that the physical environment has a substantial role in the health and well-being of patients. Staff also felt that this approach is most effective for those in the less advanced stages of dementia. Despite the high level of support, the current degree of implementation appears to be varied.

Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review.

PubMed

Panza, F; Solfrizzi, V; Barulli, M R; Bonfiglio, C; Guerra, V; Osella, A; Seripa, D; Sabbà, C; Pilotto, A; Logroscino, G

2015-03-01

A prolonged preclinical phase of more than two decades before the onset of dementia suggested that initial brain changes of Alzheimer's disease (AD) and the symptoms of advanced AD may represent a unique continuum. Given the very limited therapeutic value of drugs currently used in the treatment of AD and dementia, preventing or postponing the onset of AD and delaying or slowing its progression are becoming mandatory. Among possible reversible risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors were associated with the development of dementia and late-life cognitive disorders, opening new avenues for the prevention of these diseases. Among diet-associated factors, coffee is regularly consumed by millions of people around the world and owing to its caffeine content, it is the best known psychoactive stimulant resulting in heightened alertness and arousal and improvement of cognitive performance. Besides its short-term effect, some case-control and cross-sectional and longitudinal population-based studies evaluated the long-term effects on brain function and provided some evidence that coffee, tea, and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia. In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men. The findings on the association of coffee, tea, and caffeine consumption or plasma caffeine levels with incident mild cognitive impairment and its progression to dementia were too limited to draw any conclusion. Furthermore, for dementia and AD prevention, some studies with baseline examination in midlife pointed to a lack of association, although other case-control and longitudinal population-based studies with briefer follow-up periods supported favourable effects of coffee, tea, and caffeine consumption against AD. Larger studies with longer follow-up periods should be encouraged, addressing other potential bias and confounding sources, so hopefully opening new ways for diet-related prevention of dementia and AD.

Economic Impact of Dementia by Disease Severity: Exploring the Relationship between Stage of Dementia and Cost of Care in Taiwan

PubMed Central

Ku, Li-Jung Elizabeth; Pai, Ming-Chyi; Shih, Pei-Yu

2016-01-01

Objective Given the shortage of cost-of-illness studies in dementia outside of the Western population, the current study estimated the annual cost of dementia in Taiwan and assessed whether different categories of care costs vary by severity using multiple disease-severity measures. Methods This study included 231 dementia patient–caregiver dyads in a dementia clinic at a national university hospital in southern Taiwan. Three disease measures including cognitive, functional, and behavioral disturbances were obtained from patients based on medical history. A societal perspective was used to estimate the total costs of dementia according to three cost sub-categories. The association between dementia severity and cost of care was examined through bivariate and multivariate analyses. Results Total costs of care for moderate dementia patient were 1.4 times the costs for mild dementia and doubled from mild to severe dementia among our community-dwelling dementia sample. Multivariate analysis indicated that functional declines had a greater impact on all cost outcomes as compared to behavioral disturbance, which showed no impact on any costs. Informal care costs accounted for the greatest share in total cost of care for both mild (42%) and severe (43%) dementia patients. Conclusions Since the total costs of dementia increased with severity, providing care to delay disease progression, with a focus on maintaining patient physical function, may reduce the overall cost of dementia. The greater contribution of informal care to total costs as opposed to social care also suggests a need for more publicly-funded long-term care services to assist family caregivers of dementia patients in Taiwan. PMID:26859891

Evolving early (pre-dementia) Alzheimer's disease trials: suit the outcomes to the population and study design.

PubMed

Doody, R S

2010-04-01

Assuming that some cases of Alzheimer's disease (AD) could be prevented or delayed, prevention trials will be developed for this neurodegenerative condition. Initially, stakeholders will have to agree about the definition of prevention-true primary prevention, meaning the prevention of AD neuropathological changes; the prevention of clinical signs and symptoms that often augur AD; or preventing the progression of signs and symptoms to full-blown dementia. True primary prevention trials will have to rely completely upon neuroimaging or biomarker outcomes that reflect AD pathology. On the other hand, trials designed to prevent signs and symptoms of dementia will require researchers to agree on the phenomenology that would constitute an unequivocal endpoint: cognitive worsening on one or more measure compared to a normative group; development of Mild cognitive impairment (MCI); or development of Alzheimer's dementia. Prevention trials utilizing any of these outcomes in the general public will be large, will have to utilize low risk public health interventions, and might therefore have only a small impact (treatment effect size), especially if the studies are too short or the study populations are too diverse. An alternative to interventions aimed at the general public would be any attempt to prevent signs and symptoms of dementia in individuals thought to be at an increased risk for clinical dementia. These trials could try to reduce the development of signs and symptoms of dementia in cognitively normal subjects, or they could try to prevent progression from some form of Mild Cognitive Impairment to AD, or they could have the more subtle goal of reducing the accumulation of subclinical deficits in MCI subjects. If the populations for these trials are limited to individuals who have abnormal laboratory and neuroimaging studies associated with AD neuropathology, the results will not generalize to biomarker-negative, at risk individuals, who are likely to constitute the majority of any clinically relevant study population. Outcome measures for each study design will depend upon the characteristics of the study.

Association between Traumatic Brain Injury and Late Life Neurodegenerative Conditions and Neuropathological Findings

PubMed Central

Crane, Paul K.; Gibbons, Laura E.; Dams-O’Connor, Kristen; Trittschuh, Emily; Leverenz, James B.; Keene, C. Dirk; Sonnen, Joshua; Montine, Thomas J.; Bennett, David A.; Leurgans, Sue; Schneider, Julie A.; Larson, Eric B.

2016-01-01

IMPORTANCE There is great interest in the late effects of traumatic brain injury (TBI). OBJECTIVE To determine whether TBI with loss of consciousness (LOC) is associated with increased risk for clinical and neuropathological findings of Alzheimer’s disease, Parkinson’s disease, and other dementias. Our primary hypothesis was that TBI with LOC would be associated with increased risk for Alzheimer’s disease and neurofibrillary tangles. DESIGN Prospective cohort studies which follow all participants (Religious Orders Study and the Memory and Aging Project, ROS and MAP) or all consenting participants (Adult Changes in Thought, ACT) to autopsy. Studies performed annual (ROS and MAP) or biennial (ACT) cognitive and clinical testing to identify incident cases of dementia and Alzheimer’s disease. SETTING Members of a Seattle-area healthcare delivery system (ACT); priests and nuns living in orders across the US (ROS), and Chicago-area adults in retirement communities (MAP). PARTICIPANTS 7,130 older adults; 1,589 came to autopsy. EXPOSURE Self reported TBI reported when free of dementia, categorized as <1 hour vs. > 1 hour of LOC. MAIN OUTCOMES AND MEASURES Clinical: incident all-cause dementia, Alzheimer’s disease, and Parkinson’s disease (all studies), and incident mild cognitive impairment and progression of parkinsonian signs (ROS and MAP). Neuropathology: neurofibrillary tangles, neuritic plaques, microinfarcts, cystic infarcts, Lewy bodies, and hippocampal sclerosis (all studies). RESULTS 865 participants reported a history of TBI with LOC. In >45,000 person-years of follow-up, there were 1,537 incident dementia and 117 incident Parkinson’s disease cases. There was no association between TBI with LOC and incident dementia or Alzheimer’s disease. There were associations between TBI with LOC and incident Parkinson’s disease and progression of parkinsonian signs. There was no association between TBI with LOC and neurofibrillary tangles or neuritic plaques. There was an association between TBI with LOC and Lewy bodies, and with microinfarcts, though numbers of people with these findings were small. CONCLUSIONS AND RELEVANCE Pooled clinical and neuropathology data from three prospective cohort studies indicate that TBI with LOC is associated with risk of Lewy body accumulation, progression of parkinsonism, and Parkinson’s disease, but not dementia, Alzheimer’s disease, neuritic plaques, or neurofibrillary tangles. PMID:27400367

The Bedford Alzheimer nursing-severity scale to assess dementia severity in advanced dementia: a nonparametric item response analysis and a study of its psychometric characteristics.

PubMed

Galindo-Garre, Francisca; Hendriks, Simone A; Volicer, Ladislav; Smalbrugge, Martin; Hertogh, Cees M P M; van der Steen, Jenny T

2014-02-01

The Bedford Alzheimer Nursing-Severity Scale (BANS-S) assesses disease severity in patients with advanced Alzheimer's disease. Since Alzheimer is a progressive disease, studying the hierarchy of the items in the scale can be useful to evaluate the progression of the disease. Data from 164 Alzheimer's patients and 186 patients with other dementia were analyzed using the Mokken Scaling Methodology to determine whether respondents can be ordered in the trait dementia severity, and to study whether an ordering between the items exist. The scalability of the scale was evaluated by the H coefficient. Results showed that the BANS-S is a reliable and medium scale (0.4≤H<0.5) for the Alzheimer group. All items with the exception of the item about mobility could be ordered. When later item was eliminated from the scale, the H coefficient decreased indicating that the scalability of the scale in the original form is more accurate than in the shorter version. For the other dementia group, the BANS-S did not fit any of the Mokken Scaling models because the scale was not unidimensional. In this group, a shorter version of the scale without the sleeping cycle item and the mobility item has better reliability and scalability properties than the original scale.

Alzheimer's Disease-Related Dementias Summit 2016: National research priorities.

PubMed

Corriveau, Roderick A; Koroshetz, Walter J; Gladman, Jordan T; Jeon, Sophia; Babcock, Debra; Bennett, David A; Carmichael, S Thomas; Dickinson, Susan L-J; Dickson, Dennis W; Emr, Marian; Fillit, Howard; Greenberg, Steven M; Hutton, Michael L; Knopman, David S; Manly, Jennifer J; Marder, Karen S; Moy, Claudia S; Phelps, Creighton H; Scott, Paul A; Seeley, William W; Sieber, Beth-Anne; Silverberg, Nina B; Sutherland, Margaret L; Taylor, Angela; Torborg, Christine L; Waddy, Salina P; Gubitz, Amelie K; Holtzman, David M

2017-12-05

Goal 1 of the National Plan to Address Alzheimer's Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease-related dementias by 2025. To help inform the research agenda toward achieving this goal, the NIH hosts periodic summits that set and refine relevant research priorities for the subsequent 5 to 10 years. This proceedings article summarizes the 2016 Alzheimer's Disease-Related Dementias Summit, including discussion of scientific progress, challenges, and opportunities in major areas of dementia research, including mixed-etiology dementias, Lewy body dementia, frontotemporal degeneration, vascular contributions to cognitive impairment and dementia, dementia disparities, and dementia nomenclature. © 2017 American Academy of Neurology.

Neuropsychiatric symptoms as risk factors for progression from CIND to dementia: the Cache County Study.

PubMed

Peters, M E; Rosenberg, P B; Steinberg, M; Norton, M C; Welsh-Bohmer, K A; Hayden, K M; Breitner, J; Tschanz, J T; Lyketsos, C G

2013-11-01

To examine the association of neuropsychiatric symptom (NPS) severity with risk of transition to all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD). Survival analysis of time to dementia, AD, or VaD onset. Population-based study. 230 participants diagnosed with cognitive impairment, no dementia (CIND) from the Cache County Study of Memory Health and Aging were followed for a mean of 3.3 years. The Neuropsychiatric Inventory (NPI) was used to quantify the presence, frequency, and severity of NPS. Chi-squared statistics, t-tests, and Cox proportional hazard ratios were used to assess associations. The conversion rate from CIND to all-cause dementia was 12% per year, with risk factors including an APOE ε4 allele, lower Mini-Mental State Examination, lower 3MS, and higher CDR sum-of-boxes. The presence of at least one NPS was a risk factor for all-cause dementia, as was the presence of NPS with mild severity. Nighttime behaviors were a risk factor for all-cause dementia and of AD, whereas hallucinations were a risk factor for VaD. These data confirm that NPS are risk factors for conversion from CIND to dementia. Of special interest is that even NPS of mild severity are a risk for all-cause dementia or AD. Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Neuropsychiatric symptoms as risk factors for progression from CIND to dementia: The Cache County Study

PubMed Central

Peters, ME; Rosenberg, PB; Steinberg, M; Norton, MC; Welsh-Bohmer, KA; Hayden, KM; Breitner, J; Tschanz, JT; CG, Lyketsos

2012-01-01

Objectives To examine the association of neuropsychiatric symptom (NPS) severity with risk of transition to all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). Design Survival analysis of time to dementia, AD, or VaD onset. Setting Population-based study. Participants 230 participants diagnosed with cognitive impairment, no dementia (CIND) from the Cache County Study of Memory Health and Aging were followed for a mean of 3.3 years. Measurements The Neuropsychiatric Inventory (NPI) was used to quantify the presence, frequency, and severity of NPS. Chi-square statistics, t-tests, and Cox proportional hazard ratios were used to assess associations. Results The conversion rate from CIND to all-cause dementia was 12% per year, with risk factors including an APOE ε4 allele, lower MMSE, lower 3MS, and higher CDR sum-of-boxes. The presence of at least one NPS was a risk factor for all-cause dementia, as was the presence of NPS with mild severity. Nighttime behaviors were a risk factor for all-cause dementia and of AD, while hallucinations were a risk factor for VaD. Conclusions These data confirm that NPS are risk factors for conversion from CIND to dementia. Of special interest is that even NPS of mild severity are a risk for all-cause dementia or AD. PMID:23567370

Genetic Alzheimer Disease and Sporadic Dementia With Lewy Bodies: A Comorbidity Presenting as Primary Progressive Aphasia.

PubMed

Picková, Tereza; Matěj, Radoslav; Bezdicek, Ondrej; Keller, Jiří; van der Zee, Julie; Van Broeckhoven, Christine; Cséfalvay, Zsolt; Rusina, Robert

2017-03-01

We report a 44-year-old woman, with a family history of early-onset dementia, presenting with primary progressive aphasia. This clinically variable syndrome has multiple underlying pathologies, and correlations between clinical manifestations and postmortem neuropathologic findings are controversial. Our patient suffered worsening language impairment with major word-finding difficulties but preserved comprehension. She also developed episodic memory impairment. Her condition progressed to dementia with behavioral changes. Magnetic resonance imaging showed early left perisylvian and bitemporal atrophy. The patient died shortly afterward from colon cancer. Neuropathologic examination revealed advanced early-onset Alzheimer and Lewy body disease, plus a clinically nonrelevant metastasis of her colon cancer in her left parietal lobe. Genetic examination revealed a p.Glu184Asp mutation in the presenilin1 gene. Our findings confirm the importance of a thorough appreciation for the clinical and neuropathologic correlations in patients with atypical neurodegenerative dementias.

Friedrich Nietzsche's mental illness--general paralysis of the insane vs. frontotemporal dementia.

PubMed

Orth, M; Trimble, M R

2006-12-01

For a long time it was thought that Nietzsche suffered from general paralysis of the insane (GPI). However, this diagnosis has been questioned recently, and alternative diagnoses have been proposed. We have charted Friedrich Nietzsche's final fatal illness, and viewed the differential diagnosis in the light of recent neurological understandings of dementia syndromes. It is unclear that Nietzsche ever had syphilis. He lacked progressive motor and other neurological features of a progressive syphilitic central nervous system (CNS) infection and lived at least 12 years following the onset of his CNS signs, which would be extremely rare for patients with untreated GPI. Finally, his flourish of productivity in 1888 would be quite uncharacteristic of GPI, but in keeping with reports of burgeoning creativity at some point in the progression of frontotemporal dementia (FTD). We suggest that Nietzsche did not have GPI, but died from a chronic dementia, namely FTD.

Utilisation of formal and informal care and services at home among persons with dementia: a cross-sectional study.

PubMed

Bökberg, Christina; Ahlström, Gerd; Karlsson, Staffan

2017-09-04

The progression of dementia disease implies increasing needs for both informal and formal care and services but also risk of institutionalisation. To better adjust care and services in the phase preceding institutionalisation it is important to find out whether utilisation of formal and informal care and services is determined by increased needs and by who meets the needs. The aim was to compare persons with dementia (65+) with different levels of cognitive impairment, regarding utilisation of formal and informal care and service at home. The participants consisted of 177 persons with dementia ≥65 years old and at risk of nursing home admission, divided into groups according to their cognitive function. Structured interviews were conducted based on questionnaires about type and amount of formal and informal care utilised, as well as questions regarding cognitive impairment, dependency in activities of daily living (ADLs) and neuropsychiatric symptoms. To analyse the data, descriptive and comparative statistics were used. The findings revealed that the group with severe dementia used significantly more help with ADLs and supervision in terms of time (number of hours and days) provided by the informal caregiver, compared with the group with moderate dementia. Utilisation of formal care and services was highest in the group with the most severe cognitive impairments (Standardized Mini-Mental State Examination score of <9). The group with severe dementia were more dependent in ADLs and had more neuropsychiatric symptoms (hallucinations and motor disturbances). They were younger and more often cohabitated with the informal caregiver, compared with the group with moderate dementia. This study shows that in the phase preceding institutionalisation the ADL and supervision needs due to progression of dementia appear to tend to be met first and foremost by the informal caregivers. © 2017 Nordic College of Caring Science.

Natural course and predictors of severe disability and death in Thai patients with dementia.

PubMed

Dharmasaroja, Pornpatr A; Lolekha, Praween; Kulkantrakorn, Kongkiat; Charernboon, Thammanard; Watcharakorn, Arvemas; Piyabhan, Pritsana

2017-12-01

More than half of patients with dementia lived in countries with low and middle incomes. However, there have been few studies on the natural course of disease in these countries. The purpose of this study was to study the natural course and the predictive factors of advanced stage and death in Thai patients with dementia. Patients with dementia who were treated in neurologic and psychiatric clinic from September 2004 to February 2016, were included. Data about natural course of diseases, behavioral and psychological symptoms in dementia (BPSD) and complications were studied. 207 patients were included. Mean age was 77years old. Mean Thai Mental State Examination (TMSE) was 17.5. Alzheimer's disease was the most common cause of dementia (55%). With the mean follow-up of 39months (range from 2 to 126months), 64% of the patients had BPSD. Sixty-two patients (30%) had complications required admission. Seven patients died. Fifty-four patients (29%) ended in the advanced stage of dementia. Mean duration from diagnosis to the advanced stage was 49months. Complications that required admission usually occurred in moderate to severe dementia and were strongly associated with the advanced stage or death (OR 6.1, 95%CI 2.57-14.49, p-value<0.0001). Alzheimer's disease was the most common cause of dementia in the study. Most demented patients presented in moderate severity of dementia. Mean duration from diagnosis to the advanced stage of dementia was approximate 4-5years. Complications required admissions related to the progression to advanced stage or death. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multiple imputation for estimating the risk of developing dementia and its impact on survival.

PubMed

Yu, Binbing; Saczynski, Jane S; Launer, Lenore

2010-10-01

Dementia, Alzheimer's disease in particular, is one of the major causes of disability and decreased quality of life among the elderly and a leading obstacle to successful aging. Given the profound impact on public health, much research has focused on the age-specific risk of developing dementia and the impact on survival. Early work has discussed various methods of estimating age-specific incidence of dementia, among which the illness-death model is popular for modeling disease progression. In this article we use multiple imputation to fit multi-state models for survival data with interval censoring and left truncation. This approach allows semi-Markov models in which survival after dementia depends on onset age. Such models can be used to estimate the cumulative risk of developing dementia in the presence of the competing risk of dementia-free death. Simulations are carried out to examine the performance of the proposed method. Data from the Honolulu Asia Aging Study are analyzed to estimate the age-specific and cumulative risks of dementia and to examine the effect of major risk factors on dementia onset and death.

Coexisting cerebral infarction in Alzheimer's disease is associated with fast dementia progression: applying the National Institute for Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences Neuroimaging Criteria in Alzheimer's Disease with Concomitant Cerebral Infarction.

PubMed

Sheng, Bun; Cheng, Lik Fai; Law, Chun Bon; Li, Ho Lun; Yeung, Kwan Mo; Lau, Kwok Kwong

2007-06-01

To determine whether patients with Alzheimer's disease (AD) and coexisting cerebral infarction (CI) that satisfy the National Institute for Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) neuroimaging criteria for vascular dementia (VaD) progress faster than those who do not satisfy the neuroimaging criteria. Retrospective cohort study. Multidisciplinary memory clinic in a tertiary hospital. One hundred thirty consecutive patients with AD, with or without CI, followed up regularly for more than 1 year. The patients were classified according to the distribution and severity of CI as defined according to the NINDS-AIREN neuroimaging criteria into those with AD and no CI (AD-N), those with AD and CI not fulfilling neuroimaging criteria (AD-I), and those with AD and CI fulfilling neuroimaging criteria (AD-V), and their differences in dementia progression were tested. The loss of independence, indicated by institution admission or a clinical dementia rating (CDR) score of 3, was defined as the endpoint for a poor outcome. The mean age was 75.8, and 68.5% were women. The initial Mini-Mental State Examination (MMSE) score was 15.3+/-0.4, and the average duration of follow up was 30.4 months. Fifty-four patients had reached study endpoint at the time of analysis. AD-V (hazard ratio (HR)=3.1, 95% confidence interval (CI)=1.2-8.2), use of psychotropic drugs (HR=2.7, 95% CI=1.1-6.4), and initial MMSE score (HR=0.9, 95% CI=0.8-1.0) were independent predictors of poor outcome in the Cox regression model. In AD, co-occurrence of CI with distribution and severity as defined in the NINDS-AIREN neuroimaging criteria for VaD is associated with faster dementia progression.

Association between advanced glycation end-products and functional performance in Alzheimer's disease and mixed dementia.

PubMed

Drenth, Hans; Zuidema, Sytse U; Krijnen, Wim P; Bautmans, Ivan; van der Schans, Cees; Hobbelen, Hans

2017-09-01

People with Alzheimer's disease (AD) experience, in addition to the progressive loss of cognitive functions, a decline in functional performance such as mobility impairment and disability in activities of daily living (ADL). Functional decline in dementia is mainly linked to the progressive brain pathology. Peripheral biomechanical changes by advanced glycation end-products (AGEs) have been suggested but have yet to be thoroughly studied. A multi-center, longitudinal, one-year follow-up cohort study was conducted in 144 people with early stage AD or mixed Alzheimer's/Vascular dementia. Linear mixed model analyses was used to study associations between AGE-levels (AGE reader) and mobility (Timed Up and Go), and ADL (Groningen Activity Restriction Scale and Barthel index), respectively. A significant association between AGE levels and mobility (β = 3.57, 95%CI: 1.43-5.73) was revealed; however, no significant association between AGE levels and ADL was found. Over a one-year time span, mean AGE levels significantly increased, and mobility and ADL performance decreased. Change in AGE levels was not significantly correlated with change in mobility. This study indicates that high AGE levels could be a contributing factor to impaired mobility but lacks evidence for an association with ADL decline in people with early stage AD or mixed dementia. Future research is necessary on the reduction of functional decline in dementia regarding the effectiveness of interventions such as physical activity programs and dietary advice possibly in combination with pharmacologic strategies targeting AGE accumulation.

Tea, talk and technology: patient and public involvement to improve connected health 'wearables' research in dementia.

PubMed

Hassan, Lamiece; Swarbrick, Caroline; Sanders, Caroline; Parker, Angela; Machin, Matt; Tully, Mary P; Ainsworth, John

2017-01-01

There are a growing number of mobile phones, watches and electronic devices which can be worn on the body to track aspects of health and well-being, such as daily steps, sleep and exercise. Dementia researchers think that these devices could potentially be used as part of future research projects, for example to help spot changes in daily activity that may signal the early symptoms of dementia. We asked a range of older people, including people living with dementia and their carers, to participate in interactive discussions about how future participants might find using these devices as part of research projects. We also invited volunteers to borrow a range of devices to test at home, giving them further insights. Discussions revealed that people were generally supportive of this type of research, provided they gave informed consent and that devices were discreet, comfortable and easy to use. They also valued technical support and regular feedback on study progress to encourage ongoing participation. These findings were used to develop a pool of devices for researchers, with computer software and written guidance to help plan, design and support studies. Our work shows that when given the right opportunities, people who are affected by dementia can provide valuable insights that can enhance the design, delivery and quality of future research. Background Increasingly, researchers are recognising the potential for connected health devices, including smartphones and smartwatches, to generate high resolution data about patterns of daily activity and health outcomes. One aim of the Dementias Platform UK (DPUK) project is to provide researchers with a secure means to collect, collate and link data generated by such devices, thereby accelerating this type of research in the field of dementia. We aimed to involve members of the public in discussions about the acceptability and feasibility of different devices and research designs to inform the development of a device pool, software platform and written guidance to support future studies. Methods Over 30 people attended a series of interactive workshops, drop-in sessions and meetings in Greater Manchester. This included people living with dementia and cognitive impairments, carers and people without memory problems. Discussions were tailored to suit different audiences and focused on the feasibility and acceptability of a range of different wearable devices and research designs. We also invited volunteers to borrow a device to test at home, enabling further insights from hands-on interactions with devices. Results Discussions revealed that people were supportive of connected health dementia research in principle, provided they gave informed consent and that devices were discreet, comfortable and easy to use. Moreover, they recommended technical support and regular feedback on study progress to encourage ongoing participation. Conclusion By using a range of discussion-based and practical activities, we found it was feasible to involve people affected by dementia and use their insights to shape the development of a software platform and device pool to support future connected health dementia research. We recommend that researchers planning such studies in future pay adequate attention to designing suitable participant information, technical support and mechanisms of providing study progress updates to support sustained engagement from participants.

The Time Course of Neurolinguistic and Neuropsychological Symptoms in Three Cases of Logopenic Primary Progressive Aphasia

ERIC Educational Resources Information Center

Etcheverry, Louise; Seidel, Barbara; Grande, Marion; Schulte, Stephanie; Pieperhoff, Peter; Sudmeyer, Martin; Minnerop, Martina; Binkofski, Ferdinand; Huber, Walter; Grodzinsky, Yosef; Amunts, Katrin; Heim, Stefan

2012-01-01

Primary progressive aphasia (PPA) is a rare clinical dementia syndrome affecting predominantly language abilities. Word-finding difficulties and comprehension deficits despite relatively preserved cognitive functions are characteristic symptoms during the first two years, and distinguish PPA from other dementia types like Alzheimer's disease.…

Comparison of Informal Care Time and Costs in Different Age-Related Dementias: A Review

PubMed Central

Costa, Nadège; Ferlicoq, Laura; Derumeaux-Burel, Hélène; Rapp, Thomas; Garnault, Valérie; Gillette-Guyonnet, Sophie; Andrieu, Sandrine; Vellas, Bruno; Lamure, Michel; Grand, Alain; Molinier, Laurent

2013-01-01

Objectives. Age-related dementia is a progressive degenerative brain syndrome whose prevalence increases with age. Dementias cause a substantial burden on society and on families who provide informal care. This study aims to review the relevant papers to compare informal care time and costs in different dementias. Methods. A bibliographic search was performed on an international medical literature database (MEDLINE). All studies which assessed the social economic burden of different dementias were selected. Informal care time and costs were analyzed in three care settings by disease stages. Results. 21 studies met our criteria. Mean informal care time was 55.73 h per week for Alzheimer disease and 15.8 h per week for Parkinson disease (P = 0.0076), and the associated mean annual informal costs were $17,492 versus $3,284, respectively (P = 0.0393). Conclusion. There is a lack of data about informal care time and costs among other dementias than AD or PD. Globally, AD is the most costly in terms of informal care costs than PD, $17,492 versus $3,284, respectively. PMID:23509789

The Effects of Intellectual, Physical, and Social Activity on Further Prognosis in Mild Cognitive Impairment.

PubMed

Bidzan, Leszek; Bidzan, Mariola; Pąchalska, Maria

2016-07-19

BACKGROUND Our goal was to specify the relationship between the level of activity (intellectual, physical, and social) in persons diagnosed with mild cognitive impairment (MCI) and the further progression of cognitive dysfunction. MATERIAL AND METHODS We examined 193 patients diagnosed with MCI (according to the criteria of the Working Group on Mild Cognitive Impairment) and under treatment at our Mental Disorders Clinic. It was assumed that these persons would remain under systematic psychiatric observation until dementia was diagnosed. The present study results from a seven-year observation period. The mini-mental state examination (MMSE), the Activity Scale (with the intellectual, physical, and social subscales), and the Instrumental Activities of Daily Living (IADL) scale were used to evaluate the participants' status at baseline. The MMSE was re-administered after one year and again at the end of the observation (either upon diagnosis of dementia or after seven years). At each meeting with the participant, the clinical diagnosis was verified to determine if the patient had dementia or not. Of the 193 people initially qualified for the study, 75 were available for the final analysis. RESULTS It was found that there was no statistically significant difference in the baseline MMSE scores between the persons with stable MCI and the persons who had progressed to dementia. However, statistically significant differences in the level of activity at baseline on both the global IADL scale and the Activity Scale between those with stable MCI and those who had progressed to dementia were found. These differences were manifested in the IADL subscales for telephone use, shopping, transportation, and personal finances, and in the physical activity subscale. CONCLUSIONS An evaluation of intellectual, physical, and social activity can be useful in determining the prognosis for the future course of MCI.

The Feasibility of a Structured Cognitive Training Protocol to Address Progressive Cognitive Decline in Individuals with Vascular Dementia

ERIC Educational Resources Information Center

Mayer, Jamie F.; Bishop, Lilli A.; Murray, Laura L.

2012-01-01

Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, better known as CADASIL, is a rare, genetic form of early-onset vascular dementia. The purpose of this study was to use a modified version of Attention Process Training--II (APT-II; Sohlberg, Johnson, Paule, Raskin, & Mateer, 2001) with an…

Who pays and who benefits? How different models of shared responsibilities between formal and informal carers influence projections of costs of dementia management

PubMed Central

2011-01-01

Background The few studies that have attempted to estimate the future cost of caring for people with dementia in Australia are typically based on total prevalence and the cost per patient over the average duration of illness. However, costs associated with dementia care also vary according to the length of the disease, severity of symptoms and type of care provided. This study aimed to determine more accurately the future costs of dementia management by taking these factors into consideration. Methods The current study estimated the prevalence of dementia in Australia (2010-2040). Data from a variety of sources was recalculated to distribute this prevalence according to the location (home/institution), care requirements (informal/formal), and dementia severity. The cost of care was attributed to redistributed prevalences and used in prediction of future costs of dementia. Results Our computer modeling indicates that the ratio between the prevalence of people with mild/moderate/severe dementia will change over the three decades from 2010 to 2040 from 50/30/20 to 44/32/24. Taking into account the severity of symptoms, location of care and cost of care per hour, the current study estimates that the informal cost of care in 2010 is AU$3.2 billion and formal care at AU$5.0 billion per annum. By 2040 informal care is estimated to cost AU$11.6 billion and formal care $AU16.7 billion per annum. Interventions to slow disease progression will result in relative savings of 5% (AU$1.5 billion) per annum and interventions to delay disease onset will result in relative savings of 14% (AU$4 billion) of the cost per annum. With no intervention, the projected combined annual cost of formal and informal care for a person with dementia in 2040 will be around AU$38,000 (in 2010 dollars). An intervention to delay progression by 2 years will see this reduced to AU$35,000. Conclusions These findings highlight the need to account for more than total prevalence when estimating the costs of dementia care. While the absolute values of cost of care estimates are subject to the validity and reliability of currently available data, dynamic systems modeling allows for future trends to be estimated. PMID:21988908

Cognitive impairment categorized in community-dwelling older adults with and without dementia using in-home sensors that recognise activities of daily living

NASA Astrophysics Data System (ADS)

Urwyler, Prabitha; Stucki, Reto; Rampa, Luca; Müri, René; Mosimann, Urs P.; Nef, Tobias

2017-02-01

Cognitive impairment due to dementia decreases functionality in Activities of Daily Living (ADL). Its assessment is useful to identify care needs, risks and monitor disease progression. This study investigates differences in ADL pattern-performance between dementia patients and healthy controls using unobtrusive sensors. Around 9,600 person-hours of activity data were collected from the home of ten dementia patients and ten healthy controls using a wireless-unobtrusive sensors and analysed to detect ADL. Recognised ADL were visualized using activity maps, the heterogeneity and accuracy to discriminate patients from healthy were analysed. Activity maps of dementia patients reveal unorganised behaviour patterns and heterogeneity differed significantly between the healthy and diseased. The discriminating accuracy increases with observation duration (0.95 for 20 days). Unobtrusive sensors quantify ADL-relevant behaviour, useful to uncover the effect of cognitive impairment, to quantify ADL-relevant changes in the course of dementia and to measure outcomes of anti-dementia treatments.

Promoting continence in individuals with dementia.

PubMed

Specht, Janet K

2011-02-01

Urinary incontinence (UI) is common in individuals with dementia as the disease progresses. The primary reasons for incontinence are often not related to pathology in the urinary system but are frequently attributed to losses associated with dementia. This article discusses the scope of the problem of UI in individuals with dementia, possible causes, and assessment methods, as well as interventions that can achieve improved outcomes. Copyright 2011, SLACK Incorporated.

Effects of General Medical Health on Alzheimer Progression: the Cache County Dementia Progression Study

PubMed Central

Leoutsakos, Jeannie-Marie S.; Han, Dingfen; Mielke, Michelle M.; Forrester, Sarah N.; Tschanz, JoAnn T.; Corcoran, Chris D.; Green, Robert C.; Norton, Maria C.; Welsh-Bohmer, Kathleen A.; Lyketsos, Constantine G.

2012-01-01

Background Several observational studies suggested a link between health status and rate of decline among individuals with Alzheimer’s disease (AD). We sought to quantify the relationship in a population-based study of incident AD, and to compare global comorbidity ratings to counts of comorbid conditions and medications as predictors of AD progression. Methods Design Case-only cohort study arising from population-based longitudinal study of memory and aging. Setting Cache County, Utah Participants 335 individuals with incident AD followed for up to 11 years. Measurements Patient descriptors included sex, age, education, dementia duration at baseline, and APOE genotype. Measures of health status made at each visit included the GMHR (General Medical Health Rating), number of comorbid medical conditions, and number of non-psychiatric medications. Dementia outcomes included the Mini-Mental State Exam (MMSE), Clinical Dementia Rating – sum of boxes (CDR-sb), and the Neuropsychiatric Inventory (NPI). Results Health Status tended to fluctuate over time within individuals. None of the baseline medical variables (GMHR, comorbidities, non-psychiatric medications) were associated with differences in rates of decline in longitudinal linear mixed effects models. Over time, low GMHR ratings, but not comorbidities or medications, were associated with poorer outcomes (MMSE: β=−1.07 p=0.01; CDR-sb: β=1.79 p<0.001; NPI: β=4.57 p=0.01) Conclusions Given that time-varying GMHR, but not baseline GMHR, was associated with the outcomes, there is likely a dynamic relationship between medical and cognitive health. GMHR is a more sensitive measure of health than simple counts of comorbidities or medications. Since health status is a potentially modifiable risk factor, further study is warranted. PMID:22687143

Effects of general medical health on Alzheimer's progression: the Cache County Dementia Progression Study.

PubMed

Leoutsakos, Jeannie-Marie S; Han, Dingfen; Mielke, Michelle M; Forrester, Sarah N; Tschanz, JoAnn T; Corcoran, Chris D; Green, Robert C; Norton, Maria C; Welsh-Bohmer, Kathleen A; Lyketsos, Constantine G

2012-10-01

Several observational studies have suggested a link between health status and rate of decline among individuals with Alzheimer's disease (AD). We sought to quantify the relationship in a population-based study of incident AD, and to compare global comorbidity ratings to counts of comorbid conditions and medications as predictors of AD progression. This was a case-only cohort study arising from a population-based longitudinal study of memory and aging, in Cache County, Utah. Participants comprised 335 individuals with incident AD followed for up to 11 years. Patient descriptors included sex, age, education, dementia duration at baseline, and APOE genotype. Measures of health status made at each visit included the General Medical Health Rating (GMHR), number of comorbid medical conditions, and number of non-psychiatric medications. Dementia outcomes included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating - sum of boxes (CDR-sb), and the Neuropsychiatric Inventory (NPI). Health status tended to fluctuate over time within individuals. None of the baseline medical variables (GMHR, comorbidities, and non-psychiatric medications) was associated with differences in rates of decline in longitudinal linear mixed effects models. Over time, low GMHR ratings, but not comorbidities or medications, were associated with poorer outcomes (MMSE: β = -1.07 p = 0.01; CDR-sb: β = 1.79 p < 0.001; NPI: β = 4.57 p = 0.01). Given that time-varying GMHR, but not baseline GMHR, was associated with the outcomes, it seems likely that there is a dynamic relationship between medical and cognitive health. GMHR is a more sensitive measure of health than simple counts of comorbidities or medications. Since health status is a potentially modifiable risk factor, further study is warranted.

Predicting progression of mild cognitive impairment to dementia using neuropsychological data: a supervised learning approach using time windows.

PubMed

Pereira, Telma; Lemos, Luís; Cardoso, Sandra; Silva, Dina; Rodrigues, Ana; Santana, Isabel; de Mendonça, Alexandre; Guerreiro, Manuela; Madeira, Sara C

2017-07-19

Predicting progression from a stage of Mild Cognitive Impairment to dementia is a major pursuit in current research. It is broadly accepted that cognition declines with a continuum between MCI and dementia. As such, cohorts of MCI patients are usually heterogeneous, containing patients at different stages of the neurodegenerative process. This hampers the prognostic task. Nevertheless, when learning prognostic models, most studies use the entire cohort of MCI patients regardless of their disease stages. In this paper, we propose a Time Windows approach to predict conversion to dementia, learning with patients stratified using time windows, thus fine-tuning the prognosis regarding the time to conversion. In the proposed Time Windows approach, we grouped patients based on the clinical information of whether they converted (converter MCI) or remained MCI (stable MCI) within a specific time window. We tested time windows of 2, 3, 4 and 5 years. We developed a prognostic model for each time window using clinical and neuropsychological data and compared this approach with the commonly used in the literature, where all patients are used to learn the models, named as First Last approach. This enables to move from the traditional question "Will a MCI patient convert to dementia somewhere in the future" to the question "Will a MCI patient convert to dementia in a specific time window". The proposed Time Windows approach outperformed the First Last approach. The results showed that we can predict conversion to dementia as early as 5 years before the event with an AUC of 0.88 in the cross-validation set and 0.76 in an independent validation set. Prognostic models using time windows have higher performance when predicting progression from MCI to dementia, when compared to the prognostic approach commonly used in the literature. Furthermore, the proposed Time Windows approach is more relevant from a clinical point of view, predicting conversion within a temporal interval rather than sometime in the future and allowing clinicians to timely adjust treatments and clinical appointments.

Effects of a progressive muscle relaxation intervention on dementia symptoms, activities of daily living, and immune function in group home residents with dementia in Japan

PubMed Central

Momose, Yumiko

2016-01-01

Aim To evaluate the effects of progressive muscle relaxation on the behavioral and psychological symptoms of dementia, activities of daily living, and immune function of elderly patients with dementia in group homes. Methods The participants were ranked by their group home unit. Odd ranks were assigned to the intervention group and even ranks to the control group. The intervention group participated in progressive muscle relaxation for 15 min each day for 90 days in the group environment; the control group members continued with their normal routine. All the participants’ secretory immunoglobulin A was measured and they were assessed with the Neuropsychiatric Inventory‐Nursing Home version, Nishimura Mental State Scale for the Elderly, and Nishimura Activities of Daily Living Scale. Results The intervention group comprised 18 participants from six units and the control group comprised 19 participants from five units. After the intervention, the Neuropsychiatric Inventory scores were significantly better in the intervention group, particularly for Agitation and Anxiety. The intervention group also showed significantly lower Apathy and Irritability scores and significant improvement in the Interest, Volition, and Social relationships scores on the Mental State Scale, with improvement in the activities of daily living total. However, there was no difference in the secretory immunoglobulin A level between the groups. Conclusion The results suggest that progressive muscle relaxation improves the behavioral and psychological symptoms of dementia and activities of daily living in group home residents with dementia, but does not affect their immune function. PMID:27696678

Mild Cognitive Impairment in Parkinson's Disease-What Is It?

PubMed

Weil, Rimona S; Costantini, Alyssa A; Schrag, Anette E

2018-03-10

Mild cognitive impairment is a common feature of Parkinson's disease, even at the earliest disease stages, but there is variation in the nature and severity of cognitive involvement and in the risk of conversion to Parkinson's disease dementia. This review aims to summarise current understanding of mild cognitive impairment in Parkinson's disease. We consider the presentation, rate of conversion to dementia, underlying pathophysiology and potential biomarkers of mild cognitive impairment in Parkinson's disease. Finally, we discuss challenges and controversies of mild cognitive impairment in Parkinson's disease. Large-scale longitudinal studies have shown that cognitive involvement is important and common in Parkinson's disease and can present early in the disease course. Recent criteria for mild cognitive impairment in Parkinson's provide the basis for further study of cognitive decline and for the progression of different cognitive phenotypes and risk of conversion to dementia. Improved understanding of the underlying pathology and progression of cognitive change are likely to lead to opportunities for early intervention for this important aspect of Parkinson's disease.

A review of ethical issues in dementia.

PubMed

Johnson, Rebecca A; Karlawish, Jason

2015-10-01

Dementia raises many ethical issues. The present review, taking note of the fact that the stages of dementia raise distinct ethical issues, focuses on three issues associated with stages of dementia's progression: (1) how the emergence of preclinical and asymptomatic but at-risk categories for dementia creates complex questions about preventive measures, risk disclosure, and protection from stigma and discrimination; (2) how despite efforts at dementia prevention, important research continues to investigate ways to alleviate clinical dementia's symptoms, and requires additional human subjects protections to ethically enroll persons with dementia; and (3) how in spite of research and prevention efforts, persons continue to need to live with dementia. This review highlights two major themes. First is how expanding the boundaries of dementias such as Alzheimer's to include asymptomatic but at-risk persons generate new ethical questions. One promising way to address these questions is to take an integrated approach to dementia ethics, which can include incorporating ethics-related data collection into the design of a dementia research study itself. Second is the interdisciplinary nature of ethical questions related to dementia, from health policy questions about insurance coverage for long-term care to political questions about voting, driving, and other civic rights and privileges to economic questions about balancing an employer's right to a safe and productive workforce with an employee's rights to avoid discrimination on the basis of their dementia risk. The review highlights these themes and emerging ethical issues in dementia.

Impact of SSRI Therapy on Risk of Conversion From Mild Cognitive Impairment to Alzheimer's Dementia in Individuals With Previous Depression.

PubMed

Bartels, Claudia; Wagner, Michael; Wolfsgruber, Steffen; Ehrenreich, Hannelore; Schneider, Anja

2018-03-01

Depression is associated with an increased risk of Alzheimer's disease. Research has shown that the selective serotonin reuptake inhibitor (SSRI) citalopram decreases amyloid-β generation and plaque load. The authors evaluated the impact of SSRI treatment on CSF biomarkers and progression from mild cognitive impairment (MCI) to Alzheimer's dementia. Data sets from 755 currently nondepressed participants from the longitudinal Alzheimer's Disease Neuroimaging Initiative were evaluated by Kaplan-Meier analysis and analyses of variance and covariance with ApoE4 status and age as covariates. In MCI patients with a history of depression, long-term SSRI treatment (>4 years) was significantly associated with a delayed progression to Alzheimer's dementia by approximately 3 years, compared with short-term SSRI treatment, treatment with other antidepressants, or no treatment and compared with MCI patients without a history of depression. No differences in CSF biomarker levels were observed between treatment groups. Long-term SSRI treatment may delay progression from MCI to Alzheimer's dementia.

Visual Versus Fully Automated Analyses of 18F-FDG and Amyloid PET for Prediction of Dementia Due to Alzheimer Disease in Mild Cognitive Impairment.

PubMed

Grimmer, Timo; Wutz, Carolin; Alexopoulos, Panagiotis; Drzezga, Alexander; Förster, Stefan; Förstl, Hans; Goldhardt, Oliver; Ortner, Marion; Sorg, Christian; Kurz, Alexander

2016-02-01

Biomarkers of Alzheimer disease (AD) can be imaged in vivo and can be used for diagnostic and prognostic purposes in people with cognitive decline and dementia. Indicators of amyloid deposition such as (11)C-Pittsburgh compound B ((11)C-PiB) PET are primarily used to identify or rule out brain diseases that are associated with amyloid pathology but have also been deployed to forecast the clinical course. Indicators of neuronal metabolism including (18)F-FDG PET demonstrate the localization and severity of neuronal dysfunction and are valuable for differential diagnosis and for predicting the progression from mild cognitive impairment (MCI) to dementia. It is a matter of debate whether to analyze these images visually or using automated techniques. Therefore, we compared the usefulness of both imaging methods and both analyzing strategies to predict dementia due to AD. In MCI participants, a baseline examination, including clinical and imaging assessments, and a clinical follow-up examination after a planned interval of 24 mo were performed. Of 28 MCI patients, 9 developed dementia due to AD, 2 developed frontotemporal dementia, and 1 developed moderate dementia of unknown etiology. The positive and negative predictive values and the accuracy of visual and fully automated analyses of (11)C-PiB for the prediction of progression to dementia due to AD were 0.50, 1.00, and 0.68, respectively, for the visual and 0.53, 1.00, and 0.71, respectively, for the automated analyses. Positive predictive value, negative predictive value, and accuracy of fully automated analyses of (18)F-FDG PET were 0.37, 0.78, and 0.50, respectively. Results of visual analyses were highly variable between raters but were superior to automated analyses. Both (18)F-FDG and (11)C-PiB imaging appear to be of limited use for predicting the progression from MCI to dementia due to AD in short-term follow-up, irrespective of the strategy of analysis. On the other hand, amyloid PET is extremely useful to rule out underlying AD. The findings of the present study favor a fully automated method of analysis for (11)C-PiB assessments and a visual analysis by experts for (18)F-FDG assessments. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

DMARD use is associated with a higher risk of dementia in patients with rheumatoid arthritis: A propensity score-matched case-control study.

PubMed

Chou, Ming-Hsien; Wang, Jong-Yi; Lin, Cheng-Li; Chung, Wei-Sheng

2017-11-01

Patients with rheumatoid arthritis (RA) exhibit an increased risk of dementia. Disease-modifying antirheumatic drugs (DMARDs) are commonly used to slow RA progression, but studies investigating the relationship between DMARDs and dementia in patients with RA are lacking. We investigated the relationship between DMARDs and dementia in patients with RA. Using the National Health Insurance Research Database, patients aged ≥20years, who were newly diagnosed with RA between 2000 and 2011 were identified. Patients with RA who had dementia comprised the dementia group, and patients with RA who did not have dementia comprised the control group. The groups were matched at a 1:1 ratio by the propensity score. DMARDs were categorized into conventional synthetic DMARDs (csDMARDs) and biological DMARDs (bDMARDs). Logistic regression models were used to calculate the odds ratio and 95% confidence interval (CI) to evaluate the association between DMARD use and the risk of dementia in patients with RA. A total of 957 patients with RA and dementia, and 957 patients with RA but not dementia, were enrolled. The risk of dementia was determined to be 1.63-fold higher in patients with RA with csDMARD use than in those without csDMARD use (95% CI=1.33-2.00). No significant risk of dementia was observed in patients with RA who used bDMARDs compared with their counterparts. However, patients with RA who used hydroxychloroquine, methotrexate, and sulfasalazine exhibited significant risks of dementia, irrespective of cumulative exposure days. Patients with RA who used csDMARDs exhibit significant association with dementia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

How preserved is episodic memory in behavioral variant frontotemporal dementia?

PubMed

Hornberger, M; Piguet, O; Graham, A J; Nestor, P J; Hodges, J R

2010-02-09

Studies have shown variable memory performance in patients with behavioral variant frontotemporal dementia (bvFTD). Our study investigated whether this variability is due to the admixture of patients with true bvFTD and phenocopy patients. We also sought to compare performance of patients with bvFTD and patients with Alzheimer disease (AD). We analyzed neuropsychological memory performance in patients with a clinical diagnosis of bvFTD divided into those who progressed (n = 50) and those who remained stable (n = 39), patients with AD (n = 64), and healthy controls (n = 64). Patients with progressive bvFTD were impaired on most memory tests to a similar level to that of patients with early AD. Findings from a subset of patients with progressive bvFTD with confirmed FTLD pathology (n = 10) corroborated these findings. By contrast, patients with phenocopy bvFTD performed significantly better than progressors and patients with AD. Logistic regression revealed that patients with bvFTD can be distinguished to a high degree (85%) on the immediate recall score of a word list learning test (Rey Auditory Verbal Learning Test). Our results provide evidence for an underlying memory deficit in "real" or progressive behavioral variant frontotemporal dementia (bvFTD) similar to Alzheimer disease, though the groups differ in orientation scores, with patients with bvFTD being intact. Exclusion solely based on impaired neuropsychological memory performance can potentially lead to an underdiagnosis of FTD.

Biomarkers of aggression in dementia.

PubMed

Gotovac, Kristina; Nikolac Perković, Matea; Pivac, Nela; Borovečki, Fran

2016-08-01

Dementia is a clinical syndrome defined by progressive global impairment of acquired cognitive abilities. It can be caused by a number of underlying conditions. The most common types of dementia are Alzheimer's disease (AD), frontotemporal dementia (FTD), vascular cognitive impairment (VCI) and dementia with Lewy bodies (DLB). Despite the fact that cognitive impairment is central to the dementia, noncognitive symptoms, most commonly described nowadays as neuropsychiatric symptoms (NPS) exist almost always at certain point of the illness. Aggression as one of the NPS represents danger both for patients and caregivers and the rate of aggression correlates with the loss of independence, cognitive decline and poor outcome. Therefore, biomarkers of aggression in dementia patients would be of a great importance. Studies have shown that different genetic factors, including monoamine signaling and processing, can be associated with various NPS including aggression. There have been significant and multiple neurotransmitter changes identified in the brains of patients with dementia and some of these changes have been involved in the etiology of NPS. Aggression specific changes have also been observed in neuropathological studies. The current consensus is that the best approach for development of such biomarkers may be incorporation of genetics (polymorphisms), neurobiology (neurotransmitters and neuropathology) and neuroimaging techniques. Copyright © 2016 Elsevier Inc. All rights reserved.

Frontotemporal Dementia

PubMed Central

Olney, Nicholas T.; Spina, Salvatore; Miller, Bruce L.

2017-01-01

Frontotemporal Dementia (FTD) is a heterogeneous disorder with distinct clinical phenotypes associated with multiple neuropathologic entities. Presently, the term FTD encompasses clinical disorders that include changes in behavior, language, executive control and often motor symptoms. The core FTD spectrum disorders include: behavioral variant FTD (bvFTD), nonfluent/agrammatic variant primary progressive aphasia (nfvPPA), and semantic variant PPA (svPPA). Related FTD disorders include frontotemporal dementia with motor neuron disease (FTD-MND), progressive supranuclear palsy syndrome (PSP-S) and corticobasal syndrome (CBS). In this chapter we will discuss the clinic presentation, diagnostic criteria, neuropathology, genetics and treatments of these disorders. PMID:28410663

Association between periodontal disease and dementia: A literature review.

PubMed

Pazos, P; Leira, Y; Domínguez, C; Pías-Peleteiro, J M; Blanco, J; Aldrey, J M

2016-10-22

Periodontal disease and dementia are very prevalent, especially in elderly populations. Multiple studies have shown a link between these diseases; however, the conditions are highly heterogeneous and so is the diagnostic methodology, which may hinder interpretation and comparison of the results. The aim of this article is to provide a critical review of the literature linking these 2 processes. We retrieved 22 studies, most of which were retrospective, and analysed various methodological variables including study population, diagnosis of periodontitis, definition of dementia, adjusted variables, and results. The different aetiopathogenic mechanisms that may affect the progression and interaction of these 2 conditions were also analysed. Although available evidence indicates a positive association between periodontitis and dementia, both the strength of that association and the presence of a causal relationship have yet to be determined. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Systematic review of quantitative clinical gait analysis in patients with dementia.

PubMed

van Iersel, M B; Hoefsloot, W; Munneke, M; Bloem, B R; Olde Rikkert, M G M

2004-02-01

Diminished mobility often accompanies dementia and has a great impact on independence and quality of life. New treatment strategies for dementia are emerging, but the effects on gait remains to be studied objectively. In this review we address the general effects of dementia on gait as revealed by quantitative gait analysis. A systematic literature search with the (MESH) terms: 'dementia' and 'gait disorders' in Medline, CC, Psychlit and CinaHL between 1980-2002. Main inclusion criteria: controlled studies; patients with dementia; quantitative gait data. Seven publications met the inclusion criteria. All compared gait in Alzheimer's Disease (AD) with healthy elderly controls; one also assessed gait in Vascular Dementia (VaD). The methodology used was inconsistent and often had many shortcomings. However, there were several consistent findings: walking velocity decreased in dementia compared to healthy controls and decreased further with progressing severity of dementia. VaD was associated with a significant decrease in walking velocity compared to AD subjects. Dementia was associated with a shortened step length, an increased double support time and step to step variability. Gait in dementia is hardly analyzed in a well-designed manner. Despite this, the literature suggests that quantitative gait analysis can be sufficiently reliable and responsive to measure decline in walking velocity between subjects with and without dementia. More research is required to assess, both on an individual and a group level, how the minimal clinically relevant changes in gait in elderly demented patients should be defined and what would be the most responsive method to measure these changes.

Bilingualism as a protection against the onset of symptoms of dementia.

PubMed

Bialystok, Ellen; Craik, Fergus I M; Freedman, Morris

2007-01-28

This study examined the effect of lifelong bilingualism on maintaining cognitive functioning and delaying the onset of symptoms of dementia in old age. The sample was selected from the records of 228 patients referred to a Memory Clinic with cognitive complaints. The final sample consisted of 184 patients diagnosed with dementia, 51% of whom were bilingual. The bilinguals showed symptoms of dementia 4 years later than monolinguals, all other measures being equivalent. Additionally, the rate of decline in Mini-Mental State Examination (MMSE) scores over the 4 years subsequent to the diagnosis was the same for a subset of patients in the two groups, suggesting a shift in onset age with no change in rate of progression.

Vitamin E in aging persons with Down syndrome: A randomized, placebo-controlled clinical trial.

PubMed

Sano, Mary; Aisen, Paul S; Andrews, Howard F; Tsai, Wei-Yann; Lai, Florence; Dalton, Arthur J

2016-05-31

To determine whether vitamin E would slow the progression of cognitive deterioration and dementia in aging persons with Down syndrome (DS). A randomized, double-blind controlled clinical trial was conducted at 21 clinical sites, and researchers trained in research procedures recruited adults with DS older than 50 years to participate. Participants were randomly assigned to receive 1,000 IU of vitamin E orally twice daily for 3 years or identical placebo. The primary outcome was change on the Brief Praxis Test (BPT). Secondary outcomes included incident dementia and measures of clinical global change, cognition, function, and behavior. A total of 337 individuals were randomized, 168 to vitamin E and 169 to placebo. Both groups demonstrated deterioration on the BPT with no difference between drug and placebo. At baseline, 26% were diagnosed with dementia and there was an overall rate of incident dementia of 11%/year with no difference between groups. There was no effect on the secondary outcome measures. Though numerically higher in the treatment group, there was no difference in the number of adverse events (p = 0.079) and deaths (p = 0.086) between groups. Vitamin E did not slow the progression of cognitive deterioration in older individuals with DS. This study provides Class II evidence that vitamin E does not significantly slow the progression of cognitive deterioration in aging persons with DS. © 2016 American Academy of Neurology.

Infective dementias.

PubMed

Ironside, J W; Bell, J E

2007-12-01

A wide range of infectious diseases can result in dementia, although the identity and nature of these diseases has changed over time. Two of the most significant current groups in terms of scientific complexity are HIV/AIDS and prion diseases. In these disorders, dementia occurs either as a consequence of targeting the brain and selectively damaging neurones, or by an indirect effect of neuroinflammation. In prion diseases, both direct neurotoxicity and neuroinflammation may act to result in neuronal damage. In HIV encephalitis, the progression of the dementia is slower, perhaps reflecting indirect damage that appears to result from neuroinflammation as a main cause of neuronal death. An ever-increasing range of model systems is now available to study the neuronal damage in infectious dementias, ranging from cell culture systems to animal models, some of which, particularly in the case of prion diseases, are very well characterised and amenable to controlled manipulation in terms of both host and agent parameters. As valuable as these experimental models are, they do not allow a direct approach to an understanding of dementia, the complexities of which cannot readily be studied in vitro or in animal models, but they do allow studies of interventions and therapeutic strategies. This review summarises the current state of knowledge regarding the major infective dementias.

Scaffolding and working together: a qualitative exploration of strategies for everyday life with dementia.

PubMed

McCabe, Louise; Robertson, Jane; Kelly, Fiona

2018-03-01

living with dementia has been described as a process of continual change and adjustment, with people with dementia and their families adopting informal strategies to help manage everyday life. As dementia progresses, families increasingly rely on help from the wider community and formal support. this article reports on a secondary analysis of qualitative data from focus groups and individual interviews with people with dementia and their carers in the North of England. In total, 65 people with dementia and 82 carers took part in the research: 26 in interviews and 121 in focus groups. Focus group and interview audio recordings were transcribed verbatim. A qualitative, inductive, thematic approach was taken for data analysis. the article applies the metaphor of scaffolding to deepen understanding of the strategies used by families. Processes of scaffolding were evident across the data where families, communities, professionals and services worked together to support everyday life for people with dementia. Within this broad theme of scaffolding were three sub-themes characterising the experiences of families living with dementia: doing things together; evolving strategies; and fragility and fear of the future. families with dementia are resourceful but do need increasing support (scaffolding) to continue to live as well as possible as dementia progresses. More integrated, proactive work is required from services that recognises existing scaffolds and provides appropriate support before informal strategies become unsustainable; thus enabling people with dementia to live well for longer. © The Author(s) 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com

Knowledge of Dementia: Do family members understand dementia as a terminal condition?

PubMed

Andrews, Sharon; McInerney, Fran; Toye, Christine; Parkinson, Camillus-Anthony; Robinson, Andrew

2017-07-01

Current research identifies advanced dementia to be the terminal phase of this progressive and incurable condition. However, there has been relatively little investigation into how family members of people with advanced dementia understand their relative's condition. In this article, we report on semi-structured interviews with 10 family members of people with advanced dementia, in a residential aged care facility. Using a qualitative, descriptive design, we explored family members' understandings of dementia, whether they were aware that it was a terminal condition, and the ways they developed their understandings. Findings revealed that the majority of family members could not recognize the terminal nature of dementia. Relying on predominantly lay understandings, they had little access to formal information and most failed to conceptualize a connection between dementia and death. Moreover, family members engaged in limited dialogue with aged care staff about such issues, despite their relatives being in an advanced stage of the disease. Findings from our study suggest that how family members understand their relative's condition requires greater attention. The development of staff/family partnerships that promote shared communication about dementia and dying may enhance family members' understandings of the dementia trajectory and the types of decisions they may be faced with during the more advanced stages of the disease.

Frontotemporal Degeneration in a Child.

PubMed

Terrill, Tyler; Pascual, Juan M

2017-07-01

There is a predilection for the frontal and temporal lobes in certain cases of dementia in the adult, leading to the syndrome of frontotemporal dementia. However, this syndrome has seemed to elude the developing brain until now. We describe an example of apparently selective neurodegeneration of the frontal and temporal regions during development associated with some of the clinical, magnetic resonance imaging, and fludeoxyglucose positron emission tomography (FDG PET) scan features of canonical frontotemporal dementia in the adult. This patient does not have any of the common frontotemporal dementia-causing mutations or known progressive brain disorders of children. This patient illustrates that symptomatic, selective, and progressive vulnerability of the frontal and temporal lobes is not restricted to adulthood, expanding the phenotype of frontotemporal degeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Dementia Guide for Carers and Care Providers.

PubMed

2017-05-10

This app is for carers of people with dementia. Developed by Health Education England's Thames Valley team in partnership with the University of Reading and in collaboration with healthcare professionals and carers, it offers practical information to support users' understanding of the progressive nature of dementia and the challenges of caring for someone with the condition.

Sudden-On-Chronic Death and Complicated Grief in Bereaved Dementia Caregivers: Two Case Studies of Complicated Grief Group Therapy.

PubMed

Supiano, Katherine P; Andersen, Troy C; Haynes, Lara Burns

2015-01-01

Caring for a person with Alzheimer's disease is challenging and often has negative health and mental health effects that, for 7-20% of caregivers, persist into bereavement in the form of complicated grief. Complicated grief is a state of prolonged and ineffective mourning. An under-recognized phenomenon in dementia care and bereavement is "sudden-on-chronic death." In these situations, the caregiver is preparing for a gradual dying process from dementia, but the care recipient dies instead from a sudden death. In this study, an application of complicated grief group therapy for bereaved dementia caregivers with complicated grief is presented, and the effect of therapy with two bereaved caregivers who experienced the sudden death of their spouses who had a diagnosis of dementia is described. The unique treatment elements of complicated grief group therapy facilitated resolution of the 'trauma-like" features of bereavement and progression to a healthy grief process.

Research-based theatre: The making of I'm Still Here!

PubMed

Mitchell, Gail J; Jonas-Simpson, Christine; Ivonoffski, Vrenia

2006-07-01

This column describes the process undertaken by a team of researchers, artists, and actors to create a research-based drama about living with dementia. Researchers had several studies, guided by the human becoming theory, about what life was like when living with dementia, and an additional study in progress about the lived experience of loss for daughters whose mothers were diagnosed with Alzheimer's disease. Researchers partnered with an experienced artistic director and playwright in order to craft a script and performance that could help others understand and see life with dementia in a new light. The crafting of the script was also informed by the experiences and insights of actors, healthcare professionals, and persons living with dementia. The play premiered before a group of 100 persons and families living with dementia and has since been performed approximately 40 times to hundreds of professionals and families. The evaluation of the play, at six of the performances, is presented in this column.

Development of an exercise intervention to improve cognition in people with mild to moderate dementia: Dementia And Physical Activity (DAPA) Trial, registration ISRCTN32612072.

PubMed

Brown, Deborah; Spanjers, Katie; Atherton, Nicky; Lowe, Janet; Stonehewer, Louisa; Bridle, Chris; Sheehan, Bart; Lamb, Sarah E

2015-06-01

More than 800000 people in the UK have dementia, and it is a government priority to improve dementia care. Drug treatment options are relatively limited. The Dementia And Physical Activity (DAPA) study is a randomised trial which targets cognition in people with dementia, using an exercise programme. There is evidence to suggest that both aerobic and resistance exercise may be useful in improving cognition. Hence the intervention comprises a supervised part of twice-weekly exercise classes of one hour duration for 4 months, including aerobic exercise at moderate intensity on static bicycles, and resistance (weight training) exercise using weight vests, weight belts and dumbbells. Thereafter participants progress to unsupervised, independent exercise. Aids to behaviour modification have been incorporated into the intervention. The DAPA intervention has been designed to maximise likelihood of effectiveness and cost-effectiveness, and for delivery in the UK National Health Service. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Couples with dementia: Positioning the 'we'.

PubMed

Hydén, Lars-Christer; Nilsson, Elin

2015-11-01

The aim of this article is to investigate how spouses in couples with dementia position themselves in relation to each other by analysing their use of pronouns, especially the we. The study uses joint interviews with 11 couples. Based on a quantitative analysis of pronoun use, it is argued that the pronoun we is used by all the spouses; however, it is used less frequently by the spouses with dementia in comparison with healthy spouses. A qualitative analysis of the use of the pronoun we shows that the spouses position, experience and consider themselves as a couple and that they position and experience themselves as individuals in relation to the couple. One of the challenges for couples with dementia is to be able to retain a we in face of the progression of the dementia disease. By positioning themselves in various ways, the spouses establish and negotiate quite a complex and emotionally charged web of relationships. © The Author(s) 2013.

Long-term cognitive decline in older subjects was not attributable to non-cardiac surgery or major illness

PubMed Central

Avidan, Michael S; FCASA; Searleman, Adam C; Storandt, Martha; Barnett, Kara; Vannucci, Andrea; Saager, Leif; Xiong, Chengjie; Grant, Elizabeth A; Kaiser, Dagmar; Morris, John C; Evers, Alex S

2009-01-01

Background Persistent postoperative cognitive decline is thought to be a public health problem, but its severity may have been overestimated because of limitations in statistical methodology. This study assessed whether long-term cognitive decline occurred after surgery or illness by using an innovative approach and including participants with early Alzheimer's disease to overcome some limitations. Methods In this retrospective cohort study, three groups were identified from participants tested annually at Washington University's Alzheimer Disease Research Center in St. Louis: those with non-cardiac surgery, illness, or neither. This enabled long-term tracking of cognitive function before and after surgery and illness. The effect of surgery and illness on longitudinal cognitive course was analyzed using a general linear mixed effects model. For participants without initial dementia, time to dementia onset was analyzed using sequential Cox proportional hazards regression. Results Of the 575 participants, 214 were nondemented and 361 had very mild or mild dementia at enrollment. Cognitive trajectories did not differ among the three groups (surgery, illness, control), although demented participants declined more markedly than nondemented. Of the initially nondemented participants, 23% progressed to a clinical dementia rating greater than zero, but this was not more common following surgery or illness. Conclusions The study did not detect long-term cognitive decline independently attributable to surgery or illness nor were these events associated with accelerated progression to dementia. The decision to proceed with surgery in elderly people, including those with early Alzheimer's disease, may presently be made without factoring in the specter of persistent cognitive deterioration. PMID:19786858

Long-term cognitive decline in older subjects was not attributable to noncardiac surgery or major illness.

PubMed

Avidan, Michael S; Searleman, Adam C; Storandt, Martha; Barnett, Kara; Vannucci, Andrea; Saager, Leif; Xiong, Chengjie; Grant, Elizabeth A; Kaiser, Dagmar; Morris, John C; Evers, Alex S

2009-11-01

Persistent postoperative cognitive decline is thought to be a public health problem, but its severity may have been overestimated because of limitations in statistical methodology. This study assessed whether long-term cognitive decline occurred after surgery or illness by using an innovative approach and including participants with early Alzheimer disease to overcome some limitations. In this retrospective cohort study, three groups were identified from participants tested annually at the Washington University Alzheimer's Disease Research Center in St. Louis, Missouri: those with noncardiac surgery, illness, or neither. This enabled long-term tracking of cognitive function before and after surgery and illness. The effect of surgery and illness on longitudinal cognitive course was analyzed using a general linear mixed effects model. For participants without initial dementia, time to dementia onset was analyzed using sequential Cox proportional hazards regression. Of the 575 participants, 214 were nondemented and 361 had very mild or mild dementia at enrollment. Cognitive trajectories did not differ among the three groups (surgery, illness, control), although demented participants declined more markedly than nondemented participants. Of the initially nondemented participants, 23% progressed to a clinical dementia rating greater than zero, but this was not more common after surgery or illness. The study did not detect long-term cognitive decline independently attributable to surgery or illness, nor were these events associated with accelerated progression to dementia. The decision to proceed with surgery in elderly people, including those with early Alzheimer disease, may be made without factoring in the specter of persistent cognitive deterioration.

Self-Awareness and Self-Monitoring of Cognitive and Behavioral Deficits in Behavioral Variant Frontotemporal Dementia, Primary Progressive Aphasia and Probable Alzheimer's Disease

ERIC Educational Resources Information Center

Banks, Sarah; Weintraub, Sandra

2008-01-01

Lack of insight is a core diagnostic criterion for behavioral variant frontotemporal dementia (bvFTD), and is believed to be intact in the early stages of primary progressive aphasia (PPA). In other neurological conditions, symptom-specific insight has been noted, with behavioral symptoms appearing especially vulnerable to reduced insight.…

Late-life dementia. Review of the APA guidelines for patient management.

PubMed

Schindler, R J; Cucio, C P

2000-10-01

Management of dementia in older patients requires an individualized and multimodal approach that involves use of psychiatric, psychotherapeutic, psychosocial, and somatic tools and treatments, in addition to patient and family education. The progressive nature of dementia and the invariable presence of comorbidity complicates the management task, although symptoms characteristic of dementia's phases can provide helpful clinical clues to guide evolving care. In 1997, the American Psychiatric Association published the "Practice guideline for the treatment of patients with Alzheimer's disease and other dementias of late life." To date, this is the most comprehensive clinical guideline available to physicians caring for patients with Alzheimer's disease and other related dementias.

Prevalence and conversion to dementia of Mild Cognitive Impairment in an elderly Italian population.

PubMed

Limongi, Federica; Siviero, Paola; Noale, Marianna; Gesmundo, Antonella; Crepaldi, Gaetano; Maggi, Stefania

2017-06-01

Mild Cognitive Impairment (MCI) represents a significant risk factor for dementia but there are only a few Italian population studies on its prevalence and its rate of conversion to dementia. Aim of this study was to assess the prevalence of MCI, its subtypes, and rates of conversion to dementia 1 year later in an elderly Italian population. The data are based on an Italian multicenter population-based cohort study with both cross-sectional and longitudinal components. Two thousand three hundred thirty-seven individuals over 65 underwent screening, clinical confirmation and 1-year follow-up. The prevalence of MCI was 21.6% and the amnestic multiple domain was the most frequent subtype (63.2%). The conversion rate to dementia was 4.1% and was found only in the amnestic multiple domain and in the unclassifiable subjects, persons with cognitive deficit but neither demented nor with MCI. The prevalence of MCI in this population sample was similar to that found in other population studies using Petersen's modified MCI criteria as well as his original criteria. With regard to conversion to dementia, our results emphasize the importance to better classify the unclassifiable subjects at high risk of progression to dementia and also at risk of being undiagnosed and untreated. MCI is characterized by extreme variability and instability. Data on the prevalence and the rate of conversion from MCI to dementia are difficult to compare given the important differences from study to study especially with regard to the diagnostic criteria utilized and their operationalization.

Buying time: a rationale for examining the use of circadian rhythm and sleep interventions to delay progression of mild cognitive impairment to Alzheimer's disease.

PubMed

Landry, Glenn J; Liu-Ambrose, Teresa

2014-01-01

As of 2010, the worldwide economic impact of dementia was estimated at $604 billion USD; and without discovery of a cure or effective interventions to delay disease progression, dementia's annual global economic impact is expected to surpass $1 trillion USD as early as 2030. Alzheimer's disease (AD) is the leading cause of dementia accounting for over 75% of all cases. Toxic accumulation of amyloid beta (Aβ), either by overproduction or some clearance failure, is thought to be an underlying mechanism of the neuronal cell death characteristic of AD-though this amyloid hypothesis has been increasingly challenged in recent years. A compelling alternative hypothesis points to chronic neuroinflammation as a common root in late-life degenerative diseases including AD. Apolipoprotein-E (APOE) genotype is the strongest genetic risk factor for AD: APOE-ε4 is proinflammatory and individuals with this genotype accumulate more Aβ, are at high risk of developing AD, and almost half of all AD patients have at least one ε4 allele. Recent studies suggest a bidirectional relationship exists between sleep and AD pathology. Sleep may play an important role in Aβ clearance, and getting good quality sleep vs. poor quality sleep might reduce the AD risk associated with neuroinflammation and the ε4 allele. Taken together, these findings are particularly important given the sleep disruptions commonly associated with AD and the increased burden disrupted sleep poses for AD caregivers. The current review aims to: (1) identify individuals at high risk for dementia who may benefit most from sleep interventions; (2) explore the role poor sleep quality plays in exacerbating AD type dementia; (3) examine the science of sleep interventions to date; and (4) provide a road map in pursuit of comprehensive sleep interventions, specifically targeted to promote cognitive function and delay progression of dementia.

Helping Memory-Impaired Elders: A Guide for Caregivers. A Pacific Northwest Extension Publication. PNW 314.

ERIC Educational Resources Information Center

Schmall, Vicki L.; Cleland, Marilyn

This cooperative extension bulletin is designed to help family and professional caregivers understand dementia in later life and learn to cope more effectively with the changes resulting from a progressive dementing illness. The first three sections describe the differences between senility and dementia, causes of dementia, and adjustments that…

Feasibility of Machine-Based Prompting to Assist Persons with Dementia

ERIC Educational Resources Information Center

Bewernitz, Megan Witte; Mann, William C.; Dasler, Patricia; Belchior, Patricia

2009-01-01

Nearly 14% of people over age 71 have some form of dementia, with prevalence increasing to nearly 40% of those over age 90. As dimentia progresses, it impacts a person's independent functions and can increase the burden on caregivers. The use of assistive devices can help individuals with dementia live more independently. However, older…

Professional Carers' Experiences of Caring for Individuals with Intellectual Disability and Dementia: A Review of the Literature

ERIC Educational Resources Information Center

Cleary, Josephine; Doody, Owen

2017-01-01

The number of people with intellectual disability living into old age and developing dementia continues to increase. Dementia presents a wide range of challenges for staff due to progressive deterioration. This article presents the findings from a narrative literature review of professional caregivers' experiences of caring for individuals with…

Narrative Interest Standard: A Novel Approach to Surrogate Decision-Making for People With Dementia.

PubMed

Wilkins, James M

2017-06-17

Dementia is a common neurodegenerative process that can significantly impair decision-making capacity as the disease progresses. When a person is found to lack capacity to make a decision, a surrogate decision-maker is generally sought to aid in decision-making. Typical bases for surrogate decision-making include the substituted judgment standard and the best interest standard. Given the heterogeneous and progressive course of dementia, however, these standards for surrogate decision-making are often insufficient in providing guidance for the decision-making for a person with dementia, escalating the likelihood of conflict in these decisions. In this article, the narrative interest standard is presented as a novel and more appropriate approach to surrogate decision-making for people with dementia. Through case presentation and ethical analysis, the standard mechanisms for surrogate decision-making for people with dementia are reviewed and critiqued. The narrative interest standard is then introduced and discussed as a dementia-specific model for surrogate decision-making. Through incorporation of elements of a best interest standard in focusing on the current benefit-burden ratio and elements of narrative to provide context, history, and flexibility for values and preferences that may change over time, the narrative interest standard allows for elaboration of an enriched context for surrogate decision-making for people with dementia. More importantly, however, a narrative approach encourages the direct contribution from people with dementia in authoring the story of what matters to them in their lives.

Utility of behavioral versus cognitive measures in differentiating between subtypes of frontotemporal lobar degeneration and Alzheimer's disease.

PubMed

Heidler-Gary, Jennifer; Gottesman, Rebecca; Newhart, Melissa; Chang, Shannon; Ken, Lynda; Hillis, Argye E

2007-01-01

We hypothesized that a modified version of the Frontal Behavioral Inventory (FBI-mod), along with a few cognitive tests, would be clinically useful in distinguishing between clinically defined Alzheimer's disease (AD) and subtypes of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (dysexecutive type), progressive nonfluent aphasia, and semantic dementia. We studied 80 patients who were diagnosed with AD (n = 30) or FTLD (n = 50), on the basis of a comprehensive neuropsychological battery, imaging, neurological examination, and history. We found significant between-group differences on the FBI-mod, two subtests of the Rey Auditory Verbal Learning Test (verbal learning and delayed recall), and the Trail Making Test Part B (one measure of 'executive functioning'). AD was characterized by relatively severe impairment in verbal learning, delayed recall, and executive functioning, with relatively normal scores on the FBI-mod. Frontotemporal dementia was characterized by relatively severe impairment on the FBI-mod and executive functioning in the absence of severe impairment in verbal learning and recall. Progressive nonfluent aphasia was characterized by severe impairment in executive functioning with relatively normal scores on verbal learning and recall and FBI-mod. Finally, semantic dementia was characterized by relatively severe deficits in delayed recall, but relatively normal performance on new learning, executive functioning, and on FBI-mod. Discriminant function analysis confirmed that the FBI-mod, in conjunction with the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B categorized the majority of patients as subtypes of FTLD or AD in the same way as a full neuropsychological battery, neurological examination, complete history, and imaging. These tests may be useful for efficient clinical diagnosis, although progressive nonfluent aphasia and semantic dementia are likely to be best distinguished by language tests not included in standard neuropsychological test batteries.

Correlates Among Nocturnal Agitation, Sleep, and Urinary Incontinence in Dementia

PubMed Central

Rose, Karen; Specht, Janet; Forch, Windy

2016-01-01

Family caregivers of elders with dementia often face the challenging behaviors of nighttime agitation, sleep disturbances, and urinary incontinence. To date, no study has examined the interrelationships of these behaviors in community-dwelling persons. This single group, descriptive study employs wireless body sensors to objectively collect data on nighttime agitation, sleep, and urinary incontinence in patients with dementia in their homes over a 5- to 7-day period. The aims are to (1) examine the feasibility and acceptability of the use of body sensors in community-dwelling persons with dementia; (2) describe patterns of nocturnal agitation, sleep continuity and duration, and nighttime urinary incontinence; and (3) examine the relationships among nocturnal agitation, sleep continuity and duration, and nighttime urinary incontinence. Data collection is in early stages and is still in progress. Challenges and advantages from preliminary data collection are reported. PMID:24670931

Motor Speech Phenotypes of Frontotemporal Dementia, Primary Progressive Aphasia, and Progressive Apraxia of Speech.

PubMed

Poole, Matthew L; Brodtmann, Amy; Darby, David; Vogel, Adam P

2017-04-14

Our purpose was to create a comprehensive review of speech impairment in frontotemporal dementia (FTD), primary progressive aphasia (PPA), and progressive apraxia of speech in order to identify the most effective measures for diagnosis and monitoring, and to elucidate associations between speech and neuroimaging. Speech and neuroimaging data described in studies of FTD and PPA were systematically reviewed. A meta-analysis was conducted for speech measures that were used consistently in multiple studies. The methods and nomenclature used to describe speech in these disorders varied between studies. Our meta-analysis identified 3 speech measures which differentiate variants or healthy control-group participants (e.g., nonfluent and logopenic variants of PPA from all other groups, behavioral-variant FTD from a control group). Deficits within the frontal-lobe speech networks are linked to motor speech profiles of the nonfluent variant of PPA and progressive apraxia of speech. Motor speech impairment is rarely reported in semantic and logopenic variants of PPA. Limited data are available on motor speech impairment in the behavioral variant of FTD. Our review identified several measures of speech which may assist with diagnosis and classification, and consolidated the brain-behavior associations relating to speech in FTD, PPA, and progressive apraxia of speech.

Association of Lower Spiritual Well-Being, Social Support, Self-Esteem, Subjective Well-Being, Optimism and Hope Scores With Mild Cognitive Impairment and Mild Dementia.

PubMed

Dos Santos, Sabrina B; Rocha, Gabrielli P; Fernandez, Liana L; de Padua, Analuiza C; Reppold, Caroline T

2018-01-01

Introduction: Positive psychology (PP) constructs contribute significantly to a better quality of life for people with various diseases. There are still few studies that have evaluated the evolution of these aspects during the progression of dementia. Objective: To compare the scores for self-esteem, life satisfaction, affect, spirituality, hope, optimism and perceived support network between elderly people with mild cognitive impairment (MCI), mild dementia and moderate dementia and control group. Methods: Cross-sectional study. The sample consisted of 66 healthy controls, 15 elderly people with MCI, 25 with mild dementia and 22 with moderate dementia matched by age, gender, and schooling. The instruments used were: Spirituality Self Rating Scale (SSRS), Rosenberg Self-Esteem Scale, Medical Outcomes Study's Social Support Scale, Life Satisfaction Scale (LSS), Positive and Negative Affect Schedule (PANAS), Revised Life Orientation Test (LOT-R), and Adult Dispositional Hope Scale (ADHS). Results: The scores for spiritual well-being, social support, self-esteem, life satisfaction, positive affect, optimism, negative affect, and hope differed significantly between the groups ( p < 0.05). The individuals with MCI and mild dementia had lower spiritual well-being, social support, self-esteem, life satisfaction, positive affect, optimism and hope scores, and higher negative affect scores compared with the controls. The scores for PP constructs did not differ between the group of people with moderate dementia and the control group. Conclusion: Dementia was found to impact several PP constructs in the early stages of the disease. For individuals with greater cognitive impairment, anosognosia appears to suppress the disease's impact on these constructs.

Progression to dementia in memory clinic patients without dementia: a latent profile analysis.

PubMed

Köhler, Sebastian; Hamel, Renske; Sistermans, Nicole; Koene, Ted; Pijnenburg, Yolande A L; van der Flier, Wiesje M; Scheltens, Philip; Visser, Pieter-Jelle; Aalten, Pauline; Verhey, Frans R J; Ramakers, Inez

2013-10-08

To identify the existence of discrete cognitive subtypes among memory clinic patients without dementia and test their prognostic values. In a retrospective cohort study of 635 patients without dementia visiting the Alzheimer centers in Maastricht or Amsterdam, latent profile analysis identified cognitive subtypes based on immediate and delayed memory recall, delayed recognition, information-processing speed, attention, verbal fluency, and executive functions. Time to dementia was tested in weighted Cox proportional hazard models adjusted for confounders. Five latent classes represented participants with high-normal cognition (15%), low-normal cognition (37%), primary memory impairment in recall (MI) (36%), memory impairment in recall and recognition (MI+) (5%), and primary nonmemory impairment (NMI) (6%). Compared with low-normal cognition, participants with NMI had the highest risk of dementia (hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 3.46-10.18) followed by MI (HR = 3.05, 95% CI = 2.09-4.46) and MI+ (HR = 3.26, 95% CI = 1.72-6.17), while participants with high-normal cognition had the lowest risk (HR = 0.24, 95% CI = 0.07-0.80). Subtypes further showed differential relationships with dementia types, with MI and MI+ most often converting to Alzheimer-type dementia and NMI to other forms of dementia. Cognitive subtypes can be empirically identified in otherwise heterogeneous samples of memory clinic patients and largely confirm current strategies to distinguish between amnestic and nonamnestic impairment. Studying more homogeneous cognitive subtypes may improve understanding of disease mechanisms and outcomes.

Palliative care in advanced dementia.

PubMed

Merel, Susan E; Merel, Susan; DeMers, Shaune; Vig, Elizabeth

2014-08-01

Because neurodegenerative dementias are progressive and ultimately fatal, a palliative approach focusing on comfort, quality of life, and family support can have benefits for patients, families, and the health system. Elements of a palliative approach include discussion of prognosis and goals of care, completion of advance directives, and a thoughtful approach to common complications of advanced dementia. Physicians caring for patients with dementia should formulate a plan for end-of-life care in partnership with patients, families, and caregivers, and be prepared to manage common symptoms at the end of life in dementia, including pain and delirium. Copyright © 2014 Elsevier Inc. All rights reserved.

[At-home music therapy intervention using video phone (Skype) for elderly people with dementia].

PubMed

Hori, Miyako; Iizuka, Mieko; Nakamura, Michikazu; Aiba, Ikuko; Saito, Yufuko; Kubota, Masakazu; Urabe, Mie; Kinoshita, Ayae

2014-12-01

There are various nonpharmacological therapies available for elderly people with dementia, and these can improve quality of life and the behavioral and psychological symptoms of dementia (BPSD) that appear throughout the progression of the disease. Since a substantial number of effects have been reported for music therapy, we focused on this nonpharmacological intervention. Generally, musical therapy is provided collectively in facilities. However, the music used in this context may not consider the preferences and music abilities of each person. Therefore, in this study we created made-to-order music CDs that accounted for each participant's musical preferences and abilities. Utilizing the CDs, we conducted an intervention study of music therapy using a video phone (Skype) that elderly people with dementia can use at home. An advantage of conducting music therapy for individuals with dementia using a video phone is that those who have difficulty going to the hospital or participating in dementia-related therapy groups can participate in therapy in a familiar place. The results of this intervention showed that participants demonstrated signs of improvement as measured by the smile degree(Smile scan)and Behavior Pathology in Alzheimer's Disease (BEHAVE-AD) scale.

Mixed dementia: A review of the evidence

PubMed Central

Custodio, Nilton; Montesinos, Rosa; Lira, David; Herrera-Pérez, Eder; Bardales, Yadira; Valeriano-Lorenzo, Lucía

2017-01-01

ABSTRACT. Mixed dementia is the coexistence of Alzheimer's disease and cerebrovascular disease (CVD) in the same demented patient. Currently, its diagnosis and treatment remains a challenge for practitioners. To provide an overview of the epidemiology, pathogenesis, natural history, diagnosis, and therapy of Mixed Vascular-Alzheimer Dementia (MVAD). The literature was reviewed for articles published between 1990-2016 by using the keywords linked to MVAD. Neuropathological studies indicate that MVAD is a very common pathological finding in the elderly with a prevalence about of 22%. The distinction between Alzheimer's dementia and vascular dementia (VD) is complex because their clinical presentation can overlap. There are international criteria for the MVAD diagnosis. The pharmacologic therapy shows modest clinical benefits that are similar among all drugs used in patients with Alzheimer's dementia and VD. The non-pharmacologic therapy includes the rigorous management of cardiovascular risk factors (especially hypertension) and the promotion of a healthy diet. The diagnosis and treatment of MVAD cannot be improved without further studies. Currently available medications provide only modest clinical benefits once a patient has developed MVAD. In subjects at risk, the antihypertensive therapy and healthy diet should be recommend for preventing or slowing the progression of MVAD. PMID:29354216

Mixed dementia: A review of the evidence.

PubMed

Custodio, Nilton; Montesinos, Rosa; Lira, David; Herrera-Pérez, Eder; Bardales, Yadira; Valeriano-Lorenzo, Lucía

2017-01-01

Mixed dementia is the coexistence of Alzheimer's disease and cerebrovascular disease (CVD) in the same demented patient. Currently, its diagnosis and treatment remains a challenge for practitioners. To provide an overview of the epidemiology, pathogenesis, natural history, diagnosis, and therapy of Mixed Vascular-Alzheimer Dementia (MVAD). The literature was reviewed for articles published between 1990-2016 by using the keywords linked to MVAD. Neuropathological studies indicate that MVAD is a very common pathological finding in the elderly with a prevalence about of 22%. The distinction between Alzheimer's dementia and vascular dementia (VD) is complex because their clinical presentation can overlap. There are international criteria for the MVAD diagnosis. The pharmacologic therapy shows modest clinical benefits that are similar among all drugs used in patients with Alzheimer's dementia and VD. The non-pharmacologic therapy includes the rigorous management of cardiovascular risk factors (especially hypertension) and the promotion of a healthy diet. The diagnosis and treatment of MVAD cannot be improved without further studies. Currently available medications provide only modest clinical benefits once a patient has developed MVAD. In subjects at risk, the antihypertensive therapy and healthy diet should be recommend for preventing or slowing the progression of MVAD.

Genetics Home Reference: CHMP2B-related frontotemporal dementia

MedlinePlus

... CHMP2B -related frontotemporal dementia develop progressive problems with speech and language (aphasia). They may have trouble speaking, although they can often understand others' speech and written text. Affected individuals may also have ...

Observing conversational laughter in frontotemporal dementia

PubMed Central

Pressman, Peter S; Simpson, Michaela; Gola, Kelly; Shdo, Suzanne M; Spinelli, Edoardo G; Miller, Bruce L; Gorno-Tempini, Maria Luisa; Rankin, Katherine; Levenson, Robert W

2017-01-01

Background We performed an observational study of laughter during seminaturalistic conversations between patients with dementia and familial caregivers. Patients were diagnosed with (1) behavioural variant fronto-temporal dementia (bvFTD), (2) right temporal variant frontotemporal dementia (rtFTD), (3) semantic variant of primary progressive aphasia (svPPA), (4) non-fluent variant primary progressive aphasia (nfvPPA) or (5) early onset Alzheimer’s disease (eoAD). We hypothesised that those with bvFTD would laugh less in response to their own speech than other dementia groups or controls, while those with rtFTD would laugh less regardless of who was speaking. Methods Patients with bvFTD (n=39), svPPA (n=19), rtFTD (n=14), nfvPPA (n=16), eoAD (n=17) and healthy controls (n=156) were recorded (video and audio) while discussing a problem in their relationship with a healthy control companion. Using the audio track only, laughs were identified by trained coders and then further classed by an automated algorithm as occurring during or shortly after the participant’s own vocalisation (‘self’ context) or during or shortly after the partner’s vocalisation (‘partner’ context). Results Individuals with bvFTD, eoAD or rtFTD laughed less across both contexts of self and partner than the other groups. Those with bvFTD laughed less relative to their own speech compared with healthy controls. Those with nfvPPA laughed more in the partner context compared with healthy controls. Conclusions Laughter in response to one’s own vocalisations or those of a conversational partner may be a clinically useful measure in dementia diagnosis. PMID:28235777

Therapeutic touch and dementia care: an ongoing journey.

PubMed

Doherty, Donna; Wright, Stephen; Aveyard, Barry; Sykes, Meg

2006-12-01

Touch is considered a core aspect of care provision and therapeutic relationships. Therapeutic touch allows nurses to facilitate healing and forge therapeutic relationships through touch or non-touch and maintain channels of communication often lost in dementia as the disease progresses. This article reports the findings of a research project to examine the effectiveness of therapeutic touch in dementia care.

Varying strength of cognitive markers and biomarkers to predict conversion and cognitive decline in an early-stage-enriched mild cognitive impairment sample.

PubMed

Egli, Simone C; Hirni, Daniela I; Taylor, Kirsten I; Berres, Manfred; Regeniter, Axel; Gass, Achim; Monsch, Andreas U; Sollberger, Marc

2015-01-01

Several cognitive, neuroimaging, and cerebrospinal fluid (CSF) markers predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. However, predictors might be more or less powerful depending on the characteristics of the MCI sample. To investigate which cognitive markers and biomarkers predict conversion to AD dementia and course of cognitive functioning in a MCI sample with a high proportion of early-stage MCI patients. Variables known to predict progression in MCI patients and hypothesized to predict progression in early-stage MCI patients were selected. Cognitive (long-delay free recall, regional primacy score), imaging (hippocampal and entorhinal cortex volumes, fornix fractional anisotropy), and CSF (Aβ1-42/t-tau, Aβ1-42) variables from 36 MCI patients were analyzed with Cox regression and mixed-effect models to determine their individual and combined abilities to predict time to conversion to AD dementia and course of global cognitive functioning, respectively. Those variables hypothesized to predict the course of early-stage MCI patients were most predictive for MCI progression. Specifically, regional primacy score (a measure of word-list position learning) most consistently predicted conversion to AD dementia and course of cognitive functioning. Both the prediction of conversion and course of cognitive functioning were maximized by including CSF Aβ1-42 and fornix integrity biomarkers, respectively, indicating the complementary information carried by cognitive variables and biomarkers. Predictors of MCI progression need to be interpreted in light of the characteristics of the respective MCI sample. Future studies should aim to compare predictive strengths of markers between early-stage and late-stage MCI patients.

Postischemic dementia with Alzheimer phenotype: selectively vulnerable versus resistant areas of the brain and neurodegeneration versus β-amyloid peptide.

PubMed

Pluta, Ryszard; Jabłoński, Mirosław; Czuczwar, Stanisław J

2012-01-01

The road to clarity for postischemic dementia mechanisms has been one fraught with a wide range of complications and numerous revisions with a lack of a final solution. Importantly, brain ischemia is a leading cause of death and cognitive impairment worldwide. However, the mechanisms of progressive cognitive decline following brain ischemia are not yet certain. Data from animal models and clinical pioneering studies of brain ischemia have demonstrated an increase in expression and processing of amyloid precursor protein to a neurotoxin oligomeric β-amyloid peptide. Functional and memory brain restoration after ischemic brain injury is delayed and incomplete due to a lesion related increase in the amount of the neurotoxin amyloid protein. Moreover, ischemic injury is strongly accelerated by aging, too. In this review, we will present our current thinking about biogenesis of amyloid from the amyloid precursor protein in ischemic brain injury, and how this factor presents etiological, therapeutic and diagnostic targets that are now under consideration. Progressive injury of the ischemic brain parenchyma may be caused not only by degeneration of selectively vulnerable neurons destroyed during ischemia but also by acute and chronic damage of resistant areas of the brain and progressive damage in the blood-brain barrier. We propose that in postischemic dementia an initial ischemic injury precedes the cerebrovascular and brain parenchyma accumulation of Alzheimer disease related neurotoxin β-amyloid peptide, which in turn amplifies the neurovascular dysfunction triggering focal ischemic episodes as a vicious cycle preceding final neurodegenerative pathology. Persistent ischemic blood-brain barrier insufficiency with accumulation of neurotoxin β-amyloid protein in the brain tissue, especially in extracellular perivascular space and blood-brain barrier microvessels, may gradually, over a lifetime, progress to brain atrophy and to full-blown ischemic dementia with Alzheimer phenotype.

A 3-arm randomized controlled trial on the effects of dance movement intervention and exercises on elderly with early dementia.

PubMed

Ho, Rainbow Tin Hung; Cheung, Jacob Kai Ki; Chan, Wai Chi; Cheung, Irene Kit Man; Lam, Linda Chiu Wah

2015-10-19

Dementia is characterized by a progressive decline and deterioration of brain regions such as memory, spatial navigation and language, along with disturbances in daily functioning. Non-pharmacological interventions that offer a holistic approach by targeting cognitive functioning, prognosis and the psychological and social effects of dementia require rigorous investigation. The well-established benefits of physical activity for cognitive functioning and psychological support in dementia have been observed with dance-movement intervention. There is substantial evidence that dance-movement interventions provide emotional and social advantages. Thus, a randomized controlled trial (RCT) is planned to investigate the positive effects of a dance movement intervention, compared with mild physical exercise, on the physical and psychological well-being of elderly Chinese individuals with early dementia. A 3-arm RCT with waitlist control design will be used in this study. Two hundred and one elderly participants with very mild to mild dementia will be screened and randomized into the following groups: (i) dance movement based intervention, (ii) stretching and exercise intervention and (iii) no intervention waitlist-control group. The two intervention groups will receive a 1-h intervention, twice a week, for 12 weeks. The participants will be assessed four times over the course of 12 months: baseline before randomization, post-intervention (3 months), 6 months from baseline and 12 months from baseline. The primary outcomes will be compared between assessment points and between groups on neuropsychiatric symptoms, psychosocial well-being and cognitive and daily functioning. Secondary outcomes will assess the changes in salivary cortisol levels and their relationships with the primary outcome measures. This study will provide substantial evidence of the efficacy of a dance-movement-based intervention in slowing down dementia progression, due to its ability to act as a buffer against decline and improve areas affected by dementia. We also anticipate an association between cortisol levels and the outcome measures. The further development of this intervention into a structural program may be warranted for early psychosocial support among elderly populations. The trial has been registered in the Chinese Clinical Trial Registry ( ChiCTR-IOR-15006541 ).

Non-Native Language Use and Risk of Incident Dementia in the Elderly

PubMed Central

Sanders, Amy E.; Hall, Charles B.; Katz, Mindy J.; Lipton, Richard B.

2012-01-01

Cognitive reserve is invoked to explain the protective effects of education and cognitively-stimulating activities against all-cause dementia and Alzheimer’s disease (AD). For non-native English speakers (n-NES), speaking English may be a cognitive activity associated with lower dementia risk. We hypothesized that n-NES have lower risk of incident dementia/AD and that educational level might modify this relationship. Participants took part in the Einstein Aging Study (Bronx, NY), a longitudinal study of aging and dementia. All (n = 1779) spoke fluent English and self-reported birthplace and whether English was their first language. n-NES additionally reported mother tongue, age of English acquisition, and current percentile-use of a non-English language. Nested Cox proportional hazards models progressively adjusted for gender, race, education, and immigrant and marital status estimated hazard ratios (HR) for incident dementia/AD as a function of n-NES status. 390 (22%) participants were n-NES. 126 incident dementia cases occurred during 4174 person-years of follow-up (median 1.44; range 0–16); 101 individuals met criteria for probable/possible AD. There was no statistically-significant association between n-NES status and incident dementia in the fully-adjusted model (HR 1.26; 95% CI 0.76–2.09; p = 0.36). Results were similar for AD. Stratification of education into three groups revealed increased risk of dementia for n-NES with ≥16 years of education (HR 3.97; 95% CI 1.62–9.75; p = 0.003). We conclude that n-NES status does not appear to have an independent protective effect against incident dementia/AD, and that n-NES status may contribute to risk of dementia in an education-dependent manner. PMID:22232011

Non-native language use and risk of incident dementia in the elderly.

PubMed

Sanders, Amy E; Hall, Charles B; Katz, Mindy J; Lipton, Richard B

2012-01-01

Cognitive reserve is invoked to explain the protective effects of education and cognitively-stimulating activities against all-cause dementia and Alzheimer's disease (AD). For non-native English speakers (n-NES), speaking English may be a cognitive activity associated with lower dementia risk. We hypothesized that n-NES have lower risk of incident dementia/AD and that educational level might modify this relationship. Participants took part in the Einstein Aging Study (Bronx, NY), a longitudinal study of aging and dementia. All (n = 1779) spoke fluent English and self-reported birthplace and whether English was their first language. n-NES additionally reported mother tongue, age of English acquisition, and current percentile-use of a non-English language. Nested Cox proportional hazards models progressively adjusted for gender, race, education, and immigrant and marital status estimated hazard ratios (HR) for incident dementia/AD as a function of n-NES status. 390 (22%) participants were n-NES. 126 incident dementia cases occurred during 4174 person-years of follow-up (median 1.44; range 0-16); 101 individuals met criteria for probable/possible AD. There was no statistically-significant association between n-NES status and incident dementia in the fully-adjusted model (HR 1.26; 95% CI 0.76-2.09; p = 0.36). Results were similar for AD. Stratification of education into three groups revealed increased risk of dementia for n-NES with ≥ 16 years of education (HR 3.97; 95% CI 1.62-9.75; p = 0.003). We conclude that n-NES status does not appear to have an independent protective effect against incident dementia/AD, and that n-NES status may contribute to risk of dementia in an education-dependent manner.

[Lessons from Guam ALS/PDC study].

PubMed

Asao, Hirano

2007-11-01

An extraordinarily high incidence of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) affecting the native population was discovered on the island of Guam a half century ago. Guam ALS is identical to classic ALS clinically and pathologically while PDC is marked by progressive parkinsonism and dementia. The unusual histological finding in these fetal neurodegenerative diseases is the presence of numerous neurofibrillary tangles in a selective topographic distribution unassociated with senile plaques. There have been remarkable advances in field of age-associated neurodegenerative disease after our initial study of Guam cases. Four noteworthy topics are presented in this communication. 1) Clinically, the coexistence of parkinsonism and dementia was frequently recognized in Parkinson disease and Alzheimer disease. Some other new disease entities characterized by coexistence of parkinsonism and dementia have been reported. These include progressive supranuclear palsy, frontotemporal dementia and parkinsonism linked to chromosome 17. 2) Neuropathologically, abundant neurofibrillary tangles unassociated with senile plaques were demonstrated in many diseases such as aftermath of boxing and tangle-only dementia. Furthermore, tau-positive structures were recognized not only in neurons but in glial cells in certain diseases. Tauopathy is one of the current hot research subjects. 3) Familial aggregation of Guam ALS patients provoked investigation of familial ALS elsewhere. Familial motor neuron disease with SOD1 mutation is the target of worldwide intense investigation at the present time. SOD1 gene mutation is, however, not found in Guam ALS. 4) The most striking findings of the Guam study is the gradual decline in the incidence of ALS on Guam during a quarter century and virtual disappearance of new patients. This may be linked to a remarkable change in environment and life style of the Chamorro population. The etiology of ALS is still unknown and no new treatment is available. Guam ALS/PDC is certainly one of the most mysterious riddles among age-associated neurodegenerative diseases during the last half a century.

Polygenic risk of Alzheimer disease is associated with early- and late-life processes.

PubMed

Mormino, Elizabeth C; Sperling, Reisa A; Holmes, Avram J; Buckner, Randy L; De Jager, Philip L; Smoller, Jordan W; Sabuncu, Mert R

2016-08-02

To examine associations between aggregate genetic risk and Alzheimer disease (AD) markers in stages preceding the clinical symptoms of dementia using data from 2 large observational cohort studies. We computed polygenic risk scores (PGRS) using summary statistics from the International Genomics of Alzheimer's Project genome-wide association study of AD. Associations between PGRS and AD markers (cognitive decline, clinical progression, hippocampus volume, and β-amyloid) were assessed within older participants with dementia. Associations between PGRS and hippocampus volume were additionally examined within healthy younger participants (age 18-35 years). Within participants without dementia, elevated PGRS was associated with worse memory (p = 0.002) and smaller hippocampus (p = 0.002) at baseline, as well as greater longitudinal cognitive decline (memory: p = 0.0005, executive function: p = 0.01) and clinical progression (p < 0.00001). High PGRS was associated with AD-like levels of β-amyloid burden as measured with florbetapir PET (p = 0.03) but did not reach statistical significance for CSF β-amyloid (p = 0.11). Within the younger group, higher PGRS was associated with smaller hippocampus volume (p = 0.05). This pattern was evident when examining a PGRS that included many loci below the genome-wide association study (GWAS)-level significance threshold (16,123 single nucleotide polymorphisms), but not when PGRS was restricted to GWAS-level significant loci (18 single nucleotide polymorphisms). Effects related to common genetic risk loci distributed throughout the genome are detectable among individuals without dementia. The influence of this genetic risk may begin in early life and make an individual more susceptible to cognitive impairment in late life. Future refinement of polygenic risk scores may help identify individuals at risk for AD dementia. © 2016 American Academy of Neurology.

Polygenic risk of Alzheimer disease is associated with early- and late-life processes

PubMed Central

Sperling, Reisa A.; Holmes, Avram J.; Buckner, Randy L.; De Jager, Philip L.; Smoller, Jordan W.; Sabuncu, Mert R.

2016-01-01

Objective: To examine associations between aggregate genetic risk and Alzheimer disease (AD) markers in stages preceding the clinical symptoms of dementia using data from 2 large observational cohort studies. Methods: We computed polygenic risk scores (PGRS) using summary statistics from the International Genomics of Alzheimer's Project genome-wide association study of AD. Associations between PGRS and AD markers (cognitive decline, clinical progression, hippocampus volume, and β-amyloid) were assessed within older participants with dementia. Associations between PGRS and hippocampus volume were additionally examined within healthy younger participants (age 18–35 years). Results: Within participants without dementia, elevated PGRS was associated with worse memory (p = 0.002) and smaller hippocampus (p = 0.002) at baseline, as well as greater longitudinal cognitive decline (memory: p = 0.0005, executive function: p = 0.01) and clinical progression (p < 0.00001). High PGRS was associated with AD-like levels of β-amyloid burden as measured with florbetapir PET (p = 0.03) but did not reach statistical significance for CSF β-amyloid (p = 0.11). Within the younger group, higher PGRS was associated with smaller hippocampus volume (p = 0.05). This pattern was evident when examining a PGRS that included many loci below the genome-wide association study (GWAS)–level significance threshold (16,123 single nucleotide polymorphisms), but not when PGRS was restricted to GWAS-level significant loci (18 single nucleotide polymorphisms). Conclusions: Effects related to common genetic risk loci distributed throughout the genome are detectable among individuals without dementia. The influence of this genetic risk may begin in early life and make an individual more susceptible to cognitive impairment in late life. Future refinement of polygenic risk scores may help identify individuals at risk for AD dementia. PMID:27385740

Study protocol: EXERcise and cognition in sedentary adults with early-ONset dementia (EXERCISE-ON).

PubMed

Hooghiemstra, Astrid M; Eggermont, Laura H P; Scheltens, Philip; van der Flier, Wiesje M; Bakker, Jet; de Greef, Mathieu H G; Koppe, Peter A; Scherder, Erik J A

2012-08-16

Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia. One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an aerobic exercise program in a rehabilitation centre or a flexibility and relaxation program in a rehabilitation centre. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a daily physical activity program set at home making use of pedometers. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures. The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life. The present study is registered within The Netherlands National Trial Register (ref: NTR2124).

Study protocol: EXERcise and Cognition In Sedentary adults with Early-ONset dementia (EXERCISE-ON)

PubMed Central

2012-01-01

Background Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia. Methods/Design One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an aerobic exercise program in a rehabilitation centre or a flexibility and relaxation program in a rehabilitation centre. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a daily physical activity program set at home making use of pedometers. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures. Discussion The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life. Trial registration The present study is registered within The Netherlands National Trial Register (ref: NTR2124) PMID:22897903

Evolution of short cognitive test performance in stroke patients with vascular cognitive impairment and vascular dementia: Baseline evaluation and follow-up.

PubMed

Custodio, Nilton; Montesinos, Rosa; Lira, David; Herrera-Perez, Eder; Bardales, Yadira; Valeriano-Lorenzo, Lucia

2017-01-01

There is limited evidence about the progression of cognitive performance during the post-stroke stage. To assess the evolution of cognitive performance in stroke patients without vascular cognitive impairment (VCI), patients with vascular mild cognitive impairment (MCI), and patients with vascular dementia (VD). A prospective cohort of stroke outpatients from two secondary medical centers in Lima, Peru was studied. We performed standardized evaluations at definitive diagnosis (baseline evaluation), and control follow-ups at 6 and 12 months, including a battery of short cognitive tests: Clinical Dementia Rating (CDR), Addenbrooke's Cognitive Examination (ACE), and INECO Frontal Screening (IFS). 152 outpatients completed the follow-up, showing progressive increase in mean score on the CDR(0.34 to 0.46), contrary to the pattern observed on the ACE and IFS (78.18 to 76.48 and 23.63 to 22.24). The box plot for the CDR test showed that VCI patients had progressive worsening (0.79 to 0.16). Conversely, this trend was not observed in subjects without VCI. The box plot for the ACE and IFS showed that, for the majority of the differentiated stroke types, both non-VCI and VCI patients had progressive worsening. According to both ACE and IFS results during a 1-year follow-up, the cognitive performance of stroke patients worsened, a trend which was particularly consistent in infarction-type stroke patients.

Dementia

PubMed Central

McGuinness, B; Herron, B; Passmore, AP

2015-01-01

Dementia is a clinical diagnosis requiring new functional dependence on the basis of progressive cognitive decline. It is estimated that 1.3% of the entire UK population, or 7.1% of those aged 65 or over, have dementia. Applying these to 2013 population estimates gives an estimated number of 19,765 people living with dementia in Northern Ireland. The clinical syndrome of dementia can be due to a variety of underlying pathophysiological processes. The most common of these is Alzheimer's disease (50-75%) followed by vascular dementia (20%), dementia with Lewy bodies (5%) and frontotemporal lobar dementia (5%). The clinical symptoms and pathophysiological processes of these diseases overlap significantly. Biomarkers to aid diagnosis and prognosis are emerging. Acetylcholinesterase inhibitors and memantine are the only medications currently licensed for the treatment of dementia. The nature of symptoms mean people with dementia are more dependent and vulnerable, both socially and in terms of physical and mental health, presenting evolving challenges to society and to our healthcare systems. PMID:26170481

Evaluation of an Audio-Visual Novela to Improve Beliefs, Attitudes and Knowledge toward Dementia: A Mixed-Methods Approach.

PubMed

Grigsby, Timothy J; Unger, Jennifer B; Molina, Gregory B; Baron, Mel

2017-01-01

Dementia is a clinical syndrome characterized by progressive degeneration in cognitive ability that limits the capacity for independent living. Interventions are needed to target the medical, social, psychological, and knowledge needs of caregivers and patients. This study used a mixed methods approach to evaluate the effectiveness of a dementia novela presented in an audio-visual format in improving dementia attitudes, beliefs and knowledge. Adults from Los Angeles (N = 42, 83% female, 90% Hispanic/Latino, mean age = 42.2 years, 41.5% with less than a high school education) viewed an audio-visual novela on dementia. Participants completed surveys immediately before and after viewing the material. The novela produced significant improvements in overall knowledge (t(41) = -9.79, p < .0001) and led to positive increases in specific attitudes toward people with dementia but not in beliefs that screening would be beneficial. Qualitative results provided concordant and discordant evidence for the quantitative findings. Results indicate that an audio-visual novela can be useful for improving attitudes and knowledge about dementia, but further work is needed to investigate the relation with health disparities in screening and treatment behaviors. Audio visual novelas are an innovative format for health education and change attitudes and knowledge about dementia.

Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia

PubMed Central

Roberts, Rosebud O.; Christianson, Teresa J. H.; Kremers, Walter K.; Mielke, Michelle M.; Machulda, Mary M.; Vassilaki, Maria; Alhurani, Rabe E.; Geda, Yonas E.; Knopman, David S.; Petersen, Ronald C.

2015-01-01

IMPORTANCE To increase the opportunity to delay or prevent mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD), markers of early detection are essential. Olfactory impairment may be an important clinical marker and predictor of these conditions and may help identify persons at increased risk. OBJECTIVE To examine associations of impaired olfaction with incident MCI subtypes, and progression from MCI subtypes to AD dementia. DESIGN, SETTING, AND PARTICIPANTS Participants enrolled in the population-based, prospective Mayo Clinic Study of Aging were clinically evaluated at baseline and every 15-months thereafter, and classified as having normal cognition, MCI (amnestic, aMCI and nonamnestic, naMCI), and dementia. We administered the Brief Smell Identification Test (B-SIT) to assess olfactory function. MAIN OUTCOMES AND MEASURES Mild cognitive impairment, AD dementia, longitudinal change in cognitive performance measures. RESULTS Over a mean 3.5 years of follow-up, there were 250 incident cases of MCI among 1430 cognitively normal participants. We observed an association between decreasing olfactory identification, as measured by decrease in number of correct responses in B-SIT score, and an increased risk of aMCI. Compared to the upper B-SIT quartile (Q4, best scores), hazard ratios (HR) were 1.12; P = 0.68 for Q3; HR, 1.95; P =0.003 for Q2; and HR, 2.18; P = 0.001 (worst scores; p for trend <0.001) after adjustment for sex and education, with age as the time scale. There was no association with naMCI. There were 64 incident dementia cases among 221 prevalent MCI cases. The B-SIT score also predicted progression from aMCI to AD, with a significant dose-response with worsening B-SIT quartiles. Compared to Q4, HR estimates were 3.02, P = 0.038 for Q3; HR, 3.63; P = 0.024 for Q2; and HR, 5.20; P = 0.001 for Q1. After adjusting for key predictors of MCI risk, B-SIT (as a continuous measure) remained a significant predictor of MCI (HR, 1.10; p < 0.001), and improved the model concordance. CONCLUSIONS AND RELEVANCE Olfactory impairment predicts incident aMCI and progression from aMCI to AD. These findings are consistent with previous studies that have reported associations of olfactory impairment with cognitive impairment in late life, and suggest that olfactory tests have potential utility for screening for MCI and MCI that is likely to progress. PMID:26569387

Mild cognitive impairment, amnestic type: an epidemiologic study.

PubMed

Ganguli, Mary; Dodge, Hiroko H; Shen, Changyu; DeKosky, Steven T

2004-07-13

To estimate the prevalence and examine the course of mild cognitive impairment (MCI), amnestic type, using current criteria, within a representative community sample. Retroactive application of MCI criteria to data collected during a prospective epidemiologic study was performed. The subjects were drawn from voter registration lists, composing a cohort of 1,248 individuals with mean age of 74.6 (5.3) years, who were nondemented at entry and who were assessed biennially over 10 years of follow-up. The Petersen amnestic MCI criteria were operationalized as 1) impaired memory: Word List Delayed Recall score of <1 SD below mean; 2) normal mental status: Mini-Mental State Examination score of 25+; 3) normal daily functioning: no instrumental impairments; 4) memory complaint: subjective response to standardized question; 5) not demented: Clinical Dementia Rating Scale score of <1. At the five assessments, amnestic MCI criteria were met by 2.9 to 4.0% of the cohort. Of 40 persons with MCI at the first assessment, 11 (27%) developed dementia over the next 10 years. Over each 2-year interval, MCI persons showed increased risk of dementing (odds ratio = 3.9, 95% CI = 2.1 to 7.2); 11.1 to 16.7% progressed to Alzheimer disease and 0 to 5.0% progressed to other dementias. Over the same intervals, 11.1 to 21.2% of those with MCI remained MCI; of 33.3 to 55.6% who no longer had MCI, half had reverted to normal. In this community-based sample, 3 to 4% of nondemented persons met MCI operational criteria; despite increased risk of progressing to dementia, a substantial proportion also remained stable or reverted to normal during follow-up. Amnestic MCI as currently defined is a high-risk but unstable and heterogeneous group.

Digging Into the Mysteries of Delirium | NIH MedlinePlus the Magazine

MedlinePlus

... from dementia? Delirium is an acute change in cognitive function, primarily characterized by confusion and which may wax ... wane—whereas dementia is a progressive decline in cognitive function that occurs over months and years. Does delirium ...

Correlation between Cognition and Function across the Spectrum of Alzheimer's Disease.

PubMed

Liu-Seifert, H; Siemers, E; Selzler, K; Sundell, K; Aisen, P; Cummings, J; Raskin, J; Mohs, R

2016-01-01

Both cognitive and functional deterioration are characteristic of the clinical progression of Alzheimer's disease (AD). To systematically assess correlations between widely used measures of cognition and function across the spectrum of AD. Spearman rank correlations were calculated for cognitive and functional measures across datasets from various AD patient populations. Post-hoc analysis from existing databases. Pooled data from placebo-treated patients with mild (MMSE score ≥20 and ≤26) and moderate (MMSE score ≥16 and ≤19) AD dementia from two Phase 3 solanezumab (EXPEDITION/2) and two semagecesatat (IDENTITY/2) studies and normal, late mild cognitive impairment (LMCI) and mild AD patients from the Alzheimer's Disease Neuroimaging Initiative 2-Grand Opportunity (ADNI-2/GO). Intervention (if any): Placebo (EXPEDITION/2 and IDENTITY/2 subjects). Cognitive and functional abilities were measured in all datasets. Data were collected at baseline and every three months for 18 months in EXPEDITION and IDENTITY studies; and at baseline, 6, 12, and 24 months in the ADNI dataset. The relationship of cognition and function became stronger over time as AD patients progressed from preclinical to moderate dementia disease stages, with the magnitude of correlations dependent on disease stage and the complexity of functional task. The correlations were minimal in the normal control population, but became stronger with disease progression. This analysis found that measures of cognition and function become more strongly correlated with disease progression from preclinical to moderate dementia across multiple datasets. These findings improve the understanding of the relationship between cognitive and functional clinical measures during the course of AD progression and how cognition and function measures relate to each other in AD clinical trials.

White matter lesions and temporal lobe atrophy related to incidence of both dementia and major depression in 70-year-olds followed over 10 years.

PubMed

Gudmundsson, P; Olesen, P J; Simoni, M; Pantoni, L; Östling, S; Kern, S; Guo, X; Skoog, I

2015-05-01

A number of studies have suggested associations between dementia and depression in older adults. One reason could be that these disorders share structural correlates, such as white matter lesions (WMLs) and cortical atrophy. No study has examined whether these lesions precede both dementia and depression independently of each other in the general population. Whether WMLs and cortical atrophy on computed tomography predict dementia and depression was investigated in a population-based sample of 70-year-olds (n = 380) followed over 10 years. Exclusion criteria were dementia, major depression, history of stroke and a Mini-Mental State Examination score below 26 at baseline in 2000-2001. Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, and depression according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Primary outcomes included dementia and major depression at 10-year follow-up. Adjusted logistic regression models, including both WMLs and temporal lobe atrophy, showed that moderate to severe WMLs [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.23-12.76] and temporal lobe atrophy (OR 2.93, 95% CI 1.13-7.60) predicted dementia during a 10-year follow-up independently of major depression. Similarly, both moderate to severe WMLs (OR 3.84, 95% CI 1.25-11.76) and temporal lobe atrophy (OR 2.52, 95% CI 1.06-5.96) predicted depression even after controlling for incident dementia. White matter lesions and temporal lobe atrophy preceded 10-year incidence of both dementia and depression in 70-year-olds. Shared structural correlates could explain the reported associations between dementia and depression. These brain changes may represent independent and complementary pathways to dementia and depression. Strategies to slow progression of vascular pathology and neurodegeneration could indirectly prevent both dementia and depression in older adults. © 2015 EAN.

Guidelines for reporting methodological challenges and evaluating potential bias in dementia research

PubMed Central

Weuve, Jennifer; Proust-Lima, Cécile; Power, Melinda C.; Gross, Alden L.; Hofer, Scott M.; Thiébaut, Rodolphe; Chêne, Geneviève; Glymour, M. Maria; Dufouil, Carole

2015-01-01

Clinical and population research on dementia and related neurologic conditions, including Alzheimer’s disease, faces several unique methodological challenges. Progress to identify preventive and therapeutic strategies rests on valid and rigorous analytic approaches, but the research literature reflects little consensus on “best practices.” We present findings from a large scientific working group on research methods for clinical and population studies of dementia, which identified five categories of methodological challenges as follows: (1) attrition/sample selection, including selective survival; (2) measurement, including uncertainty in diagnostic criteria, measurement error in neuropsychological assessments, and practice or retest effects; (3) specification of longitudinal models when participants are followed for months, years, or even decades; (4) time-varying measurements; and (5) high-dimensional data. We explain why each challenge is important in dementia research and how it could compromise the translation of research findings into effective prevention or care strategies. We advance a checklist of potential sources of bias that should be routinely addressed when reporting dementia research. PMID:26397878

Intelligent Assistive Technology Applications to Dementia Care: Current Capabilities, Limitations, and Future Challenges

PubMed Central

Bharucha, Ashok J.; Anand, Vivek; Forlizzi, Jodi; Dew, Mary Amanda; Reynolds, Charles F.; Stevens, Scott; Wactlar, Howard

2009-01-01

The number of older Americans afflicted by Alzheimer disease and related dementias will triple to 13 million persons by 2050, thus greatly increasing healthcare needs. An approach to this emerging crisis is the development and deployment of intelligent assistive technologies that compensate for the specific physical and cognitive deficits of older adults with dementia, and thereby also reduce caregiver burden. The authors conducted an extensive search of the computer science, engineering, and medical databases to review intelligent cognitive devices, physiologic and environmental sensors, and advanced integrated sensor networks that may find future applications in dementia care. Review of the extant literature reveals an overwhelming focus on the physical disability of younger persons with typically nonprogressive anoxic and traumatic brain injuries, with few clinical studies specifically involving persons with dementia. A discussion of the specific capabilities, strengths, and limitations of each technology is followed by an overview of research methodological challenges that must be addressed to achieve measurable progress to meet the healthcare needs of an aging America. PMID:18849532

Exposure to nature gardens has time-dependent associations with mood improvements for people with mid- and late-stage dementia: Innovative practice.

PubMed

White, Piran Cl; Wyatt, Jonathan; Chalfont, Garuth; Bland, J Martin; Neale, Christopher; Trepel, Dominic; Graham, Hilary

2017-01-01

Exposure to green space and nature has a potential role to play in the care of people with dementia, with possible benefits including improved mood and slower disease progression. In this observational study at a dementia care facility in the UK, we used carer-assessed measures to evaluate change in mood of residents with mid- to late-stage dementia following exposure to a nature garden. We found that exposure to nature was associated with a beneficial change in patient mood. There was a non-linear relationship between time spent outdoors and mood outcome. Improvements in patient mood were associated with relatively short duration exposures to nature, and no additional measureable increases in mood were found with exposures beyond 80-90 minutes duration. Whilst further investigation is required before causality can be determined, these results raise important questions for policy about the integration of outdoor space into the design of dementia care facilities and programmes.

Altered Sense of Humor in Dementia

PubMed Central

Clark, Camilla N.; Nicholas, Jennifer M.; Gordon, Elizabeth; Golden, Hannah L.; Cohen, Miriam H.; Woodward, Felix J.; Macpherson, Kirsty; Slattery, Catherine F.; Mummery, Catherine J.; Schott, Jonathan M.; Rohrer, Jonathan D.; Warren, Jason D.

2015-01-01

Sense of humor is potentially relevant to social functioning in dementias, but has been little studied in these diseases. We designed a semi-structured informant questionnaire to assess humor behavior and preferences in patients with behavioral variant frontotemporal dementia (bvFTD; n = 15), semantic dementia (SD; n = 7), progressive nonfluent aphasia (PNFA; n = 10), and Alzheimer’s disease (AD; n = 16) versus healthy age-matched individuals (n = 21). Altered (including frankly inappropriate) humor responses were significantly more frequent in bvFTD and SD (all patients) than PNFA or AD (around 40% of patients). All patient groups liked satirical and absurdist comedy significantly less than did healthy controls. This pattern was reported premorbidly for satirical comedy in bvFTD, PNFA, and AD. Liking for slapstick comedy did not differ between groups. Altered sense of humor is particularly salient in bvFTD and SD, but also frequent in AD and PNFA. Humor may be a sensitive probe of social cognitive impairment in dementia, with diagnostic, biomarker and social implications. PMID:26444779

Using Surface Table Computers to Promote the Well-Being of People with Dementia.

PubMed

Bejan, Alexander; Murko, Patrizia; Müller, Nadine; König, Peter; Kunze, Christophe

2017-01-01

As the demographic change progresses, dementia is going to become a prevalent condition in many countries. In order to keep the Quality of Life (QoL) of People with Dementia (PwD) on a steady level, Assistive Technologies (AT) implemented on table-sized Surface Computers (SC) that promote playful and/or reminiscence-triggering activities turn out to be valuable tools for dementia care. This article gives an overview over two similar multimedia-based AT systems implemented on Microsoft PixelSense SCs and field-tested in dementia care institutions. The observations indicate that both systems can trigger positive emotions and activities as well as memories.

Quetiapine effective in treatment of inappropriate sexual behavior of lewy body disease with predominant frontal lobe signs.

PubMed

Prakash, Ravi; Pathak, Amit; Munda, Sanjay; Bagati, Dhruv

2009-01-01

Dementia of Lewy body disease is the second most common degenerative cause of dementia after Alzheimer's disease, among all the dementias. The core features are a progressive dementia, fluctuations in cognitive functions, visual hallucinations, and spontaneous parkinsonism. Rapid eye movement sleep behavior disorder, severe neuroleptic sensitivity, and low dopamine transporter uptake in basal ganglia are other suggestive features. Behavioral abnormalities are commonly present in the form of aggressive behavior, irritability, and uninhibited behaviors. These are mostly seen in the advanced stages of dementia. However, inappropriate sexual behavior is uncommonly seen in such cases. Three types of inappropriate sexual behaviors commonly found in cases of dementia are sex talks, sexual acts, and implied sexual acts. Such inappropriate sexual behaviors have not been described adequately in dementia of Lewy body disease. We report inappropriate sexual behaviors in a case of dementia of Lewy body disease, which improved rapidly after treatment with quetiapine.

Depression-dementia medius: between depression and the manifestation of dementia symptoms.

PubMed

Kobayashi, Toshiyuki; Kato, Satoshi

2011-09-01

Depression and dementia, among the most common conditions in clinical practice, sometimes coexist, sometimes succeed each other, and often confuse clinicians. In the present paper, the clinical concept of 'depression-dementia medius' (which includes pseudodementia and depression in Alzheimer's disease as exemplars) is proposed, in reference to Janet's concept of psychological tension. Because psychosomatically complex human lives are always in a state of dynamic equilibrium, it seems sensible to propose that pseudodementia and depression in Alzheimer's disease are located within a spectrum extending from depression without dementia symptoms to dementia without depression. From the Janetian viewpoint, pseudodementia is regarded as uncovered latent dementia as a result of reduced psychological tension. Dementia is more than a fixed progressive condition under this view, and is a manifestation of dynamic mental activities. Characterizing these entities through perspectives such as psychological tension may yield deep insights in clinical practice. © 2011 The Authors. Psychogeriatrics © 2011 Japanese Psychogeriatric Society.

Prevalence of Cognitive Impairment and Dementia in Malays - Epidemiology of Dementia in Singapore Study.

PubMed

Hilal, Saima; Tan, Chuen S; Xin, Xu; Amin, Shaik M; Wong, Tien Y; Chen, Christopher; Venketasubramanian, Narayanaswamy; Ikram, Mohammad K

2017-01-01

To study the prevalence of cognitive impairment and dementia in communitydwelling Malays from Singapore; and to examine differences in prevalence among Chinese and Malays. Subjects (≥ 60 years) - drawn from the Malay component of the on-going multiethnic Epidemiology of Dementia in Singapore study - were screened using locally validated Abbreviated Mental Test and Progressive Forgetfulness Questionnaire. Subsequently, screen-positive participants underwent detailed neuropsychological assessments and neuroimaging. Cognitive impairment no dementia (CIND) and dementia were diagnosed based on accepted criteria. A total of 966 Malay subjects were included, of whom 102 had CIND-mild, 135 CINDmoderate, and 27 dementia. The overall age-standardized prevalence of any cognitive impairment was 25.5%, including 2% of dementia. The prevalence of any cognitive impairment increased with age from 14·9% in those aged 60-64 years to 40.2% in age ≥80 years. Women had a higher prevalence of CIND and dementia than men. Compared to previously published data from EDIS on Chinese, Malay were nearly twice more likely to have any cognitive impairment (Odds ratios adjusted for age, demographic and cardiovascular risk factors, and ApoEε4 carrier: 2.03, 95% confidence interval: 1.48-2.77). Among elderly Malays, the overall prevalence of any cognitive impairment was 25.5%. Even with a similar protocol of recruitment and assessment and adjusting for known risk factors, the prevalence of cognitive impairment was higher in Malays compared to Chinese. Further research is needed to unravel other factors that may underlie these ethnic differences in the occurrence of cognitive impairment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers—The VMCI-Tuscany Study: Rationale, Design, and Methodology

PubMed Central

Poggesi, Anna; Salvadori, Emilia; Pantoni, Leonardo; Pracucci, Giovanni; Cesari, Francesca; Chiti, Alberto; Ciolli, Laura; Cosottini, Mirco; Del Bene, Alessandra; De Stefano, Nicola; Diciotti, Stefano; Dotti, Maria Teresa; Ginestroni, Andrea; Giusti, Betti; Gori, Anna Maria; Nannucci, Serena; Orlandi, Giovanni; Pescini, Francesca; Valenti, Raffaella; Abbate, Rosanna; Federico, Antonio; Mascalchi, Mario; Murri, Luigi; Inzitari, Domenico

2012-01-01

Dementia is one of the most disabling conditions. Alzheimer's disease and vascular dementia (VaD) are the most frequent causes. Subcortical VaD is consequent to deep-brain small vessel disease (SVD) and is the most frequent form of VaD. Its pathological hallmarks are ischemic white matter changes and lacunar infarcts. Degenerative and vascular changes often coexist, but mechanisms of interaction are incompletely understood. The term mild cognitive impairment defines a transitional state between normal ageing and dementia. Pre-dementia stages of VaD are also acknowledged (vascular mild cognitive impairment, VMCI). Progression relates mostly to the subcortical VaD type, but determinants of such transition are unknown. Variability of phenotypic expression is not fully explained by severity grade of lesions, as depicted by conventional MRI that is not sensitive to microstructural and metabolic alterations. Advanced neuroimaging techniques seem able to achieve this. Beside hypoperfusion, blood-brain-barrier dysfunction has been also demonstrated in subcortical VaD. The aim of the Vascular Mild Cognitive Impairment Tuscany Study is to expand knowledge about determinants of transition from mild cognitive impairment to dementia in patients with cerebral SVD. This paper summarizes the main aims and methodological aspects of this multicenter, ongoing, observational study enrolling patients affected by VMCI with SVD. PMID:22550606

Impaired mitochondrial energy metabolism as a novel risk factor for selective onset and progression of dementia in oldest-old subjects

PubMed Central

Zhao, Wei; Wang, Jun; Varghese, Merina; Ho, Lap; Mazzola, Paolo; Haroutunian, Vahram; Katsel, Pavel L; Gibson, Gary E; Levine, Samara; Dubner, Lauren; Pasinetti, Giulio Maria

2015-01-01

Recent evidence shows that Alzheimer disease (AD) dementia in the oldest-old subjects was associated with significantly less amyloid plaque and fibrillary tangle neuropathology than in the young-old population. In this study, using quantitative (q) PCR studies, we validated genome-wide microarray RNA studies previously conducted by our research group. We found selective downregulation of mitochondrial energy metabolism genes in the brains of oldest-old, but not young-old, AD dementia cases, despite a significant lack of classic AD neuropathology features. We report a significant decrease of genes associated with mitochondrial pyruvate metabolism, the tricarboxylic acid cycle (TCA), and glycolytic pathways. Moreover, significantly higher levels of nitrotyrosylated (3-NT)-proteins and 4-hydroxy-2-nonenal (HNE) adducts, which are indexes of cellular protein oxidation and lipid peroxidation, respectively, were detected in the brains of oldest-old subjects at high risk of developing AD, possibly suggesting compensatory mechanisms. These findings support the hypothesis that although oldest-old AD subjects, characterized by significantly lower AD neuropathology than young-old AD subjects, have brain mitochondrial metabolism impairment, which we hypothesize may selectively contribute to the development of dementia. Outcomes from this study provide novel insights into the molecular mechanisms underlying clinical dementia in young-old and oldest-old AD subjects and provide novel strategies for AD prevention and treatment in oldest-old dementia cases. PMID:25784811

Impaired mitochondrial energy metabolism as a novel risk factor for selective onset and progression of dementia in oldest-old subjects.

PubMed

Zhao, Wei; Wang, Jun; Varghese, Merina; Ho, Lap; Mazzola, Paolo; Haroutunian, Vahram; Katsel, Pavel L; Gibson, Gary E; Levine, Samara; Dubner, Lauren; Pasinetti, Giulio Maria

2015-01-01

Recent evidence shows that Alzheimer disease (AD) dementia in the oldest-old subjects was associated with significantly less amyloid plaque and fibrillary tangle neuropathology than in the young-old population. In this study, using quantitative (q) PCR studies, we validated genome-wide microarray RNA studies previously conducted by our research group. We found selective downregulation of mitochondrial energy metabolism genes in the brains of oldest-old, but not young-old, AD dementia cases, despite a significant lack of classic AD neuropathology features. We report a significant decrease of genes associated with mitochondrial pyruvate metabolism, the tricarboxylic acid cycle (TCA), and glycolytic pathways. Moreover, significantly higher levels of nitrotyrosylated (3-NT)-proteins and 4-hydroxy-2-nonenal (HNE) adducts, which are indexes of cellular protein oxidation and lipid peroxidation, respectively, were detected in the brains of oldest-old subjects at high risk of developing AD, possibly suggesting compensatory mechanisms. These findings support the hypothesis that although oldest-old AD subjects, characterized by significantly lower AD neuropathology than young-old AD subjects, have brain mitochondrial metabolism impairment, which we hypothesize may selectively contribute to the development of dementia. Outcomes from this study provide novel insights into the molecular mechanisms underlying clinical dementia in young-old and oldest-old AD subjects and provide novel strategies for AD prevention and treatment in oldest-old dementia cases.

Imaging Alzheimer's disease pathophysiology with PET

PubMed Central

Schilling, Lucas Porcello; Zimmer, Eduardo R.; Shin, Monica; Leuzy, Antoine; Pascoal, Tharick A.; Benedet, Andréa L.; Borelli, Wyllians Vendramini; Palmini, André; Gauthier, Serge; Rosa-Neto, Pedro

2016-01-01

ABSTRACT Alzheimer's disease (AD) has been reconceptualised as a dynamic pathophysiological process characterized by preclinical, mild cognitive impairment (MCI), and dementia stages. Positron emission tomography (PET) associated with various molecular imaging agents reveals numerous aspects of dementia pathophysiology, such as brain amyloidosis, tau accumulation, neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia patients. In the context of a growing shift toward presymptomatic early diagnosis and disease-modifying interventions, PET molecular imaging agents provide an unprecedented means of quantifying the AD pathophysiological process, monitoring disease progression, ascertaining whether therapies engage their respective brain molecular targets, as well as quantifying pharmacological responses. In the present study, we highlight the most important contributions of PET in describing brain molecular abnormalities in AD. PMID:29213438

Encouraging Innovation for Assistive Health Technologies in Dementia: Barriers, Enablers and Next Steps to Be Taken.

PubMed

Egan, Kieren J; Pot, Anne Margriet

2016-04-01

Innovative Assistive Health Technology (AHT) has the potential to improve the quality of life for people with dementia or their families. Although development is in its preliminary stages, research shows first promising results. Despite such progress, we are still to observe widespread integration of technology into communities. If society is to benefit from innovative AHT to assist people with dementia and their caregivers, we must deepen our understanding of the needs, barriers, and enablers of innovative AHT. In March 2015, multinational focus groups were undertaken to identify the barriers, enablers, stakeholder actions, and a future perspective for the use of AHT in dementia. This exploratory study was carried out in preparation of the first World Health Organization Ministerial Conference on the Global Action against Dementia. The focus group study identified that innovative AHT for people with dementia and caregivers is at an early stage of development; however, there is substantial promise across a range of different care needs. Focus group discussions identified internationally relevant barriers and enablers for the development of innovative AHT centring on an improved understanding for needs in dementia. There are many diverse barriers to the development of innovative AHT but none that appear insurmountable regarding the enablers that were mentioned. There is now an overriding imperative for a systematic, coordinated multistakeholder approach with the needs of people with dementia and their caregivers as the centerpiece. Copyright © 2016. Published by Elsevier Inc.

Relationship between Eating Disturbance and Dementia Severity in Patients with Alzheimer’s Disease

PubMed Central

Kai, Kyoko; Hashimoto, Mamoru; Amano, Koichiro; Tanaka, Hibiki; Fukuhara, Ryuji; Ikeda, Manabu

2015-01-01

Background Eating is one of the most important daily activities in managing patients with dementia. Although various eating disturbance occur as dementia progresses, to our knowledge, most of the studies focused on a part of eating disturbance such as swallowing and appetite. There have been few comprehensive studies including eating habits and food preference in patients with Alzheimer’s disease (AD). The aims of this study were to investigate almost all eating disturbance and to examine the relationship of eating disturbance to dementia stage in AD. Methods A total of 220 patients with AD and 30 normal elderly (NE) subjects were recruited. Eating disturbance was assessed by a comprehensive questionnaire that had been previously validated. Potential relationships between the characteristics of eating disturbance and dementia stage as classified by the Clinical Dementia Rating (CDR) were assessed. Results Overall, 81.4% of patients with AD showed some eating and swallowing disturbance, whereas only 26.7% of the NE subjects had such a disturbance. Even in an early stage, patients with AD had many types of eating disturbance; “Appetite change” was shown in nearly half of the mild AD patients (49.5%). In the moderate stage, the scores of “change of eating habits and food preference” were highest, and in the severe stage “swallowing disturbance” became critical. Conclusion In AD, the relationship of dementia stage to eating disturbance differs according to the type of eating disturbance. The relationships between various eating disturbance and the severity of dementia should be considered. PMID:26266531

Progressive Supranuclear Palsy

MedlinePlus

... NINDS Focus on Disorders Alzheimer's & Related Dementias Epilepsy Parkinson's Disease Spinal Cord Injury Traumatic Brain Injury Focus On ... diseases being studied as part of the NINDS Parkinsons Disease Biomarkers Program, which aims to discover ways to ...

Rapidly Progressive Dementia

PubMed Central

Geschwind, Michael D.

2016-01-01

Purpose of Review: This article presents a practical and informative approach to the evaluation of a patient with a rapidly progressive dementia (RPD). Recent Findings: Prion diseases are the prototypical causes of RPD, but reversible causes of RPD might mimic prion disease and should always be considered in a differential diagnosis. Aside from prion diseases, the most common causes of RPD are atypical presentations of other neurodegenerative disorders, curable disorders including autoimmune encephalopathies, as well as some infections, and neoplasms. Numerous recent case reports suggest dural arterial venous fistulas sometimes cause RPDs. Summary: RPDs, in which patients typically develop dementia over weeks to months, require an alternative differential than the slowly progressive dementias that occur over a few years. Because of their rapid decline, patients with RPDs necessitate urgent evaluation and often require an extensive workup, typically with multiple tests being sent or performed concurrently. Jakob-Creutzfeldt disease, perhaps the prototypical RPD, is often the first diagnosis many neurologists consider when treating a patient with rapid cognitive decline. Many conditions other than prion disease, however, including numerous reversible or curable conditions, can present as an RPD. This chapter discusses some of the major etiologies for RPDs and offers an algorithm for diagnosis. PMID:27042906

Family history of frontotemporal lobar degeneration in Asia--an international multi-center research.

PubMed

Fukuhara, Ryuji; Ghosh, Amitabha; Fuh, Jong-Ling; Dominguez, Jacqueline; Ong, Paulus Anam; Dutt, Aparna; Liu, Yi-Chien; Tanaka, Hibiki; Ikeda, Manabu

2014-12-01

Previous studies in western countries have shown that about 30%-50% of patients with frontotemporal lobar degeneration (FTLD) have a positive family history, whereas the few epidemiological studies on FTLD done in Asia reported much lower frequencies. It is not clear the reason why the frequencies of FTLD with positive family history were lower in Asia. Furthermore, these findings were not from studies focused on family history. Therefore, it is necessary to conduct further studies on the family history of FTLD in Asia. This international multi-center research aims to investigate the family histories in patients with FTLD and related neurodegenerative diseases such as progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and motor neuron diseases in a larger Asian cohort. Participants were collected from five countries: India, Indonesia, Japan, Taiwan, and Philippines. All patients were diagnosed with behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive non-fluent aphasia (PA), frontotemporal dementia with motor neuron disease (FTD/MND), PSP, and corticobasal degeneration (CBD) according to international consensus criteria. Family histories of FTLD and related neurodegenerative diseases were investigated in each patient. Ninety-one patients were included in this study. Forty-two patients were diagnosed to have bvFTD, two patients had FTD/MND, 22 had SD, 15 had PA, one had PA/CBS, five had CBS and four patients had PSP. Family history of any FTLD spectrum disorder was reported in 9.5% in bvFTD patients but in none of the SD or PA. In contrast to patients of the western countries, few Asian FTLD patients have positive family histories of dementia.

Association between late-onset depression and incident dementia in Chinese older persons.

PubMed

Tam, C W C; Lam, L C W

2013-12-01

OBJECTIVE. Previous studies have shown that depression is a precursor / prodrome or susceptible state for the development of dementia. This study aimed to examine the relationship between late-onset depression and subsequent cognitive and functional decline in a cohort of non-demented older Chinese persons at their 2-year follow-up and investigate for possible predictors of cognitive decline. METHODS. A total of 81 depressed subjects and 468 non-depressed community controls were recruited. RESULTS. Subjects with late-onset depression showed significantly more incident Clinical Dementia Rating (CDR) scale decline (odds ratio = 3.87, 95% confidence interval = 2.23-6.70) and dementia (odds ratio = 3.44, 95% confidence interval = 1.75-6.77) than those without depression. A higher proportion of depressed CDR 0 subjects had CDR and functional decline than their non-depressed counterparts. Depressed CDR 0.5 subjects had significantly higher rates of functional decline and lower rates of improvement in CDR than their non-depressed counterparts. CONCLUSION. Diagnosis of depression was a robust predictor of incident very mild dementia (i.e. CDR of 0.5) and depression severity was a predictor of progression to dementia from CDR of 0.5. The association between depression and the risk of CDR decline and dementia was observed in non-demented Chinese subjects. Depression was also associated with persistent mild cognitive deficits in CDR 0.5 subjects.

Dementia Etiologies and Remedies in Traditional Persian Medicine; A Review of Medicinal Plants and Phytochemistry.

PubMed

Shirbeigi, Laila; Dalfardi, Behnam; Abolhassanzadeh, Zohreh; Nejatbakhsh, Fatemeh

2018-01-01

Dementia is a chronic neurodegenerative disease causing progressive and gradual impairment of different brain's cognitive functions. The prevalence of dementia is about 3 to 7% in different parts of the world. The aim of this study was to determine the etiologies of dementia according to the Traditional Persian Medicine scientists' viewpoint and introduce their recommended herbal remedies for this disease. The authors explored six main Traditional Persian Medicine textbooks for the disease of dementia, its etiologies and related recommended herbal treatments. Two main keywords of "Lisarghes" and" Nesyan" were searched for this purpose. Medical databases, including PubMed, Scopus, Google Scholar, and Science Direct were searched for related articles published between 1966 and 2016 to review the pharmacological components and active ingredients of suggested herbal medicines. According to the Traditional Persian Medicine, dementia is resulted from brain dystemperament, a condition caused by cold and moist or cold and dry tempers. To treat this disease, Traditional Persian scientists recommended various herbal remedies. Current studies have demonstrated that some of these medicinal plants have beneficial effects for the aforementioned disease, including acetyl cholinesterase inhibitory function, neuroprotective effects, and memory enhancing role. The Traditional Persian Medicine literature suggested different herbal remedies for treating dementia. Modern studies support the usefulness of some of these medicines. However, the effect of a large number of these remedies has remained unexamined, a matter which needs to be investigated in future researches. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cognitive impairment and cardiovascular diseases in the elderly. A heart-brain continuum hypothesis.

PubMed

Abete, Pasquale; Della-Morte, David; Gargiulo, Gaetano; Basile, Claudia; Langellotto, Assunta; Galizia, Gianluigi; Testa, Gianluca; Canonico, Vincenzo; Bonaduce, Domenico; Cacciatore, Francesco

2014-11-01

The aging population is increasing and, therefore, a higher prevalence of cardiac disease is emerging; including hypertension, coronary artery disease, atrial fibrillation and chronic heart failure. Large cohort studies have revealed a relationship among increased risk for cognitive impairment and dementia in cardiovascular diseases probably due to embolic stroke or chronic cerebral hypoperfusion. Thus, the aim of the present review is to overview the studies that investigate the presence and/or the development of cognitive impairments and dementia in patients with varied types of cardiovascular disease. Finally, a continuum among hypertension, coronary artery disease, atrial fibrillation and chronic heart failure with to the development of cognitive impairment and progression to dementia has been hypothesized. Copyright © 2014 Elsevier B.V. All rights reserved.

Reduction of RPT6/S8 (a Proteasome Component) and Proteasome Activity in the Cortex is Associated with Cognitive Impairment in Lewy Body Dementia

PubMed Central

Alghamdi, Amani; Vallortigara, Julie; Howlett, David R.; Broadstock, Martin; Hortobágyi, Tibor; Ballard, Clive; Thomas, Alan J.; O’Brien, John T.; Aarsland, Dag; Attems, Johannes; Francis, Paul T.; Whitfield, David R.

2017-01-01

Lewy body dementia is the second most common neurodegenerative dementia and is pathologically characterized by α-synuclein positive cytoplasmic inclusions, with varying amounts of amyloid-β (Aβ) and hyperphosphorylated tau (tau) aggregates in addition to synaptic loss. A dysfunctional ubiquitin proteasome system (UPS), the major proteolytic pathway responsible for the clearance of short lived proteins, may be a mediating factor of disease progression and of the development of α-synuclein aggregates. In the present study, protein expression of a key component of the UPS, the RPT6 subunit of the 19S regulatory complex was determined. Furthermore, the main proteolytic-like (chymotrypsin- and PGPH-) activities have also been analyzed. The middle frontal (Brodmann, BA9), inferior parietal (BA40), and anterior cingulate (BA24) gyrus’ cortex were selected as regions of interest from Parkinson’s disease dementia (PDD, n = 31), dementia with Lewy bodies (DLB, n = 44), Alzheimer’s disease (AD, n = 16), and control (n = 24) brains. Clinical and pathological data available included the MMSE score. DLB, PDD, and AD were characterized by significant reductions of RPT6 (one-way ANOVA, p < 0.001; Bonferroni post hoc test) in prefrontal cortex and parietal cortex compared with controls. Strong associations were observed between RPT6 levels in prefrontal, parietal cortex, and anterior cingulate gyrus and cognitive impairment (p = 0.001, p = 0.001, and p = 0.008, respectively). These findings highlight the involvement of the UPS in Lewy body dementia and indicate that targeting the UPS may have the potential to slow down or reduce the progression of cognitive impairment in DLB and PDD. PMID:28269775

Observing conversational laughter in frontotemporal dementia.

PubMed

Pressman, Peter S; Simpson, Michaela; Gola, Kelly; Shdo, Suzanne M; Spinelli, Edoardo G; Miller, Bruce L; Gorno-Tempini, Maria Luisa; Rankin, Katherine; Levenson, Robert W

2017-05-01

We performed an observational study of laughter during seminaturalistic conversations between patients with dementia and familial caregivers. Patients were diagnosed with (1) behavioural variant frontotemporal dementia (bvFTD), (2) right temporal variant frontotemporal dementia (rtFTD), (3) semantic variant of primary progressive aphasia (svPPA), (4) non-fluent variant primary progressive aphasia (nfvPPA) or (5) early onset Alzheimer's disease (eoAD). We hypothesised that those with bvFTD would laugh less in response to their own speech than other dementia groups or controls, while those with rtFTD would laugh less regardless of who was speaking. Patients with bvFTD (n=39), svPPA (n=19), rtFTD (n=14), nfvPPA (n=16), eoAD (n=17) and healthy controls (n=156) were recorded (video and audio) while discussing a problem in their relationship with a healthy control companion. Using the audio track only, laughs were identified by trained coders and then further classed by an automated algorithm as occurring during or shortly after the participant's own vocalisation ('self' context) or during or shortly after the partner's vocalisation ('partner' context). Individuals with bvFTD, eoAD or rtFTD laughed less across both contexts of self and partner than the other groups. Those with bvFTD laughed less relative to their own speech comparedwith healthy controls. Those with nfvPPA laughed more in the partner context compared with healthy controls. Laughter in response to one's own vocalisations or those of a conversational partner may be a clinically useful measure in dementia diagnosis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Dural arteriovenous fistula as a treatable dementia.

PubMed

Enofe, Ikponmwosa; Thacker, Ike; Shamim, Sadat

2017-04-01

Dementia is a chronic loss of neurocognitive function that is progressive and irreversible. Although rare, dural arteriovenous fistulas (DAVFs) could present with a rapid decline in neurocognitive function with or without Parkinson-like symptoms. DAVFs represent a potentially treatable and reversible cause of dementia. Here, we report the case of an elderly woman diagnosed with a DAVF after presenting with new-onset seizures, deteriorating neurocognitive function, and Parkinson-like symptoms.

Dural arteriovenous fistula as a treatable dementia

PubMed Central

Enofe, Ikponmwosa; Thacker, Ike

2017-01-01

Dementia is a chronic loss of neurocognitive function that is progressive and irreversible. Although rare, dural arteriovenous fistulas (DAVFs) could present with a rapid decline in neurocognitive function with or without Parkinson-like symptoms. DAVFs represent a potentially treatable and reversible cause of dementia. Here, we report the case of an elderly woman diagnosed with a DAVF after presenting with new-onset seizures, deteriorating neurocognitive function, and Parkinson-like symptoms. PMID:28405088

Non-Alzheimer’s dementia 2

PubMed Central

Walker, Zuzana; Possin, Katherine L; Boeve, Bradley F; Aarsland, Dag

2018-01-01

The broad importance of dementia is undisputed, with Alzheimer’s disease justifiably getting the most attention. However, dementia with Lewy bodies and Parkinson’s disease dementia, now called Lewy body dementias, are the second most common type of degenerative dementia in patients older than 65 years. Despite this, Lewy body dementias receive little attention and patients are often misdiagnosed, leading to less than ideal management. Over the past 10 years, considerable effort has gone into improving diagnostic accuracy by refining diagnostic criteria and using imaging and other biomarkers. Dementia with Lewy bodies and Parkinson’s disease dementia share the same pathophysiology, and effective treatments will depend not only on successful treatment of symptoms but also on targeting the pathological mechanisms of disease, ideally before symptoms and clinical signs develop. We summarise the most pertinent progress from the past 10 years, outlining some of the challenges for the future, which will require refinement of diagnosis and clarification of the pathogenesis, leading to disease-modifying treatments. PMID:26595642

The experience of lived space in persons with dementia: a systematic meta-synthesis.

PubMed

Førsund, Linn Hege; Grov, Ellen Karine; Helvik, Anne-Sofie; Juvet, Lene Kristine; Skovdahl, Kirsti; Eriksen, Siren

2018-02-01

Identifying how persons with dementia experience lived space is important for enabling supportive living environments and creating communities that compensate for the fading capabilities of these persons. Several single studies have explored this topic; however, few studies have attempted to explicitly review and synthesize this research literature. The aim of this systematic meta-synthesis was therefore to interpret and synthesize knowledge regarding persons with dementia's experience of space. A systematic, computerized search of AgeLine, CINAHL Complete, Embase, Medline and PsycINFO was conducted using a search strategy that combined MeSH terms and text words for different types of dementia with different descriptions of experience. Studies with 1) a sample of persons with dementia, 2) qualitative interviews as a research method and 3) a description of experiences of lived space were included. The search resulted in 1386 articles, of which 136 were identified as eligible and were read and assessed using the CASP criteria. The analysis was inspired by qualitative content analyses. This interpretative qualitative meta-synthesis included 45 articles encompassing interviews with 672 persons with dementia. The analysis showed that living in one's own home and living in long-term care established different settings and posed diverse challenges for the experience of lived space in persons with dementia. The material revealed four main categories that described the experience of lived space: (1) belonging; (2) meaningfulness; (3) safety and security; and (4) autonomy. It showed how persons with dementia experienced a reduction in their lived space due to the progression of dementia. A comprehensive understanding of the categories led to the latent theme: "Living with dementia is like living in a space where the walls keep closing in". This meta-synthesis reveals a process whereby lived space gradually becomes smaller for persons with dementia. This underscores the importance of being aware of the experiences of persons with dementia and the spatial dimensions of their life-world. To sustain person-centred care and support the preservation of continuity and identity, one must acknowledge not only the physical and social environment but also space as an existential experience for persons with dementia.

Cognitive decline in Parkinson disease

PubMed Central

Aarsland, Dag; Creese, Byron; Politis, Marios; Chaudhuri, K. Ray; ffytche, Dominic H.; Weintraub, Daniel; Ballard, Clive

2017-01-01

Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition — or even reversal to normal cognition — is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results. PMID:28257128

Everyday conversation in dementia: a review of the literature to inform research and practice.

PubMed

Kindell, Jacqueline; Keady, John; Sage, Karen; Wilkinson, Ray

2017-07-01

There has been increasing interest in dementia care in recent years, including how practitioners, service providers and society in general can help individuals to live well with the condition. An important aspect to this is provision of advice to ensure conversation partners effectively support the person with dementia in conversation. To provide a descriptive review of the literature examining everyday conversation in dementia in order to inform practice and research. This review used a method specifically developed for reviewing conversation analytic and related literature. A range of databases were searched using key words and explicitly described inclusion criteria leading to a final corpus of 50 titles. Using this qualitative methodology, each paper was examined and data extracted. The contribution of each of these is described and the implications for practice and research are outlined. This review examined studies into conversation in Alzheimer's disease, vascular dementia and Lewy body dementia, grouping these into: early influential studies; work drawing on positioning theory; studies using social and linguistic approaches; collaborative storytelling; formulaic language; studies specifically using conversation analysis; and conversation as a target for individualized therapy. In addition, more recent work examining primary progressive aphasia and behavioural variant frontotemporal dementia was explored. Overall, this review indicates that research examining conversation in natural settings provides a rich source of data to explore not just the challenges within conversation for those taking part, but also the skills retained by the person with dementia. An important aspect of this understanding is the notion that these skills relate not only to information exchange but also aspects of social interaction. The role of others in scaffolding the conversation abilities of the person with dementia and the potential of this for developing interventions are discussed. The review indicates that interventions targeting conversation in dementia are often advocated in the literature but currently such approaches remain to be systematically evaluated. In addition, many of the important insights arising from these studies have yet to inform multidisciplinary dementia care practice. © 2016 The Authors International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.

Everyday conversation in dementia: a review of the literature to inform research and practice

PubMed Central

Keady, John; Sage, Karen; Wilkinson, Ray

2016-01-01

Abstract Background There has been increasing interest in dementia care in recent years, including how practitioners, service providers and society in general can help individuals to live well with the condition. An important aspect to this is provision of advice to ensure conversation partners effectively support the person with dementia in conversation. Aims To provide a descriptive review of the literature examining everyday conversation in dementia in order to inform practice and research. Methods & Procedures This review used a method specifically developed for reviewing conversation analytic and related literature. A range of databases were searched using key words and explicitly described inclusion criteria leading to a final corpus of 50 titles. Using this qualitative methodology, each paper was examined and data extracted. The contribution of each of these is described and the implications for practice and research are outlined. Main Contribution This review examined studies into conversation in Alzheimer's disease, vascular dementia and Lewy body dementia, grouping these into: early influential studies; work drawing on positioning theory; studies using social and linguistic approaches; collaborative storytelling; formulaic language; studies specifically using conversation analysis; and conversation as a target for individualized therapy. In addition, more recent work examining primary progressive aphasia and behavioural variant frontotemporal dementia was explored. Overall, this review indicates that research examining conversation in natural settings provides a rich source of data to explore not just the challenges within conversation for those taking part, but also the skills retained by the person with dementia. An important aspect of this understanding is the notion that these skills relate not only to information exchange but also aspects of social interaction. The role of others in scaffolding the conversation abilities of the person with dementia and the potential of this for developing interventions are discussed. Conclusions & Implications The review indicates that interventions targeting conversation in dementia are often advocated in the literature but currently such approaches remain to be systematically evaluated. In addition, many of the important insights arising from these studies have yet to inform multidisciplinary dementia care practice. PMID:27891726

Differences of Behavioral and Psychological Symptoms of Dementia in Disease Severity in Four Major Dementias

PubMed Central

Kazui, Hiroaki; Yoshiyama, Kenji; Kanemoto, Hideki; Suzuki, Yukiko; Sato, Shunsuke; Hashimoto, Mamoru; Ikeda, Manabu; Tanaka, Hibiki; Hatada, Yutaka; Matsushita, Masateru; Nishio, Yoshiyuki; Mori, Etsuro; Tanimukai, Satoshi; Komori, Kenjiro; Yoshida, Taku; Shimizu, Hideaki; Matsumoto, Teruhisa; Mori, Takaaki; Kashibayashi, Tetsuo; Yokoyama, Kazumasa; Shimomura, Tatsuo; Kabeshita, Yasunobu; Adachi, Hiroyoshi; Tanaka, Toshihisa

2016-01-01

Background/Aims Behavioral and psychological symptoms of dementia (BPSDs) negatively impact the prognosis of dementia patients and increase caregiver distress. The aims of this study were to clarify the differences of trajectories of 12 kinds of BPSDs by disease severity in four major dementias and to develop charts showing the frequency, severity, and associated caregiver distress (ACD) of BPSDs using the data of a Japan multicenter study (J-BIRD). Methods We gathered Neuropsychiatric Inventory (NPI) data of patients with Alzheimer’s disease (AD; n = 1091), dementia with Lewy bodies (DLB; n = 249), vascular dementia (VaD; n = 156), and frontotemporal lobar degeneration (FTLD; n = 102) collected during a 5-year period up to July 31, 2013 in seven centers for dementia in Japan. The NPI composite scores (frequency × severity) of 12 kinds of items were analyzed using a principal component analysis (PCA) in each dementia. The factor scores of the PCA were compared in each dementia by disease severity, which was determined with Clinical Dementia Rating (CDR). Results Significant increases with higher CDR scores were observed in 1) two of the three factor scores which were loaded for all items except euphoria in AD, 2) two of the four factor scores for apathy, aberrant motor behavior (AMB), sleep disturbances, agitation, irritability, disinhibition, and euphoria in DLB, and 3) one of the four factor scores for apathy, depression, anxiety, and sleep disturbances in VaD. However, no increases were observed in any of the five factor scores in FTLD. Conclusions As dementia progresses, several BPSDs become more severe, including 1) apathy and sleep disturbances in AD, DLB, and VaD, 2) all of the BPSDs except euphoria in AD, 3) AMB, agitation, irritability, disinhibition, and euphoria in DLB, and 4) depression and anxiety in VaD. Trajectories of BPSDs in FTLD were unclear. PMID:27536962

FDG-PET and CSF biomarker accuracy in prediction of conversion to different dementias in a large multicentre MCI cohort.

PubMed

Caminiti, Silvia Paola; Ballarini, Tommaso; Sala, Arianna; Cerami, Chiara; Presotto, Luca; Santangelo, Roberto; Fallanca, Federico; Vanoli, Emilia Giovanna; Gianolli, Luigi; Iannaccone, Sandro; Magnani, Giuseppe; Perani, Daniela

2018-01-01

In this multicentre study in clinical settings, we assessed the accuracy of optimized procedures for FDG-PET brain metabolism and CSF classifications in predicting or excluding the conversion to Alzheimer's disease (AD) dementia and non-AD dementias. We included 80 MCI subjects with neurological and neuropsychological assessments, FDG-PET scan and CSF measures at entry, all with clinical follow-up. FDG-PET data were analysed with a validated voxel-based SPM method. Resulting single-subject SPM maps were classified by five imaging experts according to the disease-specific patterns, as "typical-AD", "atypical-AD" (i.e. posterior cortical atrophy, asymmetric logopenic AD variant, frontal-AD variant), "non-AD" (i.e. behavioural variant FTD, corticobasal degeneration, semantic variant FTD; dementia with Lewy bodies) or "negative" patterns. To perform the statistical analyses, the individual patterns were grouped either as "AD dementia vs. non-AD dementia (all diseases)" or as "FTD vs. non-FTD (all diseases)". Aβ42, total and phosphorylated Tau CSF-levels were classified dichotomously, and using the Erlangen Score algorithm. Multivariate logistic models tested the prognostic accuracy of FDG-PET-SPM and CSF dichotomous classifications. Accuracy of Erlangen score and Erlangen Score aided by FDG-PET SPM classification was evaluated. The multivariate logistic model identified FDG-PET "AD" SPM classification (Expβ = 19.35, 95% C.I. 4.8-77.8, p < 0.001) and CSF Aβ42 (Expβ = 6.5, 95% C.I. 1.64-25.43, p < 0.05) as the best predictors of conversion from MCI to AD dementia. The "FTD" SPM pattern significantly predicted conversion to FTD dementias at follow-up (Expβ = 14, 95% C.I. 3.1-63, p < 0.001). Overall, FDG-PET-SPM classification was the most accurate biomarker, able to correctly differentiate either the MCI subjects who converted to AD or FTD dementias, and those who remained stable or reverted to normal cognition (Expβ = 17.9, 95% C.I. 4.55-70.46, p < 0.001). Our results support the relevant role of FDG-PET-SPM classification in predicting progression to different dementia conditions in prodromal MCI phase, and in the exclusion of progression, outperforming CSF biomarkers.

Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia.

PubMed

Roberts, Rosebud O; Christianson, Teresa J H; Kremers, Walter K; Mielke, Michelle M; Machulda, Mary M; Vassilaki, Maria; Alhurani, Rabe E; Geda, Yonas E; Knopman, David S; Petersen, Ronald C

2016-01-01

To increase the opportunity to delay or prevent mild cognitive impairment (MCI) or Alzheimer disease (AD) dementia, markers of early detection are essential. Olfactory impairment may be an important clinical marker and predictor of these conditions and may help identify persons at increased risk. To examine associations of impaired olfaction with incident MCI subtypes and progression from MCI subtypes to AD dementia. Participants enrolled in the population-based, prospective Mayo Clinic Study of Aging between 2004 and 2010 were clinically evaluated at baseline and every 15 months through 2014. Participants (N = 1630) were classified as having normal cognition, MCI (amnestic MCI [aMCI] and nonamnestic MCI [naMCI]), and dementia. We administered the Brief Smell Identification Test (B-SIT) to assess olfactory function. Mild cognitive impairment, AD dementia, and longitudinal change in cognitive performance measures. Of the 1630 participants who were cognitively normal at the time of the smell test, 33 died before follow-up and 167 were lost to follow-up. Among the 1430 cognitively normal participants included, the mean (SD) age was 79.5 (5.3) years, 49.4% were men, the mean duration of education was 14.3 years, and 25.4% were APOE ε4 carriers. Over a mean 3.5 years of follow-up, there were 250 incident cases of MCI among 1430 cognitively normal participants. We observed an association between decreasing olfactory identification, as measured by a decrease in the number of correct responses in B-SIT score, and an increased risk of aMCI. Compared with the upper B-SIT quartile (quartile [Q] 4, best scores), hazard ratios (HRs) (95% CI) were 1.12 (0.65-1.92) for Q3 (P = .68); 1.95 (1.25-3.03) for Q2 (P = .003); and 2.18 (1.36-3.51) for Q1 (P = .001) (worst scores; P for trend <.001) after adjustment for sex and education, with age as the time scale. There was no association with naMCI. There were 64 incident dementia cases among 221 prevalent MCI cases. The B-SIT score also predicted progression from aMCI to AD dementia, with a significant dose-response with worsening B-SIT quartiles. Compared with Q4, HR (95% CI) estimates were 3.02 (1.06-8.57) for Q3 (P = .04); 3.63 (1.19-11.10) for Q2 (P = .02); and 5.20 (1.90-14.20) for Q1 (P = .001). After adjusting for key predictors of MCI risk, B-SIT (as a continuous measure) remained a significant predictor of MCI (HR, 1.10 [95% CI, 1.04-1.16]; P < .001) and improved the model concordance. Olfactory impairment is associated with incident aMCI and progression from aMCI to AD dementia. These findings are consistent with previous studies that have reported associations of olfactory impairment with cognitive impairment in late life and suggest that olfactory tests have potential utility for screening for MCI and MCI that is likely to progress.

The Spectrum of Mutations in Progranulin

PubMed Central

Yu, Chang-En; Bird, Thomas D.; Bekris, Lynn M.; Montine, Thomas J.; Leverenz, James B.; Steinbart, Ellen; Galloway, Nichole M.; Feldman, Howard; Woltjer, Randall; Miller, Carol A.; Wood, Elisabeth McCarty; Grossman, Murray; McCluskey, Leo; Clark, Christopher M.; Neumann, Manuela; Danek, Adrian; Galasko, Douglas R.; Arnold, Steven E.; Chen-Plotkin, Alice; Karydas, Anna; Miller, Bruce L.; Trojanowski, John Q.; Lee, Virginia M.-Y.; Schellenberg, Gerard D.; Van Deerlin, Vivianna M.

2010-01-01

Background Mutation in the progranulin gene (GRN) can cause frontotemporal dementia (FTD). However, it is unclear whether some rare FTD-related GRN variants are pathogenic and whether neurodegenerative disorders other than FTD can also be caused by GRN mutations. Objectives To delineate the range of clinical presentations associated with GRN mutations and to define pathogenic candidacy of rare GRN variants. Design Case-control study. Setting Clinical and neuropathology dementia research studies at 8 academic centers. Participants Four hundred thirty-four patients with FTD, including primary progressive aphasia, semantic dementia, FTD/amyotrophic lateral sclerosis (ALS), FTD/motor neuron disease, corticobasal syndrome/corticobasal degeneration, progressive supranuclear palsy, Pick disease, dementia lacking distinctive histopathology, and pathologically confirmed cases of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U); and 111 non-FTD cases (controls) in which TDP-43 deposits were a prominent neuropathological feature, including subjects with ALS, Guam ALS and/or parkinsonism dementia complex, Guam dementia, Alzheimer disease, multiple system atrophy, and argyrophilic grain disease. Main Outcome Measures Variants detected on sequencing of all 13 GRN exons and at least 80 base pairs of flanking introns, and their pathogenic candidacy determined by in silico and ex vivo splicing assays. Results We identified 58 genetic variants that included 26 previously unknown changes. Twenty-four variants appeared to be pathogenic, including 8 novel mutations. The frequency of GRN mutations was 6.9% (30 of 434) of all FTD-spectrum cases, 21.4% (9 of 42) of cases with a pathological diagnosis of FTLD-U, 16.0% (28 of 175) of FTD-spectrum cases with a family history of a similar neurodegenerative disease, and 56.2% (9 of 16) of cases of FTLD-U with a family history. Conclusions Pathogenic mutations were found only in FTD-spectrum cases and not in other related neurodegenerative diseases. Haploinsufficiency of GRN is the predominant mechanism leading to FTD. PMID:20142524

Does vigorous exercise have a neuroprotective effect in Parkinson disease?

PubMed Central

2011-01-01

Parkinson disease (PD) is progressive, with dementia and medication-refractory motor problems common reasons for late-stage nursing-home placement. Increasing evidence suggests that ongoing vigorous exercise/physical fitness may favorably influence this progression. Parkinsonian animal models reveal exercise-related protection from dopaminergic neurotoxins, apparently mediated by brain neurotrophic factors and neuroplasticity (predicted from in vitro studies). Similarly, exercise consistently improves cognition in animals, also linked to enhanced neuroplasticity and increased neurotrophic factor expression. In these animal models, immobilization has the opposite effect. Brain-derived neurotrophic factor (BDNF) may mediate at least some of this exercise benefit. In humans, exercise increases serum BDNF, and this is known to cross the blood–brain barrier. PD risk in humans is significantly reduced by midlife exercise, documented in large prospective studies. No studies have addressed whether exercise influences dementia risk in PD, but exercised patients with PD improve cognitive scores. Among seniors in general, exercise or physical fitness has not only been associated with better cognitive scores, but midlife exercise significantly reduces the later risk of both dementia and mild cognitive impairment. Finally, numerous studies in seniors with and without dementia have reported increased cerebral gray matter volumes associated with physical fitness or exercise. These findings have several implications for PD clinicians. 1) Ongoing vigorous exercise and physical fitness should be highly encouraged. 2) PD physical therapy programs should include structured, graduated fitness instruction and guidance for deconditioned patients with PD. 3) Levodopa and other forms of dopamine replenishment therapy should be utilized to achieve the maximum capability and motivation for patients to maintain fitness. PMID:21768599

Self-perceived memory complaints predict progression to Alzheimer disease. The LADIS study.

PubMed

Verdelho, Ana; Madureira, Sofia; Moleiro, Carla; Santos, Catarina O; Ferro, José M; Erkinjuntti, Timo; Poggesi, Anna; Pantoni, Leonardo; Fazekas, Franz; Scheltens, Philip; Waldemar, Gunhild; Wallin, Anders; Inzitari, Domenico

2011-01-01

Memory complaints are frequent in the elderly but its implications in cognition over time remain a controversial issue. Our objective was to evaluate the risk of self perceived memory complaints in the evolution for future dementia. The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes (WMC) on the transition of independent elderly subjects into disability. Independent elderly were enrolled due to the presence of WMC. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and a neuropsychological battery. Dementia and subtypes of dementia were classified. Self perceived memory complaints in independent elderly were collected during the interview. MRI was performed at entry and at the end of the study. 639 subjects were included (74.1 ± 5 years old, 55% women, 9.6 ± 3.8 years of schooling). At end of follow-up, 90 patients were demented (vascular dementia, 54; Alzheimer's disease (AD) and AD with vascular component, 34; frontotemporal dementia, 2). Using Cox regression analysis, we found that self perceived memory complaints were a strong predictor of AD and AD with vascular component during the follow-up (β = 2.7, p = 0.008; HR = 15.5, CI 95% [2.04, 117.6]), independently of other confounders, namely depressive symptoms, WMC severity, medial temporal lobe atrophy, and global cognition status at baseline. Self perceived memory complaints did not predict vascular dementia. In the LADIS study, self perceived memory complaints predicted AD but not vascular dementia in elderly subjects with WMC living independently.

The heterogeneity and natural history of mild cognitive impairment of visual memory predominant type.

PubMed

Ye, Byoung Seok; Chin, Juhee; Kim, Seong Yoon; Lee, Jung-Sun; Kim, Eun-Joo; Lee, Yunhwan; Hong, Chang Hyung; Choi, Seong Hye; Park, Kyung Won; Ku, Bon D; Moon, So Young; Kim, SangYun; Han, Seol-Hee; Lee, Jae-Hong; Cheong, Hae-Kwan; Park, Sun Ah; Jeong, Jee Hyang; Na, Duk L; Seo, Sang Won

2015-01-01

We evaluate the longitudinal outcomes of amnestic mild cognitive impairment (aMCI) according to the modality of memory impairment involved. We recruited 788 aMCI patients and followed them up. aMCI patients were categorized into three groups according to the modality of memory impairment: Visual-aMCI, only visual memory impaired; Verbal-aMCI, only verbal memory impaired; and Both-aMCI, both visual and verbal memory impaired. Each aMCI group was further categorized according to the presence or absence of recognition failure. Risk of progression to dementia was compared with pooled logistic regression analyses while controlling for age, gender, education, and interval from baseline. Of the sample, 219 (27.8%) aMCI patients progressed to dementia. Compared to the Visual-aMCI group, Verbal-aMCI (OR = 1.98, 95% CI = 1.19-3.28, p = 0.009) and Both-aMCI (OR = 3.05, 95% CI = 1.97-4.71, p < 0.001) groups exhibited higher risks of progression to dementia. Memory recognition failure was associated with increased risk of progression to dementia only in the Visual-aMCI group, but not in the Verbal-aMCI and Both-aMCI groups. The Visual-aMCI without recognition failure group were subcategorized into aMCI with depression, small vessel disease, or accelerated aging, and these subgroups showed a variety of progression rates. Our findings underlined the importance of heterogeneous longitudinal outcomes of aMCI, especially Visual-aMCI, for designing and interpreting future treatment trials in aMCI.

Improved design of prodromal Alzheimer's disease trials through cohort enrichment and surrogate endpoints.

PubMed

Macklin, Eric A; Blacker, Deborah; Hyman, Bradley T; Betensky, Rebecca A

2013-01-01

Alzheimer's disease (AD) trials initiated during or before the prodrome are costly and lengthy because patients are enrolled long before clinical symptoms are apparent, when disease progression is slow. We hypothesized that design of such trials could be improved by: 1) selecting individuals at moderate near-term risk of progression to AD dementia (the current clinical standard) and 2) by using short-term surrogate endpoints that predict progression to AD dementia. We used a longitudinal cohort of older, initially non-demented, community-dwelling participants (n = 358) to derive selection criteria and surrogate endpoints and tested them in an independent national data set (n = 6,243). To identify a "mid-risk" subgroup, we applied conditional tree-based survival models to Clinical Dementia Rating (CDR) scale scores and common neuropsychological tests. In the validation cohort, a time-to-AD dementia trial applying these mid-risk selection criteria to a pool of all non-demented individuals could achieve equivalent power with 47% fewer participants than enrolling at random from that pool. We evaluated surrogate endpoints measureable over two years of follow-up based on cross-validated concordance between predictions from Cox models and observed time to AD dementia. The best performing surrogate, rate of change in CDR sum-of-boxes, did not reduce the trial duration required for equivalent power using estimates from the validation cohort, but alternative surrogates with better ability to predict time to AD dementia should be able to do so. The approach tested here might improve efficiency of prodromal AD trials using other potential measures and could be generalized to other diseases with long prodromal phases.

Improved design of prodromal Alzheimer’s disease trials through cohort enrichment and surrogate endpoints

PubMed Central

Macklin, Eric A.; Blacker, Deborah; Hyman, Bradley T.; Betensky, Rebecca A.

2013-01-01

Summary Alzheimer’s disease (AD) trials initiated during or before the prodrome are costly and lengthy because patients are enrolled long before clinical symptoms are apparent, when disease progression is slow. We hypothesized that design of such trials could be improved by: (1) selecting individuals at moderate near-term risk of progression to AD dementia (the current clinical standard) and (2) by using short-term surrogate endpoints that predict progression to AD dementia. We used a longitudinal cohort of older, initially non-demented, community-dwelling participants (n=358) to derive selection criteria and surrogate endpoints and tested them in an independent national data set (n=6,243). To identify a “mid-risk” subgroup, we applied conditional tree-based survival models to Clinical Dementia Rating (CDR) scale scores and common neuropsychological tests. In the validation cohort, a time-to-AD dementia trial applying these mid-risk selection criteria to a pool of all non-demented individuals could achieve equivalent power with 47% fewer participants than enrolling at random from that pool. We evaluated surrogate endpoints measureable over two years of follow-up based on cross-validated concordance between predictions from Cox models and observed time to AD dementia. The best performing surrogate, rate of change in CDR sum-of-boxes, did not reduce the trial duration required for equivalent power using estimates from the validation cohort, but alternative surrogates with better ability to predict time to AD dementia should be able to do so. The approach tested here might improve efficiency of prodromal AD trials using other potential measures and could be generalized to other diseases with long prodromal phases. PMID:23629586

Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview.

PubMed

Libro, Rosaliana; Giacoppo, Sabrina; Soundara Rajan, Thangavelu; Bramanti, Placido; Mazzon, Emanuela

2016-04-21

The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the more common. Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required. In particular, the attention of researchers has been focused on phytochemical compounds that have shown antioxidative, anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties and that could represent important resources in the discovery of drug candidates against dementia. In this review, we summarize the neuroprotective effects of the main phytochemicals belonging to the polyphenol, isothiocyanate, alkaloid and cannabinoid families in the prevention and treatment of the most common kinds of dementia. We believe that natural phytochemicals may represent a promising sources of alternative medicine, at least in association with therapies approved to date for dementia.

Dementia-friendly design resource.

PubMed

Baillie, Jonathan

2014-02-01

Although estimates suggest that, on average, some 30 per cent of all patients in general acute medical wards may have some form of dementia, Stirling University's Dementia Services Development Centre (DSDC), one of the leading international knowledge centres working to improve the lives of dementia sufferers, says progress in designing healthcare facilities that address such patients' needs has been 'patchy at best'. With the number of individuals living with dementia expected to double in the next 25 years, the DSDC has recently worked with Edinburgh-based architects, Burnett Pollock Associates, to develop an online resource that clearly illustrates, via 15 simulated 'dementia-friendly' healthcare 'spaces', some of the key principles to consider when designing effectively for this fast-growing group. HEJ editor, Jonathan Baillie, attended the launch of the so-called 'Virtual Hospital'.

Frontal lobe dementia and motor neuron disease.

PubMed Central

Neary, D; Snowden, J S; Mann, D M; Northen, B; Goulding, P J; Macdermott, N

1990-01-01

Four patients are described, in whom a profound and rapidly progressive dementia occurred in association with clinical features of motor neuron disease. The pattern of dementia indicated impaired frontal lobe function, confirmed by reduced tracer uptake in the frontal lobes on single photon emission computed tomography (SPECT). Pathological examination of the brains of two patients revealed frontal-lobe atrophy, with mild gliosis and spongiform change. The spinal cord changes were consistent with motor neuron disease. The clinical picture and pathological findings resembled those of dementia of frontal-lobe type and were distinct from those of Alzheimer's disease. The findings have implications for the understanding of the spectrum of non-Alzheimer forms of primary degenerative dementia. Images PMID:2303828

The Impact of Awareness of and Concern About Memory Performance on the Prediction of Progression From Mild Cognitive Impairment to Alzheimer Disease Dementia.

PubMed

Munro, Catherine E; Donovan, Nancy J; Amariglio, Rebecca E; Papp, Kate V; Marshall, Gad A; Rentz, Dorene M; Pascual-Leone, Alvaro; Sperling, Reisa A; Locascio, Joseph J; Vannini, Patrizia

2018-05-03

To investigate the relationship of awareness of and concern about memory performance to progression from mild cognitive impairment (MCI) to Alzheimer disease (AD) dementia. Participants (n = 33) had a diagnosis of MCI at baseline and a diagnosis of MCI or AD dementia at follow-up. Participants were categorized as "Stable-MCI" if they retained an MCI diagnosis at follow-up (mean follow-up = 18.0 months) or "Progressor-MCI" if they were diagnosed with AD dementia at follow-up (mean follow-up = 21.6 months). Awareness was measured using the residual from regressing a participant's objective memory score onto their subjective complaint score (i.e., residual<0 indicates overestimation of performance). Concern was assessed using a questionnaire examining the degree of concern when forgetting. Logistic regression was used to determine whether the presence of these syndromes could predict future diagnosis of AD dementia, and repeated measures analysis of covariance tests were used to examine longitudinal patterns of these syndromes. Baseline anosognosia was apparent in the Progressor-MCI group, whereas participants in the Stable-MCI group demonstrated relative awareness of their memory performance. Baseline awareness scores successfully predicted whether an individual would progress to AD-dementia. Neither group showed change in awareness of performance over time. Neither group showed differences in concern about memory performance at baseline or change in concern about performance over time. These data suggest that anosognosia may appear prior to the onset of AD dementia, while anosodiaphoria likely does not appear until later in the AD continuum. Additionally, neither group showed significant changes in awareness or concern over time, suggesting that change in these variables may happen over longer periods. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Barriers, motivators, and facilitators of physical activity in dementia patients: A systematic review.

PubMed

van Alphen, Helena J M; Hortobágyi, Tibor; van Heuvelen, Marieke J G

2016-01-01

Physical activity (PA) has the potential to slow the progression of dementia patients' cognitive and physical decline. A better understanding of the factors that facilitate or hamper dementia patients' PA participation will increase the success rate of implementing PA in dementia patients' daily care. We systematically screened the barriers, motivators, and facilitators of PA participation in dementia patients, complementing previous analyses of quantitative correlates of PA in community-dwelling dementia patients. Systematic searches yielded 78 potential studies of which seven met the eligibility criteria including 39 dementia patients and 36 caregivers (33 spouses and three daughters). We identified 35 barriers, 26 motivators, and 21 facilitators related to PA. We reduced these factors to six themes within the social-ecological model. Prominent barriers to PA were physical and mental limitations and difficulties with guidance and organization of PA by caregivers. Motivators included the motivation to maintain physical and mental health and participate in preferred PA options. Facilitators included strategies to avoid health problems, providing support and guidance for PA, and access to convenient and personalized PA options. The emerging picture suggests that dementia patients' PA participation will increase if service providers become familiar with the health benefits of PA, the characteristics of PA programs, methods of delivery, and the concepts of how such programs can be personalized to and synchronized with patients' individual needs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Discrete Neural Correlates for the Recognition of Negative Emotions: Insights from Frontotemporal Dementia

PubMed Central

Kumfor, Fiona; Irish, Muireann; Hodges, John R.; Piguet, Olivier

2013-01-01

Patients with frontotemporal dementia have pervasive changes in emotion recognition and social cognition, yet the neural changes underlying these emotion processing deficits remain unclear. The multimodal system model of emotion proposes that basic emotions are dependent on distinct brain regions, which undergo significant pathological changes in frontotemporal dementia. As such, this syndrome may provide important insight into the impact of neural network degeneration upon the innate ability to recognise emotions. This study used voxel-based morphometry to identify discrete neural correlates involved in the recognition of basic emotions (anger, disgust, fear, sadness, surprise and happiness) in frontotemporal dementia. Forty frontotemporal dementia patients (18 behavioural-variant, 11 semantic dementia, 11 progressive nonfluent aphasia) and 27 healthy controls were tested on two facial emotion recognition tasks: The Ekman 60 and Ekman Caricatures. Although each frontotemporal dementia group showed impaired recognition of negative emotions, distinct associations between emotion-specific task performance and changes in grey matter intensity emerged. Fear recognition was associated with the right amygdala; disgust recognition with the left insula; anger recognition with the left middle and superior temporal gyrus; and sadness recognition with the left subcallosal cingulate, indicating that discrete neural substrates are necessary for emotion recognition in frontotemporal dementia. The erosion of emotion-specific neural networks in neurodegenerative disorders may produce distinct profiles of performance that are relevant to understanding the neurobiological basis of emotion processing. PMID:23805313

Hyperthyroid dementia: clinicoradiological findings and response to treatment.

PubMed

Fukui, T; Hasegawa, Y; Takenaka, H

2001-02-15

Dementia associated with hyperthyroidism is less well documented than is hypothyroid dementia. Therapeutic response of hyperthyroid dementia and associated cerebral circulatory and/or metabolic abnormalities has not been elucidated. We described a patient with hyperthyroid dementia and clinicoradiological response to treatment. Single photon emission computed tomographic (SPECT) study was repeated and analyzed semiquantitatively. A 67-year-old man experienced progressive impairments of attention, memory, constructive skills and behavior as well as hand tremor and weight loss of two-year duration. Laboratory findings were compatible with Graves' disease. The initial SPECT showed diffuse tracer uptake defect with an accentuation in the bilateral temporoparietal regions. Clinical and SPECT findings both suggested concurrent "possible" Alzheimer's disease. However, initial treatment with a beta-blocker improved behavior and attention-related cognitive functions as well as tracer uptake in the frontal lobes. Subsequent treatment with additional methimazole then improved memory and constructive abilities when a euthyroid state was established. Uptake defect in the temporoparietal regions also responded gradually to the medication. We suggest that the present patient represent hyperthyroid dementia, which responds favorably to treatment with regard to clinical symptoms and SPECT findings. We also suggest that thyroid function be measured in patients with "possible" Alzheimer's disease because treatable hyperthyroid dementia may not be identified.

Buying time: a rationale for examining the use of circadian rhythm and sleep interventions to delay progression of mild cognitive impairment to Alzheimer’s disease

PubMed Central

Landry, Glenn J.; Liu-Ambrose, Teresa

2014-01-01

As of 2010, the worldwide economic impact of dementia was estimated at $604 billion USD; and without discovery of a cure or effective interventions to delay disease progression, dementia’s annual global economic impact is expected to surpass $1 trillion USD as early as 2030. Alzheimer’s disease (AD) is the leading cause of dementia accounting for over 75% of all cases. Toxic accumulation of amyloid beta (Aβ), either by overproduction or some clearance failure, is thought to be an underlying mechanism of the neuronal cell death characteristic of AD—though this amyloid hypothesis has been increasingly challenged in recent years. A compelling alternative hypothesis points to chronic neuroinflammation as a common root in late-life degenerative diseases including AD. Apolipoprotein-E (APOE) genotype is the strongest genetic risk factor for AD: APOE-ε4 is proinflammatory and individuals with this genotype accumulate more Aβ, are at high risk of developing AD, and almost half of all AD patients have at least one ε4 allele. Recent studies suggest a bidirectional relationship exists between sleep and AD pathology. Sleep may play an important role in Aβ clearance, and getting good quality sleep vs. poor quality sleep might reduce the AD risk associated with neuroinflammation and the ε4 allele. Taken together, these findings are particularly important given the sleep disruptions commonly associated with AD and the increased burden disrupted sleep poses for AD caregivers. The current review aims to: (1) identify individuals at high risk for dementia who may benefit most from sleep interventions; (2) explore the role poor sleep quality plays in exacerbating AD type dementia; (3) examine the science of sleep interventions to date; and (4) provide a road map in pursuit of comprehensive sleep interventions, specifically targeted to promote cognitive function and delay progression of dementia. PMID:25538616

Patient with rapidly evolving neurological disease with neuropathological lesions of Creutzfeldt-Jakob disease, Lewy body dementia, chronic subcortical vascular encephalopathy and meningothelial meningioma.

PubMed

Vita, Maria Gabriella; Tiple, Dorina; Bizzarro, Alessandra; Ladogana, Anna; Colaizzo, Elisa; Capellari, Sabina; Rossi, Marcello; Parchi, Piero; Masullo, Carlo; Pocchiari, Maurizio

2017-04-01

We report a case of rapidly evolving neurological disease in a patient with neuropathological lesions of Creutzfeldt-Jakob disease (CJD), Lewy body dementia (LBD), chronic subcortical vascular encephalopathy and meningothelial meningioma. The coexistence of severe multiple pathologies in a single patient strengthens the need to perform accurate clinical differential diagnoses in rapidly progressive dementias. © 2016 Japanese Society of Neuropathology.

Online support and education for dementia caregivers: overview, utilization, and initial program evaluation.

PubMed

Glueckauf, Robert L; Ketterson, Timothy U; Loomis, Jeffrey S; Dages, Pat

2004-01-01

Family caregivers of older adults with progressive dementia (e.g., Alzheimer's disease) are confronted with a variety of challenges in providing assistance to their loved ones, such as dealing with persistent, repetitive questions, managing episodes of agitation and aggressive responding, as well as monitoring hygiene and self-care activities. Although professional and governmental organizations have called for the creation of community-based education and support programs, a significant proportion of dementia caregivers in the United States continue to receive little or no formal instruction in responding effectively to these anxiety-provoking situations. This paper describes the development and implementation of Alzheimer's Caregiver Support Online (also known as AlzOnline), an Internet- and telephone-based education and support network for caregivers of individuals with progressive dementia. An outcome analysis of a Robert Wood Johnson Foundation-funded strategic marketing initiative to promote the use of AlzOnline is reviewed, followed by a presentation of the findings of an initial program evaluation. Finally, future directions for online caregiver evaluation research are proposed.

Evolution of short cognitive test performance in stroke patients with vascular cognitive impairment and vascular dementia: Baseline evaluation and follow-up

PubMed Central

Custodio, Nilton; Montesinos, Rosa; Lira, David; Herrera-Perez, Eder; Bardales, Yadira; Valeriano-Lorenzo, Lucia

2017-01-01

ABSTRACT. There is limited evidence about the progression of cognitive performance during the post-stroke stage. Objective: To assess the evolution of cognitive performance in stroke patients without vascular cognitive impairment (VCI), patients with vascular mild cognitive impairment (MCI), and patients with vascular dementia (VD). Methods: A prospective cohort of stroke outpatients from two secondary medical centers in Lima, Peru was studied. We performed standardized evaluations at definitive diagnosis (baseline evaluation), and control follow-ups at 6 and 12 months, including a battery of short cognitive tests: Clinical Dementia Rating (CDR), Addenbrooke's Cognitive Examination (ACE), and INECO Frontal Screening (IFS). Results: 152 outpatients completed the follow-up, showing progressive increase in mean score on the CDR(0.34 to 0.46), contrary to the pattern observed on the ACE and IFS (78.18 to 76.48 and 23.63 to 22.24). The box plot for the CDR test showed that VCI patients had progressive worsening (0.79 to 0.16). Conversely, this trend was not observed in subjects without VCI. The box plot for the ACE and IFS showed that, for the majority of the differentiated stroke types, both non-VCI and VCI patients had progressive worsening. Conclusion: According to both ACE and IFS results during a 1-year follow-up, the cognitive performance of stroke patients worsened, a trend which was particularly consistent in infarction-type stroke patients. PMID:29354218

Caregivers’ understanding of dementia predicts patients’ comfort at death: a prospective observational study

PubMed Central

2013-01-01

Background Patients with dementia frequently do not receive adequate palliative care which may relate to poor understanding of the natural course of dementia. We hypothesized that understanding that dementia is a progressive and terminal disease is fundamental to a focus on comfort in dementia, and examined how family and professional caregivers’ understanding of the nature of the disease was associated with patients’ comfort during the dying process. Methods We enrolled 372 nursing home patients from 28 facilities in The Netherlands in a prospective observational study (2007 to 2010). We studied both the families and the physicians (73) of 161 patients. Understanding referred to families’ comprehension of complications, prognosis, having been counseled on these, and perception of dementia as “a disease you can die from” (5-point agreement scale) at baseline. Physicians reported on this perception, prognosis and having counseled on this. Staff-assessed comfort with the End-of-Life in Dementia - Comfort Assessment in Dying (EOLD-CAD) scale. Associations between understanding and comfort were assessed with generalized estimating equations, structural equation modeling, and mediator analyses. Results A family’s perception of dementia as “a disease you can die from” predicted higher patient comfort during the dying process (adjusted coefficient −0.8, 95% confidence interval (CI): −1.5; -0.06 point increment disagreement). Family and physician combined perceptions (−0.9, CI: −1.5; -0.2; 9-point scale) were also predictive, including in less advanced dementia. Forty-three percent of the families perceived dementia as a disease you can die from (agreed completely, partly); 94% of physicians did. The association between combined perception and higher comfort was mediated by the families’ reporting of a good relationship with the patient and physicians’ perception that good care was provided in the last week. Conclusions Awareness of the terminal nature of dementia may improve patient comfort at the end of life. Educating families on the nature of dementia may be an important part of advance care planning. PMID:23577637

Role of EEG as Biomarker in the Early Detection and Classification of Dementia

PubMed Central

Al-Qazzaz, Noor Kamal; Ali, Sawal Hamid Bin MD.; Ahmad, Siti Anom; Chellappan, Kalaivani; Islam, Md. Shabiul; Escudero, Javier

2014-01-01

The early detection and classification of dementia are important clinical support tasks for medical practitioners in customizing patient treatment programs to better manage the development and progression of these diseases. Efforts are being made to diagnose these neurodegenerative disorders in the early stages. Indeed, early diagnosis helps patients to obtain the maximum treatment benefit before significant mental decline occurs. The use of electroencephalogram as a tool for the detection of changes in brain activities and clinical diagnosis is becoming increasingly popular for its capabilities in quantifying changes in brain degeneration in dementia. This paper reviews the role of electroencephalogram as a biomarker based on signal processing to detect dementia in early stages and classify its severity. The review starts with a discussion of dementia types and cognitive spectrum followed by the presentation of the effective preprocessing denoising to eliminate possible artifacts. It continues with a description of feature extraction by using linear and nonlinear techniques, and it ends with a brief explanation of vast variety of separation techniques to classify EEG signals. This paper also provides an idea from the most popular studies that may help in diagnosing dementia in early stages and classifying through electroencephalogram signal processing and analysis. PMID:25093211

Role of EEG as biomarker in the early detection and classification of dementia.

PubMed

Al-Qazzaz, Noor Kamal; Ali, Sawal Hamid Bin Md; Ahmad, Siti Anom; Chellappan, Kalaivani; Islam, Md Shabiul; Escudero, Javier

2014-01-01

The early detection and classification of dementia are important clinical support tasks for medical practitioners in customizing patient treatment programs to better manage the development and progression of these diseases. Efforts are being made to diagnose these neurodegenerative disorders in the early stages. Indeed, early diagnosis helps patients to obtain the maximum treatment benefit before significant mental decline occurs. The use of electroencephalogram as a tool for the detection of changes in brain activities and clinical diagnosis is becoming increasingly popular for its capabilities in quantifying changes in brain degeneration in dementia. This paper reviews the role of electroencephalogram as a biomarker based on signal processing to detect dementia in early stages and classify its severity. The review starts with a discussion of dementia types and cognitive spectrum followed by the presentation of the effective preprocessing denoising to eliminate possible artifacts. It continues with a description of feature extraction by using linear and nonlinear techniques, and it ends with a brief explanation of vast variety of separation techniques to classify EEG signals. This paper also provides an idea from the most popular studies that may help in diagnosing dementia in early stages and classifying through electroencephalogram signal processing and analysis.

Trajectories of cognitive function in dementia-free subjects: Radiation Effects Research Foundation Adult Health Study.

PubMed

Yamada, Michiko; Landes, Reid D; Mimori, Yasuyo; Nagano, Yoshito; Sasaki, Hideo

2015-04-15

To investigate associations between age, sex, education, and birth cohort and global cognitive decline among a population that would most likely not progress to dementia. A total of 1538 dementia-free subjects aged 60 to 80years in 1992 were followed up through 2011 without dementia occurrence. We assessed cognitive function using the Cognitive Ability Screening Instrument (CASI). Using stepwise-like model selection procedure, we built mixed-effects models for initial cognition and longitudinal cognition. Initial CASI scores for younger age and more years of formal education were higher than those for older and less education. Sex did not show a significant effect. In the longitudinal analysis, cognitive decline became more rapid with increasing age. Sex and education did not modify the degree of deterioration with age. CASI scores were higher for younger cohorts and men due to differences in education levels. Among dementia-free subjects, age is an important predictor of cognitive function level and cognitive decline. Education level affects cognitive function level, but did not affect cognitive decline. The results have implications not only for elucidation of the aging process, but also for reference in dementia screening. Copyright © 2015 Elsevier B.V. All rights reserved.

Association of Lower Spiritual Well-Being, Social Support, Self-Esteem, Subjective Well-Being, Optimism and Hope Scores With Mild Cognitive Impairment and Mild Dementia

PubMed Central

dos Santos, Sabrina B.; Rocha, Gabrielli P.; Fernandez, Liana L.; de Padua, Analuiza C.; Reppold, Caroline T.

2018-01-01

Introduction: Positive psychology (PP) constructs contribute significantly to a better quality of life for people with various diseases. There are still few studies that have evaluated the evolution of these aspects during the progression of dementia. Objective: To compare the scores for self-esteem, life satisfaction, affect, spirituality, hope, optimism and perceived support network between elderly people with mild cognitive impairment (MCI), mild dementia and moderate dementia and control group. Methods: Cross-sectional study. The sample consisted of 66 healthy controls, 15 elderly people with MCI, 25 with mild dementia and 22 with moderate dementia matched by age, gender, and schooling. The instruments used were: Spirituality Self Rating Scale (SSRS), Rosenberg Self-Esteem Scale, Medical Outcomes Study’s Social Support Scale, Life Satisfaction Scale (LSS), Positive and Negative Affect Schedule (PANAS), Revised Life Orientation Test (LOT-R), and Adult Dispositional Hope Scale (ADHS). Results: The scores for spiritual well-being, social support, self-esteem, life satisfaction, positive affect, optimism, negative affect, and hope differed significantly between the groups (p < 0.05). The individuals with MCI and mild dementia had lower spiritual well-being, social support, self-esteem, life satisfaction, positive affect, optimism and hope scores, and higher negative affect scores compared with the controls. The scores for PP constructs did not differ between the group of people with moderate dementia and the control group. Conclusion: Dementia was found to impact several PP constructs in the early stages of the disease. For individuals with greater cognitive impairment, anosognosia appears to suppress the disease’s impact on these constructs. PMID:29666594

The Effects of White Noise on Agitated Behaviors, Mental Status, and Activities of Daily Living in Older Adults With Dementia.

PubMed

Lin, Li-Wei; Weng, Shu-Chuan; Wu, Hua-Shan; Tsai, Lu-Jen; Lin, Ya-Ling; Yeh, Shu-Hui

2018-02-01

The aging of society is a global trend, and care of older adults with dementia is an urgent challenge. As dementia progresses, patients exhibit negative emotions, memory disorders, sleep disorders, and agitated behavior. Agitated behavior is one of the most difficult problems for family caregivers and healthcare providers to handle when caring for older adults with dementia. The aim of this study was to investigate the effectiveness of white noise in improving agitated behavior, mental status, and activities of daily living in older adults with dementia. An experimental research design was used to study elderly participants two times (pretest and posttest). Six dementia care centers in central and southern Taiwan were targeted to recruit participants. There were 63 participants: 28 were in the experimental group, and 35 were in the comparison group. Experimental group participants received 20 minutes of white noise consisting of ocean, rain, wind, and running water sounds between 4 and 5 P.M. daily over a period of 4 weeks. The comparison group received routine care. Questionnaires were completed, and observations of agitated behaviors were collected before and after the intervention. Agitated behavior in the experimental group improved significantly between pretest and posttest. Furthermore, posttest scores on the Mini-Mental Status Examination and Barthel Index were slightly better for this group than at pretest. However, the experimental group registered no significant difference in mental status or activities of daily living at posttest. For the comparison group, agitated behavior was unchanged between pretest and posttest. The results of this study support white noise as a simple, convenient, and noninvasive intervention that improves agitated behavior in older adults with dementia. These results may provide a reference for related healthcare providers, educators, and administrators who care for older adults with dementia.

Estimated prevalence of dementia based on analysis of drug databases in the Region of Madrid (Spain).

PubMed

de Hoyos-Alonso, M C; Bonis, J; Tapias-Merino, E; Castell, M V; Otero, A

2016-01-01

The progressive rise in dementia prevalence increases the need for rapid methods that complement population-based prevalence studies. To estimate the prevalence of dementia in the population aged 65 and older based on use of cholinesterase inhibitors and memantine. Descriptive study of use and prescription of cholinesterase inhibitors and/or memantine in 2011 according to 2 databases: Farm@drid (pharmacy billing records for the Region of Madrid) and BIFAP (database for pharmacoepidemiology research in primary care, with diagnosis and prescription records). We tested the comparability of drug use results from each database using the chi-square test and prevalence ratios. The prevalence of dementia in Madrid was estimated based on the dose per 100 inhabitants/day, adjusting the result for data obtained from BIFAP on combination treatment in the general population (0.37%) and the percentage of dementia patients undergoing treatment (41.13%). Cholinesterase inhibitors and memantine were taken by 2.08% and 0.72% of Madrid residents aged 65 and older was respectively. Both databases displayed similar results for use of these drugs. The estimated prevalence of dementia in individuals aged 65 and older is 5.91% (95% CI%, 5.85-5.95) (52 287 people), and it is higher in women (7.16%) than in men (4.00%). The estimated prevalence of dementia is similar to that found in population-based studies. Analysing consumption of specific dementia drugs can be a reliable and inexpensive means of updating prevalence data periodically and helping rationalise healthcare resources. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

A selenium species in cerebrospinal fluid predicts conversion to Alzheimer's dementia in persons with mild cognitive impairment.

PubMed

Vinceti, Marco; Chiari, Annalisa; Eichmüller, Marcel; Rothman, Kenneth J; Filippini, Tommaso; Malagoli, Carlotta; Weuve, Jennifer; Tondelli, Manuela; Zamboni, Giovanna; Nichelli, Paolo F; Michalke, Bernhard

2017-12-19

Little is known about factors influencing progression from mild cognitive impairment to Alzheimer's dementia. A potential role of environmental chemicals and specifically of selenium, a trace element of nutritional and toxicological relevance, has been suggested. Epidemiologic studies of selenium are lacking, however, with the exception of a recent randomized trial based on an organic selenium form. We determined concentrations of selenium species in cerebrospinal fluid sampled at diagnosis in 56 participants with mild cognitive impairment of nonvascular origin. We then investigated the relation of these concentrations to subsequent conversion from mild cognitive impairment to Alzheimer's dementia. Twenty-one out of the 56 subjects developed Alzheimer's dementia during a median follow-up of 42 months; four subjects developed frontotemporal dementia and two patients Lewy body dementia. In a Cox proportional hazards model adjusting for age, sex, duration of sample storage, and education, an inorganic selenium form, selenate, showed a strong association with Alzheimer's dementia risk, with an adjusted hazard ratio of 3.1 (95% confidence interval 1.0-9.5) in subjects having a cerebrospinal fluid content above the median level, compared with those with lower concentration. The hazard ratio of Alzheimer's dementia showed little departure from unity for all other inorganic and organic selenium species. These associations were similar in analyses that measured exposure on a continuous scale, and also after excluding individuals who converted to Alzheimer's dementia at the beginning of the follow-up. These results indicate that higher amounts of a potentially toxic inorganic selenium form in cerebrospinal fluid may predict conversion from mild cognitive impairment to Alzheimer's dementia.

Basal ganglia calcification as a putative cause for cognitive decline.

PubMed

de Oliveira, João Ricardo Mendes; de Oliveira, Matheus Fernandes

2013-01-01

Basal ganglia calcifications (BGC) may be present in various medical conditions, such as infections, metabolic, psychiatric and neurological diseases, associated with different etiologies and clinical outcomes, including parkinsonism, psychosis, mood swings and dementia. A literature review was performed highlighting the main neuropsychological findings of BGC, with particular attention to clinical reports of cognitive decline. Neuroimaging studies combined with neuropsychological analysis show that some patients have shown progressive disturbances of selective attention, declarative memory and verbal perseveration. Therefore, the calcification process might represent a putative cause for dementia syndromes, suggesting a probable link among calcinosis, the aging process and eventually with neuronal death. The increasing number of reports available will foster a necessary discussion about cerebral calcinosis and its role in determining symptomatology in dementia patients.

Lifestyle-related factors in predementia and dementia syndromes.

PubMed

Solfrizzi, Vincenzo; Capurso, Cristiano; D'Introno, Alessia; Colacicco, Anna Maria; Santamato, Andrea; Ranieri, Maurizio; Fiore, Pietro; Capurso, Antonio; Panza, Francesco

2008-01-01

Cognitive decline and dementia have a deep impact on the health and quality of life of older subjects and their caregivers. Since the therapeutic options currently available have demonstrated limited efficacy, the search for preventive strategies for cognitive decline and dementia are mandatory. A possible role of lifestyle-related factors was recently proposed for age-related changes of cognitive function, predementia syndromes and the cognitive decline of degenerative (Alzheimer's disease [AD]) or vascular origin. At present, cumulative evidence suggests that vascular risk factors may be important in the development of mild cognitive impairment (MCI), dementia and AD. Moderate alcohol drinking has been proposed as a protective factor against MCI and dementia in several longitudinal studies, but contrasting findings also exist. The Mediterranean diet could therefore be an interesting model with which to further study the association between dietary patterns and cognitive functioning, given the suggested role of many components of this diet (monounsaturated fatty acids, polyunsaturated fatty acids, cereals and red wine) in contrasting cognitive impairment and dementia. The association between low education and predementia and dementia syndromes is supported by the majority of studies, but very few studies have investigated whether this association may be attributed with lifestyle factors that covary with education. Studies in the literature seem to identify in physical exercise one promising strategy in decreasing cognitive decline, but some of the limitations of these studies do not allow us to draw definite conclusions. At present, in older subjects, healthy diets, antioxidant supplements, the prevention of nutritional deficiencies, and moderate physical activity could be considered the first line of defense against the development and progression of predementia and dementia syndromes. However, in most cases, these were only observational studies, and results are awaited from large multicenter randomized clinical trials in older persons that may clarify the possible synergy, for example, between moderate exercise, physical activity and healthy Mediterranean diet on cognition in the elderly.

Dementia in the oldest old: a multi-factorial and growing public health issue.

PubMed

Gardner, Raquel C; Valcour, Victor; Yaffe, Kristine

2013-01-01

The population of oldest old, or people aged 85 and older, is growing rapidly. A better understanding of dementia in this population is thus of increasing national and global importance. In this review, we describe the major epidemiological studies, prevalence, clinical presentation, neuropathological and imaging features, risk factors, and treatment of dementia in the oldest old. Prevalence estimates for dementia among those aged 85+ ranges from 18 to 38%. The most common clinical syndromes are Alzheimer's dementia, vascular dementia, and mixed dementia from multiple etiologies. The rate of progression appears to be slower than in the younger old. Single neuropathological entities such as Alzheimer's dementia and Lewy body pathology appear to have declining relevance to cognitive decline, while mixed pathology with Alzheimer's disease, vascular disease (especially cortical microinfarcts), and hippocampal sclerosis appear to have increasing relevance. Neuroimaging data are sparse. Risk factors for dementia in the oldest old include a low level of education, poor mid-life general health, low level of physical activity, depression, and delirium, whereas apolipoprotein E genotype, late-life hypertension, hyperlipidemia, and elevated peripheral inflammatory markers appear to have less relevance. Treatment approaches require further study, but the oldest old may be more prone to negative side effects compared with younger patients and targeted therapies may be less efficacious since single pathologies are less frequent. We also highlight the limitations and challenges of research in this area, including the difficulty of defining functional decline, a necessary component for a dementia diagnosis, the lack of normative neuropsychological data, and other shortcomings inherent in existing diagnostic criteria. In summary, our understanding of dementia in the oldest old has advanced dramatically in recent years, but more research is needed, particularly among varied racial, ethnic, and socioeconomic groups, and with respect to biomarkers such as neuroimaging, modifiable risk factors, and therapy.

Dementia in the oldest old: a multi-factorial and growing public health issue

PubMed Central

2013-01-01

The population of oldest old, or people aged 85 and older, is growing rapidly. A better understanding of dementia in this population is thus of increasing national and global importance. In this review, we describe the major epidemiological studies, prevalence, clinical presentation, neuropathological and imaging features, risk factors, and treatment of dementia in the oldest old. Prevalence estimates for dementia among those aged 85+ ranges from 18 to 38%. The most common clinical syndromes are Alzheimer's dementia, vascular dementia, and mixed dementia from multiple etiologies. The rate of progression appears to be slower than in the younger old. Single neuropathological entities such as Alzheimer's dementia and Lewy body pathology appear to have declining relevance to cognitive decline, while mixed pathology with Alzheimer's disease, vascular disease (especially cortical microinfarcts), and hippocampal sclerosis appear to have increasing relevance. Neuroimaging data are sparse. Risk factors for dementia in the oldest old include a low level of education, poor mid-life general health, low level of physical activity, depression, and delirium, whereas apolipoprotein E genotype, late-life hypertension, hyperlipidemia, and elevated peripheral inflammatory markers appear to have less relevance. Treatment approaches require further study, but the oldest old may be more prone to negative side effects compared with younger patients and targeted therapies may be less efficacious since single pathologies are less frequent. We also highlight the limitations and challenges of research in this area, including the difficulty of defining functional decline, a necessary component for a dementia diagnosis, the lack of normative neuropsychological data, and other shortcomings inherent in existing diagnostic criteria. In summary, our understanding of dementia in the oldest old has advanced dramatically in recent years, but more research is needed, particularly among varied racial, ethnic, and socioeconomic groups, and with respect to biomarkers such as neuroimaging, modifiable risk factors, and therapy. PMID:23809176

Functioning and disability analysis by using WHO Disability Assessment Schedule 2.0 in older adults Taiwanese patients with dementia.

PubMed

Huang, Shih-Wei; Chang, Kwang-Hwa; Escorpizo, Reuben; Chi, Wen-Chou; Yen, Chia-Feng; Liao, Hua-Fang; Chang, Feng-Hang; Chiu, Wen-Ta; Lin, Jia-Wei; Liou, Tsan-Hon

2016-08-01

To analyse the disability status of elderly Taiwanese dementia patients by using the World Health Organisation Disability Assessment Schedule 2.0 (WHODAS 2.0). We enrolled 12 126 disabled elderly (>65 years) patients with dementia during July 2012-January 2014 from the Taiwan Data Bank of Persons with Disability. Trained interviewers evaluated the standardised scores in the six WHODAS 2.0 domains. Student's t test was used for comparing WHODAS 2.0 scores of male and female dementia patients with different age groups. The study population comprised 12 126 patients; 7612 were women and 4514 were men. The WHODAS 2.0 scores showed that the dementia patients had global activity limitation and participation restriction in all domains. Dementia-induced disability was prominent in male patients in all of the domains of the WHODAS 2.0. The domains of life activities, getting along with people and cognition were more strongly affected than the other domains. However, women experienced more rapid functional decline than men did as they aged. The data analysed in this large-scale, population-based study revealed crucial information on dementia-induced disability in elderly patients on the basis of the WHODAS 2.0 framework. Implications for rehabilitation Dementia patients have global functional disability in all domains of WHODAS 2.0 and multidisciplinary team is needed for rehabilitation programme intervention for these patients. When considering the rehabilitation resource and strategy, the domains of cognition, activities of daily living and life activities should be focussed. When dementia patients aged 65-75 years old, male patients got more restriction of function than female and more medical resource allocation for disabled male patients is recommended. With ageing, female dementia patients exhibited more rapid functional decline than male patients did and more budget about rehabilitation for maintain functional and dementia progression is crucial for female patients.

Evidence of demyelination in mild cognitive impairment and dementia using a direct and specific magnetic resonance imaging measure of myelin content.

PubMed

Bouhrara, Mustapha; Reiter, David A; Bergeron, Christopher M; Zukley, Linda M; Ferrucci, Luigi; Resnick, Susan M; Spencer, Richard G

2018-04-18

We investigated brain demyelination in aging, mild cognitive impairment (MCI), and dementia using magnetic resonance imaging of myelin. Brains of young and old controls and old subjects with MCI, Alzheimer's disease, or vascular dementia were scanned using our recently developed myelin water fraction (MWF) mapping technique, which provides greatly improved accuracy over previous comparable methods. Maps of MWF, a direct and specific myelin measure, and relaxation times and magnetization transfer ratio, indirect and nonspecific measures, were constructed. MCI subjects showed decreased MWF compared with old controls. Demyelination was greater in Alzheimer's disease or vascular dementia. As expected, decreased MWF was accompanied by decreased magnetization transfer ratio and increased relaxation times. The young subjects showed greater myelin content than the old subjects. We believe this to be the first demonstration of myelin loss in MCI, Alzheimer's disease, and vascular dementia using a method that provides a quantitative magnetic resonance imaging-based measure of myelin. Our findings add to the emerging evidence that myelination may represent an important biomarker for the pathology of MCI and dementia. This study supports the investigation of the role of myelination in MCI and dementia through use of this quantitative magnetic resonance imaging approach in clinical studies of disease progression, relationship of functional status to myelination status, and therapeutics. Furthermore, mapping MWF may permit myelin to serve as a therapeutic target in clinical trials. Copyright © 2018. Published by Elsevier Inc.

Associations Between Ankle-Brachial Index and Cognitive Function: Results From the Lifestyle Interventions and Independence for Elders Trial.

PubMed

Espeland, Mark A; Newman, Anne B; Sink, Kaycee; Gill, Thomas M; King, Abby C; Miller, Michael E; Guralnik, Jack; Katula, Jeff; Church, Timothy; Manini, Todd; Reid, Kieran F; McDermott, Mary M

2015-08-01

The objective of this study was to evaluate cross-sectional and longitudinal associations between ankle-brachial index (ABI) and indicators of cognitive function. Randomized clinical trial (Lifestyle Interventions and Independence for Elders Trial). Eight US academic centers. A total of 1601 adults ages 70-89 years, sedentary, without dementia, and with functional limitations. Baseline ABI and interviewer- and computer-administered cognitive function assessments were obtained. These assessments were used to compare a physical activity intervention with a health education control. Cognitive function was reassessed 24 months later (interviewer-administered) and 18 or 30 months later (computer-administered) and central adjudication was used to classify individuals as having mild cognitive impairment, probable dementia, or neither. Lower ABI had a modest independent association with poorer cognitive functioning at baseline (partial r = 0.09; P < .001). Although lower baseline ABI was not associated with overall changes in cognitive function test scores, it was associated with higher odds for 2-year progression to a composite of either mild cognitive impairment or probable dementia (odds ratio 2.60 per unit lower ABI; 95% confidence interval 1.06-6.37). Across 2 years, changes in ABI were not associated with changes in cognitive function. In an older cohort sedentary individuals with dementia and with functional limitations, lower baseline ABI was independently correlated with cognitive function and associated with greater 2-year risk for progression to mild cognitive impairment or probable dementia. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

The impact of community-based arts and health interventions on cognition in people with dementia: a systematic literature review.

PubMed

Young, Rhea; Camic, Paul M; Tischler, Victoria

2016-01-01

Dementia is a progressive condition, affecting increasing numbers of people, characterised by cognitive decline. The current systematic review aimed to evaluate research pertaining to the impact of arts and health interventions on cognition in people with dementia. A literature search was conducted utilising PsychInfo, Cochrane Reviews, Web of Science, Medline and British Humanities Index databases. Seventeen studies were included in the review, including those related to literary, performing and visual arts. The review highlighted this as an emerging area of research with the literature consisting largely of small-scale studies with methodological limitations including lack of control groups and often poorly defined samples. All the studies suggested, however, that arts-based activities had a positive impact on cognitive processes, in particular on attention, stimulation of memories, enhanced communication and engagement with creative activities. The existent literature suggests that arts activities are helpful interventions within dementia care. A consensus has yet to emerge, however, about the direction for future research including the challenge of measurement and the importance of methodological flexibility. It is suggested that further research address some of these limitations by examining whether the impact of interventions vary depending on cognitive ability and to continue to assess how arts interventions can be of use across the stages of dementia.

Neuropsychiatric Symptoms of Dementia: Consent, Quality of Life, and Dignity

PubMed Central

Passmore, Michael J.

2013-01-01

Degenerative forms of dementia are progressive, incurable, fatal, and likely to cause suffering in conjunction with personal incapacity. Timely diagnostic disclosure and counseling can facilitate important advance care planning. The risk of harm associated with neuropsychiatric symptoms (NPS) of dementia often has to be balanced against the risk of harm associated with medication management of NPS. A palliative care framework can help preserve autonomy, quality of life, comfort, and dignity for patients with NPS. PMID:23853768

Molecular imaging of Alzheimer disease pathology.

PubMed

Kantarci, K

2014-06-01

Development of molecular imaging agents for fibrillar β-amyloid positron-emission tomography during the past decade has brought molecular imaging of Alzheimer disease pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal individuals and patients with mild cognitive impairment and Alzheimer disease indicate that β-amyloid deposition can be detected many years before the onset of symptoms with molecular imaging, and its progression can be followed longitudinally. The utility of β-amyloid PET in the differential diagnosis of Alzheimer disease is greatest when there is no pathologic overlap between 2 dementia syndromes, such as in frontotemporal lobar degeneration and Alzheimer disease. However β-amyloid PET alone may be insufficient in distinguishing dementia syndromes that commonly have overlapping β-amyloid pathology, such as dementia with Lewy bodies and vascular dementia, which represent the 2 most common dementia pathologies after Alzheimer disease. The role of molecular imaging in Alzheimer disease clinical trials is growing rapidly, especially in an era when preventive interventions are designed to eradicate the pathology targeted by molecular imaging agents. © 2014 by American Journal of Neuroradiology.

Guidelines for reporting methodological challenges and evaluating potential bias in dementia research.

PubMed

Weuve, Jennifer; Proust-Lima, Cécile; Power, Melinda C; Gross, Alden L; Hofer, Scott M; Thiébaut, Rodolphe; Chêne, Geneviève; Glymour, M Maria; Dufouil, Carole

2015-09-01

Clinical and population research on dementia and related neurologic conditions, including Alzheimer's disease, faces several unique methodological challenges. Progress to identify preventive and therapeutic strategies rests on valid and rigorous analytic approaches, but the research literature reflects little consensus on "best practices." We present findings from a large scientific working group on research methods for clinical and population studies of dementia, which identified five categories of methodological challenges as follows: (1) attrition/sample selection, including selective survival; (2) measurement, including uncertainty in diagnostic criteria, measurement error in neuropsychological assessments, and practice or retest effects; (3) specification of longitudinal models when participants are followed for months, years, or even decades; (4) time-varying measurements; and (5) high-dimensional data. We explain why each challenge is important in dementia research and how it could compromise the translation of research findings into effective prevention or care strategies. We advance a checklist of potential sources of bias that should be routinely addressed when reporting dementia research. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Endpoints for Pre-Dementia AD Trials: A Report from the EU/US/CTAD Task Force

PubMed Central

Vellas, B.; Bateman, R.; Blennow, K.; Frisoni, G.; Johnson, K.; Katz, R.; Langbaum, J.; Marson, D.; Sperling, R.; Wessels, A.; Salloway, S.; Doody, R.; Aisen, P.

2015-01-01

For Alzheimer’s disease treatment trials that focus on the pre-dementia stage of disease, outcome measures are needed that will enable assessment of disease progression in patients who are clinically normal. The EU/US CTAD Task Force, an international collaboration of investigators from industry, academia, non-profit foundations, and regulatory agencies, met in Philadelphia, Pennsylvania, USA, on November 19, 2014 to discuss existing and novel outcome assessments that may be useful in pre-dementia trials. Composite measures that assess changes in episodic memory, executive function, global cognition, and global function have recently been developed by a number of groups and appear to be sensitive at this stage. Functional measures that involve real-life complex tasks also appear to capture early subtle changes in pre-dementia subjects and have the advantage of representing clinically meaningful change. Patient reported outcomes and novel CSF and imaging biomarkers have also shown promise. More studies are needed to validate all of these tests in the pre-dementia population. Many of them have been incorporated as exploratory measures in ongoing or planned trials. PMID:26247004

Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors

PubMed Central

Kalaria, Raj N; Maestre, Gladys E; Arizaga, Raul; Friedland, Robert P; Galasko, Doug; Hall, Kathleen; Luchsinger, José A; Ogunniyi, Adesola; Perry, Elaine K; Potocnik, Felix; Prince, Martin; Stewart, Robert; Wimo, Anders; Zhang, Zhen-Xin; Antuono, Piero

2010-01-01

Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (≥5%) in certain Asian and Latin American countries, but consistently low (1–3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for ∼30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE ε4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions. PMID:18667359

Living With Dementia in Correctional Settings: A Case Report.

PubMed

Peacock, Shelley; Hodson, Alexandra; MacRae, Rhoda; Peternelj-Taylor, Cindy

2018-04-24

The prison population is aging at an alarming rate and many older persons have the potential to develop dementia while in prison. This case report aims to explore the needs of older people living with dementia in prison and discusses the interventions that exist to address these needs. As the condition progresses, persons with dementia become increasingly reliant on the support of others for their health and well-being because of the increasing complexity of physical healthcare and psychosocial needs. Very few interventions are cited in the research literature regarding the use, acceptability, and/or effectiveness of programming for people living with dementia in prison. To support the unique and complex needs of these persons, research is needed to guide the development of evidence-informed dementia programs and services as well as consideration of interdisciplinary collaboration with community organizations.

The long reach of Alzheimer's disease: patients, practice, and policy.

PubMed

Bynum, Julie P W

2014-04-01

The impact of Alzheimer's disease and related dementias reaches well beyond the health care needs of the person with dementia. As dementia inexorably progresses, the patient becomes increasingly dependent on others for basic daily care and routine tasks, a physically safe environment, and protection from exploitation or abuse. Addressing the diverse medical and social care needs of the burgeoning US population with Alzheimer's disease and related dementias requires the adoption of a broad-based policy framework and agenda that explicitly acknowledge the complex and unique needs of people with dementia and the impacts of dementia on caregivers and society at large. Public policies related to social service providers, agencies that provide appropriate housing, financial and legal services, and law enforcement must complement other policies focused on prevention and risk reduction, effective treatment development, and efficient health care delivery.

Living to the bitter end? A personalist approach to euthanasia in persons with severe dementia.

PubMed

Gastmans, Chris; De Lepeleire, Jan

2010-02-01

The number of people suffering from dementia will rise considerably in the years to come. This will have important implications for society. People suffering from dementia have to rely on relatives and professional caregivers when their disorder progresses. Some people want to determine for themselves their moment of death, if they should become demented. They think that the decline in personality caused by severe dementia is shocking and unacceptable. In this context, some people consider euthanasia as a way to avoid total deterioration. In this article, we discuss some practical and ethical dilemmas regarding euthanasia in persons with severe dementia based on an advance euthanasia directive. We are using a personalist approach in dealing with these ethical dilemmas.

The Role of Context in Remembering Familiar Persons: Insights from Semantic Dementia

ERIC Educational Resources Information Center

Joubert, Sven; Mauries, Sandrine; Barbeau, Emmanuel; Ceccaldi, Mathieu; Poncet, Michel

2004-01-01

Semantic dementia (SD) is a progressive condition characterized by an insidious and gradual breakdown in semantic knowledge. Patients suffering from this condition gradually lose their knowledge of objects and their attributes, concepts, famous persons, and public events. In contrast, these patients maintain a striking preservation of…

[Indications for percutaneous endoscopic gastrostomy in patients with disorders of the nervous system].

PubMed

Ehler, E; Geier, P; Dostál, V; Novotná, A; Vyhnálek, P; Hájek, J; Sákra, L

2002-05-01

Percutaneous endoscopic gastrostomy (PEG) is an efficient endoscopic method that ensures enteral nutrition for a longer period of time in patients who cannot take food per os. This method is also indicated in patients suffering from disorders of the central or peripheral nervous system which developed suddenly, such as a stroke or craniocerebral injuries, or gradually, such as amyotrophic lateral sclerosis (ALS), dementia, and multiple sclerosis. It has become common practice in the cooperation between neurologists and a gastroenterologists to use PEG in patients hospitalized in a neurological ward with encephalomalacy and haemorrhage, or craniocerebral injuries (after the patient recovers from the acute stage of the disease and is transferred to a neurological ICU), as well as in patients with ALS in a progressive stage. We gradually extend the indications of PEG for other patients with neurological disorders such as patients suffering from dementia, progressive multiple sclerosis, Parkinson's disease, and progressive polyneuropathy. Of 62 patients hospitalized in a neurological ward during a period of 4.5 years, 56 patients suffered from sudden disorders of the nervous system (strokes and craniocerebral injuries) and 6 patients had gradually progressing neurological diseases (ALS, multiple sclerosis, Parkinson's disease, dementia, and polyneuropathy).

Energy expenditure in frontotemporal dementia: a behavioural and imaging study

PubMed Central

Ahmed, Rebekah M; Landin-Romero, Ramon; Collet, Tinh-Hai; van der Klaauw, Agatha A; Devenney, Emma; Henning, Elana; Kiernan, Matthew C; Piguet, Olivier; Farooqi, I Sadaf; Hodges, John R

2017-01-01

Abstract See Finger (doi:10.1093/aww312) for a scientific commentary on this article. Abnormal eating behaviour and metabolic parameters including insulin resistance, dyslipidaemia and body mass index are increasingly recognized as important components of neurodegenerative disease and may contribute to survival. It has previously been established that behavioural variant frontotemporal dementia is associated with abnormal eating behaviour characterized by increased sweet preference. In this study, it was hypothesized that behavioural variant frontotemporal dementia might also be associated with altered energy expenditure. A cohort of 19 patients with behavioural variant frontotemporal dementia, 13 with Alzheimer’s disease and 16 (age- and sex-matched) healthy control subjects were studied using Actiheart devices (CamNtech) to assess resting and stressed heart rate. Actiheart devices were fitted for 7 days to measure sleeping heart rate, activity levels, and resting, active and total energy expenditure. Using high resolution structural magnetic resonance imaging the neural correlates of increased resting heart rate were investigated including cortical thickness and region of interest analyses. In behavioural variant frontotemporal dementia, resting (P = 0.001), stressed (P = 0.037) and sleeping heart rate (P = 0.038) were increased compared to control subjects, and resting heart rate (P = 0.020) compared to Alzheimer disease patients. Behavioural variant frontotemporal dementia was associated with decreased activity levels compared to controls (P = 0.002) and increased resting energy expenditure (P = 0.045) and total energy expenditure (P = 0.035). Increased resting heart rate correlated with behavioural (Cambridge Behavioural Inventory) and cognitive measures (Addenbrooke’s Cognitive Examination). Increased resting heart rate in behavioural variant frontotemporal dementia correlated with atrophy involving the mesial temporal cortex, insula, and amygdala, regions previously suggested to be involved exclusively in social and emotion processing in frontotemporal dementia. These neural correlates overlap the network involved in eating behaviour in frontotemporal dementia, suggesting a complex interaction between eating behaviour, autonomic function and energy homeostasis. As such the present study suggests that increased heart rate and autonomic changes are prevalent in behavioural variant frontotemporal dementia, and are associated with changes in energy expenditure. An understanding of these changes and neural correlates may have potential relevance to disease progression and prognosis. PMID:27789521

High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia

PubMed Central

Cao, Chuanhai; Loewenstein, David A.; Lin, Xiaoyang; Zhang, Chi; Wang, Li; Duara, Ranjan; Wu, Yougui; Giannini, Alessandra; Bai, Ge; Cai, Jianfeng; Greig, Maria; Schofield, Elizabeth; Ashok, Raj; Small, Brent; Potter, Huntington; Arendash, Gary W.

2017-01-01

Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer’s disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65–88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2–4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (−51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 µM) in MCI subjects were associated with no conversion to dementia during the ensuing 2–4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI. PMID:22430531

Prevalence of Hippocampal Sclerosis in a Clinicopathologically Characterized Cohort.

PubMed

Malek-Ahmadi, Michael; Kahlon, Vickram; Adler, Charles H; Obradov, Aleksandra; Thind, Kabir; Shill, Holly A; Sue, Lucia I; Caviness, John N; Jacobson, Sandra; Sabbagh, Marwan N

2013-01-01

Hippocampal sclerosis (HS) is a neuropathological finding that frequently occurs with pathologies, such as Alzheimer's disease (AD). Prevalence estimates of HS in autopsy-confirmed dementia samples have varied between 0.4% and 24.5%. However, the prevalence of HS within other pathologic groups has not been well characterized. Utilizing a sample of 910 prospectively followed and clinicopathologically confirmed dementia cases, we determined the prevalence of HS among the sample and within specific pathologic groups. HS prevalence of the sample was compared to reported HS prevalence rates in other autopsy-confirmed dementia samples. The age range of the sample was 43 to 106 years, with a mean of 81.49±8.45. Of the 910 cases, 505 were male and 405 were female. For the entire sample, the average educational level was 14.59±2.65years. Of the 910 individuals, 47 (5.16%) cases had HS pathology present at autopsy. Among the 561 AD cases, 26 (4.43%) had HS pathology present. The frontotemporal dementia (FTD)/Pick's group had the highest percentage of cases with HS pathology (23.08%) followed by primary progressive aphasia (PPA) (16.67%) and Parkinson's disease with dementia (PDD) (5.34%). The HS prevalence rate of this study was not significantly different from all but 2 studies. The prevalence of HS pathology in this sample of autopsy-confirmed dementia cases was similar to other reported HS prevalence rates. This study is the first to report the presence of HS pathology in PDD cases.

Driving and Dementia: A Review of the Literature

PubMed Central

Brown, Laura B.; Ott, Brian R.

2012-01-01

The purpose of this article is to review the literature on the ability of individuals with dementia to drive an automobile. Based on a review of the literature, several factors were identified that may be useful in differentiating between people with dementia who presently remain safe drivers from those who have progressed to impaired driving. These factors include disease duration and severity, sex, patient self-assessment, family assessment, neuropsychological measures, findings on road evaluations, and driving simulator testing. The approach of the physician to driving and dementia is addressed, including in-office screening, referral for on-road driving assessments, and the potential for physician reporting to state agencies. PMID:15533995

Enacted and implied stigma for dementia in a community in south-west Nigeria.

PubMed

Adebiyi, Akindele O; Fagbola, Motunrayo A; Olakehinde, Olaide; Ogunniyi, Adesola

2016-07-01

Dementia is a chronic progressive disease that mostly affects the elderly. There is often a stigma surrounding dementia patients because of poor awareness about the disease. In Nigeria, this stigma and related attitudes have not been fully explored. In this study, we assessed the attitude of people towards demented individuals in a transitional community in Nigeria. The study used a mixed methods approach. Focused group discussions exploring the concept of dementia were conducted among six community groups, and quantitative data was obtained from an interviewer-administered questionnaire. A total of 313 respondents were selected with a cluster sampling technique. Only 212 respondents (67.7%) were aware of dementia. 'Memory loss disease', 'ageing disease', 'disease of insanity', 'brain disorder', 'disease of forgetfulness', and 'dull brain' are the common names used to describe dementia in the community. Enacted stigma was evident as 36% of respondents felt dementia was associated with shame and embarrassment in the community. Implied stigma was evident in another third that opined that demented individuals would prefer not to know or let others know that they have the disease. Also, 28% were of the opinion that people do not take those with dementia seriously. Of the 22 (10.4%) that reported having received structured information about dementia, 16 (72.7%) got the information from health facilities. Qualitative data revealed the presence of enacted stigma in the community as some referred to affected individuals by derogatory names such as 'madman'. Some statements from the focus group discussion participants also gave useful insights into the scorn with which demented individuals are sometimes treated. The presence of enacted and implied stigma related to dementia within the community calls for concern. More research efforts are needed to unravel the burden of stigma within communities and best practice for stigma-reducing interventions. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

Clinical features and multidisciplinary approaches to dementia care

PubMed Central

Grand, Jacob HG; Caspar, Sienna; MacDonald, Stuart WS

2011-01-01

Dementia is a clinical syndrome of widespread progressive deterioration of cognitive abilities and normal daily functioning. These cognitive and behavioral impairments pose considerable challenges to individuals with dementia, along with their family members and caregivers. Four primary dementia classifications have been defined according to clinical and research criteria: 1) Alzheimer’s disease; 2) vascular dementias; 3) frontotemporal dementias; and 4) dementia with Lewy bodies/Parkinson’s disease dementia. The cumulative efforts of multidisciplinary healthcare teams have advanced our understanding of dementia beyond basic descriptions, towards a more complete elucidation of risk factors, clinical symptoms, and neuropathological correlates. The characterization of disease subtypes has facilitated targeted management strategies, advanced treatments, and symptomatic care for individuals affected by dementia. This review briefly summarizes the current state of knowledge and directions of dementia research and clinical practice. We provide a description of the risk factors, clinical presentation, and differential diagnosis of dementia. A summary of multidisciplinary team approaches to dementia care is outlined, including management strategies for the treatment of cognitive impairments, functional deficits, and behavioral and psychological symptoms of dementia. The needs of individuals with dementia are extensive, often requiring care beyond traditional bounds of medical practice, including pharmacologic and non-pharmacologic management interventions. Finally, advanced research on the early prodromal phase of dementia is reviewed, with a focus on change-point models, trajectories of cognitive change, and threshold models of pathological burden. Future research goals are outlined, with a call to action for social policy initiatives that promote preventive lifestyle behaviors, and healthcare programs that will support the growing number of individuals affected by dementia. PMID:21655340

A Pilot Study of Immune and Mood Outcomes of a Community-Based Intervention for Dementia Caregivers: The PLST Intervention

PubMed Central

Garand, Linda; Buckwalter, Kathleen C.; Lubaroff, David M.; Tripp-Reimer, Toni; Frantz, Rita A.; Ansley, Timothy N.

2010-01-01

Providing care to a family member with dementia is conceptualized as a chronic stressor with adverse psychological and physical effects. The purpose of this pilot study was to evaluate mood and immune outcomes of caregivers exposed to a community-based psychoeducational nursing intervention based on the Progressively Lowered Stress Threshold (PLST) model. The PLST intervention is designed to strengthen the psychological resources of dementia caregivers by teaching methods of preventing and/or managing behavioral problems exhibited by the person with dementia. Mood and immune outcomes were compared between caregivers randomly assigned to receive either the PLST or a comparison intervention. Results of this pilot study suggest that caregivers who received the PLST intervention demonstrated significantly stronger T-cell proliferative responses to both PHA and ConA, indicating an improvement in T-cell immune function immediately after the in-home intervention (T2) and again after six months of telephone support for application of the PLST model (T3). Findings do not support the hypothesis that the PLST intervention had a significant effect on total mood disturbance or NK cell cytotoxicity over the course of the study. PMID:12143075

Care and Service at Home for Persons With Dementia in Europe.

PubMed

Bökberg, Christina; Ahlström, Gerd; Leino-Kilpi, Helena; Soto-Martin, Maria E; Cabrera, Esther; Verbeek, Hilde; Saks, Kai; Stephan, Astrid; Sutcliffe, Caroline; Karlsson, Staffan

2015-09-01

To describe available and utilized formal care and service at home for persons with dementia, from diagnosis to end-of-life stage, in eight European countries. A descriptive cross-country design concerning eight European countries as a part of the European research project RightTimePlaceCare. The research team in each country used a mapping system to collect country-specific information concerning dementia care and service system. The mapping system consists of 50 types of care and service activities. Sixteen of the 50 predefined activities concerning care and service at home were selected for this study and subdivided into three categories, following the stages of dementia. Availability was reported to be higher than utilization, and the findings indicated more similarities than differences among the eight countries involved. Even though there were several available activities of "basic care and services" and "healthcare interventions," they were utilized by few in most countries. Furthermore, "specialized dementia care and services" were sparsely available and even more sparsely utilized in the participating countries. The findings indicated that persons with dementia in Europe received formal care and service on a general, basic level but seldom adjusted to their specific needs. This study describes the gap between service provision and utilization enabling nurses to develop individually adjusted care plans for persons with dementia during the progress of the disease. The findings do not include matters of quality of care or how to best organize effective care and services. However, the activities of care and services presented here should shed light on what room there is for improvement when it comes to enabling persons with dementia to go on living at home. © 2015 Sigma Theta Tau International.

Cognitive impairment, dementia, and personality stability among older adults

PubMed Central

Terracciano, Antonio; Stephan, Yannick; Luchetti, Martina; Sutin, Angelina R.

2017-01-01

There is contrasting evidence on personality stability in advanced age, and limited knowledge on the impact of cognitive impairment and dementia on trait stability. Group- and individual-level longitudinal analyses of the five major dimensions of personality assessed twice over 4-years (N = 9,935) suggest that rank-order stability was progressively lower with advancing age (from rtt = 0.68 for age 50–60 to rtt = 0.58 for age >80 years). Stability was low in the dementia group (rtt = 0.43), and this was not simply due to lower reliability given that internal consistency remained adequate in the dementia group. Among individuals with no cognitive impairment or dementia, there was no association between stability and age (rtt = 0.70 even for age >80). These results suggest that the lower personality stability in older adults is not due to age but cognitive impairment and dementia. PMID:29214858

Behavioral symptoms related to cognitive impairment.

PubMed

Dillon, Carol; Serrano, Cecilia M; Castro, Diego; Leguizamón, Patricio Perez; Heisecke, Silvina L; Taragano, Fernando E

2013-01-01

Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and related dementias. On one hand, behavioral symptoms in patients with mild cognitive impairment (MCI) can indicate an increased risk of progressing to dementia. On the other hand, mild behavioral impairment (MBI) in patients who usually have normal cognition indicates an increased risk of developing dementia. Whatever the cause, all dementias carry a high rate of NPI. These symptoms can be observed at any stage of the disease, may fluctuate over its course, are a leading cause of stress and overload for caregivers, and increase rates of hospitalization and early institutionalization for patients with dementia. The clinician should be able to promptly recognize NPI through the use of instruments capable of measuring their frequency and severity to support diagnosis, and to help monitor the treatment of behavioral symptoms. The aims of this review are to describe and update the construct 'MBI' and to revise the reported NPS related to prodromal stages of dementia (MCI and MBI) and dementia stages of Alzheimer's disease and frontotemporal lobar degeneration.

Dementia Research: Populations, Progress, Problems, and Predictions.

PubMed

Hunter, Sally; Smailagic, Nadja; Brayne, Carol

2018-05-16

Alzheimer's disease (AD) is a clinicopathologically defined syndrome leading to cognitive impairment. Following the recent failures of amyloid-based randomized controlled trials to change the course of AD, there are growing calls for a re-evaluation of basic AD research. Epidemiology offers one approach to integrating the available evidence. Here we examine relationships between evidence from population-based, clinicopathological studies of brain aging and a range of hypotheses from all areas of AD research. We identify various problems, including a lack of systematic approach to measurement of clinical and neuropathological factors associated with dementia in experimental and clinical settings, poor understanding of the strengths and weaknesses of different observational and experimental designs, a lack of clarity in relation to disease definitions from the clinical, neuropathological, and molecular perspectives, inadequate characterization of brain aging in the human population, difficulties in translation between laboratory-based and population-based evidence bases, and a lack of communication between different sections of the dementia research community. Population studies highlight complexity and predict that therapeutic approaches based on single disease features will not be successful. Better characterization of brain aging in the human population is urgently required to select biomarkers and therapeutic targets that are meaningful to human disease. The generation of detailed and reliable evidence must be addressed before progress toward therapeutic interventions can be made.

Paratonia: a Delphi procedure for consensus definition.

PubMed

Hobbelen, Johannes S M; Koopmans, Raymond T C M; Verhey, Frans R J; Van Peppen, Roland P S; de Bie, Rob A

2006-01-01

Paratonia is a motor problem that develops during the course of dementia. Definitions of paratonia used in the literature differ considerably, which has clinical implications and may lead to an undesirable heterogeneity in study populations. For this reason, we initiated a Delphi procedure with known experts in the field to establish an operational consensus definition of paratonia. The Delphi procedure involved an anonymous and multistage approach presented as a questionnaire, with each stage building on the results of the previous one in order to reach consensus on the definition of paratonia. Eight of 17 experts agreed to participate in the study. After 4 rounds, the participants reached consensus on the following definition: paratonia is a form of hypertonia with an involuntary variable resistance during passive movement. The nature of paratonia may change with progression of dementia (eg, from active assistance (aka Mitgehen) to active resistance). The degree of resistance depends on the speed of movement (eg, slow > low resistance, fast > high resistance). The degree of paratonia is proportional to the amount of force applied and increases with progression of dementia. The resistance to passive movement is in any direction and there is no clasp-knife phenomenon. The Delphi procedure resulted in a comprehensive, operational definition of paratonia. Future research should focus on the reliability and validity of this definition.

Effects of FDA approved medications for Alzheimer’s disease on clinical progression

PubMed Central

Mielke, Michelle M.; Leoutsakos, Jeannie-Marie; Corcoran, Chris D.; Green, Robert C.; Norton, Maria C.; Welsh-Bohmer, Kathleen A.; Tschanz, JoAnn T.; Lyketsos, Constantine G.

2011-01-01

Background Observational studies suggest cholinesterase inhibitors and/or memantine may delay clinical progression of Alzheimer’s disease (AD) in 40% of individuals taking the medications. Given this response and existence of side effects, we sought to quantify medication use and benefits in a population-based study of incident AD cases. Methods The Cache County Dementia Progression study (DPS) enrolled and followed a cohort of 327 incident AD cases up to 9 years. Drug exposure was expressed using a persistency index (PI), calculated as total years of drug use divided by total years of observation. Linear mixed effects models examined PI, and interactions with sex and APOE ε4, as predictors of clinical progression on the Mini-Mental State Exam (MMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-Sum). Results Sixty-nine participants (21.1%) ever used cholinesterase inhibitors or memantine. There was a strong three-way interaction between PI, sex, and time. Among women, a higher PI (i.e. greater duration of use) of cholinesterase inhibitors was associated with slower progression on the MMSE and CDR-Sum, particularly among those with an APOE ε4 allele. In contrast, higher PI was associated with faster progression in males. Conclusion A low percentage of individuals with AD in the community are taking cholinesterase inhibitors or memantine. This study suggests that women, particularly those with an APOE ε4 allele, may receive the most benefit from these medications. With the newly approved increased dose of donepezil, it will be imperative to determine whether a higher dose is needed in men or whether other factors warrant consideration. PMID:22301194

The missing link between sleep disorders and age-related dementia: recent evidence and plausible mechanisms.

PubMed

Zhang, Feng; Zhong, Rujia; Li, Song; Chang, Raymond Chuen-Chung; Le, Weidong

2017-05-01

Sleep disorders are among the most common clinical problems and possess a significant concern for the geriatric population. More importantly, while around 40% of elderly adults have sleep-related complaints, sleep disorders are more frequently associated with co-morbidities including age-related neurodegenerative diseases and mild cognitive impairment. Recently, increasing evidence has indicated that disturbed sleep may not only serve as the consequence of brain atrophy, but also contribute to the pathogenesis of dementia and, therefore, significantly increase dementia risk. Since the current therapeutic interventions lack efficacies to prevent, delay or reverse the pathological progress of dementia, a better understanding of underlying mechanisms by which sleep disorders interact with the pathogenesis of dementia will provide possible targets for the prevention and treatment of dementia. In this review, we briefly describe the physiological roles of sleep in learning/memory, and specifically update the recent research evidence demonstrating the association between sleep disorders and dementia. Plausible mechanisms are further discussed. Moreover, we also evaluate the possibility of sleep therapy as a potential intervention for dementia.

Education and dementia in the context of the cognitive reserve hypothesis: a systematic review with meta-analyses and qualitative analyses.

PubMed

Meng, Xiangfei; D'Arcy, Carl

2012-01-01

Cognitive reserve (CR) or brain reserve capacity explains why individuals with higher IQ, education, or occupational attainment have lower risks of developing dementia, Alzheimer's disease (AD) or vascular dementia (VaD). The CR hypothesis postulates that CR reduces the prevalence and incidence of AD or VaD. It also hypothesizes that among those who have greater initial cognitive reserve (in contrast to those with less reserve) greater brain pathology occurs before the clinical symptoms of disease becomes manifest. Thus clinical disease onset triggers a faster decline in cognition and function, and increased mortality among those with initial greater cognitive reserve. Disease progression follows distinctly separate pathological and clinical paths. With education as a proxy we use meta-analyses and qualitative analyses to review the evidence for the CR hypothesis. We searched PubMed, PsycoINFO, EMBASE, HealthStar, and Scopus databases from January 1980 to June 2011 for observational studies with clear criteria for dementia, AD or VaD and education. One hundred and thirty-three articles with a variety of study designs met the inclusion criteria. Prevalence and incidence studies with odds ratios (ORs), relative risks or original data were included in the meta-analyses. Other studies were reviewed qualitatively. The studies covered 437,477 subjects. Prevalence and incidence studies with pooled ORs of 2.61 (95%CI 2.21-3.07) and 1.88 (95%CI 1.51-2.34) respectively, showed low education increased the risk of dementia. Heterogeneity and sensitivity tests confirmed the evidence. Generally, study characteristics had no effect on conclusions. Qualitative analyses also showed the protective effects of higher education on developing dementia and with clinical disease onset hastening a decline in cognition and function, and greater brain pathology. This systematic review and meta-analyses covering a wide range of observational studies and diverse settings provides robust support for the CR hypothesis. The CR hypothesis suggests several avenues for dementia prevention.

Novel drug target identification for the treatment of dementia using multi-relational association mining.

PubMed

Nguyen, Thanh-Phuong; Priami, Corrado; Caberlotto, Laura

2015-07-08

Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia.

Novel drug target identification for the treatment of dementia using multi-relational association mining

PubMed Central

Nguyen, Thanh-Phuong; Priami, Corrado; Caberlotto, Laura

2015-01-01

Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia. PMID:26154857

Auditory hedonic phenotypes in dementia: A behavioural and neuroanatomical analysis

PubMed Central

Fletcher, Phillip D.; Downey, Laura E.; Golden, Hannah L.; Clark, Camilla N.; Slattery, Catherine F.; Paterson, Ross W.; Schott, Jonathan M.; Rohrer, Jonathan D.; Rossor, Martin N.; Warren, Jason D.

2015-01-01

Patients with dementia may exhibit abnormally altered liking for environmental sounds and music but such altered auditory hedonic responses have not been studied systematically. Here we addressed this issue in a cohort of 73 patients representing major canonical dementia syndromes (behavioural variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive nonfluent aphasia (PNFA) amnestic Alzheimer's disease (AD)) using a semi-structured caregiver behavioural questionnaire and voxel-based morphometry (VBM) of patients' brain MR images. Behavioural responses signalling abnormal aversion to environmental sounds, aversion to music or heightened pleasure in music (‘musicophilia’) occurred in around half of the cohort but showed clear syndromic and genetic segregation, occurring in most patients with bvFTD but infrequently in PNFA and more commonly in association with MAPT than C9orf72 mutations. Aversion to sounds was the exclusive auditory phenotype in AD whereas more complex phenotypes including musicophilia were common in bvFTD and SD. Auditory hedonic alterations correlated with grey matter loss in a common, distributed, right-lateralised network including antero-mesial temporal lobe, insula, anterior cingulate and nucleus accumbens. Our findings suggest that abnormalities of auditory hedonic processing are a significant issue in common dementias. Sounds may constitute a novel probe of brain mechanisms for emotional salience coding that are targeted by neurodegenerative disease. PMID:25929717

[Efficacy of an occupational group therapy in degenerative dementias: a controlled study in the nursing home setting].

PubMed

Pickel, Sabine; Grässel, Elmar; Luttenberger, Katharina

2011-11-01

We investigated the effectiveness of an occupational group therapy, tailored to dementia patients, performed regularly 6 days a week, on everyday-practical capabilities and dementia-related behavior. Fifty-six dementia patients in one nursing home in Northern Bavaria (Germany) were observed for 6 months: 28 patients in a therapy group and 28 patients in a matched controlled group. Performance tests, ADAS-kog and E-ADL-Test, were carried out blinded. Data were analyzed using adjusted mean differences for baseline and 6-months follow-up data and multiple regression analysis. The therapy leads to stabilization of everyday-practical capabilities (adjusted mean difference 4.0; 95 % CI 1.6-6.3; p = 0.002) and of dementia-related behavior (adjusted mean difference -6.8; 95 % CI -11.8--1.8; p = 0.009) compared to deterioration in the control group who received treatment as usual. The effect power (Cohen d) on everyday-practical capabilities is |0.83|. The therapy had no significant effect on cognitive capacity. An occupational therapy program directed particularly to everyday-practical activities cannot slow the progression of all dementia-related symptoms, but has a main target effect on everyday-practical capabilities. © Georg Thieme Verlag KG Stuttgart · New York.

Families Who Care: Assisting African American and Rural Caregivers Dealing with Dementia. A Replication Plan.

ERIC Educational Resources Information Center

Coogle, Constance L., Ed.; Finley, Ruth B., Ed.

This Replication Plan describes an Administration on Aging funded Project, "Assisting Caregivers of Black and Rural Elders with Dementia: Progressive Training through Trusted Resources." The project directly developed the capacities of trusted community leaders (n=69) who served as trainers of African American and rural family caregivers…

Atrial fibrillation incrementally increases dementia risk across all CHADS2 and CHA2DS2VASc strata in patients receiving long-term warfarin.

PubMed

Graves, Kevin G; May, Heidi T; Jacobs, Victoria; Bair, Tami L; Stevens, Scott M; Woller, Scott C; Crandall, Brian G; Cutler, Michael J; Day, John D; Mallender, Charles; Osborn, Jeffrey S; Peter Weiss, J; Jared Bunch, T

2017-06-01

Patients with atrial fibrillation (AF) are at higher risk for developing dementia. Warfarin is a common therapy for the prevention of thromboembolism in AF, valve replacement, and thrombosis patients. The extent to which AF itself increases dementia risk remains unknown. A total 6030 patients with no history of dementia and chronically anticoagulated with warfarin were studied. Warfarin management was provided through a Clinical Pharmacy Anticoagulation Service. Patients were stratified by warfarin indication of AF (n=3015) and non-AF (n=3015) and matched by propensity score (±0.01). Patients were stratified by the congestive heart failure, hypertension, age >75 years, diabetes, stroke (CHADS 2 ) score calculated at the time of warfarin initiation and followed for incident dementia. The average age of the AF cohort was 69.3±11.2 years, and 52.7% were male; average age of non-AF cohort was 69.3±10.9 years, and 51.5% were male. Increasing CHADS 2 score was associated with increased dementia incidence, P trend=.004. When stratified by warfarin indication, AF patients had an increased risk of dementia incidence. After multivariable adjustment, AF patients continued to display a significantly increased risk of dementia when compared with non-AF patients across all CHADS 2 scores strata. In patients receiving long-term warfarin therapy, dementia risk increased with increasing CHADS 2 scores. However, the presence of AF was associated with higher rates of dementia across all CHADS 2 score strata. These data suggest that AF contributes to the risk of dementia and that this risk is not solely attributable to anticoagulant use. Dementia may be an end manifestation of a systemic disease state, and AF likely contributes to its progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Syndromes of Rapidly Progressive Cognitive Decline-Our Experience

PubMed Central

Chandra, Sadanandavalli Retnaswami; Viswanathan, Lakshminarayanapuram Gopal; Pai, Anupama Ramakanth; Wahatule, Rahul; Alladi, Suvarna

2017-01-01

Background: Dementias are fairly slowly progressive degenerative diseases of brain for which treatment options are very less and carry a lot of burden on family and society. A small percentage of them are rapidly progressive and mostly carry a different course outcome. However, there are no definite criteria other than the time line for these patients. Aims: The aim of this was to identify and categorize the causes and course of rapidly progressive dementias seen in our center. Settings and Design: Patients who presented with rapid deterioration of cognitive functions within weeks to 1 year between 2011 and December 2016 were evaluated. Patients and Methods: All patients underwent all mandatory tests for dementia including brain imaging. Complete vasculitis workup, autoimmune encephalitis profile including Voltage Gated Potassium Channel, N-methyl-D-aspartic acid receptor, glutamic acid-decarboxylase, thyroid-peroxidase antibody, cerebrospinal fluid, and other special tests such as duodenal biopsy and paraneoplastic workup were done based on clinical indications. Results and Conclusions: Out of 144 patients 42 had immune-mediated encephalopathy, 18 had Creutzfeldt-Jakob disease, 3 had Vitamin B12 deficiency, 63 had infection with neurocysticercosis, 7 had tuberculosis, 2 had HIV, 1 had herpes simplex encephalitis, 1 had neurosyphilis, 1 Whipples disease, 1 had Subacute Sclerosing Panencephalitis, 1 had Mass lesion, 3 had Frontotemporal dementia, and 3 had small vessel disease. Good majority of these patients have infective and immune-mediated causes and less number belong to degenerative group. Therefore, caution is needed to look for treatable cause as it carries a different treatment options and outcome. PMID:28936074

Mild cognitive decline. A position statement of the Cognitive Decline Group of the European Innovation Partnership for Active and Healthy Ageing (EIPAHA).

PubMed

Apostolo, Joao; Holland, Carol; O'Connell, Matthew D L; Feeney, Joanne; Tabares-Seisdedos, Rafael; Tadros, George; Campos, Elzbieta; Santos, Nadine; Robertson, Deirdre A; Marcucci, Maura; Varela-Nieto, Isabel; Crespo-Facorro, Benedicto; Vieta, Eduard; Navarro-Pardo, Esperanza; Selva-Vera, Gabriel; Balanzá-Martínez, Vicent; Cano, Antonio

2016-01-01

Mild cognitive impairment (MCI) is a term used to describe a level of decline in cognition which is seen as an intermediate stage between normal ageing and dementia, and which many consider to be a prodromal stage of neurodegeneration that may become dementia. That is, it is perceived as a high risk level of cognitive change. The increasing burden of dementia in our society, but also our increasing understanding of its risk factors and potential interventions, require diligent management of MCI in order to find strategies that produce effective prevention of dementia. To update knowledge regarding mild cognitive impairment, and to bring together and appraise evidence about the main features of clinical interest: definitions, prevalence and stability, risk factors, screening, and management and intervention. Literature review and consensus of expert opinion. MCI describes a level of impairment in which deteriorating cognitive functions still allow for reasonable independent living, including some compensatory strategies. While there is evidence for some early risk factors, there is still a need to more precisely delineate and distinguish early manifestations of frank dementia from cognitive impairment that is less likely to progress to dementia, and furthermore to develop improved prospective evidence for positive response to intervention. An important limitation derives from the scarcity of studies that take MCI as an endpoint. Strategies for effective management suffer from the same limitation, since most studies have focused on dementia. Behavioural changes may represent the most cost-effective approach. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

All Is Not Lost: Positive Behaviors in Alzheimer's Disease and Behavioral-Variant Frontotemporal Dementia with Disease Severity.

PubMed

Midorikawa, Akira; Leyton, Cristian E; Foxe, David; Landin-Romero, Ramon; Hodges, John R; Piguet, Olivier

2016-09-06

Anecdotal evidence indicates that some patients with dementia exhibit novel or increased positive behaviors, such as painting or singing, after the disease onset. Due to the lack of objective measures, however, the frequency and nature of these changes has not been formally investigated. This study aimed to systematically identify changes in these behaviors in the two most common younger-onset dementia syndromes: Alzheimer's disease (AD) and behavioral-variant frontotemporal dementia (bvFTD). Sixty-three caregivers of patients with dementia (32 caregivers of AD patients and 31 caregivers of bvFTD patients) participated in the study. Caregivers rated the presence and frequency of positive and negative behavior changes after the onset of dementia using the Hypersensory and Social/Emotional Scale (HSS) questionnaire, focusing on three domains: sensory processing, cognitive skills, and social/emotional processing. Six composites scores were obtained reflecting these three domains (two composite scores for each domain). Differences across scores and ratios of increased and decreased behaviors were analyzed between AD and bvFTD, at different disease severity levels. After disease onset, significant changes in the sensory processing domain were observed across disease severity levels, particularly in AD. Composite scores of the other domains did not change significantly. Importantly, however, some novel or increased positive behaviors were present in between 10% (Music activities) and 70% (Hypersensitivity) of AD and bvFTD patients, regardless of disease severity. We provide the first systematic investigation of positive behaviors in AD and bvFTD. The newly developed HSS questionnaire is a valid measure to characterize changes and progression of positive behaviors in patients with dementia.

Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease.

PubMed

Cholerton, Brenna; Johnson, Catherine O; Fish, Brian; Quinn, Joseph F; Chung, Kathryn A; Peterson-Hiller, Amie L; Rosenthal, Liana S; Dawson, Ted M; Albert, Marilyn S; Hu, Shu-Ching; Mata, Ignacio F; Leverenz, James B; Poston, Kathleen L; Montine, Thomas J; Zabetian, Cyrus P; Edwards, Karen L

2018-05-01

Identification of factors associated with progression of cognitive symptoms in Parkinson's disease (PD) is important for treatment planning, clinical care, and design of future clinical trials. The current study sought to identify whether prediction of cognitive progression is aided by examining baseline cognitive features, and whether this differs according to stage of cognitive disease. Participants with PD in the Pacific Udall Center Clinical Consortium who had longitudinal data available and were nondemented at baseline were included in the study (n = 418). Logistic and Cox regression models were utilized to examine the relationship between cognitive, demographic, and clinical variables with risk and time to progression from no cognitive impairment to mild cognitive impairment (PD-MCI) or dementia (PDD), and from PD-MCI to PDD. Processing speed (OR = 1.05, p = 0.009) and working memory (OR = 1.01, p = 0.03) were associated with conversion to PDD among those with PD-MCI at baseline, over and above demographic variables. Conversely, the primary predictive factor in the transition from no cognitive impairment to PD-MCI or PDD was male sex (OR = 4.47, p = 0.004), and males progressed more rapidly than females (p = 0.01). Further, among females with shorter disease duration, progression was slower than for their male counterparts, and poor baseline performance on semantic verbal fluency was associated with shorter time to cognitive impairment in females but not in males. This study provides evidence for sex differences in the progression to cognitive impairment in PD, while specific cognitive features become more important indicators of progression with impending conversion to PDD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bilingualism delays the onset of behavioral but not aphasic forms of frontotemporal dementia.

PubMed

Alladi, Suvarna; Bak, Thomas H; Shailaja, Mekala; Gollahalli, Divyaraj; Rajan, Amulya; Surampudi, Bapiraju; Hornberger, Michael; Duggirala, Vasanta; Chaudhuri, Jaydip Ray; Kaul, Subhash

2017-05-01

Bilingualism has been found to delay onset of dementia and this has been attributed to an advantage in executive control in bilinguals. However, the relationship between bilingualism and cognition is complex, with costs as well as benefits to language functions. To further explore the cognitive consequences of bilingualism, the study used Frontotemporal dementia (FTD) syndromes, to examine whether bilingualism modifies the age at onset of behavioral and language variants of Frontotemporal dementia (FTD) differently. Case records of 193 patients presenting with FTD (121 of them bilingual) were examined and the age at onset of the first symptoms were compared between monolinguals and bilinguals. A significant effect of bilingualism delaying the age at onset of dementia was found in behavioral variant FTD (5.7 years) but not in progressive nonfluent aphasia (0.7 years), semantic dementia (0.5 years), corticobasal syndrome (0.4 years), progressive supranuclear palsy (4.3 years) and FTD-motor neuron disease (3 years). On dividing all patients predominantly behavioral and predominantly aphasic groups, age at onset in the bilingual behavioral group (62.6) was over 6 years higher than in the monolingual patients (56.5, p=0.006), while there was no difference in the aphasic FTD group (60.9 vs. 60.6 years, p=0.851). The bilingual effect on age of bvFTD onset was shown independently of other potential confounding factors such as education, gender, occupation, and urban vs rural dwelling of subjects. To conclude, bilingualism delays the age at onset in the behavioral but not in the aphasic variants of FTD. The results are in line with similar findings based on research in stroke and with the current views of the interaction between bilingualism and cognition, pointing to advantages in executive functions and disadvantages in lexical tasks. Copyright © 2017 Elsevier Ltd. All rights reserved.

International Psychogeriatric Association consensus statement on defining and measuring treatment benefits in dementia.

PubMed

Katona, Cornelius; Livingston, Gill; Cooper, Claudia; Ames, David; Brodaty, Henry; Chiu, Edmond

2007-06-01

Current symptomatic treatments for dementia have only modest efficacy. Assessing meaningful benefits in this variably progressive syndrome is complex and difficult. This consensus statement was generated by an international group representing caregivers, organizations and professionals with expertise in dementia. We recommend the statement of clear, pre-defined diagnostic and severity criteria and outcome measures, which include functional and executive capacity, in treatment trials. Outcomes can include effects on people with dementia (PWD) with regard to cognition, behavioral and psychological symptoms, quality of life, global assessments, and activities of daily living, and must be tailored to the education and culture of the participants. Outcomes can also appropriately encompass effects on caregivers. New instruments may be needed, as validation of many existing measures has been in relatively homogenous populations. Treatment goals can be to prevent dementia emerging, or in those with established dementia to slow deterioration, and to postpone, stabilize or improve symptoms. Comparisons between treatment groups should be on the basis of clinically relevant measures with both risk and benefit reported for all participants regardless of whether or not they continue to receive treatment throughout the trial. Characterization of any groups that respond well to treatment has been unsuccessful to date, but may be facilitated in the future by measurement of putative biomarkers. Despite considerable recent progress and several 'candidate' biomarkers, none is yet satisfactory for determining diagnosis, severity, progression or prediction of response. To provide meaningful data, economic analyses should use up-to-date, country-specific data. Health economic measures should be incorporated as secondary outcomes in all Phase 3 trials since health systems are concerned with cost-effectiveness as well as clinical outcome. Health utility measures are not, however, validated satisfactorily in dementia, thus calling into question previous health economic analyses. While current drugs appear to reduce the amount of family caregiver time required by PWD, these costs fall in the main on older individuals who often exert little political leverage, rather than on society at large. Traditionally, elderly people have been marginalized in the political process. The growth in the older population across the world, and their potential for increasing political empowerment may lead to a radical re-evaluation of the economics of treatment in dementia.

Mild cognitive impairment: searching for the prodrome of Alzheimer's disease.

PubMed

Rosenberg, Paul B; Lyketsos, Constantine

2008-01-01

The concept of mild cognitive impairment (MCI) identifies persons who are neither cognitively normal nor demented. There is increasing evidence that MCI defines a group of persons who are at near-term risk of developing dementia and particularly Alzheimer's disease (AD). MCI thus constitutes an attractive target population for preventive treatments of AD. MCI is associated with aging and is more prevalent than dementia. There are several clinical and biological markers that are predictive of MCI prognosis, including depressive symptoms, cognitive deficits, brain imaging and neurochemical findings. The clinician needs to be especially alert to depressive and other mood symptoms which are common in MCI and potentially treatable. Trials of current medications for prevention of MCI progression to dementia have been largely negative. There are observational data suggesting that lifestyle modifications including exercise, leisure activities, cognitive stimulation, and social activities may be effective for prevention of MCI progression. There are many novel therapies currently in trials for early AD, and if effective they may prove to be helpful in prevention of MCI progression as well.

How does dementia with Lewy bodies start? prodromal cognitive changes in REM sleep behavior disorder.

PubMed

Génier Marchand, Daphné; Postuma, Ronald B; Escudier, Frédérique; De Roy, Jessie; Pelletier, Amélie; Montplaisir, Jacques; Gagnon, Jean-François

2018-04-17

We describe the progression of cognitive decline and identify the predictive values of cognitive tests in three groups of REM sleep behavior disorder (RBD) patients classified at their last follow-up as having Parkinson's disease (PD), dementia with Lewy bodies (DLB), or still-idiopathic. Patients (n = 109) underwent polysomnographic, neurological, and neuropsychological assessments. We used linear mixed-model analyses to compare the progression of cognitive test performance between the three groups over a 3-year prodromal period, and performed linear regressions for a 6-year prodromal period. We compared the proportions of patients with clinically impaired performance (z scores < -1.5). DLB patients were pair-matched according to age, sex, and education to healthy controls (2:1 ratio), and receiver operating characteristic curves were performed to identify the psychometric properties of cognitive tests to predict dementia. At follow-up, 38 patients (35%) developed a neurodegenerative disorder: 20 had PD and 18 DLB. Cognitive performance changes over time were strongly associated with later development of dementia. Clear deficits in attention and executive functions were observed 6 years before diagnosis. Verbal episodic learning and memory deficits started later, deviating from normal approximately 5 to 6 years and becoming clinically impaired at 1 to 2 years before diagnosis. Visuospatial abilities progressed variably, with inconsistent prodromal latencies. The Trail Making Test (part B), Verbal Fluency (semantic), and Rey Auditory-Verbal Learning Test (total, immediate, and delayed recalls) were the best predictors for dementia (area under the curve = 0.90-0.97). Prodromal DLB is detectible up to 6 years before onset. For clinical utility, the Trail Making Test (part B) best detects early prodromal dementia stages, whereas Verbal Fluency (semantic) and verbal episodic learning tests are best for monitoring changes over time. Ann Neurol 2018. © 2018 American Neurological Association.

Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

ClinicalTrials.gov

2017-05-11

Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

Dementia, Preclinical Studies in Neurodegeneration and its Potential for Translational Medicine in South America

PubMed Central

Cardona-Gómez, Gloria Patricia; Lopera, Francisco

2016-01-01

Latin-American people with dementia will increase to an astounding 368% in 2050, higher than USA and Europe. In addition, to sporadic dementia type like Alzheimer, and vascular dementia (VaD) progression after Cerebrovascular disease is also found. These incidences are increased in Colombia by specific populations affected with pure Neurodegenerative and VaDs like Autosomical Dominant familial Alzheimer’s disease (AD) and Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). In spite of the enormous human effort with and economical effort and investment costs, neither sporadic nor genetic kinds of dementia progression have been prevented or blocked yet. Currently, there exist several animal models that partially solve the understanding of the neurodegenerative etiopathogenesis and its treatment. However, when the potential therapies are translated to humans, those do not work or present a limited action. Main difficulties are the diverse comorbility associated to the cause and/or several affected brain regions, reducing the efficacy of some therapies which are limited to a tissue-specific action or modulating a kind of neurotransmission. Global investigation suggests that a general prevention could be achieved with the improvement in the quality of lifestyle, including healthy diet, physical and mental activity, and avoiding mechanical or chemical pro-inflammatory events in an early stage in the most of non-communicable diseases. In this review article, we present some molecular targets and preclinical studies in animal models to propose strategies that could be useful in a future translation to prevent or block neurodegeneration: one is gene therapy; silencing pathogenic genes in critical brain areas where excitotoxicity arise and spread. Another is to take advantage of the natural source and its wide biodiversity of natural products that are capable of identifying, by the blocking and prevention of neurodegeneration. On the other side, the casuistic of pure dementias in the Latin-American region gives an exceptional opportunity to understand the pathogenesis in these human populations. Further, this is in support of the basic and clinical researchers working on an interaction for a better understanding and medical care of mixed dementias, which have more complex factors than pure ones. However, to promote the translation of any therapeutical alternative is necessary to clarify the normative and the protocols for developing clinical trials with original candidates or work upon strategies proposed from South-American countries. PMID:28066230

Consensus statement of the International Summit on Intellectual Disability and Dementia related to end-of-life care in advanced dementia.

PubMed

McCallion, Philip; Hogan, Mary; Santos, Flavia H; McCarron, Mary; Service, Kathryn; Stemp, Sandy; Keller, Seth; Fortea, Juan; Bishop, Kathleen; Watchman, Karen; Janicki, Matthew P

2017-11-01

Adults with intellectual disability are affected by dementia at equivalent and elevated rates, many surviving into advanced age. End of life care and support considerations come into play among these individuals when most are in the advanced stage of dementia. A preliminary report summarizing available literature and making initial recommendations was developed by a workgroup, reviewed by all conference participants and then was finalized by the workgroup. The International Summit on Intellectual Disability and Dementia produced a report on End of life care in advanced dementia that provides a synthesis statement which encompasses defining the state of advanced dementia, proposes use of palliative care services (including hospice) and recommends special efforts for enabling advanced directives and advance care planning prior to the extensive progression of dementia. The Summit further recommended that when aiding adults with advanced dementia, the following be undertaken: integrative efforts between intellectual disability and palliative care providers, specialized training for carers on end of life care and supports, and involvement of adults with intellectual disability early on in their advance care planning. The Consensus recommendations will ensure greater and more appropriate support at end of life for persons with intellectual disabilities and advanced dementia. © 2017 John Wiley & Sons Ltd.

Neuropathology of dementia in Parkinson's disease: a prospective, community-based study.

PubMed

Aarsland, Dag; Perry, Robert; Brown, Andrew; Larsen, Jan P; Ballard, Clive

2005-11-01

Twenty-two patients with Parkinson's disease drawn from a community-based study were followed prospectively until their deaths. Even though 18 patients had dementia, none fulfilled Braak and Braak or The National Institute on Aging and Ronald and Nancy Reagan Institute of the Alzheimer's Association, whereas all patients had limbic or neocortical Lewy body disease. The Lewy body score and Braak and Braak stage were significantly associated with the rate of cognitive decline, but only the Lewy body score was associated with the rate of cognitive decline in the univariate analyses. This study strongly suggests that Lewy body disease is the main substrate driving the progression of cognitive impairment in Parkinson's disease.

Biomarkers for Cognitive Impairment in Parkinson Disease

PubMed Central

Shi, Min; Huber, Bertrand R.; Zhang, Jing

2010-01-01

Cognitive impairment, including dementia, is commonly seen in those afflicted with Parkinson disease (PD), particularly at advanced disease stages. Pathologically, PD with dementia (PD-D) is most often associated with the presence of cortical Lewy bodies, as is the closely related dementia with Lewy bodies (DLB). Both PD-D and DLB are also frequently complicated by the presence of neurofibrillary tangles and amyloid plaques, features most often attributed to Alzheimer disease. Biomarkers are urgently needed to differentiate among these disease processes and predict dementia in PD as well as monitor responses of patients to new therapies. A few clinical assessments, along with structural and functional neuroimaging, have been utilized in the last few years with some success in this area. Additionally, a number of other strategies have been employed to identify biochemical/molecular biomarkers associated with cognitive impairment and dementia in PD, e.g., targeted analysis of candidate proteins known to be important to PD pathogenesis and progression in cerebrospinal fluid or blood. Finally, interesting results are emerging from preliminary studies with unbiased and high throughput genomic, proteomic and metabolomic techniques. The current findings and perspectives of applying these strategies and techniques are reviewed in this article, together with potential areas of advancement. PMID:20522092

Combined fulminant frontotemporal dementia and amyotrophic lateral sclerosis associated with an I113T SOD1 mutation.

PubMed

Katz, Jonathan S; Katzberg, Hans D; Woolley, Susan C; Marklund, Stefan L; Andersen, Peter M

2012-10-01

Mutations in the gene for superoxide dismutase type 1 cause amyotrophic lateral sclerosis (ALS), but are not thought to be associated with frontotemporal dementia (FTD). A lack of detailed case reports is one reason, among others, for this skepticism. This case report comments on a patient with familial ALS caused by I113T mutation in the SOD1 gene presenting with progressive cognitive and behavioral decline two years before developing progressive motor degeneration. In conclusion, this case provides evidence that SOD1 mutations can be associated with FTD.

UK research spend in 2008 and 2012: comparing stroke, cancer, coronary heart disease and dementia

PubMed Central

Luengo-Fernandez, Ramon; Leal, Jose; Gray, Alastair

2015-01-01

Objective To assess UK governmental and charity research funding in 2012 for cancer, coronary heart disease (CHD), dementia and stroke, and to make comparisons with 2008 levels. Design Analysis of research expenditure. Setting United Kingdom. Main outcome measures We identified UK governmental agencies and charities providing health research funding to determine the 2012 levels of funding for cancer, CHD, dementia and stroke. Levels of research funding were compared to burden of disease measures, including prevalence, disability adjusted life years and economic burden. Results The combined research funding into cancer, CHD, dementia and stroke by governmental and charity organisations in 2012 was £856 million, of which £544 million (64%) was devoted to cancer, £166 million (19%) to CHD, £90 million (11%) to dementia and £56 million (7%) to stroke. For every £10 of health and social care costs attributable to each disease, cancer received £1.08 in research funding, CHD £0.65, stroke £0.19 and dementia £0.08. A considerable shift in the distribution of government research funding was observed between 2008 and 2012. In 2008, 66% of governmental research funding into the four conditions under study was devoted to cancer, 21% to CHD, 9% to dementia and 4% to stroke. In 2012, the proportions devoted to dementia and stroke had increased to 21% and 12%, respectively, with cancer accounting for 45% of total research spend. Conclusions Although there has been much progress by government to increase levels of research funding for dementia and stroke, these areas remain underfunded when compared with the burden of disease. PMID:25869683

UK research spend in 2008 and 2012: comparing stroke, cancer, coronary heart disease and dementia.

PubMed

Luengo-Fernandez, Ramon; Leal, Jose; Gray, Alastair

2015-04-13

To assess UK governmental and charity research funding in 2012 for cancer, coronary heart disease (CHD), dementia and stroke, and to make comparisons with 2008 levels. Analysis of research expenditure. United Kingdom. We identified UK governmental agencies and charities providing health research funding to determine the 2012 levels of funding for cancer, CHD, dementia and stroke. Levels of research funding were compared to burden of disease measures, including prevalence, disability adjusted life years and economic burden. The combined research funding into cancer, CHD, dementia and stroke by governmental and charity organisations in 2012 was £856 million, of which £544 million (64%) was devoted to cancer, £166 million (19%) to CHD, £90 million (11%) to dementia and £56 million (7%) to stroke. For every £10 of health and social care costs attributable to each disease, cancer received £1.08 in research funding, CHD £0.65, stroke £0.19 and dementia £0.08. A considerable shift in the distribution of government research funding was observed between 2008 and 2012. In 2008, 66% of governmental research funding into the four conditions under study was devoted to cancer, 21% to CHD, 9% to dementia and 4% to stroke. In 2012, the proportions devoted to dementia and stroke had increased to 21% and 12%, respectively, with cancer accounting for 45% of total research spend. Although there has been much progress by government to increase levels of research funding for dementia and stroke, these areas remain underfunded when compared with the burden of disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Alzheimer's Caregiver Support Online: lessons learned, initial findings and future directions.

PubMed

Glueckauf, Robert L; Loomis, Jeffrey S

2003-01-01

Family caregivers of older adults with progressive dementia (e.g., Alzheimer's disease) are faced with a variety of emotional and behavioral difficulties, such as dealing with persistent, repetitive questions, managing agitation and depression, and monitoring hygiene and self-care activities. Although professional and governmental organizations have called for the creation of community-based education and support programs, most dementia caregivers continue to receive little or no formal instruction in responding effectively to these challenges. The current paper describes the development and implementation of Alzheimer's Caregiver Support Online, a Web- and telephone-based education and support network for caregivers of individuals with progressive dementia. Lessons learned from the first two years of this state-supported initiative are discussed, followed by the findings of a Robert Wood Johnson Foundation-funded strategic marketing initiative and an initial program evaluation of AlzOnline's Positive Caregiving classes. Finally, clinical implications and future directions for program development and evaluation research are proposed.

End-stage dementia spark of life: reliability and validity of the "GATOS" questionnaire.

PubMed

Tsoucalas, Gregory; Bourelia, Stamati; Kalogirou, Vaso; Giatsiou, Styliani; Mavrogiannaki, Eirini; Gatos, Georgios; Galanos, Antonis; Repana, Olga; Iliadou, Eleni; Antoniou, Antonis; Sgantzos, Markos; Gatos, Konstantinos

2015-01-01

Fl oor effects are present in most dementia assessment tools as dementia progresses and the in-depth assessment of patients considered more or less on vegetative state is questionable. To develop a questionnaire (the "Gatos Clinical Test-GCT") for the assessment of end-stage demented patients. Five hundred patients with dementia of various causes and an MMSE score between 0 and 2 were enrolled in the study. The GCT consists of 14 closed type questions rated on a Likert scale. The total score is used to evaluate patient's dementia. Various aspects of validity and reliability (including face, content and structural validity as well as test-retest reliability) were examined. Three subscales "Autonomy/Alertness", "Gnosias" and "Somatokinetic function" were defined, with a Cronbach equal to 0.851, 0.756 and 0.598 respectively. The GCT subscales and total score were statistically significant higher in patients with MMSE score 1 or 2 compared with those with MMSE score 0 (p<0.0005). Patients with GCT total score less than 12.5 had 75% probability to have zero MMSE score. The "GATOS" questionnaire is a valid and reliable test for patients with severe dementia, aiming at identification of those patients who could sustain some quality of life. It is a relatively short and easy to administer tool. As dementia prevalence is expected to rise further worldwide we believe that GCT could offer valuable services to health professionals, caregivers and patients.

[Progressive visual agnosia].

PubMed

Sugimoto, Azusa; Futamura, Akinori; Kawamura, Mitsuru

2011-10-01

Progressive visual agnosia was discovered in the 20th century following the discovery of classical non-progressive visual agnosia. In contrast to the classical type, which is caused by cerebral vascular disease or traumatic injury, progressive visual agnosia is a symptom of neurological degeneration. The condition of progressive visual loss, including visual agnosia, and posterior cerebral atrophy was named posterior cortical atrophy (PCA) by Benson et al. (1988). Progressive visual agnosia is also observed in semantic dementia (SD) and other degenerative diseases, but there is a difference in the subtype of visual agnosia associated with these diseases. Lissauer (1890) classified visual agnosia into apperceptive and associative types, and it in most cases, PCA is associated with the apperceptive type. However, SD patients exhibit symptoms of associative visual agnosia before changing to those of semantic memory disorder. Insights into progressive visual agnosia have helped us understand the visual system and discover how we "perceive" the outer world neuronally, with regard to consciousness. Although PCA is a type of atypical dementia, its diagnosis is important to enable patients to live better lives with appropriate functional support.

Plasma proteins predict conversion to dementia from prodromal disease

PubMed Central

Hye, Abdul; Riddoch-Contreras, Joanna; Baird, Alison L.; Ashton, Nicholas J.; Bazenet, Chantal; Leung, Rufina; Westman, Eric; Simmons, Andrew; Dobson, Richard; Sattlecker, Martina; Lupton, Michelle; Lunnon, Katie; Keohane, Aoife; Ward, Malcolm; Pike, Ian; Zucht, Hans Dieter; Pepin, Danielle; Zheng, Wei; Tunnicliffe, Alan; Richardson, Jill; Gauthier, Serge; Soininen, Hilkka; Kłoszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon

2014-01-01

Background The study aimed to validate previously discovered plasma biomarkers associated with AD, using a design based on imaging measures as surrogate for disease severity and assess their prognostic value in predicting conversion to dementia. Methods Three multicenter cohorts of cognitively healthy elderly, mild cognitive impairment (MCI), and AD participants with standardized clinical assessments and structural neuroimaging measures were used. Twenty-six candidate proteins were quantified in 1148 subjects using multiplex (xMAP) assays. Results Sixteen proteins correlated with disease severity and cognitive decline. Strongest associations were in the MCI group with a panel of 10 proteins predicting progression to AD (accuracy 87%, sensitivity 85%, and specificity 88%). Conclusions We have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints. PMID:25012867

Plasma proteins predict conversion to dementia from prodromal disease.

PubMed

Hye, Abdul; Riddoch-Contreras, Joanna; Baird, Alison L; Ashton, Nicholas J; Bazenet, Chantal; Leung, Rufina; Westman, Eric; Simmons, Andrew; Dobson, Richard; Sattlecker, Martina; Lupton, Michelle; Lunnon, Katie; Keohane, Aoife; Ward, Malcolm; Pike, Ian; Zucht, Hans Dieter; Pepin, Danielle; Zheng, Wei; Tunnicliffe, Alan; Richardson, Jill; Gauthier, Serge; Soininen, Hilkka; Kłoszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon

2014-11-01

The study aimed to validate previously discovered plasma biomarkers associated with AD, using a design based on imaging measures as surrogate for disease severity and assess their prognostic value in predicting conversion to dementia. Three multicenter cohorts of cognitively healthy elderly, mild cognitive impairment (MCI), and AD participants with standardized clinical assessments and structural neuroimaging measures were used. Twenty-six candidate proteins were quantified in 1148 subjects using multiplex (xMAP) assays. Sixteen proteins correlated with disease severity and cognitive decline. Strongest associations were in the MCI group with a panel of 10 proteins predicting progression to AD (accuracy 87%, sensitivity 85%, and specificity 88%). We have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Cognitive correlates of α4β2 nicotinic acetylcholine receptors in mild Alzheimer's dementia.

PubMed

Sabri, Osama; Meyer, Philipp M; Gräf, Susanne; Hesse, Swen; Wilke, Stephan; Becker, Georg-Alexander; Rullmann, Michael; Patt, Marianne; Luthardt, Julia; Wagenknecht, Gudrun; Hoepping, Alexander; Smits, Rene; Franke, Annegret; Sattler, Bernhard; Tiepolt, Solveig; Fischer, Steffen; Deuther-Conrad, Winnie; Hegerl, Ulrich; Barthel, Henryk; Schönknecht, Peter; Brust, Peter

2018-06-01

In early Alzheimer's dementia, there is a need for PET biomarkers of disease progression with close associations to cognitive dysfunction that may aid to predict further cognitive decline and neurodegeneration. Amyloid biomarkers are not suitable for that purpose. The α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs) are widely abundant in the human brain. As neuromodulators they play an important role in cognitive functions such as attention, learning and memory. Post-mortem studies reported lower expression of α4β2-nAChRs in more advanced Alzheimer's dementia. However, there is ongoing controversy whether α4β2-nAChRs are reduced in early Alzheimer's dementia. Therefore, using the recently developed α4β2-nAChR-specific radioligand (-)-18F-flubatine and PET, we aimed to quantify the α4β2-nAChR availability and its relationship to specific cognitive dysfunction in mild Alzheimer's dementia. Fourteen non-smoking patients with mild Alzheimer's dementia, drug-naïve for cholinesterase therapy, were compared with 15 non-smoking healthy controls matched for age, sex and education by applying (-)-18F-flubatine PET together with a neuropsychological test battery. The one-tissue compartment model and Logan plot method with arterial input function were used for kinetic analysis to obtain the total distribution volume (VT) as the primary, and the specific binding part of the distribution volume (VS) as the secondary quantitative outcome measure of α4β2-nAChR availability. VS was determined by using a pseudo-reference region. Correlations between VT within relevant brain regions and Z-scores of five cognitive functions (episodic memory, executive function/working memory, attention, language, visuospatial function) were calculated. VT (and VS) were applied for between-group comparisons. Volume of interest and statistical parametric mapping analyses were carried out. Analyses revealed that in patients with mild Alzheimer's dementia compared to healthy controls, there was significantly lower VT, especially within the hippocampus, fronto-temporal cortices, and basal forebrain, which was similar to comparisons of VS. VT decline in Alzheimer's dementia was associated with distinct domains of impaired cognitive functioning, especially episodic memory and executive function/working memory. Using (-)-18F-flubatine PET in patients with mild Alzheimer's dementia, we show for the first time a cholinergic α4β2-nAChR deficiency mainly present within the basal forebrain-cortical and septohippocampal cholinergic projections and a relationship between lower α4β2-nAChR availability and impairment of distinct cognitive domains, notably episodic memory and executive function/working memory. This shows the potential of (-)-18F-flubatine as PET biomarker of cholinergic α4β2-nAChR dysfunction and specific cognitive decline. Thus, if validated by longitudinal PET studies, (-)-18F-flubatine might become a PET biomarker of progression of neurodegeneration in Alzheimer's dementia.

Cognitive assessments for the early diagnosis of dementia after stroke

PubMed Central

Al-Qazzaz, Noor Kamal; Ali, Sawal Hamid; Ahmad, Siti Anom; Islam, Shabiul

2014-01-01

The early detection of poststroke dementia (PSD) is important for medical practitioners to customize patient treatment programs based on cognitive consequences and disease severity progression. The aim is to diagnose and detect brain degenerative disorders as early as possible to help stroke survivors obtain early treatment benefits before significant mental impairment occurs. Neuropsychological assessments are widely used to assess cognitive decline following a stroke diagnosis. This study reviews the function of the available neuropsychological assessments in the early detection of PSD, particularly vascular dementia (VaD). The review starts from cognitive impairment and dementia prevalence, followed by PSD types and the cognitive spectrum. Finally, the most usable neuropsychological assessments to detect VaD were identified. This study was performed through a PubMed and ScienceDirect database search spanning the last 10 years with the following keywords: “post-stroke”; “dementia”; “neuro-psychological”; and “assessments”. This study focuses on assessing VaD patients on the basis of their stroke risk factors and cognitive function within the first 3 months after stroke onset. The search strategy yielded 535 articles. After application of inclusion and exclusion criteria, only five articles were considered. A manual search was performed and yielded 14 articles. Twelve articles were included in the study design and seven articles were associated with early dementia detection. This review may provide a means to identify the role of neuropsychological assessments as early PSD detection tests. PMID:25246795

Prognosis of Mild Cognitive Impairment in General Practice: Results of the German AgeCoDe Study

PubMed Central

Kaduszkiewicz, Hanna; Eisele, Marion; Wiese, Birgitt; Prokein, Jana; Luppa, Melanie; Luck, Tobias; Jessen, Frank; Bickel, Horst; Mösch, Edelgard; Pentzek, Michael; Fuchs, Angela; Eifflaender-Gorfer, Sandra; Weyerer, Siegfried; König, Hans-Helmut; Brettschneider, Christian; van den Bussche, Hendrik; Maier, Wolfgang; Scherer, Martin; Riedel-Heller, Steffi G.

2014-01-01

PURPOSE The concept of mild cognitive impairment (MCI) has recently been introduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as mild neurocognitive disorder, making it a formal diagnosis. We investigated the prognostic value of such a diagnosis and analyzed the determinants of the future course of MCI in the AgeCoDe study (German Study on Ageing, Cognition, and Dementia in Primary Care Patients). METHODS We recruited 357 patients with MCI aged 75 years or older from primary care practices and conducted follow-up with interviews for 3 years. Depending on the course of impairment over time, the patients were retrospectively split into 4 groups representing remittent, fluctuating, stable, and progressive courses of MCI. We performed ordinal logistic regression analysis and classification and regression tree (CART) analysis. RESULTS Overall, 41.5% of the patients had remission of symptoms with normal cognitive function 1.5 and 3 years later, 21.3% showed a fluctuating course, 14.8% had stable symptoms, and 22.4% had progression to dementia. Patients were at higher risk for advancing from one course to the next along this spectrum if they had symptoms of depression, impairment in more than 1 cognitive domain, or more severe cognitive impairment, or were older. The result on a test of the ability to learn and reproduce new material 10 minutes later was the best indicator at baseline for differentiating between remittent and progressive MCI. Symptoms of depression modified the prognosis. CONCLUSIONS In primary care, about one-quarter of patients with MCI have progression to dementia within the next 3 years. Assessments of memory function and depressive symptoms are helpful in predicting a progressive vs a remittent course. When transferring the concept of MCI into clinical diagnostic algorithms (eg, DSM-5), however, we should not forget that three-quarters of patients with MCI stayed cognitively stable or even improved within 3 years. They should not be alarmed unnecessarily by receiving such a diagnosis. PMID:24615312

Energy expenditure in frontotemporal dementia: a behavioural and imaging study.

PubMed

Ahmed, Rebekah M; Landin-Romero, Ramon; Collet, Tinh-Hai; van der Klaauw, Agatha A; Devenney, Emma; Henning, Elana; Kiernan, Matthew C; Piguet, Olivier; Farooqi, I Sadaf; Hodges, John R

2017-01-01

SEE FINGER DOI101093/AWW312 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Abnormal eating behaviour and metabolic parameters including insulin resistance, dyslipidaemia and body mass index are increasingly recognized as important components of neurodegenerative disease and may contribute to survival. It has previously been established that behavioural variant frontotemporal dementia is associated with abnormal eating behaviour characterized by increased sweet preference. In this study, it was hypothesized that behavioural variant frontotemporal dementia might also be associated with altered energy expenditure. A cohort of 19 patients with behavioural variant frontotemporal dementia, 13 with Alzheimer's disease and 16 (age- and sex-matched) healthy control subjects were studied using Actiheart devices (CamNtech) to assess resting and stressed heart rate. Actiheart devices were fitted for 7 days to measure sleeping heart rate, activity levels, and resting, active and total energy expenditure. Using high resolution structural magnetic resonance imaging the neural correlates of increased resting heart rate were investigated including cortical thickness and region of interest analyses. In behavioural variant frontotemporal dementia, resting (P = 0.001), stressed (P = 0.037) and sleeping heart rate (P = 0.038) were increased compared to control subjects, and resting heart rate (P = 0.020) compared to Alzheimer disease patients. Behavioural variant frontotemporal dementia was associated with decreased activity levels compared to controls (P = 0.002) and increased resting energy expenditure (P = 0.045) and total energy expenditure (P = 0.035). Increased resting heart rate correlated with behavioural (Cambridge Behavioural Inventory) and cognitive measures (Addenbrooke's Cognitive Examination). Increased resting heart rate in behavioural variant frontotemporal dementia correlated with atrophy involving the mesial temporal cortex, insula, and amygdala, regions previously suggested to be involved exclusively in social and emotion processing in frontotemporal dementia. These neural correlates overlap the network involved in eating behaviour in frontotemporal dementia, suggesting a complex interaction between eating behaviour, autonomic function and energy homeostasis. As such the present study suggests that increased heart rate and autonomic changes are prevalent in behavioural variant frontotemporal dementia, and are associated with changes in energy expenditure. An understanding of these changes and neural correlates may have potential relevance to disease progression and prognosis. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Establishing robust cognitive dimensions for characterization and differentiation of patients with Alzheimer's disease, mild cognitive impairment, frontotemporal dementia and depression.

PubMed

Beck, Irene R; Schmid, Nicole S; Berres, Manfred; Monsch, Andreas U

2014-06-01

The diagnosis of mild cognitive impairment (MCI) and dementia requires detailed neuropsychological examinations. These examinations typically yield a large number of outcome variables, which may complicate the interpretation and communication of results. The purposes of this study were the following: (i) to reduce a large data set of interrelated neuropsychological variables to a smaller number of cognitive dimensions; (ii) to create a common metric for these dimensions (z-scores); and (iii) to study the ability of the cognitive dimensions to distinguish between groups of patients with different types of cognitive impairment. We tested 1646 patients with different forms of dementia or with a major depression with a standard (n = 632) or, if cognitively less affected, a challenging neuropsychological battery (n = 1014). To identify the underlying cognitive dimensions of the two test batteries, maximum likelihood factor analyses with a promax rotation were conducted. To interpret the sum scores of the factors as standard scores, we divided them by the standard deviation of a cognitively healthy sample (n = 1145). The factor analyses yielded seven factors for each test battery. The cognitive dimensions in both test batteries distinguished patients with different forms of dementia (MCI, Alzheimer's dementia or frontotemporal dementia) and patients with major depression. Furthermore, patients with stable MCI could be separated from patients with progressing MCI. Discriminant analyses with an independent new sample of patients (n = 306) revealed that the new dimension scores distinguished new samples of patients with MCI from patients with Alzheimer's dementia with high accuracy. These findings suggest that these cognitive dimensions may benefit neuropsychological diagnostics. © 2013 The Authors International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

Establishing robust cognitive dimensions for characterization and differentiation of patients with Alzheimer's disease, mild cognitive impairment, frontotemporal dementia and depression

PubMed Central

Beck, Irene R; Schmid, Nicole S; Berres, Manfred; Monsch, Andreas U

2014-01-01

Objective The diagnosis of mild cognitive impairment (MCI) and dementia requires detailed neuropsychological examinations. These examinations typically yield a large number of outcome variables, which may complicate the interpretation and communication of results. The purposes of this study were the following: (i) to reduce a large data set of interrelated neuropsychological variables to a smaller number of cognitive dimensions; (ii) to create a common metric for these dimensions (z-scores); and (iii) to study the ability of the cognitive dimensions to distinguish between groups of patients with different types of cognitive impairment. Methods We tested 1646 patients with different forms of dementia or with a major depression with a standard (n = 632) or, if cognitively less affected, a challenging neuropsychological battery (n = 1014). To identify the underlying cognitive dimensions of the two test batteries, maximum likelihood factor analyses with a promax rotation were conducted. To interpret the sum scores of the factors as standard scores, we divided them by the standard deviation of a cognitively healthy sample (n = 1145). Results The factor analyses yielded seven factors for each test battery. The cognitive dimensions in both test batteries distinguished patients with different forms of dementia (MCI, Alzheimer's dementia or frontotemporal dementia) and patients with major depression. Furthermore, patients with stable MCI could be separated from patients with progressing MCI. Discriminant analyses with an independent new sample of patients (n = 306) revealed that the new dimension scores distinguished new samples of patients with MCI from patients with Alzheimer's dementia with high accuracy. Conclusion These findings suggest that these cognitive dimensions may benefit neuropsychological diagnostics. PMID:24227657

Disease progression model for Clinical Dementia Rating–Sum of Boxes in mild cognitive impairment and Alzheimer’s subjects from the Alzheimer’s Disease Neuroimaging Initiative

PubMed Central

Samtani, Mahesh N; Raghavan, Nandini; Novak, Gerald; Nandy, Partha; Narayan, Vaibhav A

2014-01-01

Background The objective of this analysis was to develop a nonlinear disease progression model, using an expanded set of covariates that captures the longitudinal Clinical Dementia Rating Scale–Sum of Boxes (CDR–SB) scores. These were derived from the Alzheimer’s Disease Neuroimaging Initiative ADNI-1 study, of 301 Alzheimer’s disease and mild cognitive impairment patients who were followed for 2–3 years. Methods The model describes progression rate and baseline disease score as a function of covariates. The covariates that were tested fell into five groups: a) hippocampal volume; b) serum and cerebrospinal fluid (CSF) biomarkers; c) demographics and apolipoprotein Epsilon 4 (ApoE4) allele status; d) baseline cognitive tests; and e) disease state and comedications. Results Covariates associated with baseline disease severity were disease state, hippocampal volume, and comedication use. Disease progression rate was influenced by baseline CSF biomarkers, Trail-Making Test part A score, delayed logical memory test score, and current level of impairment as measured by CDR–SB. The rate of disease progression was dependent on disease severity, with intermediate scores around the inflection point score of 10 exhibiting high disease progression rate. The CDR–SB disease progression rate in a typical patient, with late mild cognitive impairment and mild Alzheimer’s disease, was estimated to be approximately 0.5 and 1.4 points/year, respectively. Conclusions In conclusion, this model describes disease progression in terms of CDR–SB changes in patients and its dependency on novel covariates. The CSF biomarkers included in the model discriminate mild cognitive impairment subjects as progressors and nonprogressors. Therefore, the model may be utilized for optimizing study designs, through patient population enrichment and clinical trial simulations. PMID:24926196

The association between physical dependency and the presence of neuropsychiatric symptoms, with the admission of people with dementia to a long-term care institution: a prospective observational cohort study.

PubMed

Risco, Ester; Cabrera, Esther; Jolley, David; Stephan, Astrid; Karlsson, Staffan; Verbeek, Hilde; Saks, Kai; Hupli, Maija; Sourdet, Sandrine; Zabalegui, Adelaida

2015-05-01

Dementia is a progressive neurological disorder that causes a high degree of dependency. This dependency has been defined as an increased need for assistance due to deterioration in cognition and physical functioning, and changes in behavior. Highly dependent people with dementia are more likely to be institutionalized. To investigate the association between specific categories of physical dependency and the presence of neuropsychiatric symptoms in people with dementia admitted to a long-term care institution. A prospective observational cohort study. Home care and long-term care institutions in eight European countries. People with dementia living at home but at risk of institutionalization and recently institutionalized people with dementia. Baseline and 3-month follow-up interviews were performed between November, 2010 and April, 2012. The sample consisted of 116 recently institutionalized dementia sufferers and 949 people with dementia still living at home. Physical dependency was measured using the Katz Activity of Daily Living index, and neuropsychiatric symptoms were assessed through The Neuropsychiatric Inventory. Specific categories of dependency were analyzed by performing a logistic regression analysis. This followed examination of baseline characteristics to define the degree of physical dependency, as factors associated with institutionalization, and evaluation of the same characteristics at 3-month follow-up to detect changes in the degree of physical dependency and neuropsychiatric symptoms associated with recent admission to a long-term care institution. Toileting, dressing and continence dependency was higher in institutionalized people than in those receiving home-care. Delusion, hallucination, agitation, anxiety, apathy, motor-disturbances, night-time behavior and eating disorders were also worse in the institutionalized. Logistic regression analysis showed that independent factors significantly associated with being recently institutionalized were toileting (odds ratio=2.3; 95% confidence interval=1.43-3.71) and motor disturbances (odds ratio=1.81; 95% confidence interval=1.15-2.87). This study supports the association between type and degree of physical dependency in people with dementia and long-term institutionalization. Institutionalization is associated with physical dependency and the presence of neuropsychiatric symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Selenium attenuates apoptosis, inflammation and oxidative stress in the blood and brain of aged rats with scopolamine-induced dementia.

PubMed

Demirci, Kadir; Nazıroğlu, Mustafa; Övey, İshak Suat; Balaban, Hasan

2017-04-01

A potent antioxidant, selenium might modulate dementia-induced progression of brain and blood oxidative and apoptotic injuries. The present study explores whether selenium protects against experimental dementia (scopolamine, SCOP)-induced brain, and blood oxidative stress, apoptosis levels, and cytokine production in rats. Thirty-two rats were equally divided into four groups. The first group was used as an untreated control. The second group was treated with SCOP to induce dementia. The third and fourth groups received 1.5 mg/kg selenium (sodium selenite) and SCOP + selenium, respectively. Dementia was induced in the second and forth groups by intraperitoneal SCOP (1 mg/kg) administration. Brain, plasma, and erythrocyte lipid peroxidation levels as well as plasma TNF-α, interleukin (IL)-1β, and IL-4 levels were high in the SCOP group though they were low in selenium treatments. Selenium and selenium + SCOP treatments increased the lowered glutathione peroxidase activity, reduced glutathione, vitamins A and E concentrations in the brain, erythrocytes and plasma of the SCOP group. Apoptotic value expressions as active caspase-3, procaspase-9, and PARP were also increased by SCOP, while they were decreased by selenium and selenium + SCOP treatments. In conclusion, selenium induced protective effects against experimental dementia-induced brain, and blood oxidative injuries and apoptosis through regulation of cytokine production, vitamin E, glutathione concentrations, and glutathione peroxidase activity.

Different Cognitive Frailty Models and Health- and Cognitive-related Outcomes in Older Age: From Epidemiology to Prevention

PubMed Central

Panza, Francesco; Lozupone, Madia; Solfrizzi, Vincenzo; Sardone, Rodolfo; Dibello, Vittorio; Di Lena, Luca; D’Urso, Francesca; Stallone, Roberta; Petruzzi, Massimo; Giannelli, Gianluigi; Quaranta, Nicola; Bellomo, Antonello; Greco, Antonio; Daniele, Antonio; Seripa, Davide; Logroscino, Giancarlo

2018-01-01

Frailty, a critical intermediate status of the aging process that is at increased risk for negative health-related events, includes physical, cognitive, and psychosocial domains or phenotypes. Cognitive frailty is a condition recently defined by operationalized criteria describing coexisting physical frailty and mild cognitive impairment (MCI), with two proposed subtypes: potentially reversible cognitive frailty (physical frailty/MCI) and reversible cognitive frailty (physical frailty/pre-MCI subjective cognitive decline). In the present article, we reviewed the framework for the definition, different models, and the current epidemiology of cognitive frailty, also describing neurobiological mechanisms, and exploring the possible prevention of the cognitive frailty progression. Several studies suggested a relevant heterogeneity with prevalence estimates ranging 1.0–22.0% (10.7–22.0% in clinical-based settings and 1.0–4.4% in population-based settings). Cross-sectional and longitudinal population-based studies showed that different cognitive frailty models may be associated with increased risk of functional disability, worsened quality of life, hospitalization, mortality, incidence of dementia, vascular dementia, and neurocognitive disorders. The operationalization of clinical constructs based on cognitive impairment related to physical causes (physical frailty, motor function decline, or other physical factors) appears to be interesting for dementia secondary prevention given the increased risk for progression to dementia of these clinical entities. Multidomain interventions have the potential to be effective in preventing cognitive frailty. In the near future, we need to establish more reliable clinical and research criteria, using different operational definitions for frailty and cognitive impairment, and useful clinical, biological, and imaging markers to implement intervention programs targeted to improve frailty, so preventing also late-life cognitive disorders. PMID:29562543

A study on the mortality patterns of missing and deceased persons with dementia who died due to wandering.

PubMed

Kikuchi, Kazunori; Ijuin, Mutsuo; Awata, Shuichi; Suzuki, Takao

2016-01-01

To clarify the mortality patterns derived from differences in the causes of death and to subsequently promote search activity and prevent the death of missing persons. The Ministry of Health, Labour and Welfare (MHLW) performed a mail survey using a self-administered questionnaire. The families of all 388 deceased dementia patients from among all of the missing persons reports involving dementia patients that were submitted to the police in 2013, and the 10,322 missing persons with dementia (or suspected cases) were the subjects of this survey. The survey was conducted from January 5 to February 2 in 2015. We analyzed the data provided by the MHLW on 61 cases in which the cause of death was recorded; the factors that were related to the differences in the causes of death were examined using a chi-squared test (Fisher's direct method) and a residual analysis. Based on previous studies, we classified the causes of death into three categories: "drowning," "hypothermia," and "others (e.g., traumatic injury, disease progression)." When the cause of death was hypothermia, death often occurred between three to four days from the time that the deceased individual went missing. A significantly higher number of patients who died of other causes were found to have died on the day that they went missing. More than 40% of the drowning cases occurred on the day that the deceased individual went missing. We identified 3 patterns of mortality: (1) death on the day that the deceased individual went missing due to traumatic injury, disease progression, drowning, and other causes; (2) death due to hypothermia within a few days after the deceased individual went missing; and (3) patterns other than (1) and (2).

Hippocampal tau pathology is related to neuroanatomical connections: an ageing population-based study.

PubMed

Lace, G; Savva, G M; Forster, G; de Silva, R; Brayne, C; Matthews, F E; Barclay, J J; Dakin, L; Ince, P G; Wharton, S B

2009-05-01

Deposits of abnormally phosphorylated tau protein are found in numerous neurodegenerative disorders; the 'tauopathies', which include Alzheimer's and Pick's diseases, but tau pathology is also found in the ageing brain. Variation in tau pathology in brain ageing and its relationship to development of tauopathies and cognitive impairment remains unclear. We aimed to determine the extent and pattern of spread of tau pathology in the hippocampus, a susceptible region important in dementia and milder states of memory impairment, using hippocampal samples from the elderly population-based Medical Research Council Cognitive Function and Ageing Study neuropathology cohort. Tau deposition was assessed in hippocampal anatomical sub-regions using the AT8 antibody to phosphorylated tau and isoform-specific antibodies to 3 and 4-repeat tau (RD3 and RD4). Abeta pathology was also assessed. In this population sample, which includes the full ageing spectrum from individuals with no cognitive impairment to those with dementia satisfying clinico-pathology criteria for Alzheimer's disease, we have demonstrated a high prevalence at death of tau pathology. AT8, Abeta, RD3 and RD4 showed similar regional distribution and increased RD3 was noted in late-stage ghost tangles. Abeta was shown to be a poor explanatory variable for tau pathology. Tau deposition progressed in a hierarchical manner. Hippocampal input regions and projection zones (such as lateral entorhinal cortex, CA1/subiculum border and outer molecular layer of dentate) were initially affected, with anterograde progression though the hippocampal circuitry. Six hippocampal tau anatomical stages were defined, each linking projectionally to their adjacent stages, suggesting spread of tau malfunction through neuroanatomical pathways in hippocampal ageing. These stages were significantly associated with dementia, and may provide a clinically useful tool in the clinico-pathological assessment of dementia and mild cognitive impairment.

Assessing dementia in resource-poor regions.

PubMed

Maestre, Gladys E

2012-10-01

The numbers and proportions of elderly are increasing rapidly in developing countries, where prevalence of dementia is often high. Providing cost-effective services for dementia sufferers and their caregivers in these resource-poor regions poses numerous challenges; developing resources for diagnosis must be the first step. Capacity building for diagnosis involves training and education of healthcare providers, as well as the general public, development of infrastructure, and resolution of economic and ethical issues. Recent progress in some low-to-middle-income countries (LMICs) provides evidence that partnerships between wealthy and resource-poor countries, and between developing countries, can improve diagnostic capabilities. Without the involvement of the mental health community of developed countries in such capacity-building programs, dementia in the developing world is a disaster waiting to happen.

[Concept and effectiveness of a treatment program for patients with dementia and their relatives. Results from the Bad Aibling Alzheimer Disease Therapy Center].

PubMed

Romero, B; Wenz, M

2002-04-01

A short-term residential treatment programme designed to prepare patients with dementia and caregivers for life with a progressive disease was evaluated in a pre-treatment post-treatment design. The multicomponent programme included: 1) intensive rehabilitation for patients, based on the concept of Self-Maintenance Therapy, and 2) an intervention programme for caregivers. Based on the concept of Self-Maintenance Therapy, it was hypothesised that experiences which are in accordance with patients' self-system would support patients' well-being, reduce psychopathological symptoms and facilitate social participation. In this study treatment effects in FTLD are analysed and compared with treatment effects in AD. The results for both groups show a consistent improvement in patients' depression and in other psychopathological symptoms, which can be seen as directly beneficial for patients. Following treatment, caregivers also felt less depressed, less mentally fatigued and restless, and more relaxed. It was predicted that FTLD patients challenge caregivers in a different way compared to patients with AD due to the particular profile of cognitive and psychiatric problems but there are no significant differences between groups. Further controlled follow-up studies are needed to evaluate the effects of the intervention as dementia progresses and to address hypotheses about factors responsible for benefits as well as for treatment resistance.

Physiological phenotyping of dementias using emotional sounds.

PubMed

Fletcher, Phillip D; Nicholas, Jennifer M; Shakespeare, Timothy J; Downey, Laura E; Golden, Hannah L; Agustus, Jennifer L; Clark, Camilla N; Mummery, Catherine J; Schott, Jonathan M; Crutch, Sebastian J; Warren, Jason D

2015-06-01

Emotional behavioral disturbances are hallmarks of many dementias but their pathophysiology is poorly understood. Here we addressed this issue using the paradigm of emotionally salient sounds. Pupil responses and affective valence ratings for nonverbal sounds of varying emotional salience were assessed in patients with behavioral variant frontotemporal dementia (bvFTD) (n = 14), semantic dementia (SD) (n = 10), progressive nonfluent aphasia (PNFA) (n = 12), and AD (n = 10) versus healthy age-matched individuals (n = 26). Referenced to healthy individuals, overall autonomic reactivity to sound was normal in Alzheimer's disease (AD) but reduced in other syndromes. Patients with bvFTD, SD, and AD showed altered coupling between pupillary and affective behavioral responses to emotionally salient sounds. Emotional sounds are a useful model system for analyzing how dementias affect the processing of salient environmental signals, with implications for defining pathophysiological mechanisms and novel biomarker development.

Occupational Attainment as Risk Factor for Progression from Mild Cognitive Impairment to Alzheimer's Disease: A CREDOS Study.

PubMed

Myung, Woojae; Lee, Chunsoo; Park, Jin Hong; Woo, Sook-Young; Kim, Seonwoo; Kim, Sangha; Chung, Jae Won; Kang, Hyo Shin; Lim, Shinn-Won; Choi, Junbae; Na, Duk L; Kim, Seong Yoon; Lee, Jae-Hong; Han, Seol-Heui; Choi, Seong Hye; Kim, Sang Yun; Carroll, Bernard J; Kim, Doh Kwan

2017-01-01

High occupational attainment has been known as a marker of cognitive reserve. Previous studies in the general population have shown that high occupational attainment is associated with reduced risk of Alzheimer's disease (AD). However, few studies have assessed the effect of occupational attainment on the clinical course of mild cognitive impairment (MCI). In this study, we evaluated whether individuals with high occupational attainment show more frequent progression from MCI to AD. Participants (n = 961) with MCI were recruited from a nationwide, hospital-based multi-center cohort, and were followed for up to 60 months (median: 17.64, interquartile range [12.36, 29.28]). We used Cox regression for competing risks to analyze the effect of occupational attainment on development of AD, treating dementia other than AD as a competing risk. Among the 961 individuals with MCI, a total of 280 (29.1%) converted to dementia during the follow-up period. The risk of progression to AD was higher in the individuals with high occupational attainment after controlling for potential confounders (hazard ratio = 1.83, 95% confidence interval = 1.25-2.69, p = 0.002). High occupational attainment in individuals with MCI is an independent risk factor for higher progression rate of MCI to AD. This result suggests that the protective effect of high occupational attainment against cognitive decline disappears in the MCI stage, and that careful assessment of occupational history can yield important clinical information for prognosis in individuals with MCI.

Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia

PubMed Central

Hodges, John R.; Knopman, David; Mendez, Mario F.; Kramer, Joel H.; Neuhaus, John; van Swieten, John C.; Seelaar, Harro; Dopper, Elise G. P.; Onyike, Chiadi U.; Hillis, Argye E.; Josephs, Keith A.; Boeve, Bradley F.; Kertesz, Andrew; Seeley, William W.; Rankin, Katherine P.; Johnson, Julene K.; Gorno-Tempini, Maria-Luisa; Rosen, Howard; Prioleau-Latham, Caroline E.; Lee, Albert; Kipps, Christopher M.; Lillo, Patricia; Piguet, Olivier; Rohrer, Jonathan D.; Rossor, Martin N.; Warren, Jason D.; Fox, Nick C.; Galasko, Douglas; Salmon, David P.; Black, Sandra E.; Mesulam, Marsel; Weintraub, Sandra; Dickerson, Brad C.; Diehl-Schmid, Janine; Pasquier, Florence; Deramecourt, Vincent; Lebert, Florence; Pijnenburg, Yolande; Chow, Tiffany W.; Manes, Facundo; Grafman, Jordan; Cappa, Stefano F.; Freedman, Morris; Grossman, Murray; Miller, Bruce L.

2011-01-01

Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). ‘Probable’ behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia ‘with definite frontotemporal lobar degeneration’ requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer’s disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met ‘possible’ criteria, and 104 (76%) met criteria for ‘probable’ behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with ‘possible’ and ‘probable’ criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines. PMID:21810890

A longitudinal study of behavior in frontotemporal dementia and primary progressive aphasia.

PubMed

Marczinski, Cecile A; Davidson, Wilda; Kertesz, Andrew

2004-12-01

To evaluate the construct validity of the Frontal Behavioral Inventory (FBI) and to describe the evolution of the behavioral abnormalities of the behavioral and aphasic presentations of frontotemporal dementia (FTD) by means of a 3-year longitudinal study. The FBI is a standardized behavioral questionnaire useful in the diagnosis and quantification of the personality and behavior disorder FTD. Patients who had three consecutive yearly assessments with the FBI were selected, 12 with the behavioral variant of FTD (FTD-bv) and 14 with Primary Progressive Aphasia (PPA). FBI scores rose as the disease progressed in both the FTD-bv and PPA groups over the 3 years of testing. Initial mean FBI scores of the FTD-bv group were above the cutoff for FTD as established for this diagnosis with previous standardization. By the third year, the mean FBI score of PPA patients was also above the established cutoff for FTD. The outcome of the study demonstrates that the FBI is sensitive to changes in behavior and personality in both variants of FTD. The FBI can be used to describe the evolution of symptoms and the course of the illness of Pick complex patients who present initially with FTD-bv or who present with PPA and subsequently develop the behavioral disorder.

Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study.

PubMed

Richard, Edo; Gouw, Alida A; Scheltens, Philip; van Gool, Willem A

2010-03-01

White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.

On the right side? A longitudinal study of left- versus right-lateralized semantic dementia.

PubMed

Kumfor, Fiona; Landin-Romero, Ramon; Devenney, Emma; Hutchings, Rosalind; Grasso, Roberto; Hodges, John R; Piguet, Olivier

2016-03-01

The typical presentation of semantic dementia is associated with marked, left predominant anterior temporal lobe atrophy and with changes in language. About 30% of individuals, however, present with predominant right anterior temporal lobe atrophy, usually accompanied by behavioural changes and prosopagnosia. Here, we aimed to establish whether these initially distinct clinical presentations evolve into a similar syndrome at the neural and behavioural level. Thirty-one patients who presented with predominant anterior temporal lobe atrophy were included. Based on imaging, patients were categorized as either predominant left (n = 22) or right (n = 9) semantic dementia. Thirty-three Alzheimer's disease patients and 25 healthy controls were included for comparison. Participants completed the Addenbrooke's Cognitive Examination, a Face and Emotion Processing Battery and the Cambridge Behavioural Inventory, and underwent magnetic resonance imaging annually. Longitudinal neuroimaging analyses showed greater right temporal pole atrophy in left semantic dementia than Alzheimer's disease, whereas right semantic dementia showed greater orbitofrontal and left temporal lobe atrophy than Alzheimer's disease. Importantly, direct comparisons between semantic dementia groups revealed that over time, left semantic dementia showed progressive thinning in the right temporal pole, whereas right semantic dementia showed thinning in the orbitofrontal cortex and anterior cingulate. Behaviourally, longitudinal analyses revealed that general cognition declined in all patients. In contrast, patients with left and right semantic dementia showed greater emotion recognition decline than Alzheimer's disease. In addition, left semantic dementia showed greater motivation loss than Alzheimer's disease. Correlational analyses revealed that emotion recognition was associated with right temporal pole, right medial orbitofrontal and right fusiform integrity, while changes in motivation were associated with right temporal pole cortical thinning. While left and right semantic dementia show distinct profiles at presentation, both phenotypes develop deficits in emotion recognition and behaviour. These findings highlight the pervasive socio-emotional deficits in frontotemporal dementia, even in patients with an initial language presentation. These changes reflect right anterior temporal and orbitofrontal cortex degeneration, underscoring the role of these regions in social cognition and behaviour. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The effects of computer-assisted cognitive rehabilitation on Alzheimer's dementia patients memories.

PubMed

Hwang, Jung-Ha; Cha, Hyun-Gyu; Cho, Young-Seok; Kim, Tae-Sue; Cho, Hyuk-Shin

2015-09-01

[Purpose] The purpose of the present study was to conduct Computer-Assisted Cognitive Rehabilitation (COMCOG) to examine the effects of COMCOG on Alzheimer's dementia patients' memories. [Subjects] Thirty-five patients diagnosed with Alzheimer's dementia received COMCOG for 30 minutes per day, five days per week for four weeks. [Methods] Before and after the COMCOG intervention, subjects' cognitive functions were evaluated using the Cognitive Assessment Reference Diagnosis System (CARDS) and Mini-Mental State Examination-Korea (MMSE-K) test. [Results] According to the results of the evaluation, among the CARDS scores of the subjects who received COMCOG, the scores of the delayed 10-word list, delayed 10-object list, recognition 10-object, and recent memory significantly increased while the scores of recognition 10-word significantly decreased after intervention compared to before intervention. In addition, among the MMSE-K items, the orientation, registration, and recall showed significant increases. [Conclusion] Based on these results, delay in the progress of memory deterioration can be expected when COMCOG is conducted for Alzheimer's dementia patients who show declines in cognitive functions.

The validity of the family history method for identifying Alzheimer disease.

PubMed

Li, G; Aryan, M; Silverman, J M; Haroutunian, V; Perl, D P; Birstein, S; Lantz, M; Marin, D B; Mohs, R C; Davis, K L

1997-05-01

To examine the validity of the family history method for identifying Alzheimer disease (AD) by comparing family history and neuropathological diagnoses. Seventy-seven former residents of the Jewish Home and Hospital for the Aged, New York, NY, with neuropathological evaluations on record were blindly assessed for the presence of dementia and, if present, the type of dementia through family informants by telephone interviews. The Alzheimer's Disease Risk Questionnaire was used to collect demographic information and screen for possible dementia. If dementia was suspected, the Dementia Questionnaire was administered to assess the course and type of dementia, i.e., primary progressive dementia (PPD, likely AD), multiple infarct dementia, mixed dementia (i.e., PPD and multiple infarct dementia), and other dementias based on the modified Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria. Sixty (77.9%) of 77 elderly subjects were classified as having dementia and 17 (22.1%) were without dementia by family history evaluation. Of the 60 elderly subjects with dementia, 57 (95%) were found at autopsy to have had neuropathological changes related to dementia. The sensitivity of the family history diagnosis for dementia with related neuropathological change was 0.84 (57 of 68) and the specificity was 0.67 (6 of 9). Using family history information to differentiate the type of dementia, the sensitivity for definite or probable AD (with or without another condition) was 0.69 (36 of 51) and the specificity was 0.73 (19 of 26). The majority (9 of 15) of patients testing false negative for PPD had a history of stroke associated with onset of memory changes, excluding a diagnosis of PPD. Identifying dementia, in general, and AD, in particular, has an acceptable sensitivity and specificity. As is true for direct clinical diagnosis, the major issue associated with misclassifying AD in a family history assessment is the masking effects of a coexisting non-AD dementia or dementia-related disorders, such as stroke. Including mixed cases, ie, PPD and multiple infarct dementia in estimates of the familial risk for AD can reduce the extent of underestimation of PPD.

Parkinson's disease with mild cognitive impairment: severe cortical thinning antedates dementia.

PubMed

Gasca-Salas, Carmen; García-Lorenzo, Daniel; Garcia-Garcia, David; Clavero, Pedro; Obeso, José A; Lehericy, Stephane; Rodríguez-Oroz, María C

2017-07-14

Mild cognitive impairment (MCI) in Parkinson's disease (PD) is a risk factor for dementia and thus, it is of interest to elucidate if specific patterns of atrophy in PD-MCI patients are associated with a higher risk of developing dementia. We aim to define pattern(s) of regional atrophy in PD-MCI patients who developed dementia during 31 months of follow-up using cortical thickness analysis Twenty-three PD-MCI patients and 18 controls underwent brain MRI and completed a neuropsychological examination at baseline, PD-MCI patients were followed after a 31 month follow-up in order to assess their progression to dementia. At follow up, 8 PD-MCI patients had converted to dementia (PD-MCI converters) whereas 15 remained as PD-MCI (PD-MCI non-converters). All patients were at least 60 years old and suffered PD ≥ 10 years. There were no baseline differences between the two groups of patients in clinical and neuropsychological variables. The cortex of PD-MCI converters was thinner than that of PD-MCI non-converters, bilaterally in the frontal, insula and the left middle temporal areas, also displaying a more widespread pattern of cortical thinning relative to the controls. This study shows that aged and long-term PD patients with MCI who convert to dementia in the short-mid term suffer a thinning of the cortex in several areas (frontal cortex, and middle temporal lobe and insula), even when their cognitive impairment was similar to that of PD-MCI non-converters. Thus, MRI analysis of cortical thickness may represent a useful measure to identify PD-MCI patients at a higher risk of developing dementia.

Cognitive Impairment and Dementia in Patients with Parkinson Disease

PubMed Central

Leverenz, James B.; Quinn, Joseph F.; Zabetian, Cyrus; Zhang, Jing; Montine, Kathleen S.; Montine, Thomas J.

2009-01-01

Parkinson disease (PD) is an already prevalent neurodegenerative disease that is poised to at least double over the next 25 years. Although best known for its characteristic movement disorder, PD is now appreciated commonly to cause cognitive impairment, including dementia, and behavioral changes. Dementia in patients with PD is consequential and has been associated with reduced quality of life, shortened survival, and increased caregiver distress. Here we review clinical presentation and progression, pathological bases, identification of genetic risk factors, development of small molecule biomarkers, and emerging treatments for cognitive impairment in patients with PD. PMID:19754405

Driving Competence in Mild Dementia with Lewy Bodies: In Search of Cognitive Predictors Using Driving Simulation

PubMed Central

Yamin, Stephanie; Stinchcombe, Arne; Gagnon, Sylvain

2015-01-01

Driving is a multifactorial behaviour drawing on multiple cognitive, sensory, and physical systems. Dementia is a progressive and degenerative neurological condition that impacts the cognitive processes necessary for safe driving. While a number of studies have examined driving among individuals with Alzheimer's disease, less is known about the impact of Dementia with Lewy Bodies (DLB) on driving safety. The present study compared simulated driving performance of 15 older drivers with mild DLB with that of 21 neurologically healthy control drivers. DLB drivers showed poorer performance on all indicators of simulated driving including an increased number of collisions in the simulator and poorer composite indicators of overall driving performance. A measure of global cognitive function (i.e., the Mini Mental State Exam) was found to be related to the overall driving performance. In addition, measures of attention (i.e., Useful Field of View, UFOV) and space processing (Visual Object and Space Perception, VOSP, Test) correlated significantly with a rater's assessment of driving performance. PMID:26713169

Stereotypic behaviors in degenerative dementias.

PubMed

Prioni, S; Fetoni, V; Barocco, F; Redaelli, V; Falcone, C; Soliveri, P; Tagliavini, F; Scaglioni, A; Caffarra, P; Concari, L; Gardini, S; Girotti, F

2012-11-01

Stereotypies are simple or complex involuntary/unvoluntary behaviors, common in fronto-temporal dementia (FTD), but not studied in other types of degenerative dementias. The aim was to investigate stereotypy frequency and type in patients with FTD, Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and Parkinson's disease with dementia (PDD) in a multicenter observational study; and to investigate the relation of stereotypies to cognitive, behavioral and motor impairment. One hundred fifty-five consecutive outpatients (45 AD, 40 FTD, 35 PSP and 35 PDD) were studied in four hospitals in northern Italy. Stereotypies were examined by the five-domain Stereotypy Rating Inventory. Cognition was examined by the Mini Mental State and Frontal Assessment Battery, neuropsychiatric symptoms by the Neuropsychiatric Inventory, and motor impairment and invalidity by the Unified Parkinson's Disease Rating Scale part III, and activities of daily living. Stereotypies were present in all groups. FTD and PDD had the greatest frequency of one-domain stereotypies; FTD also had the greatest frequency of two-or-more domain stereotypies; movement stereotypies were the most common stereotypies in all groups. AD patients had fewer stereotypies than the other groups. Stereotypies are not exclusive to FTD, but are also fairly common in PSP and PDD, though less so in AD. Stereotypies may be underpinned by dysfunctional striato-frontal circuits, known to be damaged in PSP and PDD, as well as FTD.

Raman spectroscopy of blood serum for Alzheimer's disease diagnostics: specificity relative to other types of dementia

PubMed Central

Ryzhikova, Elena; Kazakov, Oleksandr; Halamkova, Lenka; Celmins, Dzintra; Malone, Paula; Molho, Eric; Zimmerman, Earl A.; Lednev, Igor K.

2015-01-01

The key moment for efficiently and accurately diagnosing dementia occurs during the early stages. This is particularly true for Alzheimer's disease (AD). In this proof-of-concept study, we applied near infrared (NIR) Raman microspectroscopy of blood serum together with advanced multivariate statistics for the selective identification of AD. We analyzed data from 20 AD patients, 18 patients with other neurodegenerative dementias (OD) and 10 healthy control (HC) subjects. NIR Raman microspectroscopy differentiated patients with more than 95% sensitivity and specificity. We demonstrated the high discriminative power of artificial neural network (ANN) classification models, thus revealing the high potential of this developed methodology for the differential diagnosis of AD. Raman spectroscopic, blood-based tests may aid clinical assessments for the effective and accurate differential diagnosis of AD, decrease the labor, time and cost of diagnosis, and be useful for screening patient populations for AD development and progression. PMID:25256347

Small scale homelike special care units and traditional special care units: effects on cognition in dementia; a longitudinal controlled intervention study.

PubMed

Kok, Jeroen S; van Heuvelen, Marieke J G; Berg, Ina J; Scherder, Erik J A

2016-02-16

Evidence shows that living in small scale homelike Special Care Units (SCU) has positive effects on behavioural and psychological symptoms of patients with dementia. Effects on cognitive functioning in relation to care facilities, however, are scarcely investigated. The purpose of this study is to gain more insight into the effects of living in small scale homelike Special Care Units, compared to regular SCU's, on the course of cognitive functioning in dementia. A group of 67 patients with dementia who moved from a regular SCU to a small scale homelike SCU and a group of 48 patients with dementia who stayed in a regular SCU participated in the study. Cognitive and behavioural functioning was assessed by means of a neuropsychological test battery and observation scales one month before (baseline), as well as 3 (post) and 6 months (follow-up) after relocation. Comparing the post and follow-up measurement with the baseline measurement, no significant differences on separate measures of cognitive functioning between both groups were found. Additional analyses, however, on 'domain clusters' revealed that global cognitive functioning of the small scale homelike SCU group showed significantly less cognitive decline three months after the transfer (p < 0.05). Effect sizes (95% CI) show a tendency for better aspects of cognition in favour of the homelike small scaled SCU group, i.e., visual memory, picture recognition, cognitive decline as observed by representatives and the clustered domains episodic memory and global cognitive functioning. While there is no significant longitudinal effect on the progression of cognitive decline comparing small scaled homelike SCU's with regular SCU's for patients with dementia, analyses on the domain clusters and effect sizes cautiously suggest differences in favour of the small scaled homelike SCU for different aspects of cognition.

Aging related cognitive changes associated with Alzheimer's disease in Down syndrome.

PubMed

Firth, Nicholas C; Startin, Carla M; Hithersay, Rosalyn; Hamburg, Sarah; Wijeratne, Peter A; Mok, Kin Y; Hardy, John; Alexander, Daniel C; Strydom, André

2018-06-01

Individuals with Down syndrome (DS) have an extremely high genetic risk for Alzheimer's disease (AD), however, the course of cognitive decline associated with progression to dementia is ill-defined. Data-driven methods can estimate long-term trends from cross-sectional data while adjusting for variability in baseline ability, which complicates dementia assessment in those with DS. We applied an event-based model to cognitive test data and informant-rated questionnaire data from 283 adults with DS (the largest study of cognitive functioning in DS to date) to estimate the sequence of cognitive decline and individuals' disease stage. Decline in tests of memory, sustained attention/motor coordination, and verbal fluency occurred early, demonstrating that AD in DS follows a similar pattern of change to other forms of AD. Later decline was found for informant measures. Using the resulting staging model, we showed that adults with a clinical diagnosis of dementia and those with APOE 3:4 or 4:4 genotype were significantly more likely to be staged later, suggesting that the model is valid. Our results identify tests of memory and sustained attention may be particularly useful measures to track decline in the preclinical/prodromal stages of AD in DS whereas informant-measures may be useful in later stages (i.e. during conversion into dementia, or postdiagnosis). These results have implications for the selection of outcome measures of treatment trials to delay or prevent cognitive decline due to AD in DS. As clinical diagnoses are generally made late into AD progression, early assessment is essential.

Binswanger's disease: biomarkers in the inflammatory form of vascular cognitive impairment and dementia.

PubMed

Rosenberg, Gary A

2018-03-01

Vascular cognitive impairment and dementia (VCID) is a major public health concern because of the increased incidence of vascular disease in the aging population and the impact of vascular disease on Alzheimer's disease. VCID is a heterogeneous group of diseases for which there are no proven treatments. Biomarkers can be used to select more homogeneous populations. Small vessel disease is the most prevalent form of VCID and is the optimal form for treatment trials because there is a progressive course with characteristic pathological changes. Subcortical ischemic vascular disease of the Binswanger type (SIVD-BD) has a characteristic set of features that can be used both to identify patients and to follow treatment. SIVD-BD patients have clinical, neuropsychological, cerebrospinal fluid (CSF) and imaging features that can be used as biomarkers. No one feature is diagnostic, but a multimodal approach defines the SIVD-BD spectrum disorder. The most important features are large white matter lesions with axonal damage, blood-brain barrier disruption as shown by magnetic resonance imaging and CSF, and neuropsychological evidence of executive dysfunction. We have used these features to create a Binswanger Disease Scale and a probability of SIVD-BD, using a machine-learning algorithm. The patients discussed in this review are derived from published studies. Biomarkers not only aid in early diagnosis before the disease process has progressed too far for treatment, but also can indicate response to treatment. Refining the use of biomarkers will allow dementia treatment to enter the era of precision medicine. This article is part of the Special Issue "Vascular Dementia". © 2017 International Society for Neurochemistry.

Politics of science: Progress toward prevention of the dementia-Alzheimer's syndrome.

PubMed

Khachaturian, Zaven S; Khachaturian, Ara S

2015-01-01

There exist many challenges hampering the discovery and development of effective interventions to prevent dementia. Three major trends have now intersected to influence the emerging interest in disease modifying therapies that may delay or halt dementia. The three crucial factors shaping this current focus are: (1) the emergence of the longevity revolution and the impact of a aging society, (2) the effects of the US Federal investment in research in advancing knowledge about the neurobiology of aging and dementia, and (3) the problem of US legislators and health policy makers to balance the allocation of evermore scarce research funding resources. The purpose of this essay is to provide a survey of the politics of science and to describe efforts to correctly manage the high level of expectations of both the patient and research communities. The perspective offered reviews the history and evolution of the ideas to treat or prevent dementia and Alzheimer's disease as a national strategic goal. The aim is to evaluate the interplay between science and formulation of public policy for setting research priority. We use the history of developing US National Institute of Aging's extramural research programs on brain aging and Alzheimer's disease (Khachaturian, 2006; 2007) as an initial case study. Copyright © 2015 Elsevier Ltd. All rights reserved.

Music therapy for service users with dementia: a critical review of the literature.

PubMed

Blackburn, R; Bradshaw, T

2014-12-01

Dementia is an organic mental health problem that has been estimated to affect over 23 million people worldwide. With increasing life expectancy in most countries, it has been estimated that the prevalence of dementia will continue to significantly increase in the next two decades. Dementia leads to cognitive impairments most notably short-term memory loss and impairments in functioning and quality of life (QOL). National policy in the UK advocates the importance of early diagnosis, treatment and social inclusion in maintaining a good QOL. First-line treatment options often involve drug therapies aimed at slowing down the progression of the illness and antipsychotic medication to address challenging behaviours. To date, research into non-pharmacological interventions has been limited. In this manuscript, we review the literature that has reported evaluations of the effects of music therapy, a non-pharmacological intervention. The results of six studies reviewed suggest that music therapy may have potential benefits in reducing anxiety, depression and agitated behaviour displayed by elderly people with dementia as well as improving cognitive functioning and QOL. Furthermore, music therapy is a safe and low-cost intervention that could potentially be offered by mental health nurses and other carers working in residential settings. © 2014 John Wiley & Sons Ltd.

Is the time ripe for new diagnostic criteria of cognitive impairment due to cerebrovascular disease? Consensus report of the International Congress on Vascular Dementia working group.

PubMed

Perneczky, Robert; Tene, Oren; Attems, Johannes; Giannakopoulos, Panteleimon; Ikram, M Arfan; Federico, Antonio; Sarazin, Marie; Middleton, Lefkos T

2016-11-03

Long before Alzheimer's disease was established as the leading cause of dementia in old age, cerebrovascular lesions were known to cause cognitive deterioration and associated disability. Since the middle of the last century, different diagnostic concepts for vascular dementia and related syndromes were put forward, yet no widely accepted diagnostic consensus exists to date. Several international efforts, reviewed herein, are ongoing to define cognitive impairment due to cerebrovascular disease in its different stages and subtypes. The role of biomarkers is also being discussed, including cerebrospinal fluid proteins, structural and functional brain imaging, and genetic markers. The influence of risk factors, such as diet, exercise and different comorbidities, is emphasised by population-based research, and lifestyle changes are considered for the treatment and prevention of dementia. To improve the diagnosis and management of vascular cognitive impairment, further progress has to be made in understanding the relevant pathomechanisms, including shared mechanisms with Alzheimer's disease; bringing together fragmented research initiatives in coordinated international programs; testing if known risk factors are modifiable in prospective interventional studies; and defining the pre-dementia and pre-clinical stages in line with the concept of mild cognitive impairment due to Alzheimer's disease.

Office-Based Screening for Dementia in Parkinson Disease: The Montreal Parkinson Risk of Dementia Scale in 4 Longitudinal Cohorts.

PubMed

Dawson, Benjamin K; Fereshtehnejad, Seyed-Mohammad; Anang, Julius B M; Nomura, Takashi; Rios-Romenets, Silvia; Nakashima, Kenji; Gagnon, Jean-François; Postuma, Ronald B

2018-06-01

Parkinson disease dementia dramatically increases mortality rates, patient expenditures, hospitalization risk, and caregiver burden. Currently, predicting Parkinson disease dementia risk is difficult, particularly in an office-based setting, without extensive biomarker testing. To appraise the predictive validity of the Montreal Parkinson Risk of Dementia Scale, an office-based screening tool consisting of 8 items that are simply assessed. This multicenter study (Montreal, Canada; Tottori, Japan; and Parkinson Progression Markers Initiative sites) used 4 diverse Parkinson disease cohorts with a prospective 4.4-year follow-up. A total of 717 patients with Parkinson disease were recruited between May 2005 and June 2016. Of these, 607 were dementia-free at baseline and followed-up for 1 year or more and so were included. The association of individual baseline scale variables with eventual dementia risk was calculated. Participants were then randomly split into cohorts to investigate weighting and determine the scale's optimal cutoff point. Receiver operating characteristic curves were calculated and correlations with selected biomarkers were investigated. Dementia, as defined by Movement Disorder Society level I criteria. Of the 607 patients (mean [SD] age, 63.4 [10.1]; 376 men [62%]), 70 (11.5%) converted to dementia. All 8 items of the Montreal Parkinson Risk of Dementia Scale independently predicted dementia development at the 5% significance level. The annual conversion rate to dementia in the high-risk group (score, >5) was 14.9% compared with 5.8% in the intermediate group (score, 4-5) and 0.6% in the low-risk group (score, 0-3). The weighting procedure conferred no significant advantage. Overall predictive validity by the area under the receiver operating characteristic curve was 0.877 (95% CI, 0.829-0.924) across all cohorts. A cutoff of 4 or greater yielded a sensitivity of 77.1% (95% CI, 65.6-86.3) and a specificity of 87.2% (95% CI, 84.1-89.9), with a positive predictive value (as of 4.4 years) of 43.90% (95% CI, 37.76-50.24) and a negative predictive value of 96.70% (95% CI, 95.01-97.85). Positive and negative likelihood ratios were 5.94 (95% CI, 4.08-8.65) and 0.26 (95% CI, 0.17-0.40), respectively. Scale results correlated with markers of Alzheimer pathology and neuropsychological test results. Despite its simplicity, the Montreal Parkinson Risk of Dementia Scale demonstrated predictive validity equal or greater to previously described algorithms using biomarker assessments. Future studies using head-to-head comparisons or refinement of weighting would be of interest.

Reducing neuropsychiatric symptoms in persons with dementia and associated burden in family caregivers using tailored activities: Design and methods of a randomized clinical trial

PubMed Central

Gitlin, Laura N.; Piersol, Catherine Verrier; Hodgson, Nancy; Marx, Katherine; Roth, David L.; Johnson, Deidre; Samus, Quincy; Pizzi, Laura; Jutkowitz, Eric; Lyketsos, Constantine G.

2016-01-01

Among over 5 million people in the USA with dementia, neuropsychiatric symptoms (NPS) are almost universal, occurring across disease etiology and stage. If untreated, NPS can lead to significant morbidity and mortality including increased cost, distress, depression, and faster disease progression, as well as heightened burden on families. With few pharmacological solutions, , identifying nonpharmacologic strategies is critical. We describe a randomized clinical trial, the Dementia Behavior Study, to test the efficacy of an activity program to reduce significant existing NPS and associated caregiver burden at 3 and 6 months compared to a control group intervention. Occupational therapists deliver 8 in-home sessions over 3 months to assess capabilities and interests of persons with dementia, home environments, and caregiver knowledge, and readiness from which activities are developed and families trained in their use. Families learn to modify activities for future declines and use strategies to address care challenges. The comparison group controls for time and attention and involves 8 in-home sessions delivered by health educators who provide dementia education, home safety recommendations, and advanced care planning. We are randomizing 250 racially diverse families (person with dementia and primary caregiver dyads) recruited from community-based social services, conferences and media announcements. The primary outcome is change in agitation/aggression at 3 and 6 months. Secondary outcomes assess quality of life of persons with dementia, other behaviors, burden and confidence of caregivers, and cost effectiveness. If benefits are supported, this activity intervention will provide a clinically meaningful approach to prevent, reduce, and manage NPS. PMID:27339865

Chromosome 17 and hereditary dementia: linkage studies in three non-Alzheimer families and kindreds with late-onset FAD.

PubMed

Bird, T D; Wijsman, E M; Nochlin, D; Leehey, M; Sumi, S M; Payami, H; Poorkaj, P; Nemens, E; Rafkind, M; Schellenberg, G D

1997-04-01

Several previous families with differing clinical and pathologic characteristics have demonstrated linkage to the 17q21-22 region. We have performed a linkage analysis with chromosome 17 markers on three families showing autosomal dominant inheritance of non-Alzheimer dementia and 60 kindreds with late-onset familial Alzheimer's disease (FAD). Family A shows unequivocal evidence of linkage with a maximum lod score of 5.0 for marker D17S934 (theta = 0.001). This family has an unusual syndrome of a schizophrenia-like psychosis beginning in the fifth or sixth decade followed by severe dementia with an average disease duration of 13.8 years. Neuropathology from five autopsies in this family has shown marked neurofibrillary tangle formation (NFT), degeneration of the amygdala, and no amyloid plaques. This confirms the presence of a gene associated with dementia on 17q and extends the related phenotype to include schizophrenia-like symptoms and classic NFT pathology. A second family with early aphasia progressing to dementia and cortical-basal ganglion-like degeneration also has suggestive evidence for linkage to 17q. A third family with very early-onset dementia (mean, 31 years) and nonspecific pathology can be excluded from the 17q region and emphasizes additional genetic heterogeneity in non-Alzheimer hereditary dementia. Finally, we also present evidence against linkage to D17S579 in the set of 60 families with late-onset FAD, providing further evidence that the chromosome 17 gene is unlikely to be involved in the pathogenesis of typical AD.

Comparing cognition, mealtime performance, and nutritional status in people with dementia with or without ideational apraxia.

PubMed

Wu, Hua-Shan; Lin, Li-Chan

2015-03-01

To describe the prevalence rate of ideational apraxia (IA) affecting self-feeding in people with dementia, confirm the stage of dementia at which IA most commonly occurs, and compare mealtime performance and nutritional status between people with dementia (PWD) with and without IA. A cross-sectional design with between-subject comparison was used. Among the 395 potential participants recruited from dementia special care units at nine long-term care facilities in central and northern Taiwan, 98 met the operational definition of IA and were included in the PWD with IA group. From the remaining pool, 98 participants, matched for age and sex with the PWD with IA group, were randomly allocated to the PWD without IA group. Eating Behavior Scale (EBS) scores, food intake, total eating time, meal assistance, body mass index, Mini-Nutritional Assessment (MNA), and Mini-Mental State Examination scores were collected. The prevalence rate of IA affecting self-feeding in our study population of PWD was 24.8%. PWD with IA had significantly lower EBS scores, had more food intake (p < .001), spent more time being fed by caregivers, needed more verbal and feeding assistance, and had lower MNA scores than PWD without IA. Decline in the self-feeding ability of PWD affected by IA most commonly occurred in the severe stage of dementia. When dementia progresses to the late stage, staff should pay special attention to residents' mealtime performance and nutritional status. For PWD with IA, reassigning staff at mealtimes based on eating ability and providing memory training are recommended. © The Author(s) 2014.

Clinical practice with anti-dementia drugs: A revised (third) consensus statement from the British Association for Psychopharmacology.

PubMed

O'Brien, John T; Holmes, Clive; Jones, Matthew; Jones, Roy; Livingston, Gill; McKeith, Ian; Mittler, Peter; Passmore, Peter; Ritchie, Craig; Robinson, Louise; Sampson, Elizabeth L; Taylor, John-Paul; Thomas, Alan; Burns, Alistair

2017-02-01

The British Association for Psychopharmacology coordinated a meeting of experts to review and revise its previous 2011 guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A-D, with A having the strongest evidence base (from randomised controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and both structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography and single photon emission computerised tomography) brain imaging can improve diagnostic accuracy in particular situations (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for cognition in mild to moderate Alzheimer's disease (A), memantine for moderate to severe Alzheimer's disease (A) and combination therapy (cholinesterase inhibitors and memantine) may be beneficial (B). Drugs should not be stopped just because dementia severity increases (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E, nutritional supplements and Ginkgo biloba, cannot be recommended either for the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (both Parkinson's disease dementia and dementia with Lewy bodies), and memantine may be helpful (A). No drugs are clearly effective in vascular dementia, though cholinesterase inhibitors are beneficial in mixed dementia (B). Early evidence suggests multifactorial interventions may have potential to prevent or delay the onset of dementia (B). Though the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition in those with or at high risk of Alzheimer's disease are in progress. Though results of pivotal studies in early (prodromal/mild) Alzheimer's disease are awaited, results to date in more established (mild to moderate) Alzheimer's disease have been equivocal and no disease modifying agents are either licensed or can be currently recommended for clinical use.

Coping efforts and resilience among adult children who grew up with a parent with young-onset dementia: a qualitative follow-up study

PubMed Central

Johannessen, Aud; Engedal, Knut; Thorsen, Kirsten

2016-01-01

Background It is estimated that one in four persons with young-onset dementia (YOD) (<65 years old) has children younger than 18 years old at the onset of the dementia. These children experience a childhood different from what is expected. Adult children of parents with YOD are seldom addressed in research, and the impact of the dementia on the children's development over time has rarely been studied. Aim The goal of this study was to explore how adult children experienced the influence of their parents’ dementia on their own development during adolescence; what coping efforts, strategies, and resources they employed; and how they evaluated the most recent changes in their life situation. Method A follow-up, grounded theory approach in two phases was used. Qualitative interviews with 14 informants (18–30 years of age) were conducted in 2014 and one year later, in 2015. Findings Nearly all the informants expressed that their emotional well-being and their life situation were better at the second interview compared to the time of dementia onset in their parents. To overcome the difficulties of being a child of a parent with YOD, they used different instrumental, cognitive, and emotional coping strategies, subsumed analytically under the concept detachment. This category covers three subcategories of coping strategies: moving apart, greater personal distance, and calmer emotional reactions. Another category, resilience, designates combinations of the coping strategies. Vital for the development of coping resources and resilience was the need the informants had for social support—for people they saw who listened to them and responded to their needs. Conclusion Most of the informants reported that they experienced a better life situation and less emotional stress over time as their parent's dementia progressed. They developed better coping capacities and greater resilience. Vital for the development of coping resources and resilience was the need the informants had for social support. PMID:27065463

Is watching television a realistic leisure option for people with dementia?

PubMed

Gústafsdóttir, Margrét

2015-01-01

Watching television is a common leisure activity, not least among older people. However, watching television may become difficult when it is disturbed by symptoms of dementia. A total of 284 questionnaires were handed out to relatives of people with dementia in Iceland, in the Memory Clinic of the University Hospital and in specialized units for people with dementia (6 day-care units and 8 units within nursing homes). The response rate was just below 58%. Watching television was shown to play a less important role in the course of the daily life of people with dementia as soon as the symptoms of the disease became evident, and it increasingly became less relevant. So, this previous leisure activity left an ever-growing void of time to fill. However, watching television may provide an important social context for contact and togetherness during the progress of the disease, as watching television with someone close to them was important for the individuals with dementia. It is not a viable option for people with dementia to watch television on their own, but they may enjoy watching television while sharing this activity with a person close to them. This may even provide quality time.

Cross-Sectional and Longitudinal Cognitive Correlates of FDDNP PET and CSF Amyloid-β and Tau in Parkinson's Disease1.

PubMed

Buongiorno, Mariateresa; Antonelli, Francesca; Compta, Yaroslau; Fernandez, Yolanda; Pavia, Javier; Lomeña, Francisco; Ríos, José; Ramírez, Isabel; García, José Ramón; Soler, Marina; Cámara, Ana; Fernández, Manel; Basora, Misericòrdia; Salazar, Fàtima; Sanchez-Etayo, Gerard; Valldeoriola, Francesc; Barrio, Jorge Raúl; Marti, Maria Jose

2017-01-01

Tau and amyloid-β (Aβ) aggregates have been suggested to play a role in the development of dementia in Parkinson's disease (PD). Positron emission tomography (PET) with [18F]FDDNP and the determination of cerebrospinal fluid (CSF) levels of these proteins constitute a means to visualize in vivo Aβ and tau brain accumulation. Information about longitudinal changes of these CSF and PET biomarkers in PD with regard to progression to dementia is lacking. We assessed the cross-sectional and longitudinal associations of CSF and PET biomarkers of tau and Aβ with PD-related cognitive dysfunction in 6 healthy-controls (HC), 16 patients with PD without dementia (PDND), and 8 PD with dementia (PDD). All subjects underwent comprehensive neuropsychological testing, [18F]FDDNP PET, and CSF Aβ-tau determination. After 18 months, the PDND group was re-assessed clinically and by neuropsychological, PET, and CSF determinations. Cross-sectionally, PDD had higher [18F]FDDNP binding in lateral temporal regions and lower levels of CSF Aβ levels compared to PDND, with a congruent correlation between the [18F]FDDNP binding and CSF Aβ levels. Longitudinally, higher baseline lateral temporal [18F]FDDNP binding was associated to longitudinal worsening in cognitive performances and progression to dementia among subjects classified as PDND at baseline, who additionally disclosed at follow-up an increase in lateral-temporal FDDNP binding, as well as a reduction in CSF Aβ and an increase in CSF tau levels. These results confirm the relevance of these CSF and PET biomarkers to PDD, being specifically the first to show [18F]FDDNP PET as a dementia risk biomarker in PD, along with longitudinal CSF and PET changes over time.

First translational 'Think Tank' on cerebrovascular disease, cognitive impairment and dementia.

PubMed

Barone, Frank C; Gustafson, Deborah; Crystal, Howard A; Moreno, Herman; Adamski, Mateusz G; Arai, Ken; Baird, Alison E; Balucani, Clotilde; Brickman, Adam M; Cechetto, David; Gorelick, Philip; Biessels, Geert Jan; Kiliaan, Amanda; Launer, Lenore; Schneider, Julie; Sorond, Farzaneh A; Whitmer, Rachel; Wright, Clinton; Zhang, Zheng Gang

2016-02-13

As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and dementia. Thus with our more recent recognition of these relationships and our need to understand and more positively impact on this world health problem, "The Leo and Anne Albert Charitable Trust" (Gene Pranzo, Trustee with significant support from Susan Brogan, Meeting Planner) provided generous support for this inaugural international workshop that was held from April 13-16, 2015 at the beautiful Ritz Carlton Golf Resort in North Naples, Florida. Researchers from SUNY Downstate Medical Center, Brooklyn, NY organized the event by selecting the present group of translationally inclined preclinical, clinical and population scientists focused on cerebrovascular disease (CVD) risk and its progression to vascular cognitive impairment (VCI) and dementia. Participants at the workshop addressed important issues related to aging, cognition and dementia by: (1) sharing new data, information and perspectives that intersect vascular, metabolic and neurodegenerative diseases, (2) discussing gaps in translating population risk, clinical and preclinical information to the progression of cognitive loss, and (3) debating new approaches and methods to fill these gaps that can translate into future therapeutic interventions. Participants agreed on topics for group discussion prior to the meeting and focused on specific translational goals that included promoting better understanding of dementia mechanisms, the identification of potential therapeutic targets for intervention, and discussed/debated the potential utility of diagnostic/prognostic markers. Below summarizes the new data-presentations, concepts, novel directions and specific discussion topics addressed by this international translational team at our "First Leo and Anne Albert Charitable Trust 'Think Tank' VCI workshop".

Case Report: Aquatic Therapy and End-Stage Dementia.

PubMed

Becker, Bruce E; Lynch, Stacy

2018-04-01

A 54-year-old woman, retired due to progressive cognitive decline, was diagnosed with early-onset Alzheimer dementia. Conventional medication therapy for dementia had proven futile. Initial evaluation revealed a nonverbal female seated in a wheelchair, dependent on 2-person assist for all transfers and activities of daily living. She had been either nonresponsive or actively resistive for both activities of daily living and transfers in the 6 months before assessment. After a total of 17 1-hour therapy sessions over 19 weeks in a warm water therapy pool, she achieved the ability to tread water for 15 minutes, transfers improved to moderate-to-maximum assist from seated, and ambulation improved to 1000 feet with minimum-to-moderate assist of 2 persons. Communication increased to appropriate "yes," "no," and "okay" appropriate responses, and an occasional "thank you" and "very nice." The authors propose that her clinical progress may be related to her aquatic therapy intervention. IV. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Semantic Memory in the Clinical Progression of Alzheimer Disease.

PubMed

Tchakoute, Christophe T; Sainani, Kristin L; Henderson, Victor W

2017-09-01

Semantic memory measures may be useful in tracking and predicting progression of Alzheimer disease. We investigated relationships among semantic memory tasks and their 1-year predictive value in women with Alzheimer disease. We conducted secondary analyses of a randomized clinical trial of raloxifene in 42 women with late-onset mild-to-moderate Alzheimer disease. We assessed semantic memory with tests of oral confrontation naming, category fluency, semantic recognition and semantic naming, and semantic density in written narrative discourse. We measured global cognition (Alzheimer Disease Assessment Scale, cognitive subscale), dementia severity (Clinical Dementia Rating sum of boxes), and daily function (Activities of Daily Living Inventory) at baseline and 1 year. At baseline and 1 year, most semantic memory scores correlated highly or moderately with each other and with global cognition, dementia severity, and daily function. Semantic memory task performance at 1 year had worsened one-third to one-half standard deviation. Factor analysis of baseline test scores distinguished processes in semantic and lexical retrieval (semantic recognition, semantic naming, confrontation naming) from processes in lexical search (semantic density, category fluency). The semantic-lexical retrieval factor predicted global cognition at 1 year. Considered separately, baseline confrontation naming and category fluency predicted dementia severity, while semantic recognition and a composite of semantic recognition and semantic naming predicted global cognition. No individual semantic memory test predicted daily function. Semantic-lexical retrieval and lexical search may represent distinct aspects of semantic memory. Semantic memory processes are sensitive to cognitive decline and dementia severity in Alzheimer disease.

Research priorities to reduce the global burden of dementia by 2025.

PubMed

Shah, Hiral; Albanese, Emiliano; Duggan, Cynthia; Rudan, Igor; Langa, Kenneth M; Carrillo, Maria C; Chan, Kit Yee; Joanette, Yves; Prince, Martin; Rossor, Martin; Saxena, Shekhar; Snyder, Heather M; Sperling, Reisa; Varghese, Mathew; Wang, Huali; Wortmann, Marc; Dua, Tarun

2016-11-01

At the First WHO Ministerial Conference on Global Action Against Dementia in March, 2015, 160 delegates, including representatives from 80 WHO Member States and four UN agencies, agreed on a call for action to reduce the global burden of dementia by fostering a collective effort to advance research. To drive this effort, we completed a globally representative research prioritisation exercise using an adapted version of the Child Health and Nutrition Research Initiative method. We elicited 863 research questions from 201 participants and consolidated these questions into 59 thematic research avenues, which were scored anonymously by 162 researchers and stakeholders from 39 countries according to five criteria. Six of the top ten research priorities were focused on prevention, identification, and reduction of dementia risk, and on delivery and quality of care for people with dementia and their carers. Other priorities related to diagnosis, biomarkers, treatment development, basic research into disease mechanisms, and public awareness and understanding of dementia. Research priorities identified by this systematic international process should be mapped onto the global dementia research landscape to identify crucial gaps and inform and motivate policy makers, funders, and researchers to support and conduct research to reduce the global burden of dementia. Efforts are needed by all stakeholders, including WHO, WHO Member States, and civil society, to continuously monitor research investments and progress, through international platforms such as a Global Dementia Observatory. With established research priorities, an opportunity now exists to translate the call for action into a global dementia action plan to reduce the global burden of dementia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modulation of cholesterol in midlife affords cognitive advantage during ageing - a role for altered redox balance.

PubMed

Polidori, M Cristina; Pientka, Ludger; Nelles, Gereon; Griffiths, Helen R

2010-04-20

General practitioners, geriatricians, neurologists and health care professionals all over the world will be facing by 2040 the diagnostic, therapeutic and socioeconomic challenges of over 80 million people with dementia. Dementia is one of the most common diseases in the elderly which drastically affects daily life and everyday personal activities, is often associated with behavioural symptoms, personality change and numerous clinical complications and increases the risk for urinary incontinence, hip fracture, and - most markedly - the dependence on nursing care. The costs of care for patients with dementia are therefore immense. Serum cholesterol levels above 6.5 mmol/L are known to be associated with an increased RR of 1.5 and 2.1 to develop Alzheimer's disease, the most common form of dementia, and a reduction of serum cholesterol in midlife is associated with a lowered dementia risk. The aim of this work is to critically discuss some of the main results reported recently in the literature in this respect and to provide the pathophysiological rationale for the control of dyslipidemia in the prevention of dementia onset and progression.

Dementia paralytica: deterioration from communicating hydrocephalus.

PubMed Central

Giménez-Roldán, S; Benito, C; Martin, M

1979-01-01

Five patients suffering from dementia paralytica who failed to improve or deteriorated after one or several high dosage courses of penicillin, had pneumoencephalographic patterns suggesting communicating hydrocephalus. Measurements of the ventricular index, ratio of cella media to width of the temporal horn, and the callosal angle differed from that in seven cases of dementia paralytica with associated cerebral atrophy. An isotope cisternogram in three cases with communicating hydrocephalus further confirmed a blockage of the cerebrospinal fluid (CSF) at the parasagittal subarachnoid space. Three patients exhibited the full syndrome of gait apraxia, incontinence, and pyramidal tract signs associated with a severe degree of dementia. Shunting of the CSF in three cases was followed by immediate improvement in two, one in a longlasting way. No active parenchymal inflammation was observed in any of three brain biopsy samples taken during surgery, except for leptomeningeal fibrosis in one. Chronic leptomeningitis in dementia paralytica may impair subarachnoid CSF absorption with subsequent communicating hydrocephalus. Progression or inadequate responses after therapeutic dose of penicillin in dementia paralytica should prompt investigation for this complication as an alternative, effective treatment could be offered. Images PMID:469557

A figurative proverb test for dementia: rapid detection of disinhibition, excuse and confabulation, causing discommunication.

PubMed

Yamaguchi, Haruyasu; Maki, Yohko; Yamaguchi, Tomoharu

2011-12-01

Communicative disability is regarded as a prominent symptom of demented patients, and many studies have been devoted to analyze deficits of lexical-semantic operations in demented patients. However, it is often observed that even patients with preserved lexical-semantic skills might fail in interactive social communication. Whereas social interaction requires pragmatic language skills, pragmatic language competencies in demented subjects have not been well understood. We propose here a brief stress-free test to detect pragmatic language deficits, focusing on non-literal understanding of figurative expression. We hypothesized that suppression of the literal interpretation was required for figurative language interpretation.  We examined 69 demented subjects, 13 subjects with mild cognitive impairment and 61 healthy controls aged 65 years or more. The subjects were asked the meaning of a familiar proverb categorized as a figurative expression. The answers were analyzed based on five factors, and scored from 0 to 5. To consider the influence of cognitive inhibition on proverb comprehension, the scores of the Stroop Colour-Word Test were compared concerning correct and incorrect answers for each factor, respectively. Furthermore, the characteristics of answers were considered in the light of excuse and confabulation qualitatively. The proverb comprehension scores gradually decreased significantly as dementia progressed. The literal interpretation of the proverb, which showed difficulties in figurative language comprehension, was related to disinhibition. The qualitative analysis showed that excuse and confabulation increased as the dementia stage progressed. Deficits in cognitive inhibition partly explains the difficulties in interactive social communication in dementia. With qualitative analysis, asking the meaning of a proverb can be a brief test applied in a clinical setting to evaluate the stage of dementia, and to illustrate disinhibition, confabulation and excuse, which might cause discommunication and psychosocial maladjustment in demented patients. © 2011 The Authors. Psychogeriatrics © 2011 Japanese Psychogeriatric Society.

Montreal Cognitive Assessment for the diagnosis of Alzheimer's disease and other dementias.

PubMed

Davis, Daniel H J; Creavin, Sam T; Yip, Jennifer L Y; Noel-Storr, Anna H; Brayne, Carol; Cullum, Sarah

2015-10-29

Dementia is a progressive syndrome of global cognitive impairment with significant health and social care costs. Global prevalence is projected to increase, particularly in resource-limited settings. Recent policy changes in Western countries to increase detection mandates a careful examination of the diagnostic accuracy of neuropsychological tests for dementia. To determine the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) at various thresholds for dementia and its subtypes. We searched MEDLINE, EMBASE, BIOSIS Previews, Science Citation Index, PsycINFO and LILACS databases to August 2012. In addition, we searched specialised sources containing diagnostic studies and reviews, including MEDION (Meta-analyses van Diagnostisch Onderzoek), DARE (Database of Abstracts of Reviews of Effects), HTA (Health Technology Assessment Database), ARIF (Aggressive Research Intelligence Facility) and C-EBLM (International Federation of Clinical Chemistry and Laboratory Medicine Committee for Evidence-based Laboratory Medicine) databases. We also searched ALOIS (Cochrane Dementia and Cognitive Improvement Group specialized register of diagnostic and intervention studies). We identified further relevant studies from the PubMed 'related articles' feature and by tracking key studies in Science Citation Index and Scopus. We also searched for relevant grey literature from the Web of Science Core Collection, including Science Citation Index and Conference Proceedings Citation Index (Thomson Reuters Web of Science), PhD theses and contacted researchers with potential relevant data. Cross-sectional designs where all participants were recruited from the same sample were sought; case-control studies were excluded due to high chance of bias. We searched for studies from memory clinics, hospital clinics, primary care and community populations. We excluded studies of early onset dementia, dementia from a secondary cause, or studies where participants were selected on the basis of a specific disease type such as Parkinson's disease or specific settings such as nursing homes. We extracted dementia study prevalence and dichotomised test positive/test negative results with thresholds used to diagnose dementia. This allowed calculation of sensitivity and specificity if not already reported in the study. Study authors were contacted where there was insufficient information to complete the 2x2 tables. We performed quality assessment according to the QUADAS-2 criteria.Methodological variation in selected studies precluded quantitative meta-analysis, therefore results from individual studies were presented with a narrative synthesis. Seven studies were selected: three in memory clinics, two in hospital clinics, none in primary care and two in population-derived samples. There were 9422 participants in total, but most of studies recruited only small samples, with only one having more than 350 participants. The prevalence of dementia was 22% to 54% in the clinic-based studies, and 5% to 10% in population samples. In the four studies that used the recommended threshold score of 26 or over indicating normal cognition, the MoCA had high sensitivity of 0.94 or more but low specificity of 0.60 or less. The overall quality and quantity of information is insufficient to make recommendations on the clinical utility of MoCA for detecting dementia in different settings. Further studies that do not recruit participants based on diagnoses already present (case-control design) but apply diagnostic tests and reference standards prospectively are required. Methodological clarity could be improved in subsequent DTA studies of MoCA by reporting findings using recommended guidelines (e.g. STARDdem). Thresholds lower than 26 are likely to be more useful for optimal diagnostic accuracy of MoCA in dementia, but this requires confirmation in further studies.

Mild cognitive impairment: an opportunity to identify patients at high risk for progression to Alzheimer's disease.

PubMed

Levey, Allan; Lah, James; Goldstein, Felicia; Steenland, Kyle; Bliwise, Donald

2006-07-01

There is increasing evidence that subtle losses in cognitive function may be symptomatic of a transition to early Alzheimer's disease (AD). Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to AD. Of the MCI subtypes, patients with amnestic MCI (a-MCI) are at greatest risk. The objectives of this article were to review the relationship between MCI, normal aging, and AD, and to summarize recent research on the diagnosis and potential treatment of MCI. Relevant articles were identified through searches of MEDLINE and EMBASE using the terms mild cognitive impairment; cognitive impairment, no dementia; and dementia prodrome, with no restrictions as to year. Additional papers of interest were identified from the reference lists of the identified articles. The search was current as of February 2006. Guidelines and recommendations are being developed to assist physicians in diagnosing MCI, identifying its subtype and etiology, understanding the risks for conversion to AD, and managing disease progression. Given the existence of a subset of individuals with a-MCI, who are at greatest risk for progression to AD but still have high levels of cognition and function, the ability to improve symptoms and delay progression to AD would be particularly beneficial. In a 3-year, randomized, double-blind, placebo-controlled study in 769 patients with a-MCI, treatment with the cholinesterase inhibitor donepezil was associated with a significantly lower rate of progression to AD compared with placebo during the first 12 months of treatment (hazard ratio=0.42; 95% CI, 0.24-0.76; P=0.004) but not at later time points. Of other types of agents that have been investigated (antioxidants, estrogen replacement therapy, cyclooxygenase-2-selective inhibitors), none have shown significant beneficial effects in delaying cognitive decline or progression to AD. New drugs such as secretase inhibitors, small molecules that disrupt amyloid aggregation, and immunotherapies are in preclinical development. MCI involves more substantial cognitive and memory decline than normal aging and represents a significant risk factor for the development of dementia. Further research is needed into treatments to delay the conversion from MCI to AD.

Type 2 diabetes and/or its treatment leads to less cognitive impairment in Alzheimer's disease patients.

PubMed

Domínguez, Raúl O; Marschoff, Enrique R; González, Silvia E; Repetto, Marisa G; Serra, Jorge A

2012-10-01

To evaluate the cognitive performance of a homogeneous population of Alzheimer's disease (AD), non-demented Type 2 Diabetes Mellitus (DIAB), demented with concomitant diseases (AD+DIAB) and healthy control subjects. AD is a progressive dementia disorder characterized clinically by impairment of memory, cognition and behavior. Recently, a major research interest in AD has been placed on early evaluation. Diabetes is one of the clinical conditions that represent the greatest risk of developing oxidative stress and dementia. Glucose overload, leading to the development of impaired-induced insulin secretion in DIAB and has been suggested to slow or deter AD pathogenesis. The degree of cognitive impairment was determined on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) and the Folstein's Mini Mental State Examination (MMSE); the severity of dementia was quantified applying the Clinical Dementia Rating (CDR) test; the Hamilton test was employed to evaluate depressive conditions; the final population studied was 101 subjects. The cognitive deterioration is statistically significantly lower (p<0.05) in AD+DIAB patients as compared with AD patients. In this longitudinal study the superimposed diabetic condition was associated with a lower rate of cognitive decline, while diabetic non-demented patients and controls present normal scores. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Amyloid PET in neurodegenerative diseases with dementia.

PubMed

Camacho, V; Gómez-Grande, A; Sopena, P; García-Solís, D; Gómez Río, M; Lorenzo, C; Rubí, S; Arbizu, J

2018-05-15

Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased Aβ 1-42 and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on 18 F-FDG PET and temporal atrophy on MRI). Recently specific recommendations have been created as a consensus statement on the appropriate use of the imaging biomarkers, including amyloid PET: early-onset cognitive impairment/dementia, atypical forms of AD, mild cognitive impairment with early age of onset, and to differentiate between AD and other neurodegenerative diseases that occur with dementia. Amyloid PET is also contributing to the development of new therapies for AD, as well as in research studies for the study of other neurodegenerative diseases that occur with dementia where the deposition of Aβ amyloid is involved in its pathogenesis. In this paper, we review some general concepts and study the use of amyloid PET in depth and its relationship with neurodegenerative diseases and other diagnostic techniques. Copyright © 2018 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.

A taboo within a stigma? a qualitative study of managing incontinence with people with dementia living at home.

PubMed

Drennan, Vari M; Cole, Laura; Iliffe, Steve

2011-11-14

Incontinence in people with dementia is one of the factors associated with the decision to move to a care home. Managing incontinence adds to carer burden and has been reported by family carers as more difficult to manage than behavioural symptoms. Active management strategies have been reported to be associated with less carer depression. The purpose of this study was to investigate carers' perceptions of the range of incontinence problems they helped their relative with and the strategies they employed to manage these. Family carers of people with dementia living in their own homes were recruited through primary care, specialist community mental health services and voluntary organisations. Qualitative semi structured interviews were conducted either face to face or by telephone and thematically analysed. Thirty two carers were interviewed. They described a range of problems from supporting the person to remain independent in toileting, through to dealing with inappropriate behaviours, to containing and managing incontinence. All carers actively used problem solving strategies but sometimes these were not acceptable or understood by the person with dementia, particularly as the dementia progressed. Most carers reported protecting the person's dignity by not seeking health professionals help often until the point of a crisis. Once the carer has decided to seek help the responses from health professionals can be less than helpful, and carers report local health service policies on access to continence products to be inconsistent and often inappropriate to their circumstances. A few carers reported strategies for managing toileting and incontinence that have the potential for distress and harm to the person with dementia. Primary care professionals could be more proactive in enquiry, repeated over time, about toileting and incontinence problems and in giving advice and information to reduce crisis and problems.

Animal-assisted therapy and agitation and depression in nursing home residents with dementia: a matched case-control trial.

PubMed

Majić, Tomislav; Gutzmann, Hans; Heinz, Andreas; Lang, Undine E; Rapp, Michael A

2013-11-01

To investigate the efficacy of animal-assisted therapy (AAT) on symptoms of agitation/aggression and depression in nursing home residents with dementia in a randomized controlled trial. Previous studies have indicated that AAT has beneficial effects on neuropsychiatric symptoms in various psychiatric disorders but few studies have investigated the efficacy of AAT in patients suffering from dementia. Of 65 nursing home residents with dementia (mean [standard deviation] age: 81.8 [9.2] years; mean Mini-Mental State Examination score: 7.1 [0.7]), 27 matched pairs (N = 54) were randomly assigned to either treatment as usual or treatment as usual combined with AAT, administered over 10 weekly sessions. Blinded raters assessed cognitive impairment with the Mini-Mental State Examination, presence of agitation/aggression with the Cohen-Mansfield Agitation Inventory, and depression with the Dementia Mood Assessment Scale at baseline and during a period of 4 weeks after AAT intervention. In the control group, symptoms of agitation/aggression and depression significantly increased over 10 weeks; in the intervention group, patients receiving combined treatment displayed constant frequency and severity of symptoms of agitation/aggression (F1,48 = 6.43; p <0.05) and depression (F1,48 = 26.54; p <0.001). Symptom amelioration did not occur in either group. AAT is a promising option for the treatment of agitation/aggression and depression in patients with dementia. Our results suggest that AAT may delay progression of neuropsychiatric symptoms in demented nursing home residents. Further research is needed to determine its long-time effects. Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Parkinson’s disease dementia: a neural networks perspective

PubMed Central

Jahanshahi, Marjan; Foltynie, Thomas

2015-01-01

In the long-term, with progression of the illness, Parkinson’s disease dementia affects up to 90% of patients with Parkinson’s disease. With increasing life expectancy in western countries, Parkinson’s disease dementia is set to become even more prevalent in the future. However, current treatments only give modest symptomatic benefit at best. New treatments are slow in development because unlike the pathological processes underlying the motor deficits of Parkinson’s disease, the neural mechanisms underlying the dementing process and its associated cognitive deficits are still poorly understood. Recent insights from neuroscience research have begun to unravel the heterogeneous involvement of several distinct neural networks underlying the cognitive deficits in Parkinson’s disease dementia, and their modulation by both dopaminergic and non-dopaminergic transmitter systems in the brain. In this review we collate emerging evidence regarding these distinct brain networks to give a novel perspective on the pathological mechanisms underlying Parkinson’s disease dementia, and discuss how this may offer new therapeutic opportunities. PMID:25888551

Serial position effects are sensitive predictors of conversion from MCI to Alzheimer's disease dementia.

PubMed

Egli, Simone C; Beck, Irene R; Berres, Manfred; Foldi, Nancy S; Monsch, Andreas U; Sollberger, Marc

2014-10-01

It is unclear whether the predictive strength of established cognitive variables for progression to Alzheimer's disease (AD) dementia from mild cognitive impairment (MCI) varies depending on time to conversion. We investigated which cognitive variables were best predictors, and which of these variables remained predictive for patients with longer times to conversion. Seventy-five participants with MCI were assessed on measures of learning, memory, language, and executive function. Relative predictive strengths of these measures were analyzed using Cox regression models. Measures of word-list position-namely, serial position scores-together with Short Delay Free Recall of word-list learning best predicted conversion to AD dementia. However, only serial position scores predicted those participants with longer time to conversion. Results emphasize that the predictive strength of cognitive variables varies depending on time to conversion to dementia. Moreover, finer measures of learning captured by serial position scores were the most sensitive predictors of AD dementia. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Parkinson's disease dementia: a neural networks perspective.

PubMed

Gratwicke, James; Jahanshahi, Marjan; Foltynie, Thomas

2015-06-01

In the long-term, with progression of the illness, Parkinson's disease dementia affects up to 90% of patients with Parkinson's disease. With increasing life expectancy in western countries, Parkinson's disease dementia is set to become even more prevalent in the future. However, current treatments only give modest symptomatic benefit at best. New treatments are slow in development because unlike the pathological processes underlying the motor deficits of Parkinson's disease, the neural mechanisms underlying the dementing process and its associated cognitive deficits are still poorly understood. Recent insights from neuroscience research have begun to unravel the heterogeneous involvement of several distinct neural networks underlying the cognitive deficits in Parkinson's disease dementia, and their modulation by both dopaminergic and non-dopaminergic transmitter systems in the brain. In this review we collate emerging evidence regarding these distinct brain networks to give a novel perspective on the pathological mechanisms underlying Parkinson's disease dementia, and discuss how this may offer new therapeutic opportunities. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Loss of Neuroprotective Factors in Neurodegenerative Dementias: The End or the Starting Point?

PubMed Central

Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta

2017-01-01

Recent clinical, genetic and biochemical experimental evidences highlight the existence of common molecular pathways underlying neurodegenerative diseases. In this review, we will explore a key common pathological mechanism, i.e., the loss of neuroprotective factors, across the three major neurodegenerative diseases leading to dementia: Alzheimer's disease (AD), Frontotemporal dementia (FTD) and Lewy body dementia (LBD). We will report evidences that the Brain Derived Neurotrophic Factor (BDNF), the most investigated and characterized brain neurotrophin, progranulin, a multi-functional adipokine with trophic and growth factor properties, and cystatin C, a neuroprotective growth factor, are reduced in AD, FTD, and LBD. Moreover, we will review the molecular mechanism underlying the loss of neuroprotective factors in neurodegenerative diseases leading to dementia, with a special focus on endo-lysosomal pathway and intercellular communication mediated by extracellular vesicles. Exploring the shared commonality of disease mechanisms is of pivotal importance to identify novel potential therapeutic targets and to develop treatments to delay, slow or block disease progression. PMID:29249935

The time course of neurolinguistic and neuropsychological symptoms in three cases of logopenic primary progressive aphasia.

PubMed

Etcheverry, Louise; Seidel, Barbara; Grande, Marion; Schulte, Stephanie; Pieperhoff, Peter; Südmeyer, Martin; Minnerop, Martina; Binkofski, Ferdinand; Huber, Walter; Grodzinsky, Yosef; Amunts, Katrin; Heim, Stefan

2012-06-01

Primary progressive aphasia (PPA) is a rare clinical dementia syndrome affecting predominantly language abilities. Word-finding difficulties and comprehension deficits despite relatively preserved cognitive functions are characteristic symptoms during the first two years, and distinguish PPA from other dementia types like Alzheimer's disease. However, the dynamics of changes in language and non-linguistic abilities are not well understood. Most studies on progression used cross-sectional designs, which provide only limited insight into the course of the disease. Here we report the results of a longitudinal study in three cases of logopenic PPA over a period of 18 months, with exemplary longitudinal data from one patient even over 46 months. A comprehensive battery of neurolinguistic and neuropsychological tests was applied four times at intervals of six months. Over this period, deterioration of verbal abilities such as picture naming, story retelling, and semantic word recall was found, and the individual decline was quantified and compared between the three patients. Furthermore, decrease in non-verbal skills such as divided attention and increasing apraxia was observed in all three patients. In addition, inter-subject variability in the progression with different focuses was observed, with one patient developing a non-fluent PPA variant. The longitudinal, multivariate investigation of logopenic PPA thus provides novel insights into the progressive deterioration of verbal as well as non-verbal abilities. These deficits may further interact and thus form a multi-causal basis for the patients' problems in every-day life which need to be considered when planning individually targeted intervention in PPA. Copyright © 2012 Elsevier Ltd. All rights reserved.

Behavioral Interventions for Enhancing Life Participation in behavioral variant Frontotemporal Dementia and Primary Progressive Aphasia

PubMed Central

Kortte, Kathleen B.; Rogalski, Emily J.

2013-01-01

Primary progressive aphasia (PPA) and behavioral-variant frontotemporal dementia (bvFTD) are clinical syndromes under the umbrella term “frontotemporal dementia (FTD)” and are caused by a neurodegenerative disease with an onset most typically in the productive years of adulthood. The cognitive and behavioral impairments associated with FTD interfere with the successful engagement in typical life roles, such as parenting, working, and maintenance of interpersonal relationships. There are currently no treatments to stop or slow the degenerative process and there are only very limited medication options for the management of the cognitive-behavioral symptoms. However, alternative, non-pharmacological interventions may offer significant benefit to the quality of life of the diagnosed individual. The goal of this paper is to provide an overview of the approaches available through neurorehabilitation and community-based services that facilitate successful engagement in life activities and promote optimal quality of life for the individuals and families living with FTD. It is hoped that as medical providers become more familiar with behavioral interventions, referrals for services will increase thereby allowing individuals with FTD and their caregivers to learn ways to adapt, adjust, and participate in life to the fullest despite the impairments from this progressive disease. PMID:23611353

The association between late-life depression, mild cognitive impairment and dementia: is inflammation the missing link?

PubMed Central

Hermida, Adriana P; McDonald, William M; Steenland, Kyle; Levey, Allan

2015-01-01

Depression, mild cognitive impairment (MCI) and dementia are highly prevalent conditions that are increasing exponentially with similarly expanding social, medical and economic burdens. While there is a clear clinical connection between these three disorders, the mechanism of action that links them is less well understood. The lack of well-accepted biomarkers results in high levels of diagnostic subjectivity, which then greatly impacts research results when attempting to further explore their association. There is also a variety of clinical presentations of depressive syndromes, particularly in the elderly; each one may be associated with a different risk in the progression from MCI to different types of dementia. The diagnostic challenges, the importance of biomarkers and the discussion of inflammation as a possible link between depression, MCI and dementia are examined in this article. PMID:23234395

[Nutritional approaches to modulate oxidative stress that induce Alzheimer's disease. Nutritional approaches to prevent Alzheimer's disease].

PubMed

Lara, Humberto Herman; Alanís-Garza, Eduardo Javier; Estrada Puente, María Fernanda; Mureyko, Lucía Liliana; Alarcón Torres, David Alejandro; Ixtepan Turrent, Liliana

2015-01-01

Alzheimer's disease is the most common cause of dementia in the world; symptoms first appear after age 65 and have a progressive evolution. Expecting an increase on its incidence and knowing there is currently no cure for Alzheimer's disease, it is a necessity to prevent progression. The change in diet due to globalization may explain the growth of the incidence in places such as Japan and Mediterranean countries, which used to have fewer incidences. There is a direct correlation between disease progression and the increased intake of alcohol, saturated fats, and red meat. Therefore, we find obesity and higher serum levels in cholesterol due to saturated fat as a result. A way to decrease the progression of Alzheimer's is through a diet rich in polipheno/es (potent antioxidants), unsaturated fats (monounsaturated and polyunsaturated), fish, vegetable fa t, fruits with low glycemic index, and a moderate consumption of red wine. Through this potent antioxidant diet we accomplish the prevention of dementia and the progression of Alzheimer's disease. This article emphasizes the food and other components that have been demonstrated to decrease the oxidative stress related to these progressive diseases.

A dementia communication training intervention based on the VERA framework for pre-registration nurses: Part I developing and testing an implementation strategy.

PubMed

Naughton, Corina; Beard, Chloe; Tzouvara, Vasiliki; Pegram, Anne; Verity, Rebecca; Eley, Rhiannon; Hingley, David

2018-04-01

People living with dementia experience progressive difficulty in expressing physical and emotional needs. Health care staff including student nurses require training to develop compensatory communication strategies. However, there is no standardised foundation level dementia communication training within pre-registration curricula. This article describes the theoretical underpinnings and development of a foundation level dementia communication skills training based on the VERA (Validation, Emotion, Reassurance, Activity) framework. The training strategies drew on behavioural change theory using the COM-B model and Gagné's 9 Events of Instruction. The VERA framework was operationalised using a multicomponent teaching strategy. The intervention was refined based on quality improvement Plan-Do-Study-Act cycles with feedback from people living with dementia, facilitators and student nurses. Data collection used semi-structured questionnaires (n = 51) and four focus group (n = 19) interviews with students. Data analysis involved descriptive statistics and thematic analysis. The intervention was a 2.5-hour face-to-face training session delivered at the start of students' older adult unit placement with follow-up reflection sessions during placement. Training was delivered to 51 students, all students described the training as useful and would recommend it to their peers. Elements of the training that were highly valued were: opportunities to express concerns in caring for people with dementia, applying the VERA framework using role play and outlining realistic expectations of VERA. Students recognised the need for on-going training especially for more complex patients. Combining behaviour change and education theory with stakeholder feedback strengthened the development of VERA as a foundation level dementia communication training for pre-registration nurses. Copyright © 2018 Elsevier Ltd. All rights reserved.

Validity of the Korean Version of the Face, Legs, Activity, Cry, and Consolability Scale for Assessment of Pain in Dementia Patients.

PubMed

Moon, Yeonsil; Kim, Yoon Sook; Lee, Jongmin; Han, Seol Heui

2017-11-01

Pain is often associated with a more rapid progression of cognitive and functional decline, and behavioral disturbance in dementia. Therefore, it is essential to accurately assesses pain for proper intervention in patients with dementia. The Face, Legs, Activity, Cry, and Consolability (FLACC) scale is an excellent behaviour scale which includes most of the domains that are recommended by the American Geriatrics Society to evaluate when assessing pain in patients with dementia. The purpose of this study was to develop the Korean version of the FLACC (K-FLACC) and to verify its reliability and validity in assessing pain of elderly patients with dementia. We developed the K-FLACC to consist of the five domains (face, legs, activity, cry, and consolability) with scores of 0, 1, and 2 for each domain and a total score ranging from 0 to 10 as in the original FLACC. Eighty-eight patients with dementia who visited Konkuk University Medical Center were evaluated. The K-FLACC revealed good validity as compared to the Numeric Rating Scale (NRS; r = 0.617, P < 0.001) and the Face Pain Scale (FPS; r = 0.350, P = 0.001). All of the five domains of the K-FLACC were related to the NRS and FPS, in which the activity domain showed the highest correlation. Test-retest reliability was excellent, as the intra-class correlation coefficient comparing the retest to test was 0.73 (95% confidence interval, 0.59-0.82). Our results show that the K-FLACC is a suitable and valuable scale to assess pain in patients with dementia in Korea. © 2017 The Korean Academy of Medical Sciences.

Reducing neuropsychiatric symptoms in persons with dementia and associated burden in family caregivers using tailored activities: Design and methods of a randomized clinical trial.

PubMed

Gitlin, Laura N; Piersol, Catherine Verrier; Hodgson, Nancy; Marx, Katherine; Roth, David L; Johnston, Deidre; Samus, Quincy; Pizzi, Laura; Jutkowitz, Eric; Lyketsos, Constantine G

2016-07-01

Among over 5million people in the USA with dementia, neuropsychiatric symptoms (NPS) are almost universal, occurring across disease etiology and stage. If untreated, NPS can lead to significant morbidity and mortality including increased cost, distress, depression, and faster disease progression, as well as heightened burden on families. With few pharmacological solutions, identifying nonpharmacologic strategies is critical. We describe a randomized clinical trial, the Dementia Behavior Study, to test the efficacy of an activity program to reduce significant existing NPS and associated caregiver burden at 3 and 6months compared to a control group intervention. Occupational therapists deliver 8 in-home sessions over 3months to assess capabilities and interests of persons with dementia, home environments, and caregiver knowledge, and readiness from which activities are developed and families trained in their use. Families learn to modify activities for future declines and use strategies to address care challenges. The comparison group controls for time and attention and involves 8 in-home sessions delivered by health educators who provide dementia education, home safety recommendations, and advanced care planning. We are randomizing 250 racially diverse families (person with dementia and primary caregiver dyads) recruited from community-based social services, conferences and media announcements. The primary outcome is change in agitation/aggression at 3 and 6months. Secondary outcomes assess quality of life of persons with dementia, other behaviors, burden and confidence of caregivers, and cost and cost effectiveness. If benefits are supported, this activity intervention will provide a clinically meaningful approach to prevent, reduce, and manage NPS. Copyright © 2016 Elsevier Inc. All rights reserved.

The neuropsychological and neuroradiological correlates of slowly progressive visual agnosia.

PubMed

Giovagnoli, Anna Rita; Aresi, Anna; Reati, Fabiola; Riva, Alice; Gobbo, Clara; Bizzi, Alberto

2009-04-01

The case of a 64-year-old woman affected by slowly progressive visual agnosia is reported aiming to describe specific cognitive-brain relationships. Longitudinal clinical and neuropsychological assessment, combined with magnetic resonance imaging (MRI), spectroscopy, and positron emission tomography (PET) were used. Sequential neuropsychological evaluations performed during a period of 9 years since disease onset showed the appearance of apperceptive and associative visual agnosia, alexia without agraphia, agraphia, finger agnosia, and prosopoagnosia, but excluded dementia. MRI showed moderate diffuse cortical atrophy, with predominant atrophy in the left posterior cortical areas (temporal, parietal, and lateral occipital cortical gyri). 18FDG-PET showed marked bilateral posterior cortical hypometabolism; proton magnetic resonance spectroscopic imaging disclosed severe focal N-acetyl-aspartate depletion in the left temporoparietal and lateral occipital cortical areas. In conclusion, selective metabolic alterations and neuronal loss in the left temporoparietooccipital cortex may determine progressive visual agnosia in the absence of dementia.

Mitochondrial transfer RNA(Phe) mutation associated with a progressive neurodegenerative disorder characterized by psychiatric disturbance, dementia, and akinesia-rigidity.

PubMed

Young, Tim M; Blakely, Emma L; Swalwell, Helen; Carter, Janet E; Kartsounis, Luke D; O'Donovan, Dominic G; Turnbull, Douglass M; Taylor, Robert W; de Silva, Rajith N

2010-11-01

Mitochondrial diseases are characterized by wide phenotypic and genetic variability, but presentations in adults with akinetic rigidity and hyperkinetic movement disorders are rare. To describe clinically a subject with progressive neurodegeneration characterized by psychosis, dementia, and akinesia-rigidity, and to associate this phenotype with a novel mitochondrial transfer RNA(Phe) (tRNA(Phe)) (MTTF) mutation. Case description and detailed laboratory investigations of a 57-year-old woman at a university teaching hospital and a specialist mitochondrial diagnostic laboratory. Histopathological findings indicated that an underlying mitochondrial abnormality was responsible for the subject's progressive neurological disorder, with mitochondrial genome sequencing revealing a novel m.586G>A MTTF mutation. The clinical phenotypes associated with mitochondrial disorders may include akinesia-rigidity and psychosis. Our findings further broaden the spectrum of neurological disease associated with mitochondrial tRNA(Phe) mutations.

ATP Synthase, a Target for Dementia and Aging?

PubMed

Larrick, James W; Larrick, Jasmine W; Mendelsohn, Andrew R

2018-02-01

Advancing age is the biggest risk factor for development for the major life-threatening diseases in industrialized nations accounting for >90% of deaths. Alzheimer's dementia (AD) is among the most devastating. Currently approved therapies fail to slow progression of the disease, providing only modest improvements in memory. Recently reported work describes mechanistic studies of J147, a promising therapeutic molecule previously shown to rescue the severe cognitive deficits exhibited by aged, transgenic AD mice. Apparently, J147 targets the mitochondrial alpha-F1-ATP synthase (ATP5A). Modest inhibition of the ATP synthase modulates intracellular calcium to activate AMP-activated protein kinase to inhibit mammalian target of rapamycin, a known mechanism of lifespan extension from worms to mammals.

Mild traumatic brain injury: a risk factor for neurodegeneration

PubMed Central

2010-01-01

Recently, it has become clear that head trauma can lead to a progressive neurodegeneration known as chronic traumatic encephalopathy. Although the medical literature also implicates head trauma as a risk factor for Alzheimer's disease, these findings are predominantly based on clinical diagnostic criteria that lack specificity. The dementia that follows head injuries or repetitive mild trauma may be caused by chronic traumatic encephalopathy, alone or in conjunction with other neurodegenerations (for example, Alzheimer's disease). Prospective longitudinal studies of head-injured individuals, with neuropathological verification, will not only improve understanding of head trauma as a risk factor for dementia but will also enhance treatment and prevention of a variety of neurodegenerative diseases. PMID:20587081

Help-seeking intentions for early dementia diagnosis in a sample of Irish adults.

PubMed

Devoy, Susan; Simpson, Ellen Elizabeth Anne

2017-08-01

To identify factors that may increase intentions to seek help for an early dementia diagnosis. Early dementia diagnosis in Ireland is low, reducing the opportunity for intervention, which can delay progression, reduce psychological distress and increase social supports. Using the theory of planned behaviour (TPB), and a mixed methods approach, three focus groups were conducted (N = 22) to illicit attitudes and beliefs about help seeking for an early dementia diagnosis. The findings informed the development of the Help Seeking Intentions for Early Dementia Diagnosis (HSIEDD) questionnaire which was piloted and then administered to a sample of community dwelling adults from Dublin and Kildare (N = 95). Content analysis revealed participants held knowledge of the symptoms of dementia but not about available interventions. Facilitators of help seeking were family, friends and peers alongside well informed health professionals. Barriers to seeking help were a lack of knowledge, fear, loss, stigma and inaccessible services. The quantitative findings suggest the TPB constructs account for almost 28% of the variance in intentions to seek help for an early diagnosis of dementia, after controlling for sociodemographic variables and knowledge of dementia. In the final step of the regression analysis, the main predictors of help seeking were knowledge of dementia and subjective norm, accounting for 6% and 8% of the variance, respectively. Future interventions should aim to increase awareness of the support available to those experiencing early memory problems, and should highlight the supportive role that family, friends, peers and health professionals could provide.

Impact of social relationships on Alzheimer's memory impairment: mechanistic studies.

PubMed

Hsiao, Ya-Hsin; Chang, Chih-Hua; Gean, Po-Wu

2018-01-11

Alzheimer's disease (AD) is characterized by progressive memory and neuronal loss culminating in cognitive impairment that not only affects a person's living ability but also becomes a society's as well as a family's economic burden. AD is the most common form of dementia in older persons. It is expected that the number of people with AD dementia will increase dramatically in the next 30 years, projecting to 75 million in 2030 and 131.5 million in 2050 worldwide. So far, no sufficient evidence is available to support that any medicine is able to prevent or reverse the progression of the disease. Early studies have shown that social environment, particularly social relationships, can affect one's behavior and mental health. A study analyzing the correlation between loneliness and risk of developing AD revealed that lonely persons had higher risk of AD compared with persons who were not lonely. On the other hand, it has been reported that we can prevent cognitive decline and delay the onset of AD if we keep mentally active and frequently participate in social activities. In this review, we focus on the impact of social behaviors on the progression of cognitive deficit in animal models of AD with a particular emphasis on a mechanistic scheme that explains how social isolation exacerbates cognitive impairment and how social interaction with conspecifics rescues AD patients' memory deficit.

Brain Network Activation in Patients With Movement Disorders

ClinicalTrials.gov

2017-08-29

Parkinson Disease; Essential Tremor; Dystonia; Normal Pressure Hydrocephalus; Cerebellar Ataxia; Multiple System Atrophy; Progressive Supranuclear Palsy; Corticobasal Degeneration; Dementia With Lewy Bodies

Northern Manhattan Hispanic Caregiver Intervention Effectiveness Study: protocol of a pragmatic randomised trial comparing the effectiveness of two established interventions for informal caregivers of persons with dementia

PubMed Central

Luchsinger, José A; Burgio, Louis; Mittelman, Mary; Dunner, Ilana; Levine, Jed A; Kong, Jian; Silver, Stephanie; Ramirez, Mildred; Teresi, Jeanne A

2016-01-01

Introduction The prevalence of dementia is increasing without a known cure, resulting in an increasing number of informal caregivers. Caring for a person with dementia results in increased stress and depressive symptoms. There are several behavioural interventions designed to alleviate stress and depressive symptoms in caregivers of persons with dementia with evidence of efficacy. Two of the best-known interventions are the New York University Caregiver Intervention (NYUCI) and the Resources for Enhancing Alzheimer's Caregivers Health (REACH). The effectiveness of the NYUCI and REACH has never been compared. There is also a paucity of data on which interventions are more effective in Hispanics in New York City. Thus, we proposed the Northern Manhattan Hispanic Caregiver intervention Effectiveness Study (NHiCE), a pragmatic clinical trial designed to compare the effectiveness of adaptations of the NYUCI and the REACH in informal Hispanic caregivers of persons with dementia in New York City. Methods and analysis NHiCE is a 6-month randomised controlled trial comparing the effectiveness of adaptations of the NYUCI and REACH among 200 Hispanic informal adult caregivers of persons with dementia. The planned number of sessions of the NYUCI and REACH are similar. The primary outcome measures are changes from baseline to 6 months in the Zarit Caregiver Burden Scale and Geriatric Depression Scale. Our primary approach to analyses will be intent-to-treat. The primary analyses will use mixed random effects models, and a full information maximum likelihood approach, with sensitivity analyses using generalised estimating equation. Ethics and dissemination NHiCE is approved by the Institutional Review Board of Columbia University Medical Center (protocol AAAM5150). A Data Safety Monitoring Board monitors the progress of the study. Dissemination will include reports of the characteristics of the study participants, as well as a report of the results of the clinical trial. Trial registration number NCT02092987, Pre-results. PMID:27888180

Quantitative neurohistological features of frontotemporal degeneration.

PubMed

Arnold, S E; Han, L Y; Clark, C M; Grossman, M; Trojanowski, J Q

2000-01-01

Frontotemporal degeneration (FTD) is a neurodegenerative condition that has been principally associated with frontal lobe dementia. In this study, we compared neuropathological abnormalities in frontal, hippocampal, and calcarine cortices from patients assigned a diagnosis of FTD, normal elderly and Alzheimer's disease (AD). Densities of Nissl-stained neurons and lesions which were immunolabeled for tau, beta-amyloid (Abeta), alpha- and beta-synuclein, ubiquitin, glial fibrillary acidic protein (GFAP) and CD68 antigen were determined using computer-assisted, non-biased quantitative microscopy. We found that FTD frontal and hippocampal regions exhibited marked neuron loss, abundant ubiquitin-immunoreactive (ir) dystrophic neurites, GFAP-ir astrocytes, and CD68-ir microglia, while calcarine cortex was spared. No alpha- or beta-synuclein-ir lesions were observed, and neither the density of tau-ir neurofibrillary tangles nor that of Abeta-ir plaques in FTD exceeded normal controls. In addition, there were no neuropathological differences between FTD subjects who presented clinically with a frontal lobe dementia versus an AD-like dementia. These findings indicate that FTD is a category of neurodegnerative dementias with varying clinical presentations that is characterized by the progressive degeneration of select populations of cortical neurons. The molecular neurodegenerative mechanisms that lead to FTD remain to be elucidated.

Power, empowerment, and person-centred care: using ethnography to examine the everyday practice of unregistered dementia care staff.

PubMed

Scales, Kezia; Bailey, Simon; Middleton, Joanne; Schneider, Justine

2017-02-01

The social positioning and treatment of persons with dementia reflects dominant biomedical discourses of progressive and inevitable loss of insight, capacity, and personality. Proponents of person-centred care, by contrast, suggest that such loss can be mitigated within environments that preserve rather than undermine personhood. In formal organisational settings, person-centred approaches place particular responsibility on 'empowered' direct-care staff to translate these principles into practice. These staff provide the majority of hands-on care, but with limited training, recognition, or remuneration. Working within a Foucauldian understanding of power, this paper examines the complex ways that dementia care staff engage with their own 'dis/empowerment' in everyday practice. The findings, which are drawn from ethnographic studies of three National Health Service (NHS) wards and one private care home in England, are presented as a narrative exploration of carers' general experience of powerlessness, their inversion of this marginalised subject positioning, and the related possibilities for action. The paper concludes with a discussion of how Foucault's understanding of power may help define and enhance efforts to empower direct-care staff to provide person-centred care in formal dementia care settings. © 2016 Foundation for the Sociology of Health & Illness.

Longitudinal costs of caring for people with Alzheimer's disease.

PubMed

Gillespie, Paddy; O'Shea, Eamon; Cullinan, John; Buchanan, Jacqui; Bobula, Joel; Lacey, Loretto; Gallagher, Damien; Mhaolain, Aine Ni; Lawlor, Brian

2015-05-01

There has been an increasing interest in the relationship between severity of disease and costs in the care of people with dementia. Much of the current evidence is based on cross-sectional data, suggesting the need to examine trends over time for this important and growing cohort of the population. This paper estimates resource use and costs of care based on longitudinal data for 72 people with dementia in Ireland. Data were collected from the Enhancing Care in Alzheimer's Disease (ECAD) study at two time points: baseline and follow-up, two years later. Patients' dependence on others was measured using the Dependence Scale (DS), while patient function was measured using the Disability Assessment for Dementia (DAD) scale. Univariate and multivariate analysis were used to explore the effects of a range of variables on formal and informal care costs. Total costs of formal and informal care over six months rose from €9,266 (Standard Deviation (SD): 12,947) per patient at baseline to €21,266 (SD: 26,883) at follow-up, two years later. This constituted a statistically significant (p = 0.0014) increase in costs over time, driven primarily by an increase in estimated informal care costs. In the multivariate analysis, a one-point increase in the DS score, that is a one-unit increase in patient's dependence on others, was associated with a 19% increase in total costs (p = 0.0610). Higher levels of dependence in people with Alzheimer's disease are significantly associated with increased costs of informal care as the disease progresses. Formal care services did not respond to increased dependence in people with dementia, leaving it to families to fill the caring gap, mainly through increased supervision with the progress of disease.

Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer's disease.

PubMed

Portelius, Erik; Zetterberg, Henrik; Skillbäck, Tobias; Törnqvist, Ulrika; Andreasson, Ulf; Trojanowski, John Q; Weiner, Michael W; Shaw, Leslie M; Mattsson, Niklas; Blennow, Kaj

2015-11-01

Synaptic dysfunction is linked to cognitive symptoms in Alzheimer's disease. Thus, measurement of synapse proteins in cerebrospinal fluid may be useful biomarkers to monitor synaptic degeneration. Cerebrospinal fluid levels of the postsynaptic protein neurogranin are increased in Alzheimer's disease, including in the predementia stage of the disease. Here, we tested the performance of cerebrospinal fluid neurogranin to predict cognitive decline and brain injury in the Alzheimer's Disease Neuroimaging Initiative study. An in-house immunoassay was used to analyse neurogranin in cerebrospinal fluid samples from a cohort of patients who at recruitment were diagnosed as having Alzheimer's disease with dementia (n = 95) or mild cognitive impairment (n = 173), as well as in cognitively normal subjects (n = 110). Patients with mild cognitive impairment were grouped into those that remained cognitively stable for at least 2 years (stable mild cognitive impairment) and those who progressed to Alzheimer's disease dementia during follow-up (progressive mild cognitive impairment). Correlations were tested between baseline cerebrospinal fluid neurogranin levels and baseline and longitudinal cognitive impairment, brain atrophy and glucose metabolism within each diagnostic group. Cerebrospinal fluid neurogranin was increased in patients with Alzheimer's disease dementia (P < 0.001), progressive mild cognitive impairment (P < 0.001) and stable mild cognitive impairment (P < 0.05) compared with controls, and in Alzheimer's disease dementia (P < 0.01) and progressive mild cognitive impairment (P < 0.05) compared with stable mild cognitive impairment. In the mild cognitive impairment group, high baseline cerebrospinal fluid neurogranin levels predicted cognitive decline as reflected by decreased Mini-Mental State Examination (P < 0.001) and increased Alzheimer's Disease Assessment Scale-cognitive subscale (P < 0.001) scores at clinical follow-up. In addition, high baseline cerebrospinal fluid neurogranin levels in the mild cognitive impairment group correlated with longitudinal reductions in cortical glucose metabolism (P < 0.001) and hippocampal volume (P < 0.001) at clinical follow-up. Furthermore, within the progressive mild cognitive impairment group, elevated cerebrospinal fluid neurogranin levels were associated with accelerated deterioration in Alzheimer's Disease Assessment Scale-cognitive subscale (β = 0.0017, P = 0.01). These data demonstrate that cerebrospinal fluid neurogranin is increased already at the early clinical stage of Alzheimer's disease and predicts cognitive deterioration and disease-associated changes in metabolic and structural biomarkers over time. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Family caregivers' experiences of relinquishing the care of a person with dementia to a nursing home: insights from a meta-ethnographic study.

PubMed

Graneheim, Ulla H; Johansson, Anneli; Lindgren, Britt-Marie

2014-06-01

Many people with dementia are cared for in their homes by family caregivers. As the dementia progresses, admission of the family member to a nursing home becomes inevitable. The aim of this meta-ethnographic study was to describe caregivers' experiences of relinquishing the care of a family member with dementia to a nursing home. A systematic literature search of PubMed, Cinahl and PsychInfo, between the years 1992 and 2012, was performed, and 10 qualitative articles, based on 180 family caregivers' experiences, were included. The family caregivers' described their experiences as a process that went from being responsible for the decision, through living with the decision, adjusting to a new caring role and having changed relationships. They felt unprepared and lonely with these changes. They experienced loss, guilt and shame, but also feelings of relief. Their roles in the nursing home environment were to make sure that the individual needs of the person with dementia were respected and to monitor the quality of care. They wished to maintain their relationship with the person with dementia and to establish meaningful relationships with caring staff. The process of relinquishing care is similar to a crisis process, which starts with a turning point, followed by a coping face and finally the outcome of the process. The adaption to the new situation can be facilitated if the family caregivers are recognised as partners in the care of the person with dementia. The family caregivers' unique knowledge of their relatives' previous life story should be acknowledged in both care planning and daily care. Welcoming family caregivers to regular meetings with staff can contribute to increase the feeling of partnership. Offering staff clinical supervision could be one way of preparing them to deal with the emotional strain reported by family caregivers. © 2013 Nordic College of Caring Science.

The need for harmonisation and innovation of neuropsychological assessment in neurodegenerative dementias in Europe: consensus document of the Joint Program for Neurodegenerative Diseases Working Group.

PubMed

Costa, Alberto; Bak, Thomas; Caffarra, Paolo; Caltagirone, Carlo; Ceccaldi, Mathieu; Collette, Fabienne; Crutch, Sebastian; Della Sala, Sergio; Démonet, Jean François; Dubois, Bruno; Duzel, Emrah; Nestor, Peter; Papageorgiou, Sokratis G; Salmon, Eric; Sikkes, Sietske; Tiraboschi, Pietro; van der Flier, Wiesje M; Visser, Pieter Jelle; Cappa, Stefano F

2017-04-17

Cognitive, behavioural, and functional assessment is crucial in longitudinal studies of neurodegenerative dementias (NDD). Central issues, such as the definition of the study population (asymptomatic, at risk, or individuals with dementia), the detection of change/decline, and the assessment of relevant outcomes depend on quantitative measures of cognitive, behavioural, and functional status.Currently, we are far from having available reliable protocols and tools for the assessment of dementias in Europe. The main problems are the heterogeneity of the tools used across different European countries, the lack of standardisation of administration and scoring methods across centres, and the limited information available about the psychometric properties of many tests currently in widespread use. This situation makes it hard to compare results across studies carried out in different centres, thus hampering research progress, in particular towards the contribution to a "big data" common data set.We present here the results of a project funded by the Joint Program for Neurodegenerative Diseases (JPND) and by the Italian Ministry of Health. The project aimed at providing a consensus framework for the harmonisation of assessment tools to be applied to research in neurodegenerative disorders affecting cognition across Europe. A panel of European experts reviewed the current methods of neuropsychological assessment, identified pending issues, and made recommendations for the harmonisation of neuropsychological assessment of neurodegenerative dementias in Europe.A consensus was achieved on the general recommendations to be followed in developing procedures and tools for neuropsychological assessment, with the aim of harmonising tools and procedures to achieve more reliable data on the cognitive-behavioural examination. The results of this study should be considered as a first step to enhancing a common view and practise on NDD assessment across European countries.

Dementia in a retired world boxing champion: case report and literature review.

PubMed

Nowak, L A; Smith, G G; Reyes, P F

2009-01-01

Dementia in retired boxers, also referred to as "dementia pugilistica" (DP), is usually attributed to repeated concussive and subconcussive blows to the head. We report the case of a former world boxing champion whose progressive cognitive decline could be ascribed to DP, cerebral infarcts and Wernicke-Korsakoff syndrome. This case demonstrates that dementia in retired boxers may be caused and/or exacerbated by etiologic factors other than DP. We correlated the clinical features with the histochemical and immunohistochemical changes observed on autopsy brain material from a retired boxer, reviewed the literature on boxing-related dementia, and compared our findings with previous reports on DP. Neuropathologic examination revealed numerous neurofibrillary tangles (NFTs), rare neuritic plaques (NPs), multiple cerebral infarcts, fenestrated septum pellucidum, atrophic and gliotic mamillary bodies, and pale substantia nigra and locus ceruleus. Our neuropathologic data confirmed the notion that dementia in retired boxers could be due to several factors such as DP, multiple cerebral infarcts and Wernicke-Korsakoff syndrome. Our findings illustrate the need to comprehensively examine former boxers with dementia as well as carefully evaluate the neuropathologic changes that may cause or contribute to the patient's cognitive and behavioral symptoms. Such an approach is crucial in order to provide prompt and more definitive therapies.

Gait and Cognition: A Complementary Approach to Understanding Brain Function and the Risk of Falling

PubMed Central

Montero-Odasso, Manuel; Verghese, Joe; Beauchet, Olivier; Hausdorff, Jeffrey M.

2012-01-01

Until recently, clinicians and researchers have performed gait assessments and cognitive assessments separately when evaluating older adults. Increasing evidence from clinical practice, epidemiological studies, and clinical trials shows that gait and cognition are inter-related in older adults. Quantifiable alterations in gait among older adults are associated with falls, dementia, and disability. At the same time, emerging evidence indicates that early disturbances in cognitive processes such as attention, executive function, and working memory are associated with slower gait and gait instability during single and dual-task testing, and that these cognitive disturbances assist in the prediction of future mobility loss, falls, and progression to dementia. This paper reviews the importance of the gait-cognition inter-relationship in aging and presents evidence that gait assessments can provide a window into the understanding of cognitive function and dysfunctions, and fall risk in older people in clinical practice. To this end, the benefits of dual-task gait assessments (e.g., walking while performing an attention-demanding task) as a marker of fall risk are summarized. Further, we also present a potential complementary approach for reducing the risk of falls by improving certain aspects of cognition through both non-pharmacological and pharmacological treatments. Untangling the relationship between early gait disturbances and early cognitive changes may be helpful for identifying older adults at higher risk of experiencing mobility decline, falls and the progression to dementia. PMID:23110433

Neurocognitive features distinguishing primary central nervous system lymphoma from other possible causes of rapidly progressive dementia.

PubMed

Deutsch, Mariel B; Mendez, Mario F

2015-03-01

Define the neurocognitive features of primary central nervous system lymphoma (PCNSL) presenting with dementia, and compare with other causes of rapidly progressive dementia (RPD). PCNSL can present as an RPD. Differentiating PCNSL from other RPDs is critical because lymphomatous dementia may be reversible, and untreated PCNSL is fatal. We performed a meta-analysis of case reports of dementia from PCNSL (between 1950 and 2013); 20 patients (14 with lymphomatosis cerebri) met our criteria. We compared these patients to a case series of patients with RPD from Creutzfeldt-Jakob disease and other non-PCNSL etiologies (Sala et al, 2012. Alzheimer Dis Assoc Disord. 26:267-271). Median age was 66 years (range 41 to 81); 70% were men. Time from symptom onset to evaluation was <6 months in 65%. No patients had seizures; 5% had headaches; 45% had non-aphasic speech difficulty. There was significantly more memory impairment in patients with PCNSL than other RPDs and significantly less myoclonus and parkinsonism. Behavioral changes and cerebellar signs were not significantly different. Significantly more patients with PCNSL than other RPDs had white matter changes; significantly fewer had atrophy. Elevated CSF protein and pleocytosis were more frequent in PCNSL; patients with other RPDs tended to have normal CSF±14-3-3 protein. Unlike patients with RPD from other causes, those with PCNSL commonly present with impaired memory, apathy, and abnormal speech and gait, without headache, seizure, or myoclonus. White matter changes and CSF abnormalities predominate. Improved clinical awareness of PCNSL can prompt earlier diagnosis and treatment.

Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis.

PubMed

Hager, K; Kenklies, M; McAfoose, J; Engel, J; Münch, G

2007-01-01

Oxidative stress and neuronal energy depletion are characteristic biochemical hallmarks of Alzheimer's disease (AD). It is therefore conceivable that pro-energetic and antioxidant drugs such as alpha-lipoic acid might delay the onset or slow down the progression of the disease. In a previous study, 600mg alpha-lipoic acid was given daily to nine patients with AD (receiving a standard treatment with choline-esterase inhibitors) in an open-label study over an observation period of 12 months. The treatment led to a stabilization of cognitive functions in the study group, demonstrated by constant scores in two neuropsychological tests (the mini mental state exam, MMSE and the Alzheimer's disease assessment score cognitive subscale, ADAScog). In this report, we have extended the analysis to 43 patients over an observation period of up to 48 months. In patients with mild dementia (ADAScog < 15), the disease progressed extremely slowly (ADAScog: +1.2 points/year, MMSE: -0.6 points/year), in patients with moderate dementia at approximately twice the rate. However, the progression appears dramatically lower than data reported for untreated patients or patients on choline-esterase inhibitors in the second year of long-term studies. Despite the fact that this study was not double-blinded, placebo-controlled and randomized, our data suggest that treatment with alpha-lipoic acid might be a successful 'neuroprotective' therapy option for AD. However, a state-of-the-art phase II trial is needed urgently.

Graph theoretic analysis of structural connectivity across the spectrum of Alzheimer's disease: The importance of graph creation methods

PubMed Central

Phillips, David J.; McGlaughlin, Alec; Ruth, David; Jager, Leah R.; Soldan, Anja

2015-01-01

Graph theory is increasingly being used to study brain connectivity across the spectrum of Alzheimer's disease (AD), but prior findings have been inconsistent, likely reflecting methodological differences. We systematically investigated how methods of graph creation (i.e., type of correlation matrix and edge weighting) affect structural network properties and group differences. We estimated the structural connectivity of brain networks based on correlation maps of cortical thickness obtained from MRI. Four groups were compared: 126 cognitively normal older adults, 103 individuals with Mild Cognitive Impairment (MCI) who retained MCI status for at least 3 years (stable MCI), 108 individuals with MCI who progressed to AD-dementia within 3 years (progressive MCI), and 105 individuals with AD-dementia. Small-world measures of connectivity (characteristic path length and clustering coefficient) differed across groups, consistent with prior studies. Groups were best discriminated by the Randić index, which measures the degree to which highly connected nodes connect to other highly connected nodes. The Randić index differentiated the stable and progressive MCI groups, suggesting that it might be useful for tracking and predicting the progression of AD. Notably, however, the magnitude and direction of group differences in all three measures were dependent on the method of graph creation, indicating that it is crucial to take into account how graphs are constructed when interpreting differences across diagnostic groups and studies. The algebraic connectivity measures showed few group differences, independent of the method of graph construction, suggesting that global connectivity as it relates to node degree is not altered in early AD. PMID:25984446

Posterior hypoperfusion in Parkinson's disease with and without dementia measured with arterial spin labeling MRI.

PubMed

Kamagata, Koji; Motoi, Yumiko; Hori, Masaaki; Suzuki, Michimasa; Nakanishi, Atsushi; Shimoji, Keigo; Kyougoku, Shinsuke; Kuwatsuru, Ryohei; Sasai, Keisuke; Abe, Osamu; Mizuno, Yoshikuni; Aoki, Shigeki; Hattori, Nobutaka

2011-04-01

To determine whether quantitative arterial spin labeling (ASL) can be used to evaluate regional cerebral blood flow in Parkinson's disease with dementia (PDD) and without dementia (PD). Thirty-five PD patients, 11 PDD patients, and 35 normal controls were scanned by using a quantitative ASL method with a 3 Tesla MRI unit. Regional cerebral blood flow was compared in the posterior cortex using region-of-interest analysis. PD and PDD patients showed lower regional cerebral blood flow in the posterior cortex than normal controls (P = 0.002 and P = 0.001, respectively, analysis of variance with a Bonferroni post hoc test). This is the first study to detect hypoperfusion in the posterior cortex in PD and PDD patients using ASL perfusion MRI. Because ASL perfusion MRI is completely noninvasive and can, therefore, safely be used for repeated assessments, this method can be used to monitor treatment effects or disease progression in PD. Copyright © 2011 Wiley-Liss, Inc.

MRI-leukoaraiosis thresholds and the phenotypic expression of dementia

PubMed Central

Mitchell, Sandra M.; Brumback, Babette; Tanner, Jared J.; Schmalfuss, Ilona; Lamar, Melissa; Giovannetti, Tania; Heilman, Kenneth M.; Libon, David J.

2012-01-01

Objective: To examine the concept of leukoaraiosis thresholds on working memory, visuoconstruction, memory, and language in dementia. Methods: A consecutive series of 83 individuals with insidious onset/progressive dementia clinically diagnosed with Alzheimer disease (AD) or small vessel vascular dementia (VaD) completed neuropsychological measures assessing working memory, visuoconstruction, episodic memory, and language. A clinical MRI scan was used to quantify leukoaraiosis, total white matter, hippocampus, lacune, and intracranial volume. We performed analyses to detect the lowest level of leukoaraiosis associated with impairment on the neuropsychological measures. Results: Leukoaraiosis ranged from 0.63% to 23.74% of participants' white matter. Leukoaraiosis explained a significant amount of variance in working memory performance when it involved 3% or more of the white matter with curve estimations showing the relationship to be nonlinear in nature. Greater leukoaraiosis (13%) was implicated for impairment in visuoconstruction. Relationships between leukoaraiosis, episodic memory, and language measures were linear or flat. Conclusions: Leukoaraiosis involves specific threshold points for working memory and visuoconstructional tests in AD/VaD spectrum dementia. These data underscore the need to better understand the threshold at which leukoaraiosis affects and alters the phenotypic expression in insidious onset dementia syndromes. PMID:22843264

Music Perception in Dementia.

PubMed

Golden, Hannah L; Clark, Camilla N; Nicholas, Jennifer M; Cohen, Miriam H; Slattery, Catherine F; Paterson, Ross W; Foulkes, Alexander J M; Schott, Jonathan M; Mummery, Catherine J; Crutch, Sebastian J; Warren, Jason D

2017-01-01

Despite much recent interest in music and dementia, music perception has not been widely studied across dementia syndromes using an information processing approach. Here we addressed this issue in a cohort of 30 patients representing major dementia syndromes of typical Alzheimer's disease (AD, n = 16), logopenic aphasia (LPA, an Alzheimer variant syndrome; n = 5), and progressive nonfluent aphasia (PNFA; n = 9) in relation to 19 healthy age-matched individuals. We designed a novel neuropsychological battery to assess perception of musical patterns in the dimensions of pitch and temporal information (requiring detection of notes that deviated from the established pattern based on local or global sequence features) and musical scene analysis (requiring detection of a familiar tune within polyphonic harmony). Performance on these tests was referenced to generic auditory (timbral) deviance detection and recognition of familiar tunes and adjusted for general auditory working memory performance. Relative to healthy controls, patients with AD and LPA had group-level deficits of global pitch (melody contour) processing while patients with PNFA as a group had deficits of local (interval) as well as global pitch processing. There was substantial individual variation within syndromic groups. Taking working memory performance into account, no specific deficits of musical temporal processing, timbre processing, musical scene analysis, or tune recognition were identified. The findings suggest that particular aspects of music perception such as pitch pattern analysis may open a window on the processing of information streams in major dementia syndromes. The potential selectivity of musical deficits for particular dementia syndromes and particular dimensions of processing warrants further systematic investigation.

Atypical, slowly progressive behavioral variant frontotemporal dementia associated with C9ORF72 hexanucleotide expansion

PubMed Central

Khan, Baber K.; Yokoyama, Jennifer S.; Takada, Leonel T.; Sha, Sharon J.; Rutherford, Nicola. J.; Fong, Jamie C.; Karydas, Anna; Wu, Teresa; Ketelle, Robin; Baker, Matt C.; Hernandez, Mariely-Dejesus; Coppola, Giovanni; Geschwind, Daniel H.; Rademakers, Rosa; Lee, Suzee E.; Rosen, Howard J.; Rabinovici, Gil D.; Seeley, William; Rankin, Katherine P.; Boxer, Adam L.; Miller, Bruce L.

2012-01-01

Background Some patients meeting behavioral variant frontotemporal dementia (bvFTD) diagnostic criteria progress slowly and plateau at mild symptom severity. Such patients have mild neuropsychological and functional impairments, lack characteristic bvFTD brain atrophy, and have thus been referred to as bvFTD “phenocopies” or slowly progressive (bvFTD-SP). The few patients with bvFTD-SP that have been studied at autopsy have found no evidence of FTD pathology, suggesting that bvFTD-SP is neuropathologically distinct from other forms of FTD. Here, we describe two patients with bvFTD-SP with chromosome 9 open reading frame 72 (C9ORF72) hexanucleotide expansions. Methods Three hundred and eighty-four patients with FTD clinical spectrum and Alzheimer’s disease diagnoses were screened for C9ORF72 expansion. Two bvFTD-SP mutation carriers were identified. Neuropsychological and functional data, as well as brain atrophy patterns assessed using voxel-based morphometry (VBM), were compared with 44 patients with sporadic bvFTD and 85 healthy controls. Results Both patients were age 48 at baseline and met possible bvFTD criteria. In the first patient, VBM revealed thalamic and posterior insula atrophy. Over seven years, his neuropsychological performance and brain atrophy remained stable. In the second patient, VBM revealed cortical atrophy with subtle frontal and insular volume loss. Over two years, her neuropsychological and functional scores as well as brain atrophy remained stable. Conclusions C9ORF72 mutations can present with a bvFTD-SP phenotype. Some bvFTD-SP patients may have neurodegenerative pathology, and C9ORF72 mutations should be considered in patients with bvFTD-SP and a family history of dementia or motor neuron disease. PMID:22399793

Partial eNOS deficiency causes spontaneous thrombotic cerebral infarction, amyloid angiopathy and cognitive impairment.

PubMed

Tan, Xing-Lin; Xue, Yue-Qiang; Ma, Tao; Wang, Xiaofang; Li, Jing Jing; Lan, Lubin; Malik, Kafait U; McDonald, Michael P; Dopico, Alejandro M; Liao, Francesca-Fang

2015-06-24

Cerebral infarction due to thrombosis leads to the most common type of stroke and a likely cause of age-related cognitive decline and dementia. Endothelial nitric oxide synthase (eNOS) generates NO, which plays a crucial role in maintaining vascular function and exerting an antithrombotic action. Reduced eNOS expression and eNOS polymorphisms have been associated with stroke and Alzheimer's disease (AD), the most common type of dementia associated with neurovascular dysfunction. However, direct proof of such association is lacking. Since there are no reports of complete eNOS deficiency in humans, we used heterozygous eNOS(+/-) mice to mimic partial deficiency of eNOS, and determine its impact on cerebrovascular pathology and perfusion of cerebral vessels. Combining cerebral angiography with immunohistochemistry, we found thrombotic cerebral infarctions in eNOS(+/-) mice as early as 3-6 months of age but not in eNOS(+/+) mice at any age. Remarkably, vascular occlusions in eNOS(+/-) mice were found almost exclusively in three areas: temporoparietal and retrosplenial granular cortexes, and hippocampus this distribution precisely matching the hypoperfused areas identified in preclinical AD patients. Moreover, progressive cerebral amyloid angiopaphy (CAA), blood brain barrier (BBB) breakdown, and cognitive impairment were also detected in aged eNOS(+/-) mice. These data provide for the first time the evidence that partial eNOS deficiency results in spontaneous thrombotic cerebral infarctions that increase with age, leading to progressive CAA and cognitive impairments. We thus conclude that eNOS(+/-) mouse may represent an ideal model of ischemic stroke to address early and progressive damage in spontaneously-evolving chronic cerebral ischemia and thus, study vascular mechanisms contributing to vascular dementia and AD.

Social Ecological Perspectives of Tube-Feeding Older Adults with Advanced Dementia: A Systematic Literature Review.

PubMed

Douglas, Joy W; Lawrence, Jeannine C; Turner, Lori W

2017-01-01

Dementia is a progressive, debilitating disease that often results in weight loss, malnutrition, and dehydration. Feeding tubes are often prescribed; however, this practice can lead to complications. The purpose of this systematic review was to examine the use of feeding tubes in elderly demented patients from a social ecological perspective. Results indicated that family members often receive inadequate decision-making education. Many health care professionals lack knowledge of evidence-based guidelines pertaining to feeding tube use. Organizational and financial reimbursement structures influence feeding tube use. Feeding practices for patients with advanced dementia is a complex issue, warranting approaches that target each level of the Social Ecological Model.

Improvements in Limb Kinetic Apraxia by Repetition of a Newly Designed Facilitation Exercise in a Patient with Corticobasal Degeneration

ERIC Educational Resources Information Center

Kawahira, Kazumi; Noma, Tomokazu; Iiyama, Junichi; Etoh, Seiji; Ogata, Atsuko; Shimodozono, Megumi

2009-01-01

Corticobasal degeneration is a progressive neurological disorder characterized by a combination of parkinsonism and cortical dysfunction such as limb kinetic apraxia, alien limb phenomenon, and dementia. To study the effect of repetitive facilitation exercise (RFE) in a patient with corticobasal degeneration, we used a newly designed facilitation…

White matter disease independently predicts progression from mild cognitive impairment to Alzheimer's disease in a clinic cohort.

PubMed

Prasad, Kalpana; Wiryasaputra, Lynn; Ng, Amanda; Kandiah, Nagaendran

2011-01-01

The contribution of vascular pathology to the rate of progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) remains unclear. To ascertain the relative roles of cerebral white matter disease and medial temporal atrophy (MTA) in predicting progression from MCI to AD. MCI patients with baseline MRI and ≥18 months of longitudinal follow-up were evaluated. DSM-IV-TR criteria were used to diagnose conversion to dementia. MTA and white matter hyperintensity (WMH) were quantified using the Scheltens scale and modified Fazekas scale. Of a total of 171 MCI patients, 79 patients with baseline MRI and longitudinal follow-up were studied. Twenty-three MCI patients who progressed to dementia (MCI-P) were identified corresponding to a 19.4% annual risk of conversion. In MCI-P patients, the mean Mini-Mental State Examination and Montreal Cognitive Assessment decline was 1.3 and 2.9 points, respectively. MTA, periventricular WMH and deep subcortical WMH were significantly greater in the MCI-P cohort. WMH was found to predict MCI-P with an odds ratio of 7.69 (p = 0.03). MTA and deep subcortical WMH independently predict conversion from MCI to AD. Optimization of vascular risk factors among patients with MCI can potentially reduce the conversion from MCI to AD. Copyright © 2011 S. Karger AG, Basel.

State Dementia Plans and the Alzheimer's Disease Movement: Framing Diagnosis, Prognosis, and Motivation.

PubMed

Arbogast, Charlotte E; Welleford, E Ayn; Netting, F Ellen

2017-07-01

An interpretive analysis of 38 state dementia plans compares similarities and differences in diagnostic framing (problem identification/trends/issues), prognosis framing (addressing the problem), and motivational framing (calls for action) across plans. In framing diagnosis, only 6 plans used dementia alone in their titles. In framing prognosis and the subsequent call to action, state plans were consistent in their dire prognostications about the progressive and fatal consequences of the disease with a primary focus on the cost. Motivational language mirrored that of the Alzheimer's Disease (AD) Movement, from raising awareness to using inflammatory words to incite action. The language used set up the frame for clinical interventions that may not distinguish between types of dementia and could undercut the provision of person-centered care, shifts the victimization focus from persons with AD to caregivers and ultimately the state, and may subintentionally reflect cultural biases.

Functional Network Disruption in the Degenerative Dementias

PubMed Central

Pievani, Michela; de Haan, Willem; Wu, Tao; Seeley, William W; Frisoni, Giovanni B

2011-01-01

Despite considerable advances toward understanding the molecular pathophysiology of the neurodegenerative dementias, the mechanisms linking molecular changes to neuropathology and the latter to clinical symptoms remain largely obscure. Connectivity is a distinctive feature of the brain and the integrity of functional network dynamics is critical for normal functioning. A better understanding of network disruption in the neurodegenerative dementias may help bridge the gap between molecular changes, pathology and symptoms. Recent findings on functional network disruption as assessed with “resting-state” or intrinsic connectivity fMRI and EEG/MEG have shown distinct patterns of network disruption across the major neurodegenerative diseases. These network abnormalities are relatively specific to the clinical syndromes, and in Alzheimer's disease and frontotemporal dementia network disruption tracks the pattern of pathological changes. These findings may have a practical impact on diagnostic accuracy, allowing earlier detection of neurodegenerative diseases even at the pre-symptomatic stage, and tracking of disease progression. PMID:21778116

Functional correlates of musical and visual ability in frontotemporal dementia.

PubMed

Miller, B L; Boone, K; Cummings, J L; Read, S L; Mishkin, F

2000-05-01

The emergence of new skills in the setting of dementia suggests that loss of function in one brain area can release new functions elsewhere. To characterise 12 patients with frontotemporal dementia (FTD) who acquired, or sustained, new musical or visual abilities despite progression of their dementia. Twelve patients with FTD who acquired or maintained musical or artistic ability were compared with 46 patients with FTD in whom new or sustained ability was absent. The group with musical or visual ability performed better on visual, but worse on verbal tasks than did the other patients with FTD. Nine had asymmetrical left anterior dysfunction. Nine showed the temporal lobe variant of FTD. Loss of function in the left anterior temporal lobe may lead to facilitation of artistic or musical skills. Patients with the left-sided temporal lobe variant of FTD offer an unexpected window into the neurological mediation of visual and musical talents.

Prevalence of Sinusitis Detected by Magnetic Resonance Imaging in Subjects with Dementia or Alzheimer's Disease.

PubMed

Yasue, Minori; Sugiura, Saiko; Uchida, Yasue; Otake, Hironao; Teranishi, Masaaki; Sakurai, Takashi; Toba, Kenji; Shimokata, Hiroshi; Ando, Fujiko; Otsuka, Rei; Nakashima, Tsutomu

2015-01-01

It has been reported that periodontitis is associated with Alzheimer's disease. However, the association between paranasal sinusitis and Alzheimer's disease has not been studied, although olfactory dysfunction frequently precedes the progress of dementia or Alzheimer's disease. We studied 783 patients (283 men, 500 women; mean age 77.0 ± 7.9 years) who visited the Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, and 2139 control subjects who participated in a population-based study conducted by the National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA) in Japan. Sinusitis was evaluated using magnetic resonance imaging (MRI) according to the Lund-Mackay scoring system. A sinusitis score of ≥ 4 was classified as positive and a score of ≤ 3 was classified as negative. The prevalence of positive sinusitis was 6.3% in patients with a mini-mental state examination (MMSE) score of < 24 (n = 507), and 5.7% in patients with Alzheimer's disease (n = 280). The rate of positive sinusitis was7.2% in the control group. The prevalence of sinusitis was not significantly different between normal controls and patients with dementia or Alzheimer's disease after adjustments for age and sex. The rate of positive sinusitis was higher in male than in female subjects in both groups. The prevalence of sinusitis in patients with Alzheimer's disease or dementia was not higher than in the general population.

Pneumocystis Infections: MedlinePlus Health Topic

MedlinePlus

... progressive dementia in a patient... Article: Pneumocystis and interactions with host immune receptors. ... AIDSinfo (Department of Health and Human Services) Also in Spanish Centers for Disease Control ...

Progranulin: a new avenue towards the understanding and treatment of neurodegenerative disease.

PubMed

Chitramuthu, Babykumari P; Bennett, Hugh P J; Bateman, Andrew

2017-12-01

Progranulin, a secreted glycoprotein, is encoded in humans by the single GRN gene. Progranulin consists of seven and a half, tandemly repeated, non-identical copies of the 12 cysteine granulin motif. Many cellular processes and diseases are associated with this unique pleiotropic factor that include, but are not limited to, embryogenesis, tumorigenesis, inflammation, wound repair, neurodegeneration and lysosome function. Haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to frontotemporal lobar degeneration, a progressive neuronal atrophy that presents in patients as frontotemporal dementia. Frontotemporal dementia is an early onset form of dementia, distinct from Alzheimer's disease. The GRN-related form of frontotemporal lobar dementia is a proteinopathy characterized by the appearance of neuronal inclusions containing ubiquitinated and fragmented TDP-43 (encoded by TARDBP). The neurotrophic and neuro-immunomodulatory properties of progranulin have recently been reported but are still not well understood. Gene delivery of GRN in experimental models of Alzheimer's- and Parkinson's-like diseases inhibits phenotype progression. Here we review what is currently known concerning the molecular function and mechanism of action of progranulin in normal physiological and pathophysiological conditions in both in vitro and in vivo models. The potential therapeutic applications of progranulin in treating neurodegenerative diseases are highlighted. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of Acetylcholinesterase Inhibitors on Nutritional Status in Elderly Patients with Dementia: A 6-month Follow-up Study.

PubMed

Soysal, P; Isik, A T

2016-04-01

Nutritional status is one of the factors that affects disease progression, morbidity and mortality in elderly patients with dementia. The present study aimed to evaluate the effect of acetylcholinesterase inhibitor (AchEI) therapy on nutritional status and food intake in the elderly. Newly diagnosed patients with dementia, who underwent comprehensive geriatric assessment (CGA) and were followed at regular intervals, were retrospectively evaluated. A total of 116 patients, who began to receive AchEI therapy and completed 6-month follow-up period under this treatment, were enrolled in the study. Socio-demographic characteristics and data on comorbidity, polypharmacy, cognitive function, depression, activities of daily living and nutritional status (weight, Body Mass Index (BMI), Mini Nutritional Assessment (MNA)-Short Form) were recorded. The mean age of the patients was 78.0±8.9 years. There was no significant difference between baseline and 6-month BMI, weight and MNA scores of dementia patients who received AchEI therapy (p>0.05). With regard to the relation between changes in BMI, weight and MNA on the 6th month versus baseline, and donepezil, rivastigmine and galantamine therapies, no difference was determined (p>0.05). However, no worsening in food intake was observed (kappa: 0.377). When the effects of each AchEI on food intake were compared, food intake in rivastigmine treated patients was not decreased as much as it was in galantamine or donepezil treated patients (p<0.05). AchEI therapy has no unfavorable effect on nutritional status or weight in elderly patients with different types of dementia, but it seems that food intake is better in those treated by rivastigmine patch.

The stages of driving cessation for people with dementia: needs and challenges.

PubMed

Liddle, Jacki; Bennett, Sally; Allen, Shelley; Lie, David C; Standen, Bradene; Pachana, Nancy A

2013-12-01

The impact of dementia on safe driving is well recognized and is generally accepted that all people with dementia are likely to need to cease driving at some stage in the disease process. Both driving and driving cessation can have poor outcomes for people with dementia and their caregivers in terms of health, safety, community access, and well-being. Although approaches to facilitate better outcomes from driving cessation are being developed, the processes of driving cessation for people with dementia are still not fully understood. Within a descriptive phenomenological framework, semi-structured interviews were undertaken with key stakeholders, including retired drivers with dementia, family members, and health professionals. Findings from four retired drivers with dementia, 11 caregivers, and 15 health professionals characterized driving cessation for people with dementia as a process with three stages and associated challenges and needs. The early stage involved worried waiting, balancing safety with impending losses, and the challenge of knowing when to stop. The crisis stage involved risky driving or difficult transportation, acute adjustment to cessation and life without driving, and relationship conflict. The post-cessation stage was described as a long journey with ongoing battles and adjustments as well as decreased life space, and was affected by the disease progression and the exhaustion of caregiver. The concept of stages of driving cessation for people with dementia could be used to develop new approaches or adapt existing approaches to driving cessation. Interventions would need to be individualized, optimally timed, and address grief, explore realistic alternative community access, and simultaneously maintain key relationships and provide caregiver support.

Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

PubMed

Sun, Miao-Kun

2017-10-16

As the human lifespan increases, the number of people affected by age-related dementia is growing at an epidemic pace. Vascular pathology dramatically affects cognitive profiles, resulting in dementia and cognitive impairment. While vascular dementia itself constitutes a medical challenge, hypoperfusion/vascular risk factors enhance amyloid toxicity and other memory-damaging factors and hasten Alzheimer's disease (AD) and other memory disorders' progression, as well as negatively affect treatment outcome. Few therapeutic options are, however, currently available to improve the prognosis of patients with vascular dementia and cognitive impairment, mixed AD dementia with vascular pathology, or other memory disorders. Emerging evidence, however, indicates that, like AD and other memory disorders, synaptic impairment underlies much of the memory impairment in the cognitive decline of vascular cognitive impairment and vascular dementia. Effective rescues of the memory functions might be achieved through synaptic and memory therapeutics, targeting distinct molecular signaling pathways that support the formation of new synapses and maintaining their connections. Potential therapeutic agents include: 1) memory therapeutic agents that rescue synaptic and memory functions after the brain insults; 2) anti-pathologic therapeutics and an effective management of vascular risk factors; and 3) preventative therapeutic agents that achieve memory therapy through functional enhancement. Their development and potential as clinically effective memory therapeutics for vascular cognitive impairment and dementia are discussed in this review. These therapeutic agents are also likely to benefit patients with AD and/or other types of memory disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Montefiore-Einstein Center for the Aging Brain: Preliminary Data.

PubMed

Verghese, Joe; Malik, Rubina; Zwerling, Jessica

2016-11-01

Given the multifaceted nature of dementia care management, an interdisciplinary comprehensive clinical approach is necessary. We describe our one-year experience with outpatient based dementia care at the Montefiore-Einstein Center for the Aging Brain (CAB) involving an multispecialty team of geriatricians, neurologists, and neuropsychologists, supported by geriatric psychiatrists, physiatrists, and social services. The goals of the CAB is to maximize dementia outcomes, including regular monitoring of patient's health and cognition, education and support to patients, their families and caregivers; initiation of pharmacological and non-pharmacological treatments as appropriate, and the facilitation of access to clinical trials. The CAB follows a consultative model where patients referred to the center receive a comprehensive three step evaluation and management plan from Geriatric, Neuropsychology and Neurology specialists that is shared with patient, caregivers and primary care physicians. Of the 366 patients seen for cognitive complaints in our first year, 71% were women with a mean age of 74 years. Self-identified ethnicity of patients included Caucasian (26%), African-American (25%), Hispanic (18%) and multiracial (5%). Common final diagnoses assigned at the CAB included mild cognitive impairment syndromes (31%), Alzheimer's disease (20%), mixed dementia (11%), vascular dementia (9%), Frontotemporal dementia (4%) and dementia with Lewy bodies (4%). Our one-year progress report indicates that an interdisciplinary clinical dementia care model is feasible in the outpatient setting as well as highly accepted by patients, caregivers and referring physicians. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Tracking early decline in cognitive function in older individuals at risk for Alzheimer's disease dementia: the Alzheimer's Disease Cooperative Study Cognitive Function Instrument

PubMed Central

Amariglio, Rebecca E.; Donohue, Michael C.; Marshall, Gad A.; Rentz, Dorene M.; Salmon, David P.; Ferris, Steven H.; Karantzoulis, Stella; Aisen, Paul S.; Sperling, Reisa A.

2015-01-01

Importance Several large-scale Alzheimer's disease (AD) secondary prevention trials have begun to target individuals at the preclinical stage. The success of these trials depends on validated outcome measures that are sensitive to early clinical progression in individuals who are initially asymptomatic. Objective To investigate the utility of the Cognitive Function Instrument (CFI) to track early changes in cognitive function in older individuals without clinical impairment at baseline. Design, Setting, and Participants Longitudinal study over the course of 48 months at participating Alzheimer's Disease Cooperative Study (ADCS) sites. The study included 468 healthy older individuals (Clinical Dementia Rating Scale [CDR] Global = 0, above cut-off on modified Mini-Mental State Exam and Free and Cued Selective Reminding Test) (mean age= 79.4 years ±3.6). All subjects and their study partners completed the Self and Partner CFI annually. Subjects also underwent concurrent annual neuropsychological assessment and apolipoprotein E (APOE) genotyping. Main outcomes and measures Comparison of CFI scores between clinical progressors (Clinical Dementia Rating Scale [CDR] ≥ 0.5) and non-progressors (CDR remained = 0), as well as between APOE ε4 carriers and non-carriers were performed. Correlations of change between the CFI and neuropsychological performance were assessed longitudinally. Results At 48 months, group differences between clinical progressors and non-progressors were significant for CFI Self, CFI Partner, and CFI Self+Partner total scores. At month 48, APOE ε4 carriers showed greater progression than non-carriers on CFI Partner and CFI Self+Partner scores. Both CFI Self and CFI Partner scores were associated with longitudinal cognitive decline, although findings suggest self report may be more accurate early in the process, whereas accuracy of partner report improves when there is progression to cognitive impairment. Conclusions and Relevance Demonstrating long-term clinical benefit will be critical for the success of recently launched secondary prevention trials. The CFI appears to be a brief, yet informative potential outcome measure that provides insight into functional abilities at the earliest stages of disease. PMID:25706191

Ageing and dementia in low and middle income countries-Using research to engage with public and policy makers.

PubMed

Prince, Martin; Acosta, Daisy; Albanese, Emiliano; Arizaga, Raul; Ferri, Cleusa P; Guerra, Mariella; Huang, Yueqin; Jacob, K S; Jimenez-Velazquez, Ivonne Z; Rodriguez, Juan Llibre; Salas, Aquiles; Sosa, Ana Luisa; Sousa, Renata; Uwakwe, Richard; van der Poel, Rikus; Williams, Joseph; Wortmann, Marc

2008-08-01

While two thirds of the 24 million people with dementia worldwide live in low and middle income countries, very little research has been conducted to support policy making in these regions. Among the non-communicable diseases, dementia (in common with other chronic NCDs linked more to long-term disability than to mortality) has been relatively under-prioritized. International agreements, plans and policy guidelines have called for an end to ageist discrimination and a focus upon reducing disadvantage arising from poverty and the consequences of ill health. Social protection, access to good quality age-appropriate healthcare and addressing the problem of disability are all key issues. However, as yet, little progress has been made in addressing these concerns. In this review we outline the current international policy agenda for older individuals, and its specific relevance to those with dementia and other disabling non-communicable diseases. We consider the potential for epidemiological research to raise awareness, refine the policy agenda, and promote action, using the example of the dissemination strategy developed by the 10/66 Dementia Research Group.

[An Autopsy Case of Globular Glial Tauopathy Presenting with Amyotrophic Lateral Sclerosis with Dementia].

PubMed

Sasaki, Ryogen; Mimuro, Maya; Kokubo, Yasumasa; Imai, Hiroshi; Yoshida, Mari; Tomimoto, Hidekazu

2016-08-01

We report an autopsy case of globular glial tauopathy (GGT) presenting clinically with amyotrophic lateral sclerosis (ALS) with dementia. A 79-year-old female developed weakness in the right upper limb, which progressed gradually. She developed apathy and speech disorder at 80 years of age. On neurological examination, she showed signs of upper and lower motor neuron disorder and dementia, but no extrapyramidal signs. The clinical diagnosis was ALS with dementia. The autopsy revealed left predominant marked atrophy of the frontal lobe due to severe neuronal loss and Gliosis. Immunohistochemistry using anti-4-repeat tau antibody revealed numerous globular glial inclusions. Severe neurodegeneration in the primary motor cortex and corticospinal tract was observed. There were distinctive tau-positive inclusions in both Betz and anterior horn cells. TDP-43-positive inclusions in motor neurons were not detected. Sequence analysis of the tau gene revealed no mutations in exons 1-5, 7, 9-13, or the adjacent intronic sequences. GGT can cause a clinical phenotype of ALS with dementia. (Received December 28, 2015; Accepted February 23, 2016; Published August 1, 2016).

Ageing and dementia in low and middle income countries - Using research to engage with public and policy makers

PubMed Central

Prince, Martin; Acosta, Daisy; Albanese, Emiliano; Arizaga, Raul; Ferri, Cleusa P.; Guerra, Mariella; Huang, Yueqin; Jacob, Ks; Jimenez-Velazquez, Ivonne Z.; Rodriguez, Juan Llibre; Salas, Aquiles; Sosa, Ana Luisa; Sousa, Renata; Uwakwe, Richard; Van Der Poel, Rikus; Williams, Joseph; Wortmann, Marc

2008-01-01

Abstract While two thirds of the 24 million people with dementia worldwide live in low and middle income countries, very little research has been conducted to support policy making in these regions. Among the non-communicable diseases, dementia (in common with other chronic NCDs linked more to long-term disability than to mortality) has been relatively under-prioritized. International agreements, plans and policy guidelines have called for an end to ageist discrimination and a focus upon reducing disadvantage arising from poverty and the consequences of ill health. Social protection, access to good quality age-appropriate healthcare and addressing the problem of disability are all key issues. However, as yet, little progress has been made in addressing these concerns. In this review we outline the current international policy agenda for older individuals, and its specific relevance to those with dementia and other disabling non-communicable diseases. We consider the potential for epidemiological research to raise awareness, refine the policy agenda, and promote action, using the example of the dissemination strategy developed by the 10/66 Dementia Research Group. PMID:18925482

Neuropsychological study of amyotrophic lateral sclerosis and parkinsonism-dementia complex in Kii peninsula, Japan

PubMed Central

2014-01-01

Background The Kii peninsula of Japan is one of the foci of amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS/PDC) in the world. The purpose of this study is to clarify the neuropsychological features of the patients with ALS/PDC of the Kii peninsula (Kii ALS/PDC). Methods The medical interview was done on 13 patients with Kii ALS/PDC, 12 patients with Alzheimer’s disease, 10 patients with progressive supranuclear palsy, 10 patients with frontotemporal lobar degeneration and 10 patients with dementia with Lewy bodies. These patients and their carer/spouse were asked to report any history of abulia-apathy, hallucination, personality change and other variety of symptoms. Patients also underwent brain magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and neuropsychological tests comprising the Mini Mental State Examination, Raven’s Colored Progressive Matrices, verbal fluency, and Paired-Associate Word Learning Test and some of them were assessed with the Frontal Assessment Battery (FAB). Results All patients with Kii ALS/PDC had cognitive dysfunction including abulia-apathy, bradyphrenia, hallucination, decrease of extraversion, disorientation, and delayed reaction time. Brain MRI showed atrophy of the frontal and/or temporal lobes, and SPECT revealed a decrease in cerebral blood flow of the frontal and/or temporal lobes in all patients with Kii ALS/PDC. Disorientation, difficulty in word recall, delayed reaction time, and low FAB score were recognized in Kii ALS/PDC patients with cognitive dysfunction. Conclusions The core neuropsychological features of the patients with Kii ALS/PDC were characterized by marked abulia-apathy, bradyphrenia, and hallucination. PMID:25041813

Big data and data repurposing - using existing data to answer new questions in vascular dementia research.

PubMed

Doubal, Fergus N; Ali, Myzoon; Batty, G David; Charidimou, Andreas; Eriksdotter, Maria; Hofmann-Apitius, Martin; Kim, Yun-Hee; Levine, Deborah A; Mead, Gillian; Mucke, Hermann A M; Ritchie, Craig W; Roberts, Charlotte J; Russ, Tom C; Stewart, Robert; Whiteley, William; Quinn, Terence J

2017-04-17

Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group's experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9 th International Congress on Vascular Dementia (Ljubljana, 16-18 th October 2015). We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use.

Modeling the Distress of Spousal Caregivers of People with Dementia.

PubMed

Wawrziczny, Emilie; Berna, Guillaume; Ducharme, Francine; Kergoat, Marie-Jeanne; Pasquier, Florence; Antoine, Pascal

2017-01-01

The progressive mobilization of spouse caregivers who take care of a person with dementia (PWD) can lead to situations of distress. The current study sought to investigate the influence of the characteristics of the caregiving context on spousal caregiver distress. 125 spousal caregivers participated in this study. The characteristics of the caregiving context were assessed using questionnaires. We examined a moderated-mediator model (Step 1) in which we hypothesized that PWD and caregiver characteristics and dyadic determinants contribute to spousal caregiver distress. This model was compared based on the age at onset of the disease and the gender of the caregiver (Step 2). The model revealed that poor self-rated health and a lack of family support accentuated spousal caregiver distress, whereas the feeling of being prepared and level of confidence decreased spousal caregiver distress. Moreover, the quality of couple adjustment affected spousal caregiver distress, and this effect was mediated by the severity of the PWD's symptoms. Regarding the age at onset of the disease, the path between Couple Adjustment and the Care recipient's impairments was more important for caregivers of person with early-onset dementia (PEOD). Female caregivers who reported poor self-rated health experienced greater distress. It would be interesting to create a support program that would incorporate these three areas of intervention regarding the progression of the disease: first, "preparedness modules"; second, "dyadic modules" (especially for caregivers of PEOD); and third, "family modules". Specific attention should be given to female caregivers who report poor self-rated health.

Trajectories of Behavioural Disturbances Across Dementia Types.

PubMed

Linds, Alexandra B; Kirstein, Alana B; Freedman, Morris; Verhoeff, Nicolaas P L G; Wolf, Uri; Chow, Tiffany W

2015-11-01

To replicate a previous finding that the trajectory of the Neuropsychiatric Inventory (NPI) shifts in the sixth year of behavioural variant frontotemporal dementia (bvFTD). We evaluated longitudinal tracking with both the Frontal Behavioural Inventory (FBI) and NPI, comparing bvFTD against other dementias. Chart reviews over two to five years for patients with bvFTD (n=30), primary progressive aphasia (PPA, n=13) and Alzheimer's disease (AD, n=118) at an urban Canadian tertiary clinic specializing in dementia. Linear regressions of the longitudinal data tested predictors of annualized rates of change (ROC) in NPI and FBI total and subscales for apathy and disinhibition among dementia groups. The mode of the overall sample for the most advanced duration of illness observed was 5 years, with the median at 7 years. We did not find a crescendo-decrescendo pattern in scores although, for bvFTD and AD, high initial scores correlated with ensuing downward ROCs on the NPI and FBI. Educational level showed an influence on disinhibition ROCs. The FBI was no more revealing than the NPI for apathy and disinhibition scores in these dementias. A cognitive reserve effect on behavioural disturbance was supported but it may take longer than our 4 years of observing the clinical sample to record inflection points in the behavioural and psychiatric symptoms seen in bvFTD. The current data only imply that both apathy and disinhibition will diminish over the course of dementia.

Dementia-friendly communities: challenges and strategies for achieving stakeholder involvement.

PubMed

Heward, Michelle; Innes, Anthea; Cutler, Clare; Hambidge, Sarah

2017-05-01

Dementia-friendly communities (DFCs) are a UK policy initiative that aims to enable people with dementia to feel supported and included within their local community. Current approaches to DFC creation rely on stakeholder involvement, often requiring volunteer assistance. There is though a lack of evidence that examines the reality of achieving this. This paper critically assesses the challenges and strategies for achieving stakeholder involvement in DFCs. The evidence base is drawn from an inter-agency project funded by the National Health Service in the South of England where seven DFCs were developed by steering group partners and four part-time project workers (PWs). Data from the independent evaluation undertaken in the first year (2013-2014) of the project were analysed: 14 semi-structured interviews and a focus group examined PWs' experiences; while progress and key milestones are determined from monthly progress forms, good news stories, locality steering group minutes and press releases. Analysis was undertaken using a directed content analysis method, whereby data content for each locality was matched to the analytical framework that was drawn from Alzheimer's Society guidance. Challenges to achieving stakeholder involvement were identified as: establishing networks and including people representative of the local community; involving people affected by dementia; and gaining commitment from organisations. Strategies for achieving stakeholder involvement were recognised as: a sustainable approach; spreading the word; and sharing of ideas. By highlighting these challenges and the approaches that have been used within communities to overcome them, these findings form the foundation for the creation of DFC initiatives that will become embedded within communities. Stakeholder involvement is unpredictable and changeable; therefore, reliance on this approach questions the long-term sustainability of DFCs, and must be considered in future policies designed to enhance quality of life for people affected by dementia. © 2016 John Wiley & Sons Ltd.

Degradation of cognitive timing mechanisms in behavioural variant frontotemporal dementia

PubMed Central

Henley, Susie M.D.; Downey, Laura E.; Nicholas, Jennifer M.; Kinnunen, Kirsi M.; Golden, Hannah L.; Buckley, Aisling; Mahoney, Colin J.; Crutch, Sebastian J.

2014-01-01

The current study examined motor timing in frontotemporal dementia (FTD), which manifests as progressive deterioration in social, behavioural and cognitive functions. Twenty-patients fulfilling consensus clinical criteria for behavioural variant FTD (bvFTD), 11 patients fulfilling consensus clinical criteria for semantic-variant primary progressive aphasia (svPPA), four patients fulfilling criteria for nonfluent/agrammatic primary progressive aphasia (naPPA), eight patients fulfilling criteria for Alzheimer׳s disease (AD), and 31 controls were assessed on both an externally- and self-paced finger-tapping task requiring maintenance of a regular, 1500 ms beat over 50 taps. Grey and white matter correlates of deficits in motor timing were examined using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). bvFTD patients exhibited significant deficits in aspects of both externally- and self-paced tapping. Increased mean inter-response interval (faster than target tap time) in the self-paced task was associated with reduced grey matter volume in the cerebellum bilaterally, right middle temporal gyrus, and with increased axial diffusivity in the right superior longitudinal fasciculus, regions and tracts which have been suggested to be involved in a subcortical–cortical network of structures underlying timing abilities. This suggests that such structures can be affected in bvFTD, and that impaired motor timing may underlie some characteristics of the bvFTD phenotype. PMID:25447066

Treatment for Anomia in Semantic Dementia

PubMed Central

Henry, Maya L.; Beeson, Pélagie M.; Rapcsak, Steven Z.

2009-01-01

Anomia is a striking and consistent clinical feature of semantic dementia (SD), a progressive aphasia syndrome associated with focal cortical atrophy of the anterior temporal lobes. Word retrieval deficits in patients with SD have been attributed to the loss of conceptual knowledge, resulting in an impairment referred to as semantic anomia. Whereas an abundance of research has been dedicated to treatment for anomia in individuals with focal brain damage due to stroke, considerably less work has been done regarding treatment for patients with progressive language decline. The purpose of this article is to review the available literature concerning the nature and treatment of anomia in individuals with SD. Several studies have shown that new lexical learning remains possible in these patients. However, newly learned information is likely to be constrained by the learning context, and increased reliance on perceptual and autobiographical contextual information may be necessary to provide critical support for new vocabulary acquisition. There is also evidence suggesting that treatment may slow the progression of anomia over time, even affording some protective benefit to lexical items that are not yet lost. However, treatment efforts are likely to be most beneficial at early stages of the disease, when residual semantic knowledge as. well as relatively spared episodic memory may support new learning. PMID:18348092

FDG-PET in early AD diagnosis.

PubMed

Chew, Jessica; Silverman, Daniel H S

2013-05-01

FDG-PET is a valuable tool that will continue to aid in identifying AD in its prodromal and early dementia stages, distinguishing it from other causes of dementia, and tracking progression of the disease. As brain FDG-PET scans and well-trained readers of these scans are becoming more widely available to clinicians who are becoming more informed about the role FDG-PET can play in early AD diagnosis, its use is expected to increase. Copyright © 2013 Elsevier Inc. All rights reserved.

Association of Cerebrospinal Fluid Neurofilament Light Concentration With Alzheimer Disease Progression.

PubMed

Zetterberg, Henrik; Skillbäck, Tobias; Mattsson, Niklas; Trojanowski, John Q; Portelius, Erik; Shaw, Leslie M; Weiner, Michael W; Blennow, Kaj

2016-01-01

The extent to which large-caliber axonal degeneration contributes to Alzheimer disease (AD) progression is unknown. Cerebrospinal fluid (CSF) neurofilament light (NFL) concentration is a general marker of damage to large-caliber myelinated axons. To test whether CSF NFL concentration is associated with cognitive decline and imaging evidence of neurodegeneration and white matter change in AD. A commercially available immunoassay was used to analyze CSF NFL concentration in a cohort of patients with AD (n = 95) or mild cognitive impairment (MCI) (n = 192) and in cognitively normal individuals (n = 110) from the Alzheimer's Disease Neuroimaging Initiative. The study dates were January 2005 to December 2007. The NFL analysis was performed in November 2014. Correlation was investigated among baseline CSF NFL concentration and longitudinal cognitive impairment, white matter change, and regional brain atrophy within each diagnostic group. Cerebrospinal fluid NFL concentration (median [interquartile range]) was higher in the AD dementia group (1479 [1134-1842] pg/mL), stable MCI group (no progression to AD during follow-up; 1182 [923-1687] pg/mL), and progressive MCI group (MCI with progression to AD dementia during follow-up; 1336 [1061-1693] pg/mL) compared with control participants (1047 [809-1265] pg/mL) (P < .001 for all) and in the AD dementia group compared with the stable MCI group (P = .01). In the MCI group, a higher CSF NFL concentration was associated with faster brain atrophy over time as measured by changes in whole-brain volume (β = -4177, P = .003), ventricular volume (β = 1835, P < .001), and hippocampus volume (β = -54.22, P < .001); faster disease progression as reflected by decreased Mini-Mental State Examination scores (β = -1.077, P < .001) and increased Alzheimer Disease Assessment Scale cognitive subscale scores (β = 2.30, P < .001); and faster white matter intensity change (β = 598.7, P < .001). Cerebrospinal fluid NFL concentration is increased by the early clinical stage of AD and is associated with cognitive deterioration and structural brain changes over time. This finding corroborates the contention that degeneration of large-caliber axons is an important feature of AD neurodegeneration.

Roles, Responsibilities, and Relationships among Older Husbands Caring for Wives with Progressive Dementia and Other Chronic Conditions

ERIC Educational Resources Information Center

Sanders, Sara; Power, James

2009-01-01

Men are playing greater roles in the provision of care for older adults with chronic health conditions. Husbands, in particular, encounter many role transformations as they witness their wives grow in levels of dependence as a result of their illnesses. This qualitative study examines the changes that occurred in the roles, responsibilities, and…

Predictors of Cognitive and Functional Decline in Patients With Alzheimer Disease Dementia From Brazil.

PubMed

Oliveira, Fabricio F; Chen, Elizabeth S; Smith, Marilia C; Bertolucci, Paulo H F

2016-01-01

Little is known on how risk factors for Alzheimer disease (AD) dementia affect disease progression, much less for populations with low mean schooling, whereas the transcription of APOE may be regulated by nongenetic factors. In this 44-month cohort study, 214 consecutive outpatients with late-onset AD were assessed for rates of cognitive and functional decline by way of Clinical Dementia Rating and Mini-Mental State Examination (MMSE) scores, keeping blinded assessment of APOE haplotypes. Subjects were evaluated for sex, schooling, age of dementia onset, and cerebrovascular risk factors (including Framingham risk scores). Of the 214 patients, there were 146 (68.2%) women and 113 (52.8%) APOE4+ carriers. The mean age of AD onset was 73.4±6.5 years-old, negatively correlated with time to Clinical Dementia Rating >1.0 (β=-0.132; ρ<0.001), MMSE=20 (β=-0.105; ρ<0.001), and MMSE=15 (β=-0.124; ρ=0.003), more significantly for women and APOE4+ carriers. Mean schooling was 4.18±3.7 years, correlated with time to MMSE=20 and MMSE=15 for women and APOE4+ carriers. Body mass index was correlated with time to MMSE=20 only for men (ρ=0.006). The 10-year coronary heart disease risk was correlated with time to MMSE=20 only for APOE4+ carriers (ρ=0.015). These outcomes suggest interactions among genomic effects of cognitive reserve, cerebral perfusion, and hormonal changes over mechanisms of neurodegeneration.

Cholinesterase inhibitors from botanicals

PubMed Central

Ahmed, Faiyaz; Ghalib, Raza Murad; Sasikala, P.; Ahmed, K. K. Mueen

2013-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease, wherein a progressive loss of cholinergic synapses occurs in hippocampus and neocortex. Decreased concentration of the neurotransmitter, acetylcholine (ACh), appears to be critical element in the development of dementia, and the most appropriate therapeutic approach to treat AD and other form of dementia is to restore acetylcholine levels by inhibiting both major form of cholinesterase: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Consequently, researches have focused their attention towards finding cholinesterase inhibitors from natural products. A large number of such inhibitors have been isolated from medicinal plants. This review presents a comprehensive account of the advances in field of cholinesterase inhibitor phytoconstituents. The structures of some important phytoconstituents (collected through www.Chemspider.com) are also presented and the scope for future research is discussed. PMID:24347920

Various MRS application tools for Alzheimer disease and mild cognitive impairment.

PubMed

Gao, F; Barker, P B

2014-06-01

MR spectroscopy is a noninvasive technique that allows the detection of several naturally occurring compounds (metabolites) from well-defined regions of interest within the human brain. Alzheimer disease, a progressive neurodegenerative disorder, is the most common cause of dementia in the elderly. During the past 20 years, multiple studies have been performed on MR spectroscopy in patients with both mild cognitive impairment and Alzheimer disease. Generally, MR spectroscopy studies have found decreased N-acetylaspartate and increased myo-inositol in both patients with mild cognitive impairment and Alzheimer disease, with greater changes in Alzheimer disease than in mild cognitive impairment. This review summarizes the information content of proton brain MR spectroscopy and its related technical aspects, as well as applications of MR spectroscopy to mild cognitive impairment and Alzheimer disease. While MR spectroscopy may have some value in the differential diagnosis of dementias and assessing prognosis, more likely its role in the near future will be predominantly as a tool for monitoring disease response or progression in treatment trials. More work is needed to evaluate the role of MR spectroscopy as a biomarker in Alzheimer disease and its relationship to other imaging modalities. © 2014 by American Journal of Neuroradiology.

Progressively Disrupted Brain Functional Connectivity Network in Subcortical Ischemic Vascular Cognitive Impairment Patients.

PubMed

Sang, Linqiong; Chen, Lin; Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Li, Chuanming; Qiu, Mingguo

2018-01-01

Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC > SIVCIND > SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p  < 0.01) mainly involved the orbitofrontal, parietal, and temporal cortices, as well as the basal ganglia. The brain connectivity network was progressively disrupted as cognitive impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.

Dementia with Lewy bodies in an elderly Greek male due to alpha-synuclein gene mutation.

PubMed

Morfis, Litsa; Cordato, Dennis John

2006-11-01

We report the case of an elderly man of Greek background who presented with progressive cognitive decline and motor parkinsonism on a background of a strong family history of Parkinson's disease. Associated symptoms included visual hallucinations, excessive daytime drowsiness, recurrent falls, orthostatic hypotension and urinary incontinence. His major clinical symptoms and signs fulfilled consensus criteria for a clinical diagnosis of dementia with Lewy bodies. An alpha-synuclein gene mutation analysis for the G209A substitution was positive. We conclude that the alpha-synuclein (G209A) gene mutation genotype should be considered in the differential diagnosis of dementia with Lewy bodies, particularly in patients with European ancestry and a family history of Parkinson's disease.

Behavioral and language variants of frontotemporal dementia: a review of key symptoms.

PubMed

Laforce, Robert

2013-12-01

While recent advances in the development of neuroimaging and molecular biomarkers for studying neurodegenerative conditions have revolutionized the field, dementia remains a clinical diagnosis. No component of the diagnostic process is more crucial than obtaining a good history. Getting to know the first manifestations of the disease, tracking their evolution and functional impact, combined with a targeted neurological examination, further guides differential diagnosis. This paper summarizes the key symptoms of the behavioral and language variants of frontotemporal dementia. The behavioral variant of frontotemporal dementia (bvFTD) is characterized by severe changes in behavior and personality such as disinhibition, apathy, loss of empathy, or stereotypic behavior, leading to a loss of social competence. Executive functions are impaired, while memory and visuospatial skills are relatively better preserved. By contrast, the language variants or primary progressive aphasias (PPAs) are marked by prominent language disturbances that can be subclassified into a non-fluent/agrammatic variant (naPPA), a semantic variant (svPPA), and a logopenic variant (lvPPA). Although combined characterization of clinical, imaging, biological and genetic biomarkers is essential to establish a detailed diagnosis of such heterogeneous conditions, the author emphasizes the importance of accurate recognition of key symptoms that can lead to better identification of underlying neuropathology and appropriate treatment approaches.

Factors Associated with Pneumonia-caused Death in Older Adults with Autopsy-confirmed Dementia

PubMed Central

Manabe, Toshie; Mizukami, Katsuyoshi; Akatsu, Hiroyasu; Hashizume, Yoshio; Ohkubo, Takayoshi; Kudo, Koichiro; Hizawa, Nobuyuki

2017-01-01

Objective A better understanding of risk factors for pneumonia-caused death may help to improve the clinical management of dementia. Methods A retrospective observational study was conducted by reviewing the medical charts and autopsy reports of 204 patients who were admitted to hospital, underwent a post-mortem examination, and who were neuropathologically diagnosed with dementia. The risk factors for pneumonia-caused death were examined both as underlying and immediate causes of death using logistic regression models. Results A high frequency of pneumonia-caused death was observed both in underlying- (37.3%) and immediate- (44.1%) cause of death, but varied according to the subtypes of dementia. The factors related to pneumonia-caused death (underlying) were subtypes of dementia; Alzheimer's disease (odds ratio [OR], 2.891; 95% confidence interval [CI], 1.459-5.730); argyrophilic grain disease (OR, 3.148; 95% CI, 0.937-10.577); and progressive supranuclear palsy (OR, 34.921; 95% CI, 3.826-318.775), dysphagia (OR, 2.045; 95% CI, 1.047-3.994), diabetes mellitus (OR, 3.084; 95% CI, 1.180-8.061) and conversely related with heart failure (OR, 0.149; 95% CI, 0.026-0.861). Factors relating to pneumonia-caused death (immediate) were incidence of pneumonia during hospitalizations (OR, 32.579; 95%CI, 4.308-246.370), gender-male (OR, 2.060; 95% CI, 1.098-3.864), and conversely related with malignant neoplasm (OR, 0.220; 95% CI, 0.058-0.840). Conclusion The different factors relating to the pneumonia-caused death were evaluated depending on whether pneumonia was the underlying- or immediate-cause of death. Strengthening clinical management on dysphagia and diabetes mellitus, and preventing incidence of pneumonia during hospitalization appear to be the important for the terminal stage of hospitalized patients with dementia. PMID:28420838

Factors Associated with Pneumonia-caused Death in Older Adults with Autopsy-confirmed Dementia.

PubMed

Manabe, Toshie; Mizukami, Katsuyoshi; Akatsu, Hiroyasu; Hashizume, Yoshio; Ohkubo, Takayoshi; Kudo, Koichiro; Hizawa, Nobuyuki

2017-01-01

Objective A better understanding of risk factors for pneumonia-caused death may help to improve the clinical management of dementia. Methods A retrospective observational study was conducted by reviewing the medical charts and autopsy reports of 204 patients who were admitted to hospital, underwent a post-mortem examination, and who were neuropathologically diagnosed with dementia. The risk factors for pneumonia-caused death were examined both as underlying and immediate causes of death using logistic regression models. Results A high frequency of pneumonia-caused death was observed both in underlying- (37.3%) and immediate- (44.1%) cause of death, but varied according to the subtypes of dementia. The factors related to pneumonia-caused death (underlying) were subtypes of dementia; Alzheimer's disease (odds ratio [OR], 2.891; 95% confidence interval [CI], 1.459-5.730); argyrophilic grain disease (OR, 3.148; 95% CI, 0.937-10.577); and progressive supranuclear palsy (OR, 34.921; 95% CI, 3.826-318.775), dysphagia (OR, 2.045; 95% CI, 1.047-3.994), diabetes mellitus (OR, 3.084; 95% CI, 1.180-8.061) and conversely related with heart failure (OR, 0.149; 95% CI, 0.026-0.861). Factors relating to pneumonia-caused death (immediate) were incidence of pneumonia during hospitalizations (OR, 32.579; 95%CI, 4.308-246.370), gender-male (OR, 2.060; 95% CI, 1.098-3.864), and conversely related with malignant neoplasm (OR, 0.220; 95% CI, 0.058-0.840). Conclusion The different factors relating to the pneumonia-caused death were evaluated depending on whether pneumonia was the underlying- or immediate-cause of death. Strengthening clinical management on dysphagia and diabetes mellitus, and preventing incidence of pneumonia during hospitalization appear to be the important for the terminal stage of hospitalized patients with dementia.

Self-Awareness and Self-Monitoring of Cognitive and Behavioral Deficits in Behavioral Variant Frontotemporal Dementia, Primary Progressive Aphasia and Probable Alzheimer’s Disease

PubMed Central

Banks, Sarah; Weintraub, Sandra

2008-01-01

Lack of insight is a core diagnostic criterion for behavioral variant frontotemporal dementia (bvFTD), and is believed to be intact in the early stages of primary progressive aphasia (PPA). In other neurological conditions, symptom-specific insight has been noted, with behavioral symptoms appearing especially vulnerable to reduced insight. Different components of insight, self-awareness and self-monitoring, are also often considered separate phenomena. The current study compared insight in patients with PPA, bvFTD, and probable Alzheimer’s disease (PrAD) and a group of cognitively intact control subjects. Additionally, differences in insight for the domains primarily affected by the three types of dementia, namely, Behavior, Naming, and Memory, were assessed, and self-awareness and self-monitoring were compared. A total of 55 participants were enrolled. Participants were asked to complete self-estimate scales demonstrating their perceived ability immediately prior to, and immediately following a test in each domain of interest. Results indicated that PPA and normal control groups performed very similarly on control (Weight and Eyesight) and cognitive domains, whereas bvFTD and PrAD patients were unable to accurately assess Memory. All three diagnostic groups failed to accurately assess their behavioral symptoms, suggesting that this domain is vulnerable to loss of insight across diagnoses. Naming ability, in contrast, was either accurately assessed or underestimated in all groups. Finally, there were no notable differences between self-awareness and self-monitoring, potential explanations for this are examined. PMID:18194832

Sarcopenia as a Predictor of Future Cognitive Impairment in Older Adults.

PubMed

Moon, J H; Moon, J H; Kim, K M; Choi, S H; Lim, S; Park, K S; Kim, K W; Jang, H C

2016-01-01

We investigated the association between the indices of sarcopenia and future risk of cognitive impairment in older adults. Community-based prospective cohort study. Community. A total of 297 participants aged ≥65 years without cognitive impairment at baseline (mean age, 71.9 ± 6.6 years; men:women, 158:139) and who underwent cognitive evaluation at the 5-year follow-up. Sarcopenia parameters including appendicular lean mass (ALM), handgrip strength, and the Short Physical Performance Battery (SPPB) score at baseline were compared according to the later progression of mild cognitive impairment (MCI) and/or dementia. The operational criteria suggested by the Foundation for the National Institutes of Health Sarcopenia Project were used. We performed multivariate logistic regression analysis to identify the independent indicators of the progression of cognitive impairment. Among the 297 participants, 242 (81.5%) remained cognitively normal (nonprogression group), whereas 55 (18.5%) showed progression of cognitive impairment (50 subjects (16.8%) to MCI and 5 subjects (1.7%) to dementia) (progression group). Compared with the nonprogression group, subjects in the progression group were older, had a lower educational level, and had lower physical function as assessed by the SPPB; a higher percentage were depressed. Other baseline markers of sarcopenia, including the ALM-to-body mass index ratio and handgrip strength did not differ significantly between the groups. The association between a low SPPB score (<9) and progression of cognitive impairment was maintained after adjustment for conventional risk factors for cognitive impairment (hazard ratio 2.222, 95% confidence interval 1.047-4.716, P = 0.038). Decreased physical performance, as assessed by the SPPB, but not other markers of sarcopenia, was independently associated with the risk of later cognitive impairment in older adults.

Lewy Body Dementias: Dementia With Lewy Bodies and Parkinson Disease Dementia

PubMed Central

Gomperts, Stephen N.

2016-01-01

ABSTRACT Purpose of Review: This article provides an overview of the clinical features, neuropathologic findings, diagnostic criteria, and management of dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), together known as the Lewy body dementias. Recent Findings: DLB and PDD are common, clinically similar syndromes that share characteristic neuropathologic changes, including deposition of α-synuclein in Lewy bodies and neurites and loss of tegmental dopamine cell populations and basal forebrain cholinergic populations, often with a variable degree of coexisting Alzheimer pathology. The clinical constellations of DLB and PDD include progressive cognitive impairment associated with parkinsonism, visual hallucinations, and fluctuations of attention and wakefulness. Current clinical diagnostic criteria emphasize these features and also weigh evidence for dopamine cell loss measured with single-photon emission computed tomography (SPECT) imaging and for rapid eye movement (REM) sleep behavior disorder, a risk factor for the synucleinopathies. The timing of dementia relative to parkinsonism is the major clinical distinction between DLB and PDD, with dementia arising in the setting of well-established idiopathic Parkinson disease (after at least 1 year of motor symptoms) denoting PDD, while earlier cognitive impairment relative to parkinsonism denotes DLB. The distinction between these syndromes continues to be an active research question. Treatment for these illnesses remains symptomatic and relies on both pharmacologic and nonpharmacologic strategies. Summary: DLB and PDD are important and common dementia syndromes that overlap in their clinical features, neuropathology, and management. They are believed to exist on a spectrum of Lewy body disease, and some controversy persists in their differentiation. Given the need to optimize cognition, extrapyramidal function, and psychiatric health, management can be complex and should be systematic. PMID:27042903

Right anterior temporal lobe dysfunction underlies theory of mind impairments in semantic dementia.

PubMed

Irish, Muireann; Hodges, John R; Piguet, Olivier

2014-04-01

Semantic dementia is a progressive neurodegenerative disorder characterized by the amodal and profound loss of semantic knowledge attributable to the degeneration of the left anterior temporal lobe. Although traditionally conceptualized as a language disorder, patients with semantic dementia display significant alterations in behaviour and socioemotional functioning. Recent evidence points to an impaired capacity for theory of mind in predominantly left-lateralized cases of semantic dementia; however, it remains unclear to what extent semantic impairments contribute to these deficits. Further the neuroanatomical signature of such disturbance remains unknown. Here, we sought to determine the neural correlates of theory of mind performance in patients with left predominant semantic dementia (n=11), in contrast with disease-matched cases with behavioural-variant frontotemporal dementia (n=10) and Alzheimer's disease (n=10), and healthy older individuals (n=14) as control participants. Participants completed a simple cartoons task, in which they were required to describe physical and theory of mind scenarios. Irrespective of subscale, patients with semantic dementia exhibited marked impairments relative to control subjects; however, only theory of mind deficits persisted when we covaried for semantic comprehension. Voxel-based morphometry analyses revealed that atrophy in right anterior temporal lobe structures, including the right temporal fusiform cortex, right inferior temporal gyrus, bilateral temporal poles and amygdalae, correlated significantly with theory of mind impairments in the semantic dementia group. Our results point to the marked disruption of cognitive functions beyond the language domain in semantic dementia, not exclusively attributable to semantic processing impairments. The significant involvement of right anterior temporal structures suggests that with disease evolution, the encroachment of pathology into the contralateral hemisphere heralds the onset of social cognitive deficits in this syndrome.

Evaluation of the Digital Alzheimer Center: Testing Usability and Usefulness of an Online Portal for Patients with Dementia and Their Carers.

PubMed

Hattink, Bart; Droes, Rose-Marie; Sikkes, Sietske; Oostra, Ellen; Lemstra, Afina W

2016-07-21

Dementia is a progressive and highly disabling neurodegenerative disease that will likely become highly prevalent in the future due to the globally aging population. To improve health care efficiency and quality for dementia care, eHealth could help with, for example, an online portal, such as the Digital Alzheimer Center (DAC) of the Vrije Universiteit Medical Center Amsterdam. It provides up-to-date disease information, peer-to-peer contact, and methods for contacting the hospital and health professionals. We aimed to investigate the usability and usefulness of the DAC for patients with dementia and carers to get insight into the feasibility and value of this eHealth app in dementia care and to recommend potential improvements. A descriptive study among patients, carers, and health care professionals was performed. Mixed methods were used, consisting of observations (n=10, 4 people with dementia, 6 carers), an online survey (n=287; 88 patients, 199 carers), and semistructured interviews (n=18; 6 patients, 6 carers, 6 health care professionals). During the observations, participants performed a set of five different prescribed tasks on the portal. Speed, number of errors, and navigation were noted. The online survey aimed to assess users' opinions on the portal's usability and usefulness. Semistructured interviews were conducted in a subsample of patients, carers, and health care professionals to gain more in-depth information. In the usability assessment, eight categories of errors were distinguished, of which three were of critical, two of medium, and three of low severity. In the survey, 45% (40/88) of the patients and 53% (105/199) of the carers indicated they used the portal. In all, 33% (12/36) of patients and 61% (62/102) of carers found it easy to learn to work with the portal. Most considered the DAC generally useful: 65% (17/26) of patients and 78% (67/86) of carers found the DAC useful, especially for understanding dementia (patients: 64%, 16/25; carers: 62%, 53/86). In the semistructured interviews, the site was generally rated positively on usability and usefulness and being well designed. People with dementia and carers indicated it helped them to understand and deal with dementia. To our knowledge, this is the first study investigating the usability and usefulness of an Internet portal especially designed for people with dementia and their carers. An online patient portal could be a useful means to help to support patients and carers in dealing with dementia: the majority of users positively evaluated usability and usefulness of the portal, and appreciated the information on it. However, only a minority of patients found it easy to work with the portal. Good design and frequent usability testing is essential to offer a good online portal.

Perception of emotion on faces in frontotemporal dementia and Alzheimer's disease: a longitudinal study.

PubMed

Lavenu, I; Pasquier, F

2005-01-01

Frontotemporal dementia (FTD) is a neurodegenerative disease characterised by behavioural disorders that suggest abnormalities of emotional processing. In a previous study, we showed that patients with Alzheimer's disease (AD) and with FTD were equally able to distinguish a face displaying affect from one not displaying affect. However, recognition of emotion was worse in patients with FTD than in patients with AD who did not differ significantly from controls. The aim of this study was to follow up the perception of emotions on faces in these patients. The poor perception of emotion could worsen differently in AD and in FTD, with the progression of atrophy of the amygdala, the anterior temporal cortex and the orbital frontal cortex, structures that are components of the brain's emotional processing systems. Patients with AD or with FTD had to recognise and point out the name of one of seven basic emotions (anger, disgust, happiness, fear, sadness, surprise and contempt) on a set of 28 faces presented on slides at the first visit and 3 years later. Thirty-seven patients (AD = 19, FTD = 18) performed the tests initially. The two patient groups did not differ for age, sex and duration of the disease. During the follow-up, 12 patients died, 4 patients refused to perform the tests and 8 could not be tested because of the severity of the disease. Finally, 7 patients with AD and 6 patients with FTD performed the two tests at a mean delay of 40 months. All patients with AD had worse results at follow-up on the perception of emotion despite the prescription of inhibitors of cholinesterase in all patients and of selective serotonin reuptake inhibitors (SSRIs) in 4 patients. As a whole, patients with FTD had better results in the second than in the first assessment (however, 3 of them had worse results) independently of the prescription of trazodone (n = 2), other SSRIs (n = 2), or the absence of treatment (n = 2), and of possible cognitive change. Recognition of emotion on faces in AD decreases with the progression of dementia and could be related to the progression of the degeneration of the structures implicated in emotional processing systems. Inconsistency of the results in FTD may be related to impulsiveness, lack of consistency of the patients and to heterogeneity of the progression of the lesions. Copyright 2005 S. Karger AG, Basel.

A taboo within a stigma? a qualitative study of managing incontinence with people with dementia living at home

PubMed Central

2011-01-01

Background Incontinence in people with dementia is one of the factors associated with the decision to move to a care home. Managing incontinence adds to carer burden and has been reported by family carers as more difficult to manage than behavioural symptoms. Active management strategies have been reported to be associated with less carer depression. The purpose of this study was to investigate carers' perceptions of the range of incontinence problems they helped their relative with and the strategies they employed to manage these. Methods Family carers of people with dementia living in their own homes were recruited through primary care, specialist community mental health services and voluntary organisations. Qualitative semi structured interviews were conducted either face to face or by telephone and thematically analysed. Results Thirty two carers were interviewed. They described a range of problems from supporting the person to remain independent in toileting, through to dealing with inappropriate behaviours, to containing and managing incontinence. All carers actively used problem solving strategies but sometimes these were not acceptable or understood by the person with dementia, particularly as the dementia progressed. Most carers reported protecting the person's dignity by not seeking health professionals help often until the point of a crisis. Once the carer has decided to seek help the responses from health professionals can be less than helpful, and carers report local health service policies on access to continence products to be inconsistent and often inappropriate to their circumstances. A few carers reported strategies for managing toileting and incontinence that have the potential for distress and harm to the person with dementia. Conclusions Primary care professionals could be more proactive in enquiry, repeated over time, about toileting and incontinence problems and in giving advice and information to reduce crisis and problems. PMID:22081876

SAIDO learning as a cognitive intervention for dementia care: a preliminary study.

PubMed

Kawashima, Ryuta; Hiller, Deborah Lewis; Sereda, Sheryl L; Antonczak, Michelle; Serger, Kara; Gannon, Denise; Ito, Shinji; Otake, Hiroshi; Yunomae, Daisaku; Kobayashi, Akihito; Muller, Christopher; Murata, Hiroyuki; FallCreek, Stephanie

2015-01-01

The purpose of this study was to examine the beneficial effects on cognitive function by a cognitive intervention program designed for dementia care called Learning Therapy in Japan and SAIDO Learning in the United States (hereinafter "SAIDO Learning," as appropriate). SAIDO Learning is a working memory training program that uses systematized basic problems in arithmetic and language, including reading aloud, as well as writing. Twenty-three nursing home residents with dementia were assigned as an intervention group, and another 24 people with dementia at another nursing home were assigned as a control group. Both nursing homes were operated by the same organization, and residents of both nursing homes received essentially the same nursing care. Thirteen and 6 subjects of the intervention and control groups, respectively, were clinically diagnosed as Alzheimer disease (AD). After the 6-month intervention, the participants with AD of the intervention group showed statistically significant improvement in cognitive function, as measured by the Mini-Mental State Examination (MMSE) compared with the control participants. In addition, post hoc analysis revealed that the Frontal Assessment Battery at Bedside (FAB) scores of the intervention group tended to improve after 6-month intervention. Based on MDS scores, improvements in total mood severity scores also were observed, but only in the intervention group of the participants with AD. These results suggest that SAIDO Learning is an effective cognitive intervention and is useful for dementia care. An additional outcome of this intervention, which has not yet been evaluated in detail, appears to be that it promotes greater positive engagement of a diversity of nursing home staff in the residents' individual progress and care needs. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Northern Manhattan Hispanic Caregiver Intervention Effectiveness Study: protocol of a pragmatic randomised trial comparing the effectiveness of two established interventions for informal caregivers of persons with dementia.

PubMed

Luchsinger, José A; Burgio, Louis; Mittelman, Mary; Dunner, Ilana; Levine, Jed A; Kong, Jian; Silver, Stephanie; Ramirez, Mildred; Teresi, Jeanne A

2016-11-25

The prevalence of dementia is increasing without a known cure, resulting in an increasing number of informal caregivers. Caring for a person with dementia results in increased stress and depressive symptoms. There are several behavioural interventions designed to alleviate stress and depressive symptoms in caregivers of persons with dementia with evidence of efficacy. Two of the best-known interventions are the New York University Caregiver Intervention (NYUCI) and the Resources for Enhancing Alzheimer's Caregivers Health (REACH). The effectiveness of the NYUCI and REACH has never been compared. There is also a paucity of data on which interventions are more effective in Hispanics in New York City. Thus, we proposed the Northern Manhattan Hispanic Caregiver intervention Effectiveness Study (NHiCE), a pragmatic clinical trial designed to compare the effectiveness of adaptations of the NYUCI and the REACH in informal Hispanic caregivers of persons with dementia in New York City. NHiCE is a 6-month randomised controlled trial comparing the effectiveness of adaptations of the NYUCI and REACH among 200 Hispanic informal adult caregivers of persons with dementia. The planned number of sessions of the NYUCI and REACH are similar. The primary outcome measures are changes from baseline to 6 months in the Zarit Caregiver Burden Scale and Geriatric Depression Scale. Our primary approach to analyses will be intent-to-treat. The primary analyses will use mixed random effects models, and a full information maximum likelihood approach, with sensitivity analyses using generalised estimating equation. NHiCE is approved by the Institutional Review Board of Columbia University Medical Center (protocol AAAM5150). A Data Safety Monitoring Board monitors the progress of the study. Dissemination will include reports of the characteristics of the study participants, as well as a report of the results of the clinical trial. NCT02092987, Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia.

PubMed

Fanganiello, R D; Kimonis, V E; Côrte, C C; Nitrini, R; Passos-Bueno, M R

2011-04-01

Inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD) is a progressive and usually misdiagnosed autosomal dominant disorder. It is clinically characterized by a triad of features: proximal and distal myopathy, early onset Paget disease of bone (PDB), and frontotemporal dementia (FTD). It is caused by missense mutations in the valosin-containing protein (VCP) gene. We describe here the clinical and molecular findings of the first Brazilian family identified with IBMPFD. Progressive myopathy affecting the limb girdles was detected by clinical examination followed by muscle biopsy and creatine kinase measurement. PDB was suggested after anatomopathological bone examination and FTD was diagnosed by clinical, neuropsychological and language evaluations. Brain magnetic resonance revealed severe atrophy of the anterior temporal lobes, including the hippocampi. A R93C mutation in VCP was detected by direct sequencing screening in subject W (age 62) and in his mother. Four more individuals diagnosed with "dementia" were reported in this family. We also present a comprehensive genotype-phenotype correlation analysis of mutations in VCP in 182 patients from 29 families described in the literature and show that while IBM is a conspicuously penetrant symptom, PDB has a lower penetrance when associated with mutations in the AAAD1 domain and FTD has a lower penetrance when associated with mutations in the Junction (L1-D1) domain. Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad.

Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer's disease.

PubMed

Jack, Clifford R; Wiste, Heather J; Vemuri, Prashanthi; Weigand, Stephen D; Senjem, Matthew L; Zeng, Guang; Bernstein, Matt A; Gunter, Jeffrey L; Pankratz, Vernon S; Aisen, Paul S; Weiner, Michael W; Petersen, Ronald C; Shaw, Leslie M; Trojanowski, John Q; Knopman, David S

2010-11-01

Biomarkers of brain Aβ amyloid deposition can be measured either by cerebrospinal fluid Aβ42 or Pittsburgh compound B positron emission tomography imaging. Our objective was to evaluate the ability of Aβ load and neurodegenerative atrophy on magnetic resonance imaging to predict shorter time-to-progression from mild cognitive impairment to Alzheimer's dementia and to characterize the effect of these biomarkers on the risk of progression as they become increasingly abnormal. A total of 218 subjects with mild cognitive impairment were identified from the Alzheimer's Disease Neuroimaging Initiative. The primary outcome was time-to-progression to Alzheimer's dementia. Hippocampal volumes were measured and adjusted for intracranial volume. We used a new method of pooling cerebrospinal fluid Aβ42 and Pittsburgh compound B positron emission tomography measures to produce equivalent measures of brain Aβ load from either source and analysed the results using multiple imputation methods. We performed our analyses in two phases. First, we grouped our subjects into those who were 'amyloid positive' (n = 165, with the assumption that Alzheimer's pathology is dominant in this group) and those who were 'amyloid negative' (n = 53). In the second phase, we included all 218 subjects with mild cognitive impairment to evaluate the biomarkers in a sample that we assumed to contain a full spectrum of expected pathologies. In a Kaplan-Meier analysis, amyloid positive subjects with mild cognitive impairment were much more likely to progress to dementia within 2 years than amyloid negative subjects with mild cognitive impairment (50 versus 19%). Among amyloid positive subjects with mild cognitive impairment only, hippocampal atrophy predicted shorter time-to-progression (P < 0.001) while Aβ load did not (P = 0.44). In contrast, when all 218 subjects with mild cognitive impairment were combined (amyloid positive and negative), hippocampal atrophy and Aβ load predicted shorter time-to-progression with comparable power (hazard ratio for an inter-quartile difference of 2.6 for both); however, the risk profile was linear throughout the range of hippocampal atrophy values but reached a ceiling at higher values of brain Aβ load. Our results are consistent with a model of Alzheimer's disease in which Aβ deposition initiates the pathological cascade but is not the direct cause of cognitive impairment as evidenced by the fact that Aβ load severity is decoupled from risk of progression at high levels. In contrast, hippocampal atrophy indicates how far along the neurodegenerative path one is, and hence how close to progressing to dementia. Possible explanations for our finding that many subjects with mild cognitive impairment have intermediate levels of Aβ load include: (i) individual subjects may reach an Aβ load plateau at varying absolute levels; (ii) some subjects may be more biologically susceptible to Aβ than others; and (iii) subjects with mild cognitive impairment with intermediate levels of Aβ may represent individuals with Alzheimer's disease co-existent with other pathologies.

Multiple Targets for the Management of Alzheimer's Disease.

PubMed

Ahmad, Syed Sayeed; Akhtar, Salman; Jamal, Qazi Mohammad Sajid; Rizvi, Syed Mohd Danish; Kamal, Mohammad A; Khan, M Kalim A; Siddiqui, Mohd Haris

2016-01-01

AD is a progressive and irreversible neurodegenerative disease and the most common cause of dementia in the elderly population. Βeta- amyloid cascade formation along with several cytoskeleton abnormalities succeeding to the hyperphosphorylation of microtubule-associated tau protein in neurons leads to the elicitation of several neurotoxic incidents. As an outcome of these phenomena, steady growth of dementia in aged population is becoming ubiquitous in both developed and developing countries. Thus, the key aspiration is to endow with stable daily life functionality to the person suffering from dementia and to cut down or slower the symptoms of disease leading to disruptive behavior. In sight of this, the proteins amyloid-beta, BACE-1, RAGE and AChE are being aimed for the treatment of AD successfully. Currently, there are several medicines for the treatment of AD under survey like Galangin, Cymserine, Tolserine, Bisnorcymserine and Huperzine A. The article emphasizes clinical and neurobiological aspects of AD. The purpose of this review article is to provide a brief introduction of AD along with the related concept of beta-secretase, beta amyloid and neurotransmitter in the progression of disease. In the present review, we summarize the available evidence on the new therapeutic approaches that target amyloid and neurotransmitter in the AD.

[Neuro-neutrophilic Disease and Dementia].

PubMed

Hisanaga, Kinya

2016-04-01

Neuro-neutrophilic diseases are multisystem inflammatory disorders that include neuro-Behçet and neuro-Sweet disease. These disorders ectopically damage the nervous system due to the abnormal chemotaxis of neutrophils. The neutrophils' chemotaxis is induced by oral muco-cutaneous bacterial infections and the dysregulation of cytokines, including interleukins. The frequencies of human leukocyte antigen (HLA)-B51 in neuro-Behçet disease and HLA-B54 as well as Cw1 in neuro-Sweet disease significantly higher than the levels present in Japanese normal controls. Notably, their frequencies are also higher in patients exhibiting neurological complications than in patients without neurological complications. These HLA types are considered risk factors that are directly related to the etiology of these diseases. Prednisolone and colchicine, which suppress neutrophil activation, are used to treat the acute phase of both diseases. Alternatively, dapsone is prescribed to prednisolone-dependent recurrent cases of neuro-Sweet disease. Dementia is a neurological symptom of these disorders, especially in the chronic progressive subtype of neuro-Behçet disease. Other immunosuppressant drugs, including methotrexate and infliximab, are administered to patients with the chronic progressive type of neuro-Behçet disease. Neuro-neutrophilic diseases are a form of dementia considered treatable.

Multi-Infarct Dementia: A Historical Perspective.

PubMed

McKay, Erin; Counts, Scott E

2017-01-01

Multi-infarct dementia (MID), a prominent subtype of vascular dementia (VaD), has only achieved recognition in the last 4 decades. Since its original description, the characterization, etiological understanding, and therapeutic direction of MID and other VaD subtypes has progressed at an astounding rate. This paper divides the landmark discoveries and emergence of new research strategies for MID into decade-defining patterns so that a condensed picture of the total history of MID and its eventual inclusion as a VaD subtype emerges. This paper follows the first descriptive decade, a shift to a preventative focus, a renewed interest coinciding with timely advances in research technology, and a hopeful return to treatment possibilities for VaD. Concisely tracing the historical lineage of the modern understanding of MID, both as a singular entity and as part of the VaD con-stellation of disorders, provides a novel perspective on the foundation upon which future advances in combating vascular contributions to dementia will be based.

Ethical principles and pitfalls of genetic testing for dementia.

PubMed

Hedera, P

2001-01-01

Progress in the genetics of dementing disorders and the availability of clinical tests for practicing physicians increase the need for a better understanding of multifaceted issues associated with genetic testing. The genetics of dementia is complex, and genetic testing is fraught with many ethical concerns. Genetic testing can be considered for patients with a family history suggestive of a single gene disorder as a cause of dementia. Testing of affected patients should be accompanied by competent genetic counseling that focuses on probabilistic implications for at-risk first-degree relatives. Predictive testing of at-risk asymptomatic patients should be modeled after presymptomatic testing for Huntington's disease. Testing using susceptibility genes has only a limited diagnostic value at present because potential improvement in diagnostic accuracy does not justify potentially negative consequences for first-degree relatives. Predictive testing of unaffected subjects using susceptibility genes is currently not recommended because individual risk cannot be quantified and there are no therapeutic interventions for dementia in presymptomatic patients.

[Cancer treatment for patients with dementia].

PubMed

Ogawa, Asao

2014-09-01

Cancer is a disease associated with aging. In Japan, the rate of aging is estimated to be over 25%. Further, the prevalence of dementia also increases with age, and cancer patients with dementia are becoming more common. Dementia is a progressive condition characterized by impairment in memory and at least one other cognitive domain(language, praxis, gnosis, or executive function), as well as a compromised ability to perform daily functions. Impairment of short-term memory and executive function in particular are associated with an increased risk for functional decline and mortality. Assessment of cognitive function is necessary to ensure that cancer patients can provide informed consent and understand the risks, benefits, and alternatives of therapeutic treatment. The health care team needs to ascertain whether patients have the mental capacity for cancer treatment, will comply with the treatment schedule, and will understand when to seek help. Elderly cancer patients undergoing treatment need to be assessed for vulnerability with the comprehensive geriatric assessment (CGA).

Changes in cognition and behaviour in amyotrophic lateral sclerosis: nature of impairment and implications for assessment.

PubMed

Goldstein, Laura H; Abrahams, Sharon

2013-04-01

Increased awareness of cognitive and behavioural change in amyotrophic lateral sclerosis has been driven by various clinic-based and population-based studies. A frontotemporal syndrome occurs in a substantial proportion of patients, a subgroup of whom present with frontotemporal dementia. Deficits are characterised by executive and working-memory impairments, extending to changes in language and social cognition. Behaviour and social cognition abnormalities are closely similar to those reported in behavioural variant frontotemporal dementia, implying a clinical spectrum linking amyotrophic lateral sclerosis and frontotemporal dementia. Cognitive impairment should be considered in clinical management, but few specialist assessment resources are available, and thus the cognitive status of most patients is unknown. Standard assessment procedures are not appropriate to detect dysfunction due to progressive physical disability; techniques that better measure the problems encountered by this group of patients are needed to further establish disease effects. Screening instruments are needed that are validated specifically for amyotrophic lateral sclerosis, encompass the heterogeneity of impairment, and accommodate physical disability. Copyright © 2013 Elsevier Ltd. All rights reserved.

Frontotemporal Dementia in Eight Chinese Individuals

PubMed Central

Chao, Steven Z.; Rosen, Howard J.; Azor, Virgina; Ong, Hilary; Tse, Marian M.; Lai, Ngan Betty; Hou, Craig E.; Seeley, William W.; Miller, Bruce L.; Matthews, Brandy R.

2012-01-01

Frontotemporal dementia (FTD) has rarely been reported in Chinese populations. There are many potential reasons for this, including possible hesitancy on the part of patients or families to bring FTD-related symptoms to medical attention. Here, we present data on eight Chinese individuals, all of whom met criteria for the behavioral variant of FTD or the semantic variant of primary progressive aphasia. These patients presented for neurological evaluation at a relatively advanced stage. The mean MMSE score at initial presentation was 15. Behavioral symptoms were common and usually elicited during the medical history only after direct questioning. Delay in presentation was attributed to a variety of issues, including family disagreements about whether the symptoms represented a disease and lack of medical insurance. These cases illustrate that the symptoms of FTD in Chinese Americans are similar to those in Caucasians but various factors, some potentially culturally-relevant, may influence the likelihood and timing of clinical presentation for FTD, as well as other dementias. Additional study of FTD in diverse ethnic groups needs to address barriers to clinical presentation, including factors that may be culturally specific. PMID:23311888

Development of Support Service for Prevention and Recovery from Dementia and Science of Lethe

NASA Astrophysics Data System (ADS)

Otake, Mihoko

Purpose of this study is to explore service design method through the development of support service for prevention and recovery from dementia towards science of lethe. We designed and implemented conversation support service via coimagination method based on multiscale service design method, both were proposed by the author. Multiscale service model consists of tool, event, human, network, style and rule. Service elements at different scales are developed according to the model. Interactive conversation supported by coimagination method activates cognitive functions so as to prevent progress of dementia. This paper proposes theoretical bases for science of lethe. Firstly, relationship among coimagination method and three cognitive functions including division of attention, planning, episodic memory which decline at mild cognitive imparement. Secondly, thought state transition model during conversation which describes cognitive enhancement via interactive communication. Thirdly, Set Theoretical Measure of Interaction is proposed for evaluating effectiveness of conversation to cognitive enhancement. Simulation result suggests that the ideas which cannot be explored by each speaker are explored during interactive conversation. Finally, coimagination method compared with reminiscence therapy and its possibility for collaboration is discussed.

Recent Knowledge on Medicinal Plants as Source of Cholinesterase Inhibitors for the Treatment of Dementia.

PubMed

Tundis, Rosa; Bonesi, Marco; Menichini, Francesco; Loizzo, Monica R

2016-01-01

Dementia is becoming a major public health problem worldwide. The most common form of dementia is Alzheimer's disease (AD), characterized by a deficient cholinergic transmission, deposition of amyloid plaques and neurofibrillary tangles, and neuro-inflammation that result in progressive degeneration and/or death of nerve cells and cognitive impairment. At present, AD cannot be prevented or cured, so the symptomatic relief obtainable by the use of acetylcholinesterase (AChE) inhibitors is one of the therapeutic strategies. Accumulated evidence suggests that naturally occurring compounds may potentially improve memory and cognitive function, and prevent neurodegeneration. Even today the search for new neuroprotective agents of natural origin is very active. The neuroprotective effects of medicinal plants covering studies of the last years will be summarized and discussed in this review choosing a family classification with particular emphasis on extracts and isolated compounds as promising new drugs. The search of a multifunctional potential anti-AD agent able to act on different crucial targets, such as galanthamine, quercetin and timosaponin AIII, could be a useful approach to recognizing therapeutics against AD.

Amyloid and intracellular accumulation of BRI2.

PubMed

Garringer, Holly J; Sammeta, Neeraja; Oblak, Adrian; Ghetti, Bernardino; Vidal, Ruben

2017-04-01

Familial British dementia (FBD) and familial Danish dementia (FDD) are caused by mutations in the BRI 2 gene. These diseases are characterized clinically by progressive dementia and ataxia and neuropathologically by amyloid deposits and neurofibrillary tangles. Herein, we investigate BRI 2 protein accumulation in FBD, FDD, Alzheimer disease and Gerstmann-Sträussler-Scheinker disease. In FBD and FDD, we observed reduced processing of the mutant BRI 2 pro-protein, which was found accumulating intracellularly in the Golgi of neurons and glial cells. In addition, we observed an accumulation of a mature form of BRI 2 protein in dystrophic neurites, surrounding amyloid cores. Accumulation of BRI 2 was also observed in dystrophic neurites of Alzheimer disease and Gerstmann-Sträussler-Scheinker disease cases. Although it remains to be determined whether intracellular accumulation of BRI 2 may lead to cell damage in these degenerative diseases, our study provides new insights into the role of mutant BRI 2 in the pathogenesis of FBD and FDD and implicates BRI 2 as a potential indicator of neuritic damage in diseases characterized by cerebral amyloid deposition. Copyright © 2016 Elsevier Inc. All rights reserved.

Amyloid and intracellular accumulation of BRI2

PubMed Central

Garringer, Holly J.; Sammeta, Neeraja; Oblak, Adrian; Ghetti, Bernardino; Vidal, Ruben

2016-01-01

Familial British dementia (FBD) and familial Danish dementia (FDD) are caused by mutations in the BRI2 gene. These diseases are characterized clinically by progressive dementia and ataxia and neuropathologically by amyloid deposits and neurofibrillary tangles. Herein, we investigate BRI2 protein accumulation in FBD, FDD, Alzheimer disease and Gerstmann-Sträussler-Scheinker disease. In FBD and FDD, we observed reduced processing of the mutant BRI2 pro-protein, which was found accumulating intracellularly in the Golgi of neurons and glial cells. In addition, we observed an accumulation of a mature form of BRI2 protein in dystrophic neurites, surrounding amyloid cores. Accumulation of BRI2 was also observed in dystrophic neurites of Alzheimer disease and Gerstmann-Sträussler-Scheinker disease cases. Although it remains to be determined whether intracellular accumulation of BRI2 may lead to cell damage in these degenerative diseases, our study provides new insights into the role of mutant BRI2 in the pathogenesis of FBD and FDD and implicates BRI2 as a potential indicator of neuritic damage in diseases characterized by cerebral amyloid deposition. PMID:28131015

Voxel-based morphometry in autopsy proven PSP and CBD.

PubMed

Josephs, Keith A; Whitwell, Jennifer L; Dickson, Dennis W; Boeve, Bradley F; Knopman, David S; Petersen, Ronald C; Parisi, Joseph E; Jack, Clifford R

2008-02-01

The aim of this study was to compare the patterns of grey and white matter atrophy on MRI in autopsy confirmed progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and to determine whether the patterns vary depending on the clinical syndrome. Voxel-based morphometry was used to compare patterns of atrophy in 13 PSP and 11 CBD subjects and 24 controls. PSP and CBD subjects were also subdivided into those with a dominant dementia or extrapyramidal syndrome. PSP subjects showed brainstem atrophy with involvement of the cortex and underlying white matter. Frontoparietal grey and subcortical grey matter atrophy occurred in CBD. When subdivided, PSP subjects with an extrapyramidal syndrome had more brainstem atrophy and less cortical atrophy than CBD subjects with an extrapyramidal syndrome. PSP subjects with a dementia syndrome had more subcortical white matter atrophy than CBD subjects with a dementia syndrome. These results show regional differences between PSP and CBD that are useful in predicting the underlying pathology, and help to shed light on the in vivo distribution of regional atrophy in PSP and CBD.

Depressive symptoms associated with hereditary Alzheimer's disease: a case description.

PubMed

Contreras, Mónica Yicette Sánchez; Vargas, Paula Alejandra Osorio; Ramos, Lucero Rengifo; Velandia, Rafael Alarcón

The authors describe a family group studied by the Centro de Biología Molecular y Biotecnología, and the Clínica de la Memoria, las Demencias y el Envejecimiento (Universidad Tecnológica de Pereira, Colombia), and evaluate the association of depressive symptoms with Alzheimer's disease (AD). This family presented a hereditary pattern for AD characterized by an early onset of dementia symptoms, a long preclinical depressive course, and, once the first symptoms of dementia appeared, a rapid progression to severe cognitive function impairment. The authors found a high prevalence of depressive symptoms in this family and propose that the symptoms could be an important risk factor for developing AD in the presence of other risk factors such as the APOE E4 allele.

Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia.

PubMed

Duncombe, Jessica; Kitamura, Akihiro; Hase, Yoshiki; Ihara, Masafumi; Kalaria, Raj N; Horsburgh, Karen

2017-10-01

Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia. While there is considerable overlap between features of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD), it appears that cerebral hypoperfusion is the common underlying pathophysiological mechanism which is a major contributor to cognitive decline and degenerative processes leading to dementia. Sustained cerebral hypoperfusion is suggested to be the cause of white matter attenuation, a key feature common to both AD and dementia associated with cerebral small vessel disease (SVD). White matter changes increase the risk for stroke, dementia and disability. A major gap has been the lack of mechanistic insights into the evolution and progress of VCID. However, this gap is closing with the recent refinement of rodent models which replicate chronic cerebral hypoperfusion. In this review, we discuss the relevance and advantages of these models in elucidating the pathogenesis of VCID and explore the interplay between hypoperfusion and the deposition of amyloid β (Aβ) protein, as it relates to AD. We use examples of our recent investigations to illustrate the utility of the model in preclinical testing of candidate drugs and lifestyle factors. We propose that the use of such models is necessary for tackling the urgently needed translational gap from preclinical models to clinical treatments. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Frontotemporal Lobar Degeneration

PubMed Central

Rabinovici, Gil D.; Miller, Bruce L.

2010-01-01

Frontotemporal lobar degeneration (FTLD) is a clinically and pathologically heterogeneous syndrome, characterized by progressive decline in behaviour or language associated with degeneration of the frontal and anterior temporal lobes. While the seminal cases were described at the turn of the 20th century, FTLD has only recently been appreciated as a leading cause of dementia, particularly in patients presenting before the age of 65 years. Three distinct clinical variants of FTLD have been described: (i) behavioural-variant frontotemporal dementia, characterized by changes in behaviour and personality in association with frontal-predominant cortical degeneration; (ii) semantic dementia, a syndrome of progressive loss of knowledge about words and objects associated with anterior temporal neuronal loss; and (iii) progressive nonfluent aphasia, characterized by effortful language output, loss of grammar and motor speech deficits in the setting of left perisylvian cortical atrophy. The majority of pathologies associated with FTLD clinical syndromes include either tau-positive (FTLD-TAU) or TAR DNA-binding protein 43 (TDP-43)-positive (FTLD-TDP) inclusion bodies. FTLD overlaps clinically and pathologically with the atypical parkinsonian disorders corticobasal degeneration and progressive supranuclear palsy, and with amyotrophic lateral sclerosis. The majority of familial FTLD cases are caused by mutations in the genes encoding microtubule-associated protein tau (leading to FTLD-TAU) or progranulin (leading to FTLD-TDP). The clinical and pathologic heterogeneity of FTLD poses a significant diagnostic challenge, and in vivo prediction of underlying histopathology can be significantly improved by supplementing the clinical evaluation with genetic tests and emerging biological markers. Current pharmacotherapy for FTLD focuses on manipulating serotonergic or dopaminergic neurotransmitter systems to ameliorate behavioural or motor symptoms. However, recent advances in FTLD genetics and molecular pathology make the prospect of biologically driven, disease-specific therapies for FTLD seem closer than ever. PMID:20369906

Arts Participation: Counterbalancing Forces to the Social Stigma of a Dementia Diagnosis.

PubMed

Bienvenu, Beth; Hanna, Gay

2017-07-01

A diagnosis of dementia profoundly impacts a person in terms of both the functional progression of the disease and the social stigma associated with the diagnosis. A growing body of research demonstrates the effectiveness of innovative programs such as the Alzheimer's Poetry Project, Meet Me at MoMA, and TimeSlips™ in counterbalancing social stigma by building a social and emotional framework for strength-based living for people diagnosed with dementia through arts participation. These programs focus on supporting autonomy and generativity through creative expression to help sustain the social, emotional, and community fabric of people's lives in the face of significant counterbalancing forces (e.g., the disease itself, stigma, and institution-centered approaches to care). © 2017 American Medical Association. All Rights Reserved.

Conversational assessment in memory clinic encounters: interactional profiling for differentiating dementia from functional memory disorders.

PubMed

Jones, Danielle; Drew, Paul; Elsey, Christopher; Blackburn, Daniel; Wakefield, Sarah; Harkness, Kirsty; Reuber, Markus

2016-01-01

In the UK dementia is under-diagnosed, there is limited access to specialist memory clinics, and many of the patients referred to such clinics are ultimately found to have functional (non-progressive) memory disorders (FMD), rather than a neurodegenerative disorder. Government initiatives on 'timely diagnosis' aim to improve the rate and quality of diagnosis for those with dementia. This study seeks to improve the screening and diagnostic process by analysing communication between clinicians and patients during initial specialist clinic visits. Establishing differential conversational profiles could help the timely differential diagnosis of memory complaints. This study is based on video- and audio recordings of 25 initial consultations between neurologists and patients referred to a UK memory clinic. Conversation analysis was used to explore recurrent communicative practices associated with each diagnostic group. Two discrete conversational profiles began to emerge, to help differentiate between patients with dementia and functional memory complaints, based on (1) whether the patient is able to answer questions about personal information; (2) whether they can display working memory in interaction; (3) whether they are able to respond to compound questions; (4) the time taken to respond to questions; and (5) the level of detail they offer when providing an account of their memory failure experiences. The distinctive conversational profiles observed in patients with functional memory complaints on the one hand and neurodegenerative memory conditions on the other suggest that conversational profiling can support the differential diagnosis of functional and neurodegenerative memory disorders.

A decamer duplication in the 3′ region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred

PubMed Central

Vidal, Ruben; Révész, Tamas; Rostagno, Agueda; Kim, Eugene; Holton, Janice L.; Bek, Toke; Bojsen-Møller, Marie; Braendgaard, Hans; Plant, Gordon; Ghiso, Jorge; Frangione, Blas

2000-01-01

Familial Danish dementia (FDD), also known as heredopathia ophthalmo-oto-encephalica, is an autosomal dominant disorder characterized by cataracts, deafness, progressive ataxia, and dementia. Neuropathological findings include severe widespread cerebral amyloid angiopathy, hippocampal plaques, and neurofibrillary tangles, similar to Alzheimer's disease. N-terminal sequence analysis of isolated leptomeningeal amyloid fibrils revealed homology to ABri, the peptide originated by a point mutation at the stop codon of gene BRI in familial British dementia. Molecular genetic analysis of the BRI gene in the Danish kindred showed a different defect, namely the presence of a 10-nt duplication (795–796insTTTAATTTGT) between codons 265 and 266, one codon before the normal stop codon 267. The decamer duplication mutation produces a frame-shift in the BRI sequence generating a larger-than-normal precursor protein, of which the amyloid subunit (designated ADan) comprises the last 34 C-terminal amino acids. This de novo-created amyloidogenic peptide, associated with a genetic defect in the Danish kindred, stresses the importance of amyloid formation as a causative factor in neurodegeneration and dementia. PMID:10781099

[Driving ability and dementia].

PubMed

Lukas, Albert; Nikolaus, Thorsten

2009-06-01

Physiological changes in cognitive competence in the elderly are clearly different to pathological changes such as dementia. Diagnosing dementia is not to be equated with absolute driving inability. During the course of dementia, the risk of an accident increases significantly. Detailed observation and regular checks serve to determine the appropriate time to hand in the driving licence. The basis of each decision should be a detailed history of the person and his or her immediate family. Attention should be paid to incorrect driving practise, unusual behaviour and uncertainty whilst driving as well as involvement in any accidents. An MMSE score below 24 or a CCT score up to 3 should result in an additional assessment being carried out, e.g. neuro-psychological tests, driving simulator or, if necessary on-road tests performed with specialists. Also helpful is the determination of functional status. Limitations in ADL or IADL function normally indicate an advanced stage of dementia. Due to the progression of the illness, the possibility of handing in the driving licence should be addressed as soon as possible. In this context, it is helpful to consider alternative forms of transportation. Individual wishes and needs must to be balanced against general road safety requirements.

Non-pharmacological cognitive intervention for aging and dementia: Current perspectives

PubMed Central

Alves, Jorge; Magalhães, Rosana; Machado, Álvaro; Gonçalves, Óscar F; Sampaio, Adriana; Petrosyan, Agavni

2013-01-01

In recent years, cognitive difficulties associated with normal aging and dementia have been receiving increased attention from both public and scientific communities. With an increase in overall lifespan, promoting healthy cognition has become a priority and a necessity for minimizing and preventing individual and societal burdens associated with cognitive dysfunctions in the elderly. The general awareness concerning the efficacy of preventive (e.g., lifestyles) and palliative treatment strategies of cognitive impairments, related to either healthy or unhealthy trajectories in cognitive aging, is continuously rising. There are several therapeutic strategies which can be broadly classified as either pharmacological or non-pharmacological/psychosocial. In face of the modest evidence for success of pharmacological treatments, especially for dementia related impairments, psychosocial interventions are progressively considered as a complementary treatment. Despite the relative spread of psychosocial interventions in clinical settings, research in this area is rather scarce with evidence for success of these therapies remaining controversial. In this work we provide an evidence based perspective on cognitive intervention(s) for healthy aging, pre-dementia (mild cognitive impairment), and dementia populations. Current evidence and future directions for improving cognitive functions in the elderly are discussed as well. PMID:24340275

Who Is Responsible? A Man With Dementia Wanders From Home, Is Hit by a Train, and Dies.

PubMed

Young, Yuchi; Papenkov, Maksim; Nakashima, Taeko

2018-07-01

The impact of dementia and Alzheimer's disease extends far beyond the healthcare needs of the person with dementia. As the disease progresses, individuals with dementia often require ongoing formal or informal care for their basic daily routine because of behavior changes and continuing loss of cognitive function. Most of the care for people with dementia takes place at home, and the unpaid, informal caregivers are often spouses or other relatives. Providing long-term informal care at home for someone with dementia is psychologically, physically, and financially draining. The tragedy described in this case elucidates the far-reaching societal impact of dementia care and the implicit health policy considerations. In 2007, a 91-year-old Japanese man with dementia was in the care of his wife when he wandered from home, was hit by a train, and died, immediately affecting the Central Japan Railway Company operations and, subsequently, legal practice as well as Japanese elder care policy. The railway sued the man's wife and son for negligence and lost revenue, winning both trials at the local and district courts. This ruling shocked families and caregivers in Japan, where care for elderly parents traditionally falls on the oldest son, and brought attention to the complex issues related to dementia care. A decade later, we revisit this case to provoke a renewed dialogue about the matrix of responsibilities and liabilities associated with caregiving; to illuminate the unmet needs of the person with dementia, as well as his or her informal caregivers; and the financial implications related to long-term care policy. We close with 2 practical suggestions which preserve the dignity of the individual and provide reassurance for caregivers. Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Technology-based tools and services for people with dementia and carers: Mapping technology onto the dementia care pathway.

PubMed

Lorenz, Klara; Freddolino, Paul P; Comas-Herrera, Adelina; Knapp, Martin; Damant, Jacqueline

2017-01-01

The extent to which technology may be able to support people with dementia and their carers along the care pathway and in different care settings is of interest to policy makers and governments. In this paper we provide an overview of the role of technology in dementia care, treatment and support by mapping existing technologies - by function, target user and disease progression. Technologies identified are classified into seven functions: memory support, treatment, safety and security, training, care delivery, social interaction and other. Different groups of potential users are distinguished: people with mild cognitive impairment and early stages of dementia, people with moderate to severe dementia and unpaid carers and health- and social care professionals. We also identified the care settings, in which the technologies are used (or for which the technologies are developed): at home in the community and in institutional care settings. The evidence has been drawn from a rapid review of the literature, expert interviews and web and social media searches. The largest number of technologies identified aim to enhance the safety and security of people with dementia living in the community. These devices are often passive monitors, such as smoke detectors. Other safety interventions, such as panic buttons, require active intervention. The second largest number of interventions aims to enhance people's memory and includes global positioning systems devices and voice prompts. These technologies mostly target people in the early stages of dementia. A third group focusing on treatment and care delivery emerged from the literature. These interventions focus on technology-aided reminiscence or therapeutic aspects of care for people with dementia and their carers. While the review found a range of technologies available for people with dementia and carers there is very little evidence of widespread practical application. Instead, it appears that stakeholders frequently rely on everyday technologies re-purposed to meet their needs.

Distinct anatomical subtypes of the behavioural variant of frontotemporal dementia: a cluster analysis study.

PubMed

Whitwell, Jennifer L; Przybelski, Scott A; Weigand, Stephen D; Ivnik, Robert J; Vemuri, Prashanthi; Gunter, Jeffrey L; Senjem, Matthew L; Shiung, Maria M; Boeve, Bradley F; Knopman, David S; Parisi, Joseph E; Dickson, Dennis W; Petersen, Ronald C; Jack, Clifford R; Josephs, Keith A

2009-11-01

The behavioural variant of frontotemporal dementia is a progressive neurodegenerative syndrome characterized by changes in personality and behaviour. It is typically associated with frontal lobe atrophy, although patterns of atrophy are heterogeneous. The objective of this study was to examine case-by-case variability in patterns of grey matter atrophy in subjects with the behavioural variant of frontotemporal dementia and to investigate whether behavioural variant of frontotemporal dementia can be divided into distinct anatomical subtypes. Sixty-six subjects that fulfilled clinical criteria for a diagnosis of the behavioural variant of frontotemporal dementia with a volumetric magnetic resonance imaging scan were identified. Grey matter volumes were obtained for 26 regions of interest, covering frontal, temporal and parietal lobes, striatum, insula and supplemental motor area, using the automated anatomical labelling atlas. Regional volumes were divided by total grey matter volume. A hierarchical agglomerative cluster analysis using Ward's clustering linkage method was performed to cluster the behavioural variant of frontotemporal dementia subjects into different anatomical clusters. Voxel-based morphometry was used to assess patterns of grey matter loss in each identified cluster of subjects compared to an age and gender-matched control group at P < 0.05 (family-wise error corrected). We identified four potentially useful clusters with distinct patterns of grey matter loss, which we posit represent anatomical subtypes of the behavioural variant of frontotemporal dementia. Two of these subtypes were associated with temporal lobe volume loss, with one subtype showing loss restricted to temporal lobe regions (temporal-dominant subtype) and the other showing grey matter loss in the temporal lobes as well as frontal and parietal lobes (temporofrontoparietal subtype). Another two subtypes were characterized by a large amount of frontal lobe volume loss, with one subtype showing grey matter loss in the frontal lobes as well as loss of the temporal lobes (frontotemporal subtype) and the other subtype showing loss relatively restricted to the frontal lobes (frontal-dominant subtype). These four subtypes differed on clinical measures of executive function, episodic memory and confrontation naming. There were also associations between the four subtypes and genetic or pathological diagnoses which were obtained in 48% of the cohort. The clusters did not differ in behavioural severity as measured by the Neuropsychiatric Inventory; supporting the original classification of the behavioural variant of frontotemporal dementia in these subjects. Our findings suggest behavioural variant of frontotemporal dementia can therefore be subdivided into four different anatomical subtypes.

Texture Analysis of T1-Weighted and Fluid-Attenuated Inversion Recovery Images Detects Abnormalities That Correlate With Cognitive Decline in Small Vessel Disease.

PubMed

Tozer, Daniel J; Zeestraten, Eva; Lawrence, Andrew J; Barrick, Thomas R; Markus, Hugh S

2018-06-04

Magnetic resonance imaging may be useful to assess disease severity in cerebral small vessel disease (SVD), identify those individuals who are most likely to progress to dementia, monitor disease progression, and act as surrogate markers to test new therapies. Texture analysis extracts information on the relationship between signal intensities of neighboring voxels. A potential advantage over techniques, such as diffusion tensor imaging, is that it can be used on clinically obtained magnetic resonance sequences. We determined whether texture parameters (TP) were abnormal in SVD, correlated with cognitive impairment, predicted cognitive decline, or conversion to dementia. In the prospective SCANS study (St George's Cognition and Neuroimaging in Stroke), we assessed TP in 121 individuals with symptomatic SVD at baseline, 99 of whom attended annual cognitive testing for 5 years. Conversion to dementia was recorded for all subjects during the 5-year period. Texture analysis was performed on fluid-attenuated inversion recovery and T1-weighted images. The TP obtained from the SVD cohort were cross-sectionally compared with 54 age-matched controls scanned on the same magnetic resonance imaging system. There were highly significant differences in several TP between SVD cases and controls. Within the SVD population, TP were highly correlated to other magnetic resonance imaging parameters (brain volume, white matter lesion volume, lacune count). TP correlated with executive function and global function at baseline and predicted conversion to dementia, after controlling for age, sex, premorbid intelligence quotient, and magnetic resonance parameters. TP, which can be obtained from routine clinical images, are abnormal in SVD, and the degree of abnormality correlates with executive dysfunction and global cognition at baseline and decline during 5 years. TP may be useful to assess disease severity in clinically collected data. This needs testing in data clinically acquired across multiple sites. © 2018 The Authors.

Syndromic parkinsonism and dementia associated with OPA 1 missense mutations

PubMed Central

Musumeci, Olimpia; Caporali, Leonardo; Zanna, Claudia; La Morgia, Chiara; Del Dotto, Valentina; Porcelli, Anna Maria; Rugolo, Michela; Valentino, Maria Lucia; Iommarini, Luisa; Maresca, Alessandra; Barboni, Piero; Carbonelli, Michele; Trombetta, Costantino; Valente, Enza Maria; Patergnani, Simone; Giorgi, Carlotta; Pinton, Paolo; Rizzo, Giovanni; Tonon, Caterina; Lodi, Raffaele; Avoni, Patrizia; Liguori, Rocco; Baruzzi, Agostino; Toscano, Antonio; Zeviani, Massimo

2015-01-01

Objective Mounting evidence links neurodegenerative disorders such as Parkinson disease and Alzheimer disease with mitochondrial dysfunction, and recent emphasis has focused on mitochondrial dynamics and quality control. Mitochondrial dynamics and mtDNA maintenance is another link recently emerged, implicating mutations in the mitochondrial fusion genes OPA1 and MFN2 in the pathogenesis of multisystem syndromes characterized by neurodegeneration and accumulation of mtDNA multiple deletions in postmitotic tissues. Here, we report 2 Italian families affected by dominant chronic progressive external ophthalmoplegia (CPEO) complicated by parkinsonism and dementia. Methods Patients were extensively studied by optical coherence tomography (OCT) to assess retinal nerve fibers, and underwent muscle and brain magnetic resonance spectroscopy (MRS), and muscle biopsy and fibroblasts were analyzed. Candidate genes were sequenced, and mtDNA was analyzed for rearrangements. Results Affected individuals displayed a slowly progressive syndrome characterized by CPEO, mitochondrial myopathy, sensorineural deafness, peripheral neuropathy, parkinsonism, and/or cognitive impairment, in most cases without visual complains, but with subclinical loss of retinal nerve fibers at OCT. Muscle biopsies showed cytochrome c oxidase‐negative fibers and mtDNA multiple deletions, and MRS displayed defective oxidative metabolism in muscle and brain. We found 2 heterozygous OPA1 missense mutations affecting highly conserved amino acid positions (p.G488R, p.A495V) in the guanosine triphosphatase domain, each segregating with affected individuals. Fibroblast studies showed a reduced amount of OPA1 protein with normal mRNA expression, fragmented mitochondria, impaired bioenergetics, increased autophagy and mitophagy. Interpretation The association of CPEO and parkinsonism/dementia with subclinical optic neuropathy widens the phenotypic spectrum of OPA1 mutations, highlighting the association of defective mitochondrial dynamics, mtDNA multiple deletions, and altered mitophagy with parkinsonism. Ann Neurol 2015;78:21–38 PMID:25820230

Dominant hemisphere lateralization of cortical parasympathetic control as revealed by frontotemporal dementia

PubMed Central

Guo, Christine C.; Sturm, Virginia E.; Zhou, Juan; Gennatas, Efstathios D.; Trujillo, Andrew J.; Hua, Alice Y.; Crawford, Richard; Stables, Lara; Kramer, Joel H.; Rankin, Katherine; Levenson, Robert W.; Rosen, Howard J.; Miller, Bruce L.; Seeley, William W.

2016-01-01

The brain continuously influences and perceives the physiological condition of the body. Related cortical representations have been proposed to shape emotional experience and guide behavior. Although previous studies have identified brain regions recruited during autonomic processing, neurological lesion studies have yet to delineate the regions critical for maintaining autonomic outflow. Even greater controversy surrounds hemispheric lateralization along the parasympathetic–sympathetic axis. The behavioral variant of frontotemporal dementia (bvFTD), featuring progressive and often asymmetric degeneration that includes the frontoinsular and cingulate cortices, provides a unique lesion model for elucidating brain structures that control autonomic tone. Here, we show that bvFTD is associated with reduced baseline cardiac vagal tone and that this reduction correlates with left-lateralized functional and structural frontoinsular and cingulate cortex deficits and with reduced agreeableness. Our results suggest that networked brain regions in the dominant hemisphere are critical for maintaining an adaptive level of baseline parasympathetic outflow. PMID:27071080

Single photon emission tomography using 99mTc-HM-PAO in the investigation of dementia.

PubMed Central

Neary, D; Snowden, J S; Shields, R A; Burjan, A W; Northen, B; MacDermott, N; Prescott, M C; Testa, H J

1987-01-01

Single photon emission tomographic imaging of the brain using 99mTc HM-PAO was carried out in patients with a clinical diagnosis of Alzheimer's disease, non-Alzheimer frontal-lobe dementia, and progressive supranuclear palsy. Independent assessment of reductions in uptake revealed posterior hemisphere abnormalities in the majority of the Alzheimer group, and selective anterior hemisphere abnormalities in both other groups. The findings were consistent with observed patterns of mental impairment. The imaging technique has potential value in the differential diagnosis of primary cerebral atrophy. Images PMID:3499484

Semantic amnesia without dementia: documentation of a case.

PubMed

Rusconi, M L; Zago, S; Basso, A

1997-06-01

We described the case of a patient affected by a progressive semantic memory disorder associated with prevalent temporal lobe atrophy. This deficit seems to be "pure" in the sense that it has not been found to overlap with other cognitive deficits (intellectual, linguistic, perceptual, visuo-spatial etc.) for a long time. Furthermore, despite his impaired semantic knowledge, the autobiographical memory of the patient was largely intact. This case therefore represents a form of "semantic amnesia" without dementia, and supports the hypothesis that there is a partial distinction between "semantic" and "episodic" memory.

Apple juice improved behavioral but not cognitive symptoms in moderate-to-late stage Alzheimer's disease in an open-label pilot study.

PubMed

Remington, Ruth; Chan, Amy; Lepore, Alicia; Kotlya, Elizabeth; Shea, Thomas B

2010-06-01

Preclinical studies demonstrate that apple juice exerts multiple beneficial effects including reduction of central nervous system oxidative damage, suppression of Alzheimer's disease (AD) hallmarks, improved cognitive performance, and organized synaptic signaling. Herein, we initiated an open-label clinical trial in which 21 institutionalized individuals with moderate-to-severe AD consumed 2 4-oz glasses of apple juice daily for 1 month. Participants demonstrated no change in the Dementia Rating Scale, and institutional caregivers reported no change in Alzheimer's Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL) in this brief study. However, caregivers reported an approximate 27% (P < .01) improvement in behavioral and psychotic symptoms associated with dementia as quantified by the Neuropsychiatric Inventory, with the largest changes in anxiety, agitation, and delusion. This pilot study suggests that apple juice may be a useful supplement, perhaps to augment pharmacological approaches, for attenuating the decline in mood that accompanies progression of AD, which may also reduce caregiver burden.

Shining new light on treating dementia: integrating EEG neurofeedback training and near infrared photobiomodulation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Berman, Marvin H.

2017-02-01

Evidence from animal and human studies regarding the biological impact of near infrared light stimulation has significantly increased of late noting the disease modifying properties of photobiomodulation for improving physical and cognitive performance in subjects with a variety of neurodegenerative conditions. Concurrently we see a growing body of literature regarding the efficacy of operant conditioning of EEG amplitude and connectivity in remediating both cognitive and behavioral symptoms of both neuropsychiatric and neurodegenerative disorders including traumatic brain injury, ADHD, PTSD, and dementia. This presentation seeks to outline a treatment model combining these two treatment methods to stop the progression of neurodegeneration using pulsed (10hz), brief (5-20minutes) repeated (1-2x/daily) transcranial and intranasal photobiomodulation with 810nm and 1068nm near infrared phototherapy and operant conditioning of EEG amplitude and coherence. Our initial study on treating dementia with EEG biofeedback (N=37) showed neuroplasticity's potential for modifying cognitive and behavioral symptoms using the evidence from decades of neurological research that never felt the warm touch of a translational researcher's hand. The near infrared interventional studies clarified the order of treatment, i.e., tissue health and renewal were achieved, followed by neural connectivity enhancement. Significant improvements in both immediate and delayed recall and praxis memory as well as executive functioning and behavioral regulation were obtained with each intervention. The inferred synergistic impact of properly combining these approaches is what informs our current clinical applications and future research efforts examining the value of combined treatments for all dementias, parkinson's disease and age-related dry macular degeneration.

A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology.

PubMed

Alosco, Michael L; Sugarman, Michael A; Besser, Lilah M; Tripodis, Yorghos; Martin, Brett; Palmisano, Joseph N; Kowall, Neil W; Au, Rhoda; Mez, Jesse; DeCarli, Charles; Stein, Thor D; McKee, Ann C; Killiany, Ronald J; Stern, Robert A

2018-01-01

White matter hyperintensities (WMH) on magnetic resonance imaging (MRI) have been postulated to be a core feature of Alzheimer's disease. Clinicopathological studies are needed to elucidate and confirm this possibility. This study examined: 1) the association between antemortem WMH and autopsy-confirmed Alzheimer's disease neuropathology (ADNP), 2) the relationship between WMH and dementia in participants with ADNP, and 3) the relationships among cerebrovascular disease, WMH, and ADNP. The sample included 82 participants from the National Alzheimer's Coordinating Center's Data Sets who had quantitated volume of WMH from antemortem FLAIR MRI and available neuropathological data. The Clinical Dementia Rating (CDR) scale (from MRI visit) operationalized dementia status. ADNP+ was defined by moderate to frequent neuritic plaques and Braak stage III-VI at autopsy. Cerebrovascular disease neuropathology included infarcts or lacunes, microinfarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy. 60/82 participants were ADNP+. Greater volume of WMH predicted increased odds for ADNP (p = 0.037). In ADNP+ participants, greater WMH corresponded with increased odds for dementia (CDR≥1; p = 0.038). WMH predicted cerebral amyloid angiopathy, microinfarcts, infarcts, and lacunes (ps < 0.04). ADNP+ participants were more likely to have moderate-severe arteriolosclerosis and cerebral amyloid angiopathy compared to ADNP-participants (ps < 0.04). This study found a direct association between total volume of WMH and increased odds for having ADNP. In patients with Alzheimer's disease, FLAIR MRI WMH may be able to provide key insight into disease severity and progression. The association between WMH and ADNP may be explained by underlying cerebrovascular disease.

An Automated Approach to Examining Conversational Dynamics between People with Dementia and Their Carers

PubMed Central

Atay, Christina; Conway, Erin R.; Angus, Daniel; Wiles, Janet; Baker, Rosemary; Chenery, Helen J.

2015-01-01

The progressive neuropathology involved in dementia frequently causes a gradual decline in communication skills. Communication partners who are unaware of the specific communication problems faced by people with dementia (PWD) can inadvertently challenge their conversation partner, leading to distress and a reduced flow of information between speakers. Previous research has produced an extensive literature base recommending strategies to facilitate conversational engagement in dementia. However, empirical evidence for the beneficial effects of these strategies on conversational dynamics is sparse. This study uses a time-efficient computational discourse analysis tool called Discursis to examine the link between specific communication behaviours and content-based conversational engagement in 20 conversations between PWD living in residential aged-care facilities and care staff members. Conversations analysed here were baseline conversations recorded before staff members underwent communication training. Care staff members spontaneously exhibited a wide range of facilitative and non-facilitative communication behaviours, which were coded for analysis of conversation dynamics within these baseline conversations. A hybrid approach combining manual coding and automated Discursis metric analysis provides two sets of novel insights. Firstly, this study revealed nine communication behaviours that, if used by the care staff member in a given turn, significantly increased the appearance of subsequent content-based engagement in the conversation by PWD. Secondly, the current findings reveal alignment between human- and computer-generated labelling of communication behaviour for 8 out of the total 22 behaviours under investigation. The approach demonstrated in this study provides an empirical procedure for the detailed evaluation of content-based conversational engagement associated with specific communication behaviours. PMID:26658135

Effectiveness of interventions to improve family-staff relationships in the care of people with dementia in residential aged care: a systematic review protocol.

PubMed

Nguyen, Mynhi; Pachana, Nancy A; Beattie, Elizabeth; Fielding, Elaine; Ramis, Mary-Anne

2015-11-01

The objective of this review is to identify and appraise existing evidence regarding the effectiveness of interventions designed to enhance staff-family relationships for people with dementia living in residential aged care facilities.More specifically, the objectives are to identify the effectiveness of constructive communication, cooperation programs, and practices or strategies to enhance family-staff relationships. The effectiveness of these interventions will be measured by comparing the intervention to no intervention, comparing one intervention with another, or comparing pre- and post-interventions.Specifically the review question is: What are the most effective interventions for improving communication and cooperation to enhance family-staff relationships in residential aged care facilities? In our aging world, dementia is prevalent and is a serious health concern affecting approximately 35.6 million people worldwide. This figure is expected to increase two-fold by 2030 and three-fold by 2050. Although younger-onset dementia is increasingly recognized, dementia is most commonly a disease that affects the elderly. Among those aged 65 to 85, the prevalence of dementia increases exponentially, and doubles with every five-year increase in age.Dementia is defined as a syndrome, commonly chronic or progressive in nature, and caused by a range of brain disorders that affect memory, thinking and the ability to perform activities of daily living. While the rate of progression and manifestation of decline differs, all cases of dementia share a similar trajectory of decline. The progressive decline in cognitive functions and ultimately physical function that these people face affects not only the person with the disease but also their family caregivers and health care staff.The manifestation of dementia presents unique and extreme challenges for the family caregiver. Generally it causes great physical, emotional and social strain because the caregiving process is long in duration, unfamiliar, unpredictable and ambiguous. In the later stages of dementia, many family caregivers relocate their relative to a residential aged care facility, most often when the burden of care outweighs the means of the caregiver. This is especially likely when the person with dementia ages, and has lower cognitive function increased limitations in activities in daily living and poorer self-related health. As a result, approximately 50% of all persons aged 65 years or over admitted into residential aged care facilities have dementia.The relocation of a relative into a residential aged care facility can be complex and distressing for family caregivers. While relocation alleviates many issues for the family caregiver, it does not consequently reduce their stress. The stress experienced by the family caregivers who remain involved post-relocation often continues and may even worsen. This is because family caregivers are uncertain about how to transition from a direct caregiving role to a more indirect, supportive interpersonal role, and may be provided with little support from care staff in this regard. Although family caregivers experience a new form of stress post-relocation, family involvement in residential aged care settings has been shown to be beneficial to residents with dementia, their families and care staff.Family involvement is widely acknowledged to provide the resident physical and emotional healing, optimal well-being, and the sustainment of quality of life. Family caregivers benefit from improved satisfaction with the facility and experiences of care, and greater well-being. Care staff benefit from enhanced job satisfaction and greater motivation to remain in their job. The key to these positive outcomes is effective communication and strong relationships between care staff and family caregivers.Effective communication between care staff and family caregivers is crucial for residents with dementia. This is because residents with cognitive impairment may have difficulties articulating their needs, concerns and preferences effectively. Family caregivers rely on staff for information about their relative's behavior in the residential aged care facility; however they themselves have in-depth information about the resident's physical, psychosocial and emotional histories that are necessary for developing individualized care support plans. Family involvement can support care staff in reducing residents' behavioral symptoms by assisting to identify social and emotional needs, or unmet medical needs. Ineffective communication from family caregivers in conveying information to care staff may be disruptive in the caregiving process, and may lead to disagreement regarding respective roles and approaches to caring for the resident. Consequently, family caregivers may withhold information that may support care staff and improve care. They may also be concerned about negative repercussions for the resident.Care staff and family caregivers generally have differing needs and expectations. Care staff are usually in the position where they have to manage a relationship with the family, which is based on multiple roles. Perceptions of family caregivers by care staff include seeing them as colleagues, subordinates, or people who themselves may be in need of nursing care. These different perceptions lead to role ambiguity and result in separate approaches to the caregiving process.Cohen et al. suggest in their study that family involvement can benefit people with dementia in residential aged care settings, their family carers and staff; however further research is required. The relationship between care staff and family caregivers is often challenging due to problems with communication, role ambiguity of both care staff and family carers, and differing approaches to caring for the resident. These problems highlight the need for interventions to constructively enhance the quality of family-staff relationships. For example, one intervention called Partners and Caregiving has been reported as being designed to increase cooperation and effective communication between staff and family. In this study, staff and family members were randomly subjected to treatment and control conditions. The treatment group received parallel training sessions on communication and conflict resolution techniques, followed by a joint meeting with the facility administrators. The results of the study demonstrated improved outcomes in the form of improved attitudes of staff and family members towards each other, less conflict between family and staff, and fewer intentions of staff to quit. Further research is vital in order to identify effective family-staff intervention studies that can provide directions for implementation in residential aged care facilities. Furthermore, it is equally important to identify interventions that are ineffective, so as to provide insights into potential pitfalls to avoid in order to improve staff and family members' relationships and the provision of care to people living with dementia in the future.Previous systematic reviews have focused on factors associated with constructive family-staff relationships in caring for older adults in the institutional setting and the family's involvement in decision making for people with dementia in residential aged care facilites. This review will however specifically investigate interventions for improving communication and cooperation that promote effective family-staff relationships when caring for people with dementia living in residential aged care facilities.

Major depressive disorder with psychotic features may lead to misdiagnosis of dementia: a case report and review of the literature.

PubMed

Wagner, Gerhardt S; McClintock, Shawn M; Rosenquist, Peter B; McCall, W Vaughn; Kahn, David A

2011-11-01

Major depressive disorder (MDD) with psychotic features is relatively frequent in patients with greater depressive symptom severity and is associated with a poorer course of illness and greater functional impairment than MDD without psychotic features. Multiple studies have found that patients with psychotic mood disorders demonstrate significantly poorer cognitive performance in a variety of areas than those with nonpsychotic mood disorders. The Mini Mental State Examination (MMSE) and the Dementia Rating Scale, Second Edition (DRS-2) are widely used to measure cognitive functions in research on MDD with psychotic features. Established total raw score cut-offs of 24 on the MMSE and 137 on the DRS-2 in published manuals suggest possible global cognitive impairment and dementia, respectively. Limited research is available on these suggested cut-offs for patients with MDD with psychotic features. We document the therapeutic benefit of electroconvulsive therapy (ECT), which is usually associated with short-term cognitive impairment, in a 68-year-old woman with psychotic depression whose MMSE and DRS-2 scores initially suggested possible global cognitive impairment and dementia. Over the course of four ECT treatments, the patient's MMSE scores progressively increased. After the second ECT treatment, the patient no longer met criteria for global cognitive impairment. With each treatment, depression severity, measured by the 24-item Hamilton Rating Scale for Depression, improved sequentially. Thus, the suggested cut-off scores for the MMSE and the DRS-2 in patients with MDD with psychotic features may in some cases produce false-positive indications of dementia.

A home-based, carer-enhanced exercise program improves balance and falls efficacy in community-dwelling older people with dementia.

PubMed

Taylor, Morag E; Lord, Stephen R; Brodaty, Henry; Kurrle, Susan E; Hamilton, Sarah; Ramsay, Elisabeth; Webster, Lyndell; Payne, Narelle L; Close, Jacqueline C T

2017-01-01

Older people with dementia are at increased risk of physical decline and falls. Balance and mood are significant predictors of falls in this population. The aim of this study was to determine the effect of a tailored home-based exercise program in community-dwelling older people with dementia. Forty-two participants with mild to moderate dementia were recruited from routine health services. All participants were offered a six-month home-based, carer-enhanced, progressive, and individually tailored exercise program. Physical activity, quality of life, physical, and psychological assessments were administered at the beginning and end of the trial. Of 33 participants (78.6%) who completed the six-month reassessment ten (30%) reported falls and six (18%) multiple falls during the follow-up period. At reassessment, participants had better balance (sway on floor and foam), reduced concern about falls, increased planned physical activity, but worse knee extension strength and no change in depression scores. The average adherence to the prescribed exercise sessions was 45% and 22 participants (52%) were still exercising at trial completion. Those who adhered to ≥70% of prescribed sessions had significantly better balance at reassessment compared with those who adhered to <70% of sessions. This trial of a tailored home-based exercise intervention presents preliminary evidence that this intervention can improve balance, concern about falls, and planned physical activity in community-dwelling older people with dementia. Future research should determine whether exercise interventions are effective in reducing falls and elucidate strategies for enhancing uptake and adherence in this population.

Common and unique gray matter correlates of episodic memory dysfunction in frontotemporal dementia and Alzheimer's disease.

PubMed

Irish, Muireann; Piguet, Olivier; Hodges, John R; Hornberger, Michael

2014-04-01

Conflicting evidence exists regarding the integrity of episodic memory in the behavioral variant of frontotemporal dementia (bvFTD). Recent converging evidence suggests that episodic memory in progressive cases of bvFTD is compromised to the same extent as in Alzheimer's disease (AD). The underlying neural substrates of these episodic memory deficits, however, likely differ contingent on dementia type. In this study we sought to elucidate the neural substrates of episodic memory performance, across recall and recognition tasks, in both patient groups using voxel-based morphometry (VBM) analyses. We predicted that episodic memory dysfunction would be apparent in both patient groups but would relate to divergent patterns of neural atrophy specific to each dementia type. We assessed episodic memory, across verbal and visual domains, in 19 bvFTD, 18 AD patients, and 19 age- and education-matched controls. Behaviorally, patient groups were indistinguishable for immediate and delayed recall, across verbal and visual domains. Whole-brain VBM analyses revealed regions commonly implicated in episodic retrieval across groups, namely the right temporal pole, right frontal lobe, left paracingulate gyrus, and right anterior hippocampus. Divergent neural networks specific to each group were also identified. Whereas a widespread network including posterior regions such as the posterior cingulate cortex, parietal and occipital cortices was exclusively implicated in AD, the frontal and anterior temporal lobes underpinned the episodic memory deficits in bvFTD. Our results point to distinct neural changes underlying episodic memory decline specific to each dementia syndrome. Copyright © 2013 Wiley Periodicals, Inc.

Autobiographical memory and patterns of brain atrophy in frontotemporal lobar degeneration.

PubMed

McKinnon, Margaret C; Nica, Elena I; Sengdy, Pheth; Kovacevic, Natasa; Moscovitch, Morris; Freedman, Morris; Miller, Bruce L; Black, Sandra E; Levine, Brian

2008-10-01

Autobiographical memory paradigms have been increasingly used to study the behavioral and neuroanatomical correlates of human remote memory. Although there are numerous functional neuroimaging studies on this topic, relatively few studies of patient samples exist, with heterogeneity of results owing to methodological variability. In this study, fronto-temporal lobar degeneration (FTLD), a form of dementia affecting regions crucial to autobiographical memory, was used as a model of autobiographical memory loss. We emphasized the separation of episodic (recollection of specific event, perceptual, and mental state information) from semantic (factual information unspecific in time and place) autobiographical memory, derived from a reliable method for scoring transcribed autobiographical protocols, the Autobiographical Interview [Levine, B., Svoboda, E., Hay, J., Winocur, G., & Moscovitch, M. Aging and autobiographical memory: Dissociating episodic from semantic retrieval. Psychology and Aging, 17, 677-689, 2002]. Patients with the fronto-temporal dementia (FTD) and mixed fronto-temporal and semantic dementia (FTD/SD) variants of FTLD were impaired at reconstructing episodically rich autobiographical memories across the lifespan, with FTD/SD patients generating an excess of generic semantic autobiographical information. Patients with progressive nonfluent aphasia were mildly impaired for episodic autobiographical memory, but this impairment was eliminated with the provision of structured cueing, likely reflecting relatively intact medial-temporal lobe function, whereas the same cueing failed to bolster the FTD and FTD/SD patients' performance relative to that of matched comparison subjects. The pattern of episodic, but not semantic, autobiographical impairment was enhanced with disease progression on 1- to 2-year follow-up testing in a subset of patients, supplementing the cross-sectional evidence for specificity of episodic autobiographical impairment with longitudinal data. This behavioral pattern covaried with volume loss in a distributed left-lateralized posterior network centered on the temporal lobe, consistent with evidence from other patient and functional neuroimaging studies of autobiographical memory. Frontal lobe volumes, however, did not significantly contribute to this network, suggesting that frontal contributions to autobiographical episodic memory may be more complex than previously appreciated.

Interpreting "I don't know" use by persons living with dementia in Mini-Mental State Examinations.

PubMed

Hesson, Ashley M; Pichler, Heike

2016-09-01

We investigate dementia patients' use of "I don't know" (IDK) in Mini-Mental State Exams (MMSEs) using objective linguistic indicators to differentiate IDK signalling lack of knowledge (LOK) from IDK used to hedge responses, affect exam progression etc. We hypothesize that increased proportional use of LOK-IDK correlates with worsening dementia severity. 189 IDK tokens were extracted from 72 MMSE interactions and coded for linguistic/social characteristics. A data-driven, discourse position/relation-based functional taxonomy for IDK in MMSE was developed and the resulting functional distribution was subjected to multiple logistic regression. Use of LOK-IDK (vs. non-LOK-IDK) is significantly correlated (p=0.01) with clinicians' subjective ratings of patients' dementia as 'severe' vs. 'mild'/'moderate', indicating that objective sociolinguistic criteria approximate physician judgments. 92% of 'severe' patients' IDKs signalled LOK, compared to only 68% of 'mild' patients', suggesting that uncritical interpretation of IDK as signalling LOK would result in 8-32% of IDK responses being mis-scored. LOK and non-LOK uses distinguished on the basis of reliable, objective usage patterns are differentially distributed among dementia severity groups. LOK-IDK serves as a supplemental indicator of dementia severity. Correct interpretation may improve diagnostic accuracy and allow clinicians to respond supportively during cognitive assessment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The incompetent patient on the slippery slope.

PubMed

Dresser, R; Whitehouse, P J

1994-01-01

Most patients suffering from progressive dementia have thoughts, emotions, perspectives, and perceptions of a world of experience. Decisions about life-sustaining treatment should incorporate a principled approach to evaluating what life is like for these patients.

The borderland between normal aging and dementia.

PubMed

Lo, Raymond Y

2017-01-01

Alzheimer's disease (AD) has become a global health issue as the population ages. There is no effective treatment to protect against its occurrence or progression. Some argue that the lack of treatment response is due to delays in diagnosis. By the time a diagnosis of AD is made, neurodegenerative changes are at the stage where very few neurons can be salvaged by medication. The AD research community has developed the idea of mild cognitive impairment (MCI) in an attempt to find predementia patients who might benefit from potentially therapeutic drugs that have proven ineffective in the past. However, MCI is heterogeneous in terms of its underlying pathology and practicality for predicting dementia. This article first reviews the conceptual evolution of MCI as the borderland between normal aging and dementia, and then proposes that built environment and sociocultural context are two key elements in formulating a diagnosis of dementia. Dementia is more than a biomedical term. Cognitive impairment is considered a dynamic outcome of how an individual interacts with cognitive challenges. To focus on amyloid deposition as a single etiology for AD does not adequately capture the social implications and geriatric aspects of dementia. Moreover, MCI is nosologically questionable. Unlike a diagnosis of AD, for which a prototype has been well established, MCI is defined by operational criteria and there are no cases seen as typical MCI. Biofluid and imaging markers are under active development for early detection of amyloid deposition and neurofibrillary tangles in the brain, whereas vascular risks, chronic medical diseases, and polypharmacy continue to add to the complexity of dementia in old age. The paradigm of dementia care policy may shift to early diagnosis of AD pathology and comprehensive care for chronic diseases in the elderly population.

The borderland between normal aging and dementia

PubMed Central

Lo, Raymond Y.

2017-01-01

Alzheimer's disease (AD) has become a global health issue as the population ages. There is no effective treatment to protect against its occurrence or progression. Some argue that the lack of treatment response is due to delays in diagnosis. By the time a diagnosis of AD is made, neurodegenerative changes are at the stage where very few neurons can be salvaged by medication. The AD research community has developed the idea of mild cognitive impairment (MCI) in an attempt to find predementia patients who might benefit from potentially therapeutic drugs that have proven ineffective in the past. However, MCI is heterogeneous in terms of its underlying pathology and practicality for predicting dementia. This article first reviews the conceptual evolution of MCI as the borderland between normal aging and dementia, and then proposes that built environment and sociocultural context are two key elements in formulating a diagnosis of dementia. Dementia is more than a biomedical term. Cognitive impairment is considered a dynamic outcome of how an individual interacts with cognitive challenges. To focus on amyloid deposition as a single etiology for AD does not adequately capture the social implications and geriatric aspects of dementia. Moreover, MCI is nosologically questionable. Unlike a diagnosis of AD, for which a prototype has been well established, MCI is defined by operational criteria and there are no cases seen as typical MCI. Biofluid and imaging markers are under active development for early detection of amyloid deposition and neurofibrillary tangles in the brain, whereas vascular risks, chronic medical diseases, and polypharmacy continue to add to the complexity of dementia in old age. The paradigm of dementia care policy may shift to early diagnosis of AD pathology and comprehensive care for chronic diseases in the elderly population. PMID:28757769

AChE Inhibitors and NMDA Receptor Antagonists in Advanced Alzheimer's Disease.

PubMed

Glynn-Servedio, Brianna E; Ranola, Trisha Seys

2017-09-01

The objective of this article is to review the available evidence for duration of treatment with, and considerations for discontinuation of, acetylcholinesterase inhibitors and N-methyl-d-aspartate receptor antagonists in Alzheimer's disease. Literature searches of clinical trials and meta-analyses were conducted using PubMed with the search terms Alzheimer's, dementia, donepezil, galantamine, memantine, and rivastigmine. References from included trials were also used to find additional citations. 2,925 articles were initially identified. Twenty-one studies were included that looked at the use of acetylcholinesterase inhibitors and/or memantine in the treatment of moderate-to-severe Alzheimer's dementia. Several clinical trials have demonstrated small improvements in measures of cognition and activities of daily living with medications used to treat dementia. However, not all patients will benefit from treatment, and the impact of treatment on long-term outcomes, including institutionalization, remains unclear. This paper reviews the available data to support the use of acetylcholinesterase inhibitors and/or memantine in patients with advanced Alzheimer's disease, including those in nursing facilities, and reviews recommendations for consideration of therapy discontinuation. The evidence to support a specific time frame for discontinuation of Alzheimer's disease treatment is limited. It is reasonable to stop a medication if there is no noticeable benefit after the first three months of treatment or once a patient's dementia progresses to a point where there would be no meaningful benefit from continued therapy.

Neurocognitive differential diagnosis of dementing diseases: Alzheimer's Dementia, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder.

PubMed

Braaten, Alyssa J; Parsons, Thomas D; McCue, Robert; Sellers, Alfred; Burns, William J

2006-11-01

Similarities in presentation of Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder, pose differential diagnosis challenges. The current study identifies specific neuropsychological patterns of scores for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder. Neuropsychological domains directly assessed in the study included: immediate memory, delayed memory, confrontational naming, verbal fluency, attention, concentration, and executive functioning. The results reveal specific neuropsychological comparative profiles for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder. The identification of these profiles will assist in the differential diagnosis of these disorders and aid in patient treatment.

Core outcome measures for interventions to prevent or slow the progress of dementia for people living with mild to moderate dementia: Systematic review and consensus recommendations

PubMed Central

Groskreutz, Derek; Grinbergs-Saull, Anna; Howard, Rob; O’Brien, John T.; Mountain, Gail; Woods, Bob; Perneczky, Robert; McCleery, Jenny; Pickett, James; Challis, David; Charlesworth, Georgina; Featherstone, Katie; Jones, Roy; Schneider, Justine; Shepperd, Sasha; Thompson-Coon, Jo; Ballard, Clive; Burns, Alistair; Garrard, Peter; Kehoe, Patrick; Passmore, Peter; Robinson, Louise

2017-01-01

Background There are no disease-modifying treatments for dementia. There is also no consensus on disease modifying outcomes. We aimed to produce the first evidence-based consensus on core outcome measures for trials of disease modification in mild-to-moderate dementia. Methods and findings We defined disease-modification interventions as those aiming to change the underlying pathology. We systematically searched electronic databases and previous systematic reviews for published and ongoing trials of disease-modifying treatments in mild-to-moderate dementia. We included 149/22,918 of the references found; with 81 outcome measures from 125 trials. Trials involved participants with Alzheimer’s disease (AD) alone (n = 111), or AD and mild cognitive impairment (n = 8) and three vascular dementia. We divided outcomes by the domain measured (cognition, activities of daily living, biological markers, neuropsychiatric symptoms, quality of life, global). We calculated the number of trials and of participants using each outcome. We detailed psychometric properties of each outcome. We sought the views of people living with dementia and family carers in three cities through Alzheimer’s society focus groups. Attendees at a consensus conference (experts in dementia research, disease-modification and harmonisation measures) decided on the core set of outcomes using these results. Recommended core outcomes were cognition as the fundamental deficit in dementia and to indicate disease modification, serial structural MRIs. Cognition should be measured by Mini Mental State Examination or Alzheimer's Disease Assessment Scale-Cognitive Subscale. MRIs would be optional for patients. We also made recommendations for measuring important, but non-core domains which may not change despite disease modification. Limitations Most trials were about AD. Specific instruments may be superseded. We searched one database for psychometric properties. Interpretation This is the first review to identify the 81 outcome measures the research community uses for disease-modifying trials in mild-to-moderate dementia. Our recommendations will facilitate designing, comparing and meta-analysing disease modification trials in mild-to-moderate dementia, increasing their value. Trial registration PROSPERO no. CRD42015027346. PMID:28662127

Evaluation of the Digital Alzheimer Center: Testing Usability and Usefulness of an Online Portal for Patients with Dementia and Their Carers

PubMed Central

Droes, Rose-Marie; Sikkes, Sietske; Oostra, Ellen; Lemstra, Afina W

2016-01-01

Background Dementia is a progressive and highly disabling neurodegenerative disease that will likely become highly prevalent in the future due to the globally aging population. To improve health care efficiency and quality for dementia care, eHealth could help with, for example, an online portal, such as the Digital Alzheimer Center (DAC) of the Vrije Universiteit Medical Center Amsterdam. It provides up-to-date disease information, peer-to-peer contact, and methods for contacting the hospital and health professionals. Objective We aimed to investigate the usability and usefulness of the DAC for patients with dementia and carers to get insight into the feasibility and value of this eHealth app in dementia care and to recommend potential improvements. Methods A descriptive study among patients, carers, and health care professionals was performed. Mixed methods were used, consisting of observations (n=10, 4 people with dementia, 6 carers), an online survey (n=287; 88 patients, 199 carers), and semistructured interviews (n=18; 6 patients, 6 carers, 6 health care professionals). During the observations, participants performed a set of five different prescribed tasks on the portal. Speed, number of errors, and navigation were noted. The online survey aimed to assess users’ opinions on the portal’s usability and usefulness. Semistructured interviews were conducted in a subsample of patients, carers, and health care professionals to gain more in-depth information. Results In the usability assessment, eight categories of errors were distinguished, of which three were of critical, two of medium, and three of low severity. In the survey, 45% (40/88) of the patients and 53% (105/199) of the carers indicated they used the portal. In all, 33% (12/36) of patients and 61% (62/102) of carers found it easy to learn to work with the portal. Most considered the DAC generally useful: 65% (17/26) of patients and 78% (67/86) of carers found the DAC useful, especially for understanding dementia (patients: 64%, 16/25; carers: 62%, 53/86). In the semistructured interviews, the site was generally rated positively on usability and usefulness and being well designed. People with dementia and carers indicated it helped them to understand and deal with dementia. Conclusions To our knowledge, this is the first study investigating the usability and usefulness of an Internet portal especially designed for people with dementia and their carers. An online patient portal could be a useful means to help to support patients and carers in dealing with dementia: the majority of users positively evaluated usability and usefulness of the portal, and appreciated the information on it. However, only a minority of patients found it easy to work with the portal. Good design and frequent usability testing is essential to offer a good online portal. PMID:27444209

Evaluation of personalised, one-to-one interaction using Montessori-type activities as a treatment of challenging behaviours in people with dementia: the study protocol of a crossover trial.

PubMed

van der Ploeg, Eva S; O'Connor, Daniel W

2010-01-24

The agitated behaviours that accompany dementia (e.g. pacing, aggression, calling out) are stressful to both nursing home residents and their carers and are difficult to treat. Behaviours stemming from pain, major depression or psychosis benefit from treatment with analgesics, antidepressants or antipsychotics. In other cases, psychotropic medications have limited efficacy but are used very widely. Therefore, increasingly more attention has been paid to nonpharmacological interventions which are associated with fewer risks. The aim of the current study is to test if personalised one-to-one interaction activities based on Montessori principles will reduce the frequency of behavioural symptoms of dementia significantly more than a relevant control condition. We will conduct a controlled trial with randomised cross-over between conditions. Persons with moderate to severe dementia and associated behavioural problems living in aged care facilities will be included in the study. Consented, willing participants will be assigned in random order to Montessori or control blocks for two weeks then switched to the other condition. Montessori activities derive from the principles espoused by Maria Montessori and subsequent educational theorists to promote engagement in learning, namely task breakdown, guided repetition, progression in difficulty from simple to complex, and the careful matching of demands to levels of competence. The control intervention consists of conversation or reading from and looking at pictures in a newspaper to control for non-specific benefits of one-to-one interaction. Presence of target behaviour will be noted as well as level of engagement and type of affect displayed. Secondary measures also include the Cohen-Mansfield Agitation Inventory and information on time and funds spend to prepare the activities. If our results show that use of Montessori activities is effective in treating challenging behaviours in individuals with dementia, it will potentially provide a safer and more enjoyable intervention rather than reliance on pharmacology alone. Australian New Zealand Clinical Trials Registry - ACTRN12609000564257.

Systematic literature review of methodologies and data sources of existing economic models across the full spectrum of Alzheimer's disease and dementia from apparently healthy through disease progression to end of life care: a systematic review protocol.

PubMed

Karagiannidou, Maria; Wittenberg, Raphael; Landeiro, Filipa Isabel Trigo; Park, A-La; Fry, Andra; Knapp, Martin; Gray, Alastair M; Tockhorn-Heidenreich, Antje; Castro Sanchez, Amparo Yovanna; Ghinai, Isaac; Handels, Ron; Lecomte, Pascal; Wolstenholme, Jane

2018-06-08

Dementia is one of the greatest health challenges the world will face in the coming decades, as it is one of the principal causes of disability and dependency among older people. Economic modelling is used widely across many health conditions to inform decisions on health and social care policy and practice. The aim of this literature review is to systematically identify, review and critically evaluate existing health economics models in dementia. We included the full spectrum of dementia, including Alzheimer's disease (AD), from preclinical stages through to severe dementia and end of life. This review forms part of the Real world Outcomes across the Alzheimer's Disease spectrum for better care: multimodal data Access Platform (ROADMAP) project. Electronic searches were conducted in Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, Economic Literature Database, NHS Economic Evaluation Database, Cochrane Central Register of Controlled Trials, Cost-Effectiveness Analysis Registry, Research Papers in Economics, Database of Abstracts of Reviews of Effectiveness, Science Citation Index, Turning Research Into Practice and Open Grey for studies published between January 2000 and the end of June 2017. Two reviewers will independently assess each study against predefined eligibility criteria. A third reviewer will resolve any disagreement. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed using the Phillips checklist for decision analytic modelling. A narrative synthesis will be used. The results will be made available in a scientific peer-reviewed journal paper, will be presented at relevant conferences and will also be made available through the ROADMAP project. CRD42017073874. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Systematic literature review of methodologies and data sources of existing economic models across the full spectrum of Alzheimer’s disease and dementia from apparently healthy through disease progression to end of life care: a systematic review protocol

PubMed Central

Karagiannidou, Maria; Wittenberg, Raphael; Landeiro, Filipa Isabel Trigo; Park, A-La; Fry, Andra; Knapp, Martin; Tockhorn-Heidenreich, Antje; Castro Sanchez, Amparo Yovanna; Ghinai, Isaac; Handels, Ron; Lecomte, Pascal; Wolstenholme, Jane

2018-01-01

Introduction Dementia is one of the greatest health challenges the world will face in the coming decades, as it is one of the principal causes of disability and dependency among older people. Economic modelling is used widely across many health conditions to inform decisions on health and social care policy and practice. The aim of this literature review is to systematically identify, review and critically evaluate existing health economics models in dementia. We included the full spectrum of dementia, including Alzheimer’s disease (AD), from preclinical stages through to severe dementia and end of life. This review forms part of the Real world Outcomes across the Alzheimer’s Disease spectrum for better care: multimodal data Access Platform (ROADMAP) project. Methods and analysis Electronic searches were conducted in Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, Economic Literature Database, NHS Economic Evaluation Database, Cochrane Central Register of Controlled Trials, Cost-Effectiveness Analysis Registry, Research Papers in Economics, Database of Abstracts of Reviews of Effectiveness, Science Citation Index, Turning Research Into Practice and Open Grey for studies published between January 2000 and the end of June 2017. Two reviewers will independently assess each study against predefined eligibility criteria. A third reviewer will resolve any disagreement. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed using the Phillips checklist for decision analytic modelling. A narrative synthesis will be used. Ethics and dissemination The results will be made available in a scientific peer-reviewed journal paper, will be presented at relevant conferences and will also be made available through the ROADMAP project. PROSPERO registration number CRD42017073874. PMID:29884696

Evaluation of diet and life style in etiopathogenesis of senile dementia: A survey study

PubMed Central

Chaudhuri, Kundan; Samarakoon, S. M. S.; Chandola, H M; Kumar, Rajesh; Ravishankar, B.

2011-01-01

Mind and body are inseparable entities and influences each other until death. Many factors such as stress, anxiety, depression, negative thoughts, unhealthy life style, unwholesome diet etc., disturb mental and physical wellbeing. Senile dementia is the mental deterioration, i.e, loss of intellectual ability associated with old age. It causes progressive deterioration of mental faculties, e.g., memory, intellect, attention, thinking, comprehension and personality, with preservation of normal level of consciousness. Two major types of senile dementia have been identified, namely that due to generalized atrophy in the cortical area of the brain (Alzheimer's type) and that due to vascular disorders mainly due to stroke. According to DSM-IV (diagnostic and statistical manual of mental disorders), the essential feature of dementia is the development of multiple cognitive deficits that include memory impairment and at least one of the following cognitive disturbances such as aphasia, apraxia, agnosia, or a disturbance in executive function. For the present study, a standardized questionnaire in the form of proforma incorporating types of foods (madhura, amla and lavana rasayukta ahara etc.) and life style (divaswapna, ratrijagarana and manasika bhavas etc) is prepared. To assess manasika bhava, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Brief Psychiatry Rating Scale, and standardized gradations of anumana pariksha of manasika bhavas mentioned by Charaka at Vimana Sthana 4/8 were adopted. In this study, most of the patients had disturbed sleep, tendency to indulge in defective dietary habits and kapha vitiating diets and life style. On Hamilton Anxiety Rating Scale, patients had anxiety, tension, depression, difficulty in concentration, and memory. On Hamilton Depression Rating Scale, these patients had anxiety, depression, and hypochondriasis. On Brief Psychiatry Rating Scale, psychological factors affected include: anxiety, depression, somatic concern and tension, etc. The data reflects that unwholesome diet and disturbed mental health plays an important role in etiopathogenesis of senile dementia. PMID:22408297

PubMed Central

Simoncini, Costanza; Siciliano, Gabriele; Tognoni, Gloria

2017-01-01

ANT1 is one of the nuclear genes responsible of autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA multiple deletions. The course of ANT1- related adPEO is relatively benign, symptoms being generally restricted to skeletal muscle. Here we report the case of an Italian 74 years old woman with ANT1-related adPEO and dementia. Further studies are needed to assess the prevalence of central neurological manifestations in ANT1 mitochondrial disease. PMID:28690391

Nutrition and prevention of Alzheimer’s dementia

PubMed Central

Swaminathan, Arun; Jicha, Gregory A.

2014-01-01

A nutritional approach to prevent, slow, or halt the progression of disease is a promising strategy that has been widely investigated. Much epidemiologic data suggests that nutritional intake may influence the development and progression of Alzheimer’s dementia (AD). Modifiable, environmental causes of AD include potential metabolic derangements caused by dietary insufficiency and or excess that may be corrected by nutritional supplementation and or dietary modification. Many nutritional supplements contain a myriad of health promoting constituents (anti-oxidants, vitamins, trace minerals, flavonoids, lipids, …etc.) that may have novel mechanisms of action affecting cellular health and regeneration, the aging process itself, or may specifically disrupt pathogenic pathways in the development of AD. Nutritional modifications have the advantage of being cost effective, easy to implement, socially acceptable and generally safe and devoid of significant adverse events in most cases. Many nutritional interventions have been studied and continue to be evaluated in hopes of finding a successful agent, combination of agents, or dietary modifications that can be used for the prevention and or treatment of AD. The current review focuses on several key nutritional compounds and dietary modifications that have been studied in humans, and further discusses the rationale underlying their potential utility for the prevention and treatment of AD. PMID:25368575

Analysis of risk factors for mild cognitive impairment based on word list memory test results and questionnaire responses in healthy Japanese individuals registered in an online database.

PubMed

Ogawa, Masayo; Sone, Daichi; Maruo, Kazushi; Shimada, Hiroyuki; Suzuki, Keisuke; Watanabe, Hiroshi; Matsuda, Hiroshi; Mizusawa, Hidehiro

2018-01-01

Although the development of effective therapeutic drugs and radical treatment options for dementia and Alzheimer's disease (AD) remains urgent, progress in recent clinical trials of AD drugs has been less than adequate. In order to advance the progress of clinical trials, it is necessary to establish more efficient methods of recruitment. In Japan, there are registration systems stratified by mild cognitive impairment and preclinical and clinical stages of early and advanced stage dementia, but there is no registration system for healthy individuals yet. Therefore, in the present study, we developed a large-scale, internet-based health registry to investigate factors associated with cognitive function among registered participants. A total of 1038 participants completed the initial questionnaire and word list memory test. Among these participants, 353 individuals completed a second questionnaire and memory test. Stepwise multiple regression analysis was performed using IBM SPSS version 23.0 for Windows at a statistical significance level of p<0.05. We found that mood, motivation, and a decreased ability to perform activities of daily living were significantly associated with cognitive function. The results of the present study suggest that maintaining social involvement is important to prevent decreases in physical activity, daily function, mood, and motivation.

The evaluation of a healthcare passport to improve quality of care and communication for people living with dementia (EQuIP): a protocol paper for a qualitative, longitudinal study.

PubMed

Leavey, Gerard; Abbott, Aine; Watson, Max; Todd, Stephen; Coates, Vivien; McIlfactrick, Sonja; McCormack, Brendan; Waterhouse-Bradley, Bethany; Curran, Emma

2016-08-09

There is an urgent need for the development of simple communication tools that convey the strengths, assets, and healthcare needs of people living with dementia. A Healthcare Passport may improve communication with range of health and social support services, enhancing quality and continuity of care, and to permit a consideration of the challenges and how these might be managed effectively and compassionately. This study aims to evaluate the acceptability and use of this type of intervention for people living with dementia and their carers. This is a qualitative longitudinal study informed by a critical realist review. The participants will be individuals identified as having mild-moderate dementia and informal carers. The in-depth interviews will occur at three points over the course of 18 months as they use the passport. This will be supplemented by analysis of the content of the passports and information from health and social care providers on the daily practicalities of using the passport in a range of healthcare settings. By using a critical realist review and a qualitative, longitudinal approach, the study allows for the assessment of a complex intervention in a manner which goes beyond evaluating the basic efficacy of the passport, but looking more deeply at how it worked, for whom, and in what context. It has the potential to develop new data on how interventions improve communication across a range of service providers, while encouraging health and social care professionals to respect and encourage the development of self-management and retention of personhood throughout the progression of life-limiting illnesses.

Assessment of Functional Change and Cognitive Correlates in the Progression from Healthy Cognitive Aging to Dementia

PubMed Central

Schmitter-Edgecombe, Maureen; Parsey, Carolyn M.

2014-01-01

Objective There is currently limited understanding of the course of change in everyday functioning that occurs with normal aging and dementia. To better characterize the nature of this change, we evaluated the types of errors made by participants as they performed everyday tasks in a naturalistic environment. Method Participants included cognitively healthy younger adults (YA; N = 55) and older adults (OA; N =88), and individuals with mild cognitive impairment (MCI: N =55) and dementia (N = 18). Participants performed eight scripted everyday activities (e.g., filling a medication dispenser) while under direct observation in a campus apartment. Task performances were coded for the following errors: inefficient actions, omissions, substitutions, and irrelevant actions. Results Performance accuracy decreased with age and level of cognitive impairment. Relative to the YAs, the OA group exhibited more inefficient actions which were linked to performance on neuropsychological measures of executive functioning. Relative to the OAs, the MCI group committed significantly more omission errors which were strongly linked to performance on memory measures. All error types were significantly more prominent in individuals with dementia. Omission errors uniquely predicted everyday functional status as measured by both informant-report and a performance-based measure. Conclusions These findings suggest that in the progression from healthy aging to MCI, everyday task difficulties may evolve from task inefficiencies to task omission errors, leading to inaccuracies in task completion that are recognized by knowledgeable informants. Continued decline in cognitive functioning then leads to more substantial everyday errors, which compromise ability to live independently. PMID:24933485

Language, Executive Function and Social Cognition in the Diagnosis of Frontotemporal Dementia Syndromes

PubMed Central

Harciarek, Michał; Cosentino, Stephanie

2015-01-01

Frontotemporal dementia (FTD) represents a spectrum of non-Alzheimer’s degenerative conditions associated with focal atrophy of the frontal and/or temporal lobes. Frontal and temporal regions of the brain have been shown to be strongly involved in executive function, social cognition and language processing and, thus, deficits in these domains are frequently seen in patients with FTD or may even be hallmarks of a specific FTD subtype ( i.e., relatively selective and progressive language impairment in primary progressive aphasia). In this review, we have attempted to delineate how language, executive function, and social cognition may contribute to the diagnosis of FTD syndromes, namely the behavioral variant FTD as well as the language variants of FTD including the three subtypes of primary progressive aphasia (PPA): non-fluent/agrammatic, semantic, and logopenic. This review also addresses the extent to which deficits in these cognitive areas contribute to the differential diagnosis of FTD versus AD. Finally, early clinical determinants of pathology are briefly discussed and contemporary challenges to the diagnosis of FTD are presented. PMID:23611348

The established and emerging roles of astrocytes and microglia in amyotrophic lateral sclerosis and frontotemporal dementia.

PubMed

Radford, Rowan A; Morsch, Marco; Rayner, Stephanie L; Cole, Nicholas J; Pountney, Dean L; Chung, Roger S

2015-01-01

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two progressive, fatal neurodegenerative syndromes with considerable clinical, genetic and pathological overlap. Clinical symptoms of FTD can be seen in ALS patients and vice versa. Recent genetic discoveries conclusively link the two diseases, and several common molecular players have been identified (TDP-43, FUS, C9ORF72). The definitive etiologies of ALS and FTD are currently unknown and both disorders lack a cure. Glia, specifically astrocytes and microglia are heavily implicated in the onset and progression of neurodegeneration witnessed in ALS and FTD. In this review, we summarize the current understanding of the role of microglia and astrocytes involved in ALS and FTD, highlighting their recent implications in neuroinflammation, alterations in waste clearance involving phagocytosis and the newly described glymphatic system, and vascular abnormalities. Elucidating the precise mechanisms of how astrocytes and microglia are involved in ALS and FTD will be crucial in characterizing these two disorders and may represent more effective interventions for disease progression and treatment options in the future.

The established and emerging roles of astrocytes and microglia in amyotrophic lateral sclerosis and frontotemporal dementia

PubMed Central

Radford, Rowan A.; Morsch, Marco; Rayner, Stephanie L.; Cole, Nicholas J.; Pountney, Dean L.; Chung, Roger S.

2015-01-01

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two progressive, fatal neurodegenerative syndromes with considerable clinical, genetic and pathological overlap. Clinical symptoms of FTD can be seen in ALS patients and vice versa. Recent genetic discoveries conclusively link the two diseases, and several common molecular players have been identified (TDP-43, FUS, C9ORF72). The definitive etiologies of ALS and FTD are currently unknown and both disorders lack a cure. Glia, specifically astrocytes and microglia are heavily implicated in the onset and progression of neurodegeneration witnessed in ALS and FTD. In this review, we summarize the current understanding of the role of microglia and astrocytes involved in ALS and FTD, highlighting their recent implications in neuroinflammation, alterations in waste clearance involving phagocytosis and the newly described glymphatic system, and vascular abnormalities. Elucidating the precise mechanisms of how astrocytes and microglia are involved in ALS and FTD will be crucial in characterizing these two disorders and may represent more effective interventions for disease progression and treatment options in the future. PMID:26578880

Potential Role of Neuroimaging Markers for Early Diagnosis of Dementia in Primary Care.

PubMed

Teipel, Stefan; Kilimann, Ingo; Thyrian, Jochen R; Kloppel, Stefan; Hoffmann, Wolfgang

2018-01-01

The use of imaging markers for the diagnosis of predementia and early dementia stages of Alzheimer's disease (AD) has widely been explored in research settings and specialized care. The use of these markers in primary care has yet to be established. Summarize current evidence for the usefulness of imaging markers for AD in primary compared to specialized care settings. Selective overview of the literature, and pilot data on the use of MRI-based hippocampus and basal forebrain volumetry for the discrimination of AD dementia and mild cognitive impairment (MCI) cases from healthy controls in 58 cases from a primary care cohort and 58 matched cases from a memory clinic's sample. Molecular imaging marker of amyloid pathology, and volumetric markers of regional and whole brain atrophy support the diagnosis of AD dementia and MCI due to AD, and contribute to confidence in the differential diagnosis of AD and non-AD related dementias in specialized care. Limited evidence from the literature and our primary care cohort suggests that the diagnostic accuracy of volumetric imaging markers may be similar in the dementia stage of AD, but may be inferior for cases with MCI in primary compared with specialized care. Evidence is still widely lacking on the use of imaging markers for early and differential diagnosis of AD dementia, and detection of prodromal AD in primary care. Further progress to fill this gap will depend on the availability of international multimodal data from well-defined primary care cohorts. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

'Y' feel me?' How do we understand the person with dementia?

PubMed

Hughes, Julian C

2013-05-01

As dementia progresses problems of understanding emerge. Eventually spoken language can be lost. And yet, even into the severer stages of dementia, close carers can often understand the person in a variety of ways. Loss of language is not just a practical problem. It raises philosophical issues too. As Wittgenstein suggested, understanding entails grasping a form of life. Our understanding of agitated, pacing behaviour is similarly based on a unique history, on culture, on context. Hence, a philosophy gestures at the foundations of care. There is the potential to feel the person's meaning, even when it cannot be spoken. This is not simply by means of an alternative to language. The philosophy suggests that our engagement with the person is through and through. Understanding anyone is more like an aesthetic judgement than a cognitive act.

Improvement of Visuo-spatial Function Assessed by Raven’s Colored Progressive Matrices in Dementia with Lewy Bodies by Donepezil Treatment

PubMed Central

Yoshino, Yuta; Mori, Takaaki; Yoshida, Taku; Toyota, Yasutaka; Shimizu, Hideaki; Iga, Jun-ichi; Nishitani, Shusaku; Ueno, Shu-ichi

2017-01-01

Objective Donepezil is used to improve cognitive impairment of dementia with Lewy bodies (DLB). Visuo-spatial dysfunction is a well-known symptom of DLB. Non-verbal Raven’s Colored Progressive Matrices (RCPM) were used to assess both visual perception and reasoning ability in DLB subjects treated with donepezil. Methods Twenty-one DLB patients (mean age, 78.7±4.5 years) were enrolled. RCPM assessment was performed at the time of starting donepezil and within one year after starting donepezil. Results There were significant improvements of RCPM in the total scores between one year donepezil treatment (p=0.013), in both Set A score (p=0.002) and Set AB score (p=0.015), but trend in the Set B score (p=0.083). Conclusion Donepezil is useful for improving visuo-spatial impairment in DLB, but not for problem-solving impairment. PMID:28783933

Framingham risk score can predict cognitive decline progression in Alzheimer's disease.

PubMed

Viticchi, Giovanna; Falsetti, Lorenzo; Buratti, Laura; Boria, Cristiano; Luzzi, Simona; Bartolini, Marco; Provinciali, Leandro; Silvestrini, Mauro

2015-11-01

The role of vascular factors in influencing cognitive decline has been extensively investigated, and some difficulties in defining their weight in dementia pathogenesis have emerged. The aim of the study was to investigate the relevance of the Framingham cardiovascular risk profile (FCRP) in influencing cognitive deterioration in a population of Alzheimer's disease (AD) patients. Two hundred eighty-four consecutive AD patients were enrolled. For each patient, FCRP score was calculated. We did a 1-year follow-up to quantify the cognitive decline by recording changes in the Clinical Dementia Rating score. The FCRP score predicted cognitive deterioration with an area under the curve of 0.63 (95% confidence interval: 0.57-0.69; p < 0.0001). In the subpopulation of patients with a genetic increased predisposition to develop cognitive deterioration and with an advanced vascular impairment, the FCRP predictive value significantly increased with an area under the curve of 0.77 (95% confidence interval: 0.52-0.93; p < 0.05). Our findings show that FCRP can predict the progression of deterioration in AD patients. This was particularly evident in patients with major genetic and atherosclerotic risk factors. Copyright © 2015 Elsevier Inc. All rights reserved.

Neurofibrillary Tangle Stage and the Rate of Progression of Alzheimer Symptoms: Modeling Using an Autopsy Cohort and Application to Clinical Trial Design

PubMed Central

Qian, Jing; T.Hyman, Bradley; Betensky, Rebecca A.

2017-01-01

Importance The heterogeneity of rate of clinical progression among patients with Alzheimer disease leads to difficulty in providing clinical counseling and diminishes the power of clinical trials using disease-modifying agents. Objective To gain a better understanding of the factors that affect the natural history of progression in Alzheimer disease for the purpose of improving both clinical care and clinical trial design. Design, Setting, and Participants A longitudinal cohort study of aging from 2005 to 2014 in the National Alzheimer Coordinating Center. Clinical evaluation of the participants was conducted in 31 National Institute on Aging’s Alzheimer Disease Centers. Nine hundred eighty-four participants in the National Alzheimer Coordinating Center cohort study who died and underwent autopsy and met inclusion and exclusion criteria. Main Outcomes and Measures We sought to model the possibility that knowledge of neurofibrillary tangle burden in the presence of moderate or frequent plaques would add to the ability to predict clinical rate of progression during the ensuing 2 to 3 years. We examined the National Alzheimer Coordinating Center autopsy data to evaluate the effect of different neurofibrillary tangle stages on the rates of progression on several standard clinical instruments: the Clinical Dementia Rating Scale sum of boxes, a verbal memory test (logical memory), and a controlled oral word association task (vegetable naming), implementing a reverse-time longitudinal modeling approach in conjunction with latent class estimation to adjust for unmeasured sources of heterogeneity. Results Several correlations between clinical variables and neurocognitive performance suggest a basis for heterogeneity: Higher education level was associated with lower Clinical Dementia Rating Scale sum of boxes (β = −0.19; P < .001), and frequent vs moderate neuritic plaques were associated with higher Clinical Dementia Rating Scale sum of boxes (β = 1.64; P < .001) and lower logical memory score (β = −1.07; P = .005). The rate of change of the clinical and cognitive scores varied depending on Braak stage, when adjusting for plaques, age of death, sex, education, and APOE genotype. For example, comparing high vs low Braak stage with other variables fixed, the logical memory score decreased a substantial 0.38 additional units per year (95% CI, −0.70 to −0.06; P = .02). Using these data, we estimate that a 300-participant clinical trial with end point of a 20% improvement in slope in rate of change of Clinical Dementia Rating Scale sum of boxes has 89% power when all participants in the trial are from the high Braak stage, compared with 29% power if Braak stage had not used for eligibility. Conclusions and Relevance We found that knowledge of neurofibrillary tangle stage, modeled as the sort of information that could be available from tau positron-emission tomography scans and its use to determine eligibility to a trial, could dramatically improve the power of clinical trials and equivalently reduce the required sample sizes of clinical trials. PMID:28288263

Family caregivers of patients with frontotemporal dementia: An integrative review.

PubMed

Caceres, Billy A; Frank, Mayu O; Jun, Jin; Martelly, Melissa T; Sadarangani, Tina; de Sales, Paloma Cesar

2016-03-01

The purpose of this integrative review is to: (1) identify the characteristics of family caregivers of patients with frontotemporal dementia, (2) explore the impact of providing care on family caregivers' health and well-being, and (3) identify coping strategies used by family caregivers. Frontotemporal dementia is thought to be the second most common form of dementia after Alzheimer's disease. Family caregivers of patients with frontotemporal dementia face unique challenges due to its early onset, behavioral symptoms, and slow progression of decline. However, there is a dearth of research evaluating the health and wellbeing of family caregivers of patients with frontotemporal dementia. An integrative review was conducted using the Whittemore and Knafl methodology. An electronic search of the literature was conducted using four electronic databases: PubMed, Embase, CINAHL, and Web of Science. The Crowe Critical Appraisal tool was used to evaluate the quality of the selected articles. Findings of 11 articles informed this integrative review. Family caregivers of patients with frontotemporal dementia identify behavioral disturbances as most troubling. Spouses and female caregivers experience greater caregiver burden, distress, increased rates of depression, as well as decreased sleep related to behavior disturbances. Though less explored, providing care to those with behavioral disturbances may also impact caregiver physical health. Additionally, female caregivers are most likely to employ coping strategies, most commonly, adaptation and reframing. Effective interventions to reduce family caregiver burden are poorly understood but family caregivers suggest education and internet-based support groups are most helpful. Family caregivers of patients with frontotemporal dementia experience significant distress, which impacts their health and wellbeing. It is important for healthcare providers who care for patients with frontotemporal dementia to recognize the unique needs of family caregivers. Future research should focus on examining interventions and strategies to reduce caregiver burden. Copyright © 2015 Elsevier Ltd. All rights reserved.

Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer’s disease

PubMed Central

Wiste, Heather J.; Vemuri, Prashanthi; Weigand, Stephen D.; Senjem, Matthew L.; Zeng, Guang; Bernstein, Matt A.; Gunter, Jeffrey L.; Pankratz, Vernon S.; Aisen, Paul S.; Weiner, Michael W.; Petersen, Ronald C.; Shaw, Leslie M.; Trojanowski, John Q.; Knopman, David S.

2010-01-01

Biomarkers of brain Aβ amyloid deposition can be measured either by cerebrospinal fluid Aβ42 or Pittsburgh compound B positron emission tomography imaging. Our objective was to evaluate the ability of Aβ load and neurodegenerative atrophy on magnetic resonance imaging to predict shorter time-to-progression from mild cognitive impairment to Alzheimer’s dementia and to characterize the effect of these biomarkers on the risk of progression as they become increasingly abnormal. A total of 218 subjects with mild cognitive impairment were identified from the Alzheimer’s Disease Neuroimaging Initiative. The primary outcome was time-to-progression to Alzheimer’s dementia. Hippocampal volumes were measured and adjusted for intracranial volume. We used a new method of pooling cerebrospinal fluid Aβ42 and Pittsburgh compound B positron emission tomography measures to produce equivalent measures of brain Aβ load from either source and analysed the results using multiple imputation methods. We performed our analyses in two phases. First, we grouped our subjects into those who were ‘amyloid positive’ (n = 165, with the assumption that Alzheimer's pathology is dominant in this group) and those who were ‘amyloid negative’ (n = 53). In the second phase, we included all 218 subjects with mild cognitive impairment to evaluate the biomarkers in a sample that we assumed to contain a full spectrum of expected pathologies. In a Kaplan–Meier analysis, amyloid positive subjects with mild cognitive impairment were much more likely to progress to dementia within 2 years than amyloid negative subjects with mild cognitive impairment (50 versus 19%). Among amyloid positive subjects with mild cognitive impairment only, hippocampal atrophy predicted shorter time-to-progression (P < 0.001) while Aβ load did not (P = 0.44). In contrast, when all 218 subjects with mild cognitive impairment were combined (amyloid positive and negative), hippocampal atrophy and Aβ load predicted shorter time-to-progression with comparable power (hazard ratio for an inter-quartile difference of 2.6 for both); however, the risk profile was linear throughout the range of hippocampal atrophy values but reached a ceiling at higher values of brain Aβ load. Our results are consistent with a model of Alzheimer’s disease in which Aβ deposition initiates the pathological cascade but is not the direct cause of cognitive impairment as evidenced by the fact that Aβ load severity is decoupled from risk of progression at high levels. In contrast, hippocampal atrophy indicates how far along the neurodegenerative path one is, and hence how close to progressing to dementia. Possible explanations for our finding that many subjects with mild cognitive impairment have intermediate levels of Aβ load include: (i) individual subjects may reach an Aβ load plateau at varying absolute levels; (ii) some subjects may be more biologically susceptible to Aβ than others; and (iii) subjects with mild cognitive impairment with intermediate levels of Aβ may represent individuals with Alzheimer’s disease co-existent with other pathologies. PMID:20935035

Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy.

PubMed

Vanni, Nicola; Fruscione, Floriana; Ferlazzo, Edoardo; Striano, Pasquale; Robbiano, Angela; Traverso, Monica; Sander, Thomas; Falace, Antonio; Gazzerro, Elisabetta; Bramanti, Placido; Bielawski, Jacek; Fassio, Anna; Minetti, Carlo; Genton, Pierre; Zara, Federico

2014-08-01

Alterations of sphingolipid metabolism are implicated in the pathogenesis of many neurodegenerative disorders. We identified a homozygous nonsynonymous mutation in CERS1, the gene encoding ceramide synthase 1, in 4 siblings affected by a progressive disorder with myoclonic epilepsy and dementia. CerS1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18-ceramides. We demonstrated that the mutation decreases C18-ceramide levels. In addition, we showed that downregulation of CerS1 in a neuroblastoma cell line triggers ER stress response and induces proapoptotic pathways. This study demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans. © 2014 American Neurological Association.

Creutzfeldt-Jakob Disease Presenting With Dizziness and Gaze-Evoked Nystagmus: A Case Report.

PubMed

Choi, Yun-Ju; Kang, Kyung-Wook; Lee, Sae-Young; Kang, Seung-Ho; Lee, Seung-Han; Kim, Byeong C

2016-02-01

Sporadic Creutzfeldt-Jakob disease (CJD) is clinically characterized by rapidly progressive dementia combined with other cardinal symptoms, such as myoclonus, visual or cerebellar disturbances, extrapyramidal or pyramidal disturbance, and akinetic mutism. However, as an initial manifestation, focal neurologic deficits other than the aforementioned or nonspecific generalized symptoms may lead to a misdiagnosis or a delayed diagnosis. The authors report a case of 66-year-old male patient with sporadic CJD who had dizziness, gaze-evoked nystagmus (GEN), and other central eye signs (impaired smooth pursuit, saccadic dysmetria) as an initial manifestation without dementia. The central eye signs led us to perform brain magnetic resonance images, which showed abnormal cortical high-signal intensity in both the cerebral and cerebellar hemispheres including the vestibulocerebellum. We reached a presumptive diagnosis of CJD, but the findings did not meet diagnostic criteria for probable CJD at that time. Three weeks after the initial work-ups, the patient presented with typical neurological findings of CJD: rapidly progressive dementia, akinetic mutism, and myoclonus of the left arm. Cerebrospinal fluid was positive for 14-3-3 protein, and electroencephalography showed periodic sharp wave complexes. In this patient, GEN and other central eye signs provided diagnostic clues for CJD. These unusual neurological manifestations may help physicians have a thorough knowledge of early deficits of CJD.

[Pharmacological treatment of dementia: when, how and for how long. Recommendations of the Working Group on Dementia of the Catalan Society of Geriatrics and Gerontology].

PubMed

Rodríguez, Daniel; Formiga, Francesc; Fort, Isabel; Robles, María José; Barranco, Elena; Cubí, Dolors

2012-01-01

Dementia in general--and Alzheimer's disease (AD) in particular--are bound to loom large among the most acute healthcare, social, and public health problems of the 21st century. AD shows a degenerative progression that can be slowed down--yet not halted--by today's most widely accepted specific treatments (those based on cholinesterase inhibitors as well as those using memantine). There is enough evidence to consider these treatments advisable for the mild, moderate and severe phases of the illness. However, in the final stage of the disease, a decision has to be made on whether to withdraw such treatment or not. In this paper, the Working Group on Dementia for the Catalan Society of Geriatrics and Gerontology reviews the use of these specific pharmacological treatments for AD, and, drawing on the scientific evidence thus gathered, makes a series of recommendations on when, how, and for how long, the currently existing specific pharmacological treatments should be used. Copyright © 2011 SEGG. Published by Elsevier Espana. All rights reserved.

Rational decision-making about treatment and care in dementia: a contradiction in terms?

PubMed

Wolfs, Claire A G; de Vugt, Marjolein E; Verkaaik, Mike; Haufe, Marc; Verkade, Paul-Jeroen; Verhey, Frans R J; Stevens, Fred

2012-04-01

To gain caregivers' insights into the decision-making process in dementia patients with regard to treatment and care. Four focus group interviews (n=29). The decision-making process consists of three elementary components: (1) identifying an individual's needs; (2) exploring options; and (3) making a choice. The most important phase is the exploration phase as it is crucial for the acceptance of the disease. Furthermore, the decision is experienced more as an emotional choice than a rational one. It is influenced by personal preferences whereas practical aspects do not seem to play a substantial role. Several aspects make decision-making in dementia different from decision-making in the context of other chronic diseases: (1) the difficulty accepting dementia; (2) the progressive nature of dementia; (3) patient's reliance on surrogate decision-making; and (4) strong emotions. Due to these aspects, the decision-making process is very time-consuming, especially the crucial exploration phase. A more active role is required of both the caregiver and the health care professional especially in the exploration phase, enabling easier acceptance and adjustment to the disease. Acceptance is an important condition for reducing anxiety and resistance to care that may offer significant benefits in the future. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Music models aberrant rule decoding and reward valuation in dementia

PubMed Central

Clark, Camilla N; Golden, Hannah L; McCallion, Oliver; Nicholas, Jennifer M; Cohen, Miriam H; Slattery, Catherine F; Paterson, Ross W; Fletcher, Phillip D; Mummery, Catherine J; Rohrer, Jonathan D; Crutch, Sebastian J; Warren, Jason D

2018-01-01

Abstract Aberrant rule- and reward-based processes underpin abnormalities of socio-emotional behaviour in major dementias. However, these processes remain poorly characterized. Here we used music to probe rule decoding and reward valuation in patients with frontotemporal dementia (FTD) syndromes and Alzheimer’s disease (AD) relative to healthy age-matched individuals. We created short melodies that were either harmonically resolved (‘finished’) or unresolved (‘unfinished’); the task was to classify each melody as finished or unfinished (rule processing) and rate its subjective pleasantness (reward valuation). Results were adjusted for elementary pitch and executive processing; neuroanatomical correlates were assessed using voxel-based morphometry. Relative to healthy older controls, patients with behavioural variant FTD showed impairments of both musical rule decoding and reward valuation, while patients with semantic dementia showed impaired reward valuation but intact rule decoding, patients with AD showed impaired rule decoding but intact reward valuation and patients with progressive non-fluent aphasia performed comparably to healthy controls. Grey matter associations with task performance were identified in anterior temporal, medial and lateral orbitofrontal cortices, previously implicated in computing diverse biological and non-biological rules and rewards. The processing of musical rules and reward distils cognitive and neuroanatomical mechanisms relevant to complex socio-emotional dysfunction in major dementias. PMID:29186630

Neurobiology of Alzheimer’s Disease: Integrated Molecular, Physiological, Anatomical, Biomarker, and Cognitive Dimensions

PubMed Central

Raskin, Joel; Cummings, Jeffrey; Hardy, John; Schuh, Kory; Dean, Robert A.

2015-01-01

Background: Alzheimer’s disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder with interrelated molecular, physiological, anatomical, biomarker, and cognitive dimensions. Methods: This article reviews the biological changes (genetic, molecular, and cellular) underlying AD and their correlation with the clinical syndrome. Results: Dementia associated with AD is related to the aberrant production, processing, and clearance of beta-amyloid and tau. Beta-amyloid deposition in brain follows a distinct spatial progression starting in the basal neocortex, spreading throughout the hippocampus, and eventually spreading to the rest of the cortex. The spread of tau pathology through neural networks leads to a distinct and consistent spatial progression of neurofibrillary tangles, beginning in the transentorhinal and hippocampal region and spreading superolaterally to the primary areas of the neocortex. Synaptic dysfunction and cell death is shown by progressive loss of cerebral metabolic rate for glucose and progressive brain atrophy. Decreases in synapse number in the dentate gyrus of the hippocampus correlate with declining cognitive function. Amyloid changes are detectable in cerebrospinal fluid and with amyloid imaging up to 20 years prior to the onset of symptoms. Structural atrophy may be detectable via magnetic resonance imaging up to 10 years before clinical signs appear. Conclusion: This review highlights the progression of biological changes underlying AD and their association with the clinical syndrome. Many changes occur before overt symptoms are evident and biomarkers provide a means to detect AD pathology even in patients without symptoms. PMID:26412218

Health economic evaluation of treatments for Alzheimer's disease: impact of new diagnostic criteria.

PubMed

Wimo, A; Ballard, C; Brayne, C; Gauthier, S; Handels, R; Jones, R W; Jonsson, L; Khachaturian, A S; Kramberger, M

2014-03-01

The socio-economic impact of Alzheimer's disease (AD) and other dementias is enormous, and the potential economic challenges ahead are clear given the projected future numbers of individuals with these conditions. Because of the high prevalence and cost of dementia, it is very important to assess any intervention from a cost-effectiveness viewpoint. The diagnostic criteria for preclinical AD suggested by the National Institute on Aging and Alzheimer's Association workgroups in combination with the goal of effective disease-modifying treatment (DMT) are, however, a challenge for clinical practice and for the design of clinical trials. Key issues for future cost-effectiveness studies include the following: (i) the consequences for patients if diagnosis is shifted from AD-dementia to predementia states, (ii) bridging the gap between clinical trial populations and patients treated in clinical practice, (iii) translation of clinical trial end-points into measures that are meaningful to patients and policymakers/payers and (iv) how to measure long-term effects. To improve cost-effectiveness studies, long-term population-based data on disease progression, costs and outcomes in clinical practice are needed not only in dementia but also in predementia states. Reliable surrogate end-points in clinical trials that are sensitive to detect effects even in predementia states are also essential as well as robust and validated modelling methods from predementia states that also take into account comorbidities and age. Finally, the ethical consequences of early diagnosis should be considered. © 2014 The Association for the Publication of the Journal of Internal Medicine.

What are the factors associated with physical activity (PA) participation in community dwelling adults with dementia? A systematic review of PA correlates.

PubMed

Stubbs, Brendon; Eggermont, Laura; Soundy, Andrew; Probst, Michel; Vandenbulcke, Mathieu; Vancampfort, Davy

2014-01-01

PA shows promise as a modifiable lifestyle intervention to benefit pathological symptoms of dementia. However, little is known about the factors associated with participation in PA in community dwelling adults with dementia. A systematic review was undertaken to identify PA correlates. Two independent reviewers searched major electronic databases and extracted data on studies reporting quantitative correlates of PA participation in community dwelling adults with dementia. PA correlates were analyzed using the summary code approach within the socio-ecological model. Out of a potential of 118 articles, 12 met the eligibility criteria encompassing 752 participants. We conducted secondary analysis on nine data sets. Increased energy intake, resting metabolic rate, fat free mass, gait speed, global motor function, overall health related quality of life (HRQOL), physical HRQOL, higher levels of social functioning and reduced apathy were positively associated with PA. Taking ≥ four medications, dizziness, lower activities of daily living (ADL) function, a history of falls, less waking hours in the day, more autonomic problems and delirium were negatively associated with PA. Increasing age and lower global cognition were not consistently associated with PA participation. It is surprising that increasing age and lower global cognition do not appear to influence PA participation. All significant correlates should be confirmed in prospective studies with particular focus on the relationship of PA and gait speed, ADL function, falls history and dietary intake and the progression of frailty and nursing home admission as a priority. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Relationship between education and dementia: an updated systematic review.

PubMed

Sharp, Emily Schoenhofen; Gatz, Margaret

2011-01-01

The purpose of this study was to review the relationship between education and dementia. A systematic literature review was conducted of all published studies examining the relationship between education and dementia listed in the PubMed and PsycINFO databases from January 1985 to July 2010. The inclusion criteria were a measure of education and a dementia diagnosis by a standardized diagnostic procedure. Alzheimer disease and Total Dementia were the outcomes. A total of 88 study populations from 71 studies met inclusion criteria. Overall, 51 studies (58%) reported significant effects of lower education on risk for dementia, whereas 37 studies (42%) reported no significant relationship. A relationship between education and risk for dementia was more consistent in developed regions compared with developing regions. Age, sex, race/ethnicity, and geographical region moderated the relationship. Lower education was associated with a greater risk for dementia in many but not all studies. The level of education associated with risk for dementia varied by study population and more years of education did not uniformly attenuate the risk for dementia. It seemed that a more consistent relationship with dementia occurred when years of education reflected cognitive capacity, suggesting that the effect of education on risk for dementia may be best evaluated within the context of a lifespan developmental model.

Systematic review of evidence underpinning non-pharmacological therapies in dementia.

PubMed

Olley, Richard; Morales, Andrea

2017-05-15

Objective Dementia is one of the most common illnesses worldwide, and is one of the most important causes of disability in older people. Currently, dementia affects over 35million people around the globe. It is expected that this number will increase to 65.7million by 2030. Early detection, diagnosis and treatment to control the principal behaviour symptoms may help reduce these numbers and delay the progression to more advanced and dangerous stages of this disorder with resultant increase quality of life for those affected. The main goal of the present systematic literature review was to examine contemporary evidence relating to non-pharmacological therapy in the treatment of dementia. Methods To achieve the study goal, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used. Results This study identified the five most common behaviours in patients with dementia as aggression, wandering, agitation, apathy and sleep disturbances. Two non-pharmacological therapies were the most studied treatment: music therapy and aromatherapy. Ten other non-pharmacological therapies were also identified, but these lack a sufficient evidence-base. Conclusion Although all the therapies identified could be used as part of the treatment of behavioural symptoms, there is insufficient evidence relating to the indications, appropriate use and effectiveness of these therapies to apply in each behavioural treatment. Thus, the present study has demonstrated a significant research gap. What is known about the topic? Despite the widespread use of many different types of therapies, there is limited evidence regarding the efficacy of non-pharmaceutical therapies deployed in the management of behaviours of concern manifested by some people who suffer with dementia in all its forms. What does this paper add? This systematic review examines contemporary evidence from the literature to determine whether there is an evidence base available that would underpin the use of these therapies. This report on a PRISMA systematic review of the available literature demonstrates that only two therapies have some evidence to underpin the use of these non-pharmaceutical therapies and that a significant research gap is exists. What are the implications for practitioners? The implications for practitioners is that significant research effort is required to determine the efficacy of many of the therapies that are currently deployed, and thus many of the therapies used lack an evidence base at this time.

UK end-of-life care services in dementia, initiatives and sustainability: results of a national online survey.

PubMed

Amador, Sarah; Goodman, Claire; Robinson, Louise; Sampson, Elizabeth L

2016-10-14

People living and dying with non-cancer diagnoses, including dementia, have poorer access to generalist and specialist palliative care than people with cancer, and experience worse outcomes in terms of pain and symptom control, and quality and experience of care. In the UK, the National Council for Palliative Care (NCPC) ran a national survey of services for end-of-life care for people with dementia (2008) in which 16 services were identified, and reported on case studies and examples of good practice. We updated the NCPC survey to review progress in previously identified services, identify factors that lead to sustainable services and identify new initiatives in this area of care. An online survey was developed and piloted before use. Initiatives were contacted via targeted (N=63) and open call invitations. The survey was made up of 5 sections. Quantitative data were analysed using descriptive statistics. 15 services responded. They engaged in a wide range of activities predominately providing direct care (80%) and workforce development/advisory or educational activities (87%). Results suggest that sustainability of services is reliant on clinicians with a leadership role and wider system support through funding mechanisms and a minimum level of integration within normal service provision. Recent initiatives are largely built on the expertise of the nursing profession (with or without input from medical consultants), and driven mainly by the charity and hospice sector. This has generated a potential new model of care provision in end of life dementia care, 'Hospice-enabled Dementia Care'. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Translation, cross-cultural adaptation and applicability of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS)

PubMed Central

Lima-Silva, Thais Bento; Bahia, Valéria Santoro; Carvalho, Viviane Amaral; Guimarães, Henrique Cerqueira; Caramelli, Paulo; Balthazar, Márcio; Damasceno, Benito; Bottino, Cássio Machado de Campos; Brucki, Sônia Maria Dozzi; Mioshi, Eneida; Nitrini, Ricardo; Yassuda, Mônica Sanches

2013-01-01

BACKGROUND Staging scales for dementia have been devised for grading Alzheimer's disease (AD) but do not include the specific symptoms of frontotemporal lobar degeneration (FTLD). OBJECTIVE To translate and adapt the Frontotemporal Dementia Rating Scale (FTD-FRS) to Brazilian Portuguese. METHODS The cross-cultural adaptation process consisted of the following steps: translation, back-translation (prepared by independent translators), discussion with specialists, and development of a final version after minor adjustments. A pilot application was carried out with 12 patients diagnosed with bvFTD and 11 with AD, matched for disease severity (CDR=1.0). The evaluation protocol included: Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini-Mental State Examination (MMSE), Executive Interview (EXIT-25), Neuropsychiatric Inventory (NPI), Frontotemporal Dementia Rating Scale (FTD-FRS) and Clinical Dementia Rating scale (CDR). RESULTS The Brazilian version of the FTD-FRS seemed appropriate for use in this country. Preliminary results revealed greater levels of disability in bvFTD than in AD patients (bvFTD: 25% mild, 50% moderate and 25% severe; AD: 36.36% mild, 63.64% moderate). It appears that the CDR underrates disease severity in bvFTD since a relevant proportion of patients rated as having mild dementia (CDR=1.0) in fact had moderate or severe levels of disability according to the FTD-FRS. CONCLUSION The Brazilian version of the FTD-FRS seems suitable to aid staging and determining disease progression. PMID:29213863

Conversion to dementia in mild cognitive impairment diagnosed with DSM-5 criteria and with Petersen's criteria.

PubMed

Marcos, G; Santabárbara, J; Lopez-Anton, R; De-la-Cámara, C; Gracia-García, P; Lobo, E; Pírez, G; Menchón, J M; Palomo, T; Stephan, B C M; Brayne, C; Lobo, A

2016-05-01

In a background of revision of criteria for states of increased risk for progression to dementia, we compare the conversion rate to dementia and Alzheimer's disease (AD) of mild cognitive impairment (MCI) as diagnosed using DSM-5 (DSM-5-MCI) and Petersen's (P-MCI) criteria. A population representative cohort of 4057 dementia-free individuals 55+ years of age was followed up at 2.5 and 4.5 years in Zaragoza, Spain (ZARADEMP). Using the Geriatric Mental State- AGECAT for assessment, research psychiatrists diagnosed DSM-5-MCI and P-MCI following operationalized criteria. 'Conversion rate' (CR), 'annual conversion rate' (ACR), and incidence rate (IR) were calculated along with incidence rate ratio (IRR) to compare the performance of the intermediate cognitive definitions. At 4.5-year follow-up, in individuals aged 65+ years, ACRs for non-cases, P-MCI, and DSM-5-MCI were 0.8, 1.9 and 3.4, respectively, for global dementia. The IRRs were 2.9 and 5.3 for P-MCI and DSM5-MCI, respectively, being the non-cases the reference category. The corresponding values were slightly lower for AD. Conversion rate to dementia and AD was higher using DSM-5-MCI criteria than using Petersen's criteria. However, prediction of the construct still has some way to go, as most MCI individuals did not convert at 4.5-year follow-up. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Screening of Early and Late Onset Alzheimer's Disease Genetic Risk Factors in a Cohort of Dementia Patients from Liguria, Italy.

PubMed

Ferrari, Raffaele; Ferrara, Michela; Alinani, Anwar; Sutton, Roger Brian; Famà, Francesco; Picco, Agnese; Rodriguez, Guido; Nobili, Flavio; Momeni, Parastoo

2015-01-01

Cohorts from a defined geographical area enable ad hoc genotype-phenotype correlation studies providing novel and unique insight into disease. We analysed genetic risk factors associated with early and late onset Alzheimer's disease (EOAD and LOAD) in a population from Liguria (northern Italy), as part of an ongoing longitudinal study. We screened 37 AD, 8 mild cognitive impairment (MCI), 3 AD and CVD (cerebrovascular disease), 3 MCI and CVD, 8 frontotemporal dementia (FTD) and 2 progressive supranuclear palsy (PSP) patients, and 28 normal controls (NCs).We sequenced PSEN1, PSEN2 and APP (EOAD risk factors), as well as MAPT, GRN and TARDBP for all cases and NCs, and analysed the APOE, CLU, CR1 and PICALM genotypes as well as the MAPT and ACE haplotypes (LOAD risk factors) for the AD (n = 37) and AD + MCI (n = 45) cases and NCs (n = 28).We identified variants in PSEN1, PSEN2 and TARDBP across a range of phenotypes (AD, AD and CVD, FTD and PSP), suggesting that screening of all known candidate genes of Alzheimer's and non-Alzheimer's forms of dementias in all dementia cases might be warranted. The analysis of the LOAD risk factors revealed no association with AD or AD + MCI status after Bonferroni correction. Lack of association with APOE is supported by previous studies in the Italian population. Our data also evidenced: 1) a potentially protective haplotype at the PSEN2 locus; 2) a nominal association with the GWAS-risk allele A for rs3818361 in CR1 and; 3) a threefold prevalence of AD in the female population compared to men.Our results will need to be further assessed and confirmed in larger cohorts from this area. 

Evaluating the Utility of a Structured Clinical Protocol for Reducing the Impact of Behavioural and Psychological Symptoms of Dementia in Progressive Neurological Diseases: A Pilot Study.

PubMed

Ryan, Nicholas P; Scott, Laura; McPhee, Maryanne; Mathers, Susan; Davis, Marie-Claire; Maule, Roxanne; Fisher, Fiona

2018-01-01

Behavioural and psychological symptoms of dementia (BPSD) cause significant distress to both aged care residents and staff. Despite the high prevalence of BPSD in progressive neurological diseases (PNDs) such as multiple sclerosis, Huntington's disease, and Parkinson's disease, the utility of a structured clinical protocol for reducing BPSD has not been systematically evaluated in PND populations. Staff ( n = 51) and individuals with a diagnosis of PND ( n = 13) were recruited into the study, which aimed to evaluate the efficacy of a PND-specific structured clinical protocol for reducing the impact of BPSD in residential aged care (RAC) and specialist disability accommodation (SDA) facilities. Staff were trained in the clinical protocol through face-to-face workshops, which were followed by 9 weeks of intensive clinical supervision to a subset of staff ("behaviour champions"). Staff and resident outcome measures were administered preintervention and immediately following the intervention. The primary outcome was frequency and severity of BPSD, measured using the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH). The secondary outcome was staff coping assessed using the Strain in Dementia Care Scale (SDCS). In SDA, significant reductions in staff ratings of job-related stress were observed alongside a statistically significant decrease in BPSD from T1 to T2. In RAC, there was no significant time effect for BPSD or staff coping; however, a medium effect size was observed for staff job stress. Staff training and clinical support in the use of a structured clinical protocol for managing BPSD were linked to reductions in staff job stress, which may in turn increase staff capacity to identify indicators of resident distress and respond accordingly. Site variation in outcomes may relate to organisational and workforce-level barriers that may be unique to the RAC context and should be systematically addressed in future RCT studies of larger PND samples.

Considering the role of semantic memory in episodic future thinking: evidence from semantic dementia.

PubMed

Irish, Muireann; Addis, Donna Rose; Hodges, John R; Piguet, Olivier

2012-07-01

Semantic dementia is a progressive neurodegenerative condition characterized by the profound and amodal loss of semantic memory in the context of relatively preserved episodic memory. In contrast, patients with Alzheimer's disease typically display impairments in episodic memory, but with semantic deficits of a much lesser magnitude than in semantic dementia. Our understanding of episodic memory retrieval in these cohorts has greatly increased over the last decade, however, we know relatively little regarding the ability of these patients to imagine and describe possible future events, and whether episodic future thinking is mediated by divergent neural substrates contingent on dementia subtype. Here, we explored episodic future thinking in patients with semantic dementia (n=11) and Alzheimer's disease (n=11), in comparison with healthy control participants (n=10). Participants completed a battery of tests designed to probe episodic and semantic thinking across past and future conditions, as well as standardized tests of episodic and semantic memory. Further, all participants underwent magnetic resonance imaging. Despite their relatively intact episodic retrieval for recent past events, the semantic dementia cohort showed significant impairments for episodic future thinking. In contrast, the group with Alzheimer's disease showed parallel deficits across past and future episodic conditions. Voxel-based morphometry analyses confirmed that atrophy in the left inferior temporal gyrus and bilateral temporal poles, regions strongly implicated in semantic memory, correlated significantly with deficits in episodic future thinking in semantic dementia. Conversely, episodic future thinking performance in Alzheimer's disease correlated with atrophy in regions associated with episodic memory, namely the posterior cingulate, parahippocampal gyrus and frontal pole. These distinct neuroanatomical substrates contingent on dementia group were further qualified by correlational analyses that confirmed the relation between semantic memory deficits and episodic future thinking in semantic dementia, in contrast with the role of episodic memory deficits and episodic future thinking in Alzheimer's disease. Our findings demonstrate that semantic knowledge is critical for the construction of novel future events, providing the necessary scaffolding into which episodic details can be integrated. Further research is necessary to elucidate the precise contribution of semantic memory to future thinking, and to explore how deficits in self-projection manifest on behavioural and social levels in different dementia subtypes.

Reduced mismatch negativity in mild cognitive impairment: associations with neuropsychological performance.

PubMed

Mowszowski, Loren; Hermens, Daniel F; Diamond, Keri; Norrie, Louisa; Hickie, Ian B; Lewis, Simon J G; Naismith, Sharon L

2012-01-01

Mild cognitive impairment (MCI) refers to a transitory state between healthy aging and dementia. Biomarkers are needed to facilitate early identification of MCI and predict progression to dementia. One potential neurophysiological biomarker, mismatch negativity (MMN), is an event-related potential reflecting fundamental, pre-attentive cognitive processes. MMN is reduced in normal aging and dementia and in neuropsychiatric samples and is associated with verbal memory deficits and poor executive functioning. This study aimed to investigate auditory MMN and its relationship to neuropsychological performance in MCI. Twenty-eight MCI participants and fourteen controls, aged ≥50 years, underwent neurophysiological and neuropsychological assessment, and completed questionnaires pertaining to disability. Relative to controls, the MCI group demonstrated reduced temporal MMN amplitude (p < 0.01). Reduced right temporal MMN was significantly associated with poorer verbal learning (r = 0.496; p < 0.01) and reduced left temporal MMN was significantly associated with increased self-reported disability (r = -0.419; p < 0.05). These results indicate that patients with MCI exhibit altered pre-attentive information processing, which in turn is associated with memory and psychosocial deficits. These findings overall suggest that MMN may be a viable neurophysiological biomarker of underlying disease in this 'at risk' group.

The salience network causally influences default mode network activity during moral reasoning

PubMed Central

Wilson, Stephen M.; D’Esposito, Mark; Kayser, Andrew S.; Grossman, Scott N.; Poorzand, Pardis; Seeley, William W.; Miller, Bruce L.; Rankin, Katherine P.

2013-01-01

Large-scale brain networks are integral to the coordination of human behaviour, and their anatomy provides insights into the clinical presentation and progression of neurodegenerative illnesses such as Alzheimer’s disease, which targets the default mode network, and behavioural variant frontotemporal dementia, which targets a more anterior salience network. Although the default mode network is recruited when healthy subjects deliberate about ‘personal’ moral dilemmas, patients with Alzheimer’s disease give normal responses to these dilemmas whereas patients with behavioural variant frontotemporal dementia give abnormal responses to these dilemmas. We hypothesized that this apparent discrepancy between activation- and patient-based studies of moral reasoning might reflect a modulatory role for the salience network in regulating default mode network activation. Using functional magnetic resonance imaging to characterize network activity of patients with behavioural variant frontotemporal dementia and healthy control subjects, we present four converging lines of evidence supporting a causal influence from the salience network to the default mode network during moral reasoning. First, as previously reported, the default mode network is recruited when healthy subjects deliberate about ‘personal’ moral dilemmas, but patients with behavioural variant frontotemporal dementia producing atrophy in the salience network give abnormally utilitarian responses to these dilemmas. Second, patients with behavioural variant frontotemporal dementia have reduced recruitment of the default mode network compared with healthy control subjects when deliberating about these dilemmas. Third, a Granger causality analysis of functional neuroimaging data from healthy control subjects demonstrates directed functional connectivity from nodes of the salience network to nodes of the default mode network during moral reasoning. Fourth, this Granger causal influence is diminished in patients with behavioural variant frontotemporal dementia. These findings are consistent with a broader model in which the salience network modulates the activity of other large-scale networks, and suggest a revision to a previously proposed ‘dual-process’ account of moral reasoning. These findings also characterize network interactions underlying abnormal moral reasoning in frontotemporal dementia, which may serve as a model for the aberrant judgement and interpersonal behaviour observed in this disease and in other disorders of social function. More broadly, these findings link recent work on the dynamic interrelationships between large-scale brain networks to observable impairments in dementia syndromes, which may shed light on how diseases that target one network also alter the function of interrelated networks. PMID:23576128

A qualitative study of older and middle-aged adults' perception and attitudes towards dementia and dementia risk reduction.

PubMed

Kim, Sarang; Sargent-Cox, Kerry A; Anstey, Kaarin J

2015-07-01

To investigate perceptions of dementia and dementia risk reduction held by people without dementia. Dementia does not only affect individuals with dementia, but also has an impact on family and friends, society and healthcare professionals. Recent research has identified modifiable risk and protective factors for dementia. However, it is unclear what knowledge people without dementia have about these risk factors and their attitudes towards addressing these risk factors to achieve dementia risk reduction are not known. Qualitative descriptive study using focus group methodology. A focus group study was conducted in February 2011 with 34 older adults aged between 52-90 years. The long-table approach was used to identify themes and categorize data on dementia knowledge, risk and attitudes. Participants correctly identified dementia risk factors as a group. Participants' responses about their perceived likelihood of developing dementia could be classified into three distinctive themes; fear, rational and cynical perceptions. Both fear of developing dementia and the need to improve dementia knowledge were considered major motivators towards adopting healthier lifestyle and health behaviours. Lack of knowledge on risk factors for dementia was identified as a major barrier for behavioural and lifestyle change. These findings can be used to develop effective and personalized interventions that increase motivators and reduce barriers by tailoring interventions to individual's dementia risk reduction literacy and motivations to change behaviours. Greater public-health promotion and education about risk and protective factors for dementia are also necessary to increase dementia health literacy and to reduce overall dementia prevalence. © 2015 John Wiley & Sons Ltd.

Pharmacogenomics and therapeutic prospects in dementia.

PubMed

Cacabelos, Ramón

2008-03-01

Dementia is a major problem of health in developed countries. Alzheimer's disease (AD) is the main cause of dementia, accounting for 50-70% of the cases, followed by vascular dementia (30-40%) and mixed dementia (15-20%). Approximately 10-15% of direct costs in dementia are attributed to pharmacological treatment, and only 10-20% of the patients are moderate responders to conventional anti-dementia drugs, with questionable cost-effectiveness. Primary pathogenic events underlying the dementia process include genetic factors in which more than 200 different genes distributed across the human genome are involved, accompanied by progressive cerebrovascular dysfunction and diverse environmental factors. Mutations in genes directly associated with the amyloid cascade (APP, PS1, PS2) are only present in less than 5% of the AD population; however, the presence of the APOE-4 allele in the apolipoprotein E (APOE) gene represents a major risk factor for more than 40% of patients with dementia. Genotype-phenotype correlation studies and functional genomics studies have revealed the association of specific mutations in primary loci (APP, PS1, PS2) and/or APOE-related polymorphic variants with the phenotypic expression of biological traits. It is estimated that genetics accounts for 20-95% of variability in drug disposition and pharmacodynamics. Recent studies indicate that the therapeutic response in AD is genotype-specific depending upon genes associated with AD pathogenesis and/or genes responsible for drug metabolism (CYPs). In monogenic-related studies, APOE-4/4 carriers are the worst responders. In trigenic (APOE-PS1-PS2 clusters)-related studies the best responders are those patients carrying the 331222-, 341122-, 341222-, and 441112- genomic profiles. The worst responders in all genomic clusters are patients with the 441122+ genotype, indicating the powerful, deleterious effect of the APOE-4/4 genotype on therapeutics in networking activity with other AD-related genes. Cholinesterase inhibitors of current use in AD are metabolized via CYP-related enzymes. These drugs can interact with many other drugs which are substrates, inhibitors or inducers of the cytochrome P-450 system; this interaction elicits liver toxicity and other adverse drug reactions. CYP2D6-related enzymes are involved in the metabolism of more than 20% of CNS drugs. The distribution of the CYP2D6 genotypes differentiates four major categories of CYP2D6-related metabolyzer types: (a) Extensive Metabolizers (EM)(*1/*1, *1/*10)(51.61%); (b) Intermediate Metabolizers (IM) (*1/*3, *1/*4, *1/*5, *1/*6, *1/*7, *10/*10, *4/*10, *6/*10, *7/*10) (32.26%); (c) Poor Metabolizers (PM) (*4/*4, *5/*5) (9.03%); and (d) Ultra-rapid Metabolizers (UM) (*1xN/*1, *1xN/*4, Dupl) (7.10%). PMs and UMs tend to show higher transaminase activity than EMs and IMs. EMs and IMs are the best responders, and PMs and UMs are the worst responders to pharmacological treatments in AD. It seems very plausible that the pharmacogenetic response in AD depends upon the interaction of genes involved in drug metabolism and genes associated with AD pathogenesis. The establishment of clinical protocols for the practical application of pharmacogenetic strategies in AD will foster important advances in drug development, pharmacological optimization and cost-effectiveness of drugs, and personalized treatments in dementia.

Motoneuron firing in amyotrophic lateral sclerosis (ALS)

PubMed Central

de Carvalho, Mamede; Eisen, Andrew; Krieger, Charles; Swash, Michael

2014-01-01

Amyotrophic lateral sclerosis is an inexorably progressive neurodegenerative disorder involving the classical motor system and the frontal effector brain, causing muscular weakness and atrophy, with variable upper motor neuron signs and often an associated fronto-temporal dementia. The physiological disturbance consequent on the motor system degeneration is beginning to be well understood. In this review we describe aspects of the motor cortical, neuronal, and lower motor neuron dysfunction. We show how studies of the changes in the pattern of motor unit firing help delineate the underlying pathophysiological disturbance as the disease progresses. Such studies are beginning to illuminate the underlying disordered pathophysiological processes in the disease, and are important in designing new approaches to therapy and especially for clinical trials. PMID:25294995

Autobiographical memory in semantic dementia: implication for theories of limbic-neocortical interaction in remote memory.

PubMed

McKinnon, Margaret C; Black, Sandra E; Miller, Bruce; Moscovitch, Morris; Levine, Brian

2006-01-01

We examined autobiographical memory performance in two patients with semantic dementia using a novel measure, the Autobiographical Interview [Levine, Svoboda, Hay, Winocur, & Moscovitch (2002). Aging and autobiographical memory: Dissociating episodic from semantic retrieval. Psychology and Aging, 17, 677-689], that is capable of dissociating episodic and personal semantic recall under varying levels of retrieval support. Earlier reports indicated that patients with semantic dementia demonstrate autobiographical episodic memory loss following a "reverse gradient" by which recent memories are preserved relative to remote memories. We found limited evidence for this pattern at conditions of low retrieval support. When structured probing was provided, patients' autobiographical memory performance was similar to that of controls. Retesting of one patient after 1 year indicated that retrieval support was insufficient to bolster performance following progressive prefrontal volume loss, as documented with quantified structural neuroimaging. These findings are discussed in relation to theories of limbic-neocortical interaction in autobiographical memory.

Novel PSEN1 G209A mutation in early-onset Alzheimer dementia supported by structural prediction.

PubMed

An, Seong Soo A; Bagyinszky, Eva; Kim, Hye Ryoun; Seok, Ju-Won; Shin, Hae-Won; Bae, SeunOh; Kim, SangYun; Youn, Young Chul

2016-05-20

Three main genes are described as causative genes for early-onset Alzheimer dementia (EOAD): APP, PSEN1 and PSEN2. We describe a woman with EOAD had a novel PSEN1 mutation. A 54-year-old right-handed woman presented 12-year history of progressive memory decline. She was clinically diagnosed as familial Alzheimer's disease due to a PSEN1 mutation. One of two daughters also has the same mutation, G209A in the TM-IV of PS1 protein. Her mother had unspecified dementia that began at the age of 40s. PolyPhen2 and SIFT prediction suggested that G209A might be a damaging variant with high scores. 3D modeling revealed that G209A exchange could result significant changes in the PS1 protein. We report a case of EOAD having probable novel PSEN1 (G209A) mutation verified with structural prediction.

Medication appropriateness tool for co-morbid health conditions in dementia: consensus recommendations from a multidisciplinary expert panel.

PubMed

Page, A T; Potter, K; Clifford, R; McLachlan, A J; Etherton-Beer, C

2016-10-01

Medication management for people living with dementia is a complex task as it is unclear what constitutes optimal medication management in this population due to the shifting focus of health priorities and the balance between the benefits and harms of medications. This study sought expert opinion to create a consensus list to define appropriate medication management of co-morbidities for people with dementia. This study used the Delphi technique. We invited multidisciplinary experts in geriatric therapeutics including pharmacists, doctors, nurse practitioners, a patient advocate and a psychologist to participate. Participants were asked to engage into three or more rounds of questioning. Round 1 was a questionnaire comprised of one question defining dementia and seven open-ended questions about appropriate management of co-morbidities in people with dementia. Two investigators qualitatively analysed the responses to questions from Round 1 using thematic analysis. The results of this analysis were provided to participants as statements in the Round 2 survey. The participants were asked to rate their agreement with each statement on a 5-point Likert scale. The median and interquartile range (IQR) were calculated for the responses to each statement. Consensus was pre-specified as an IQR less than or equal to 1. Statements where consensus was not achieved were presented to participants in Round 3. The Round 2 median and IQR values were provided and participants were again asked to rate their agreement with each statement on a 5-point Likert scale. The statements where participants agreed or strongly agreed were included in the Medication Appropriateness Tool for Co-morbid Health conditions in Dementia criteria. Fifty-seven experts agreed to participate in the study, of whom 58% were pharmacists and 36% were medical practitioners. Fifty-five participants completed the Round 1 (95% response rate). A total of 128 statements was included in the Round 2 survey. Consensus was reached on 93 statements in Round 2 (n = 48 responders, 84% response rate) and on 18 statements in Round 3 (n = 43 responders, 75% response rate). The participants reached consensus on 111 of 128 statements. Of these statements, 67 statements were included in the Medication Appropriateness Tool for Co-morbid Health conditions in Dementia criteria. The statements were in the broad themes of preventative medication, symptom management, disease progression, psychoactive medication, treatment goals, principles of medication use, side-effects and medication reviews. This research provides consensus-based guidance for clinicians who manage co-morbid health conditions in people with dementia. © 2016 The Authors. Internal Medicine Journal by Wiley Publishing Asia Pty Ltd on behalf of Royal Australasian College of Physicians.

[Driving and dementia : An issue for general practice?!

PubMed

Leve, Verena; Ilse, Katharina; Ufert, Marie; Wilm, Stefan; Pentzek, Michael

2017-05-01

With most forms of dementia, the risk of road traffic accidents increases with disease progression. Addressing the issue of fitness to drive at an early stage can help to reduce driving-related risks and simultaneously preserve mobility. General practitioners (GPs) are central contact persons for dementia patients and their relatives in medical and psychosocial matters, and also play a key role in addressing the issue of driving safety. Identification of relevant aspects of managing fitness to drive in dementia, as well as of support requirements for German general practice. Seven focus groups with dementia patients, family caregivers and GPs were conducted in order to define the different requirements for counselling in the general practice setting. The transcribed discussions were analysed by a multiprofessional research team using content analysis. For people with dementia, declining mobility and driving cessation is related to a loss of autonomy. Addressing fitness to drive in dementia is thus a subject of conflict and uncertainty for both family caregivers and GPs. The difficulties include the assessment of fitness to drive in the general practice setting, concerns about compromising the patient-physician relationship by raising the issue of driving fitness, as well as uncertainties about the GP's own role. GPs consider the involvement of caregivers to be important to successfully address the topic of driving safety and organise alternative transport. Support is required in the form of criteria defining the time point at which fitness to drive should be assessed, information on compensation possibilities and mobility alternatives. Resource-oriented and patient-centred development of management strategies for limited mobility is needed in general practice. Finding the correct balance between documentation, adequately informing the patient and establishing patient-centred strategies represents a challenge.

The Dementia and Disability Project in Thai Elderly: rational, design, methodology and early results.

PubMed

Senanarong, Vorapun; Harnphadungkit, Kamolthip; Poungvarin, Niphon; Vannasaeng, Sathit; Chongwisal, Samut; Chakorn, Tipa; Jamjumrus, Piyanuch; Raksthaput, Atthapon; Chaichanettee, Sinisa; Aoonkaew, Nattapol; Udompunthurak, Suthipol; Doody, Rachelle S; Cummings, Jeffrey L

2013-01-10

A strong inverse relationship of functional limitation and socioeconomic status has been established in western ageing society. Functional limitation can be related to chronic diseases, disuse, cognitive decline, and ageing. Among chronic diseases in the Thai population, cerebrovascular diseases, diabetes, and arthritis are common. These factors are known to contribute to disability and poor quality of life in the elder population. Neuropsychiatric problems, cognitive decline, dementia, and cultural issues in elderly people also can alter the quality of life of the elderly. The Dementia and Disability Project in Thai Elderly (DDP) aims at comprehensively assessing community dwelling Thai elderly to understand the relationship between disability and motor function, neuropsychiatric symptoms, cognitive function, and chronic diseases. The DDP is the first study to look at the prevalence and etiology of dementia and of mild cognitive impairment (MCI) in Thai elders and to explore the relationship of cognition, disability, small vessel diseases and cortical degeneration with neuroimaging in Thai elderly people. 1998 Thai elders were screened in 2004-2006 and diagnosed as having MCI or dementia. 223 elders with MCI or dementia and cognitively normal elderly had brain magnetic resonance imaging (MRI) or at baseline. 319 elders from the 3 groups had blood tests to investigate the risks and possible etiologies of dementia including genotyping at baseline. The mean age of elders in this study is 69.51(SD=6.71, min=60, max=95) years. 689(34.9%) are men and 1284(65.1%) are women. Mean body weight was 58.36(SD=11.20) kgs. The regression model reveals that performance on gait and balance and serum triglyceride predicts activity of daily living performance (adjusted r2 = 0.280, f=2.644, p=0.003). The majority of abnormal gait in Thai elders was lower level gait disturbance. Only 1.5% (29/1952) had highest level gait disorders. 39.5% of 1964 subjects were free of chronic diseases. Treatment gap (indicating those who have untreated or inadequate treatment) of diabetes mellitus and hypertension in Thai elders in this study was 37% and 55.5% respectively. 62.6% of Thai elders have ApoE3E3 allele. Prevalence of positive ApoE4 gene in this study is 22.85%. 38.6% of Thai elders who had MRI brain study have moderate to severe white matter lesions. The large and comprehensive set of measurements in DDP allows a wide-ranging explanation of the functional and clinical features to be investigated in relation to white matter lesions or cortical atrophy of the brain in Thai elderly population. An almost 2 year follow up was made available to those with MCI and dementia and some of the cognitively normal elderly. The longitudinal design will provide great understanding of the possible contributors to disability in the elderly and to the progression of cognitive decline in Thai elders.

The dementia and disability project in Thai elderly: rational, design, methodology and early results

PubMed Central

2013-01-01

Background A strong inverse relationship of functional limitation and socioeconomic status has been established in western ageing society. Functional limitation can be related to chronic diseases, disuse, cognitive decline, and ageing. Among chronic diseases in the Thai population, cerebrovascular diseases, diabetes, and arthritis are common. These factors are known to contribute to disability and poor quality of life in the elder population. Neuropsychiatric problems, cognitive decline, dementia, and cultural issues in elderly people also can alter the quality of life of the elderly. Methods The Dementia and Disability Project in Thai Elderly (DDP) aims at comprehensively assessing community dwelling Thai elderly to understand the relationship between disability and motor function, neuropsychiatric symptoms, cognitive function, and chronic diseases. The DDP is the first study to look at the prevalence and etiology of dementia and of mild cognitive impairment (MCI) in Thai elders and to explore the relationship of cognition, disability, small vessel diseases and cortical degeneration with neuroimaging in Thai elderly people. 1998 Thai elders were screened in 2004–2006 and diagnosed as having MCI or dementia. 223 elders with MCI or dementia and cognitively normal elderly had brain magnetic resonance imaging (MRI) or at baseline. 319 elders from the 3 groups had blood tests to investigate the risks and possible etiologies of dementia including genotyping at baseline. Results The mean age of elders in this study is 69.51(SD=6.71, min=60, max=95) years. 689(34.9%) are men and 1284(65.1%) are women. Mean body weight was 58.36(SD=11.20) kgs. The regression model reveals that performance on gait and balance and serum triglyceride predicts activity of daily living performance (adjusted r2 = 0.280, f=2.644, p=0.003). The majority of abnormal gait in Thai elders was lower level gait disturbance. Only 1.5% (29/1952) had highest level gait disorders. 39.5% of 1964 subjects were free of chronic diseases. Treatment gap (indicating those who have untreated or inadequate treatment) of diabetes mellitus and hypertension in Thai elders in this study was 37% and 55.5% respectively. 62.6% of Thai elders have ApoE3E3 allele. Prevalence of positive ApoE4 gene in this study is 22.85%. 38.6% of Thai elders who had MRI brain study have moderate to severe white matter lesions. Conclusion The large and comprehensive set of measurements in DDP allows a wide-ranging explanation of the functional and clinical features to be investigated in relation to white matter lesions or cortical atrophy of the brain in Thai elderly population. An almost 2 year follow up was made available to those with MCI and dementia and some of the cognitively normal elderly. The longitudinal design will provide great understanding of the possible contributors to disability in the elderly and to the progression of cognitive decline in Thai elders. PMID:23305293

Improvement of encoding and retrieval in normal and pathological aging with word-picture paradigm.

PubMed

Iodice, Rosario; Meilán, Juan José G; Carro, Juan

2015-01-01

During the aging process, there is a progressive deficit in the encoding of new information and its retrieval. Different strategies are used in order to maintain, optimize or diminish these deficits in people with and without dementia. One of the classic techniques is paired-associate learning (PAL), which is based on improving the encoding of memories, but it has yet to be used to its full potential in people with dementia. In this study, our aim is to corroborate the importance of PAL tasks as instrumental tools for creating contextual cues, during both the encoding and retrieval phases of memory. Additionally, we aim to identify the most effective form of presenting the related items. Pairs of stimuli were shown to healthy elderly people and to patients with moderate and mild Alzheimer's disease. The encoding conditions were as follows: word/word, picture/picture, picture/word, and word/picture. Associative cued recall of the second item in the pair shows that retrieval is higher for the word/picture condition in the two groups of patients with dementia when compared to the other conditions, while word/word is the least effective in all cases. These results confirm that PAL is an effective tool for creating contextual cues during both the encoding and retrieval phases in people with dementia when the items are presented using the word/picture condition. In this way, the encoding and retrieval deficit can be reduced in these people.

Evolution of diagnostic criteria and assessments for Parkinson's disease mild cognitive impairment.

PubMed

Goldman, Jennifer G; Holden, Samantha K; Litvan, Irene; McKeith, Ian; Stebbins, Glenn T; Taylor, John-Paul

2018-04-01

Mild cognitive impairment has gained recognition as a construct and a potential prodromal stage to dementia in both Alzheimer's disease and Parkinson's disease (PD). Although mild cognitive impairment has been recognized in the Alzheimer's disease field, it is a relatively more recent topic of interest in PD. Recent advances include the development of diagnostic criteria for PD mild cognitive impairment to provide more uniform definitions for clinical and research use. Studies reveal that mild cognitive impairment in PD is frequent, but also heterogeneous, with variable clinical presentations, differences in its progression to dementia, and likely differences in underlying pathophysiology. Application of the International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment Task Force diagnostic criteria has provided insights regarding cognitive measures, functional assessments, and other key topics that may require additional refinement. Furthermore, it is important to consider definitions of PD mild cognitive impairment in the landscape of other related Lewy body disorders, such as dementia with Lewy bodies, and in the context of prodromal and early-stage PD. This article examines the evolution of mild cognitive impairment in concept and definition, particularly in PD, but also in related disorders such as Alzheimer's disease and dementia with Lewy bodies; the development and application of International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment diagnostic criteria; and insights and future directions for the field of PD mild cognitive impairment. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

The Effects of Anti-Dementia and Nootropic Treatments on the Mortality of Patients with Dementia: A Population-Based Cohort Study in Taiwan.

PubMed

Wu, Chen-Yi; Hu, Hsiao-Yun; Chow, Lok-Hi; Chou, Yiing-Jenq; Huang, Nicole; Wang, Pei-Ning; Li, Chung-Pin

2015-01-01

Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study. To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study. 12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated. The median survival time was 3.39 years (95% confidence interval [CI]: 2.88-3.79) for VaD without medication, 6.62 years (95% CI: 6.24-7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85-3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30-8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73-6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02-9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55-2.83) without medication, 1.46 (95% CI: 1.39-1.54) with nootropics, 1.05 (95% CI: 0.82-1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80-1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15-1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22-2.72). Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival.

The Effects of Anti-Dementia and Nootropic Treatments on the Mortality of Patients with Dementia: A Population-Based Cohort Study in Taiwan

PubMed Central

Wu, Chen-Yi; Hu, Hsiao-Yun; Chow, Lok-Hi; Chou, Yiing-Jenq; Huang, Nicole; Wang, Pei-Ning; Li, Chung-Pin

2015-01-01

Background Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study. Objective To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study. Methods 12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated. Results The median survival time was 3.39 years (95% confidence interval [CI]: 2.88–3.79) for VaD without medication, 6.62 years (95% CI: 6.24–7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85–3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30–8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73–6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02–9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55–2.83) without medication, 1.46 (95% CI: 1.39–1.54) with nootropics, 1.05 (95% CI: 0.82–1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80–1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15–1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22–2.72). Conclusion Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival. PMID:26098910

Cognitive leisure activities and their role in preventing dementia: a systematic review.

PubMed

Stern, Cindy; Munn, Zachary

Dementia is a debilitating syndrome that inflicts a tremendous burden of care on one's family, individual caregivers, health care professionals and on the use of resources. Existing therapeutic interventions can only help control or reduce symptoms, and slow the disease's progression. Identifying protective factors or effective prevention strategies would result in considerable benefits. Participation in cognitive leisure activities has been implicated as a possible prevention strategy. The objective of the review was to establish best practice in relation to cognitive leisure activities in preventing dementia among older adults. Randomised controlled trials (RCTs), other experimental studies, cohort studies, case-controlled studies and cross-sectional studies were considered for the review.Participants of interest were adults aged 60 years and older with or without a clinical diagnosis of dementia, living in the community or residential care setting.The review focussed on any cognitive leisure activity that required a mental response from the individual taking part in the activity e.g. reading and playing board games.The primary outcome of the review was the presence or absence of dementia, determined by cognitive function tests, mental examination scores, DSM classification (Diagnostic and Statistical Manual of Mental Disorders), and other valid dementia diagnostic tools. A search for published and unpublished literature in the English language was conducted using all major electronic databases. There was no publication date restriction. A three-step search strategy was developed using MeSH terminology and keywords to ensure that all material relevant to the review was captured. The methodological quality of included studies was assessed by two reviewers, who appraised each study independently, using standard Joanna Briggs Institute (JBI) critical appraisal tools. Data was extracted from the studies that were identified as meeting the criteria for methodological quality using the standard JBI data extraction tools. Due to the heterogeneity of populations and interventions, meta-analyses were not possible and results are presented in narrative form. Thirteen longitudinal studies were included in the review. Studies were grouped by stage of adult life participation when interventions were undertaken i.e. early-middle adulthood and late life. Five out of six studies demonstrated a positive association between engagement in activities and a reduced risk of developing Alzheimer's disease (AD) when interventions were undertaken in middle adulthood and six out of seven studies produced a positive association for late life participation. Results indicated that some activities might be more beneficial than others.Actively participating in cognitive leisure activities during mid or late life may be beneficial in preventing the risk of dementia in the elderly however the evidence is currently not strong enough to infer a direct causal relationship.Participating in selected cognitive leisure activities may be more favourable than others but currently there is no strong evidence to recommend one over the other.

Word-finding difficulty: a clinical analysis of the progressive aphasias

PubMed Central

Rohrer, Jonathan D.; Knight, William D.; Warren, Jane E.; Fox, Nick C.; Rossor, Martin N.; Warren, Jason D.

2008-01-01

The patient with word-finding difficulty presents a common and challenging clinical problem. The complaint of ‘word-finding difficulty’ covers a wide range of clinical phenomena and may signify any of a number of distinct pathophysiological processes. Although it occurs in a variety of clinical contexts, word-finding difficulty generally presents a diagnostic conundrum when it occurs as a leading or apparently isolated symptom, most often as the harbinger of degenerative disease: the progressive aphasias. Recent advances in the neurobiology of the focal, language-based dementias have transformed our understanding of these processes and the ways in which they breakdown in different diseases, but translation of this knowledge to the bedside is far from straightforward. Speech and language disturbances in the dementias present unique diagnostic and conceptual problems that are not fully captured by classical models derived from the study of vascular and other acute focal brain lesions. This has led to a reformulation of our understanding of how language is organized in the brain. In this review we seek to provide the clinical neurologist with a practical and theoretical bridge between the patient presenting with word-finding difficulty in the clinic and the evidence of the brain sciences. We delineate key illustrative speech and language syndromes in the degenerative dementias, compare these syndromes with the syndromes of acute brain damage, and indicate how the clinical syndromes relate to emerging neurolinguistic, neuroanatomical and neurobiological insights. We propose a conceptual framework for the analysis of word-finding difficulty, in order both better to define the patient's complaint and its differential diagnosis for the clinician and to identify unresolved issues as a stimulus to future work. PMID:17947337