Potential Therapeutics for Vascular Cognitive Impairment and Dementia.
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.
Meguro, Kenichi; Tanaka, Naofumi; Nakatsuka, Masahiro; Nakamura, Kei; Satoh, Masayuki
2012-11-15
The concept and diagnosis for mixed dementia is not simple, since it is difficult to identify the type and regions of cerebrovascular disease (CVD) responsible for causing dementia. An investigation is needed to confirm the presence of mixed dementia, those who met the criteria for Alzheimer's disease (AD) and those for vascular dementia (VaD). According to the community-based stroke, dementia, and bed-confinement prevention in Kurihara, northern Japan (Kurihara Project), the prevalence of dementia and dementing diseases was surveyed in 2008-2010. Five hundred and ninety people finally agreed to participate (47.0%), and 73 (12.4%) people were diagnosed with dementia according to the DSM-IV. Using MRI, intensive evaluations on CVDs were performed for the 49 dementia patients associated with CVDs (mixed dementia, VaD, and AD with CVD). For the mixed dementia group, all had left subcortical strategic CVDs. These included the caudate head and thalamus. For the VaD group, all patients had at least cortical CVDs or subcortical strategic CVDs. The AD with CVD group had non-strategic CVDs in cortical, subcortical, or other areas in 5 or 6 patients each. Two extreme concepts regarding CVD and dementia are possible. One is that there is no concept for mixed dementia or VaD. An alternative is that the vascular factor should be considered as primary. Our data showed an importance of cortical and subcortical "strategic" areas, the latter included thalamus and caudate head. Copyright © 2012 Elsevier B.V. All rights reserved.
Color perception differentiates Alzheimer's Disease (AD) from Vascular Dementia (VaD) patients.
Arnaoutoglou, N A; Arnaoutoglou, M; Nemtsas, P; Costa, V; Baloyannis, S J; Ebmeier, K P
2017-08-01
Alzheimer's Disease (AD) and Vascular Dementia (VaD) are the most common causes of dementia in older people. Both diseases appear to have similar clinical symptoms, such as deficits in attention and executive function, but specific cognitive domains are affected. Current cohort studies have shown a close relationship between αβ deposits and age-related macular degeneration (Johnson et al., 2002; Ratnayaka et al., 2015). Additionally, a close link between the thinning of the retinal nerve fiber (RNFL) and AD patients has been described, while it has been proposed that AD patients suffer from a non-specific type of color blindness (Pache et al., 2003). Our study included 103 individuals divided into three groups: A healthy control group (n = 35), AD (n = 32) according to DSM-IV-TR, NINCDS-ADRDA criteria, and VaD (n = 36) based on ΝΙΝDS-AIREN, as well as Magnetic Resonance Imaging (MRI) results. The severity of patient's cognitive impairment, was measured with the Mini-Mental State Examination (MMSE) and was classified according to the Reisberg global deterioration scale (GDS). Visual perception was examined using the Ishihara plates: "Ishihara Color Vision Test - 38 Plate." The three groups were not statistically different for demographic data (age, gender, and education). The Ishihara color blindness test has a sensitivity of 80.6% and a specificity of 87.5% to discriminate AD and VaD patients when an optimal (32.5) cut-off value of performance is used. Ishihara Color Vision Test - 38 Plate is a promising potential method as an easy and not time-consuming screening test for the differential diagnosis of dementia between AD and VaD.
Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia.
Román, Gustavo C; Kalaria, Raj N
2006-12-01
Alzheimer's disease (AD) and vascular dementia (VaD) are widely accepted as the most common forms of dementia. Cerebrovascular lesions frequently coexist with AD, creating an overlap in the clinical and pathological features of VaD and AD. This review assembles evidence for a role for cholinergic mechanisms in the pathogenesis of VaD, as has been established for AD. We first consider the anatomy and vascularization of the basal forebrain cholinergic neuronal system, emphasizing its susceptibility to the effects of arterial hypertension, sustained hypoperfusion, and ischemic cerebrovascular disease. The impact of aging and consequences of disruption of the cholinergic system in cognition and in control of cerebral blood flow are further discussed. We also summarize preclinical and clinical evidence supporting cholinergic deficits and the use of cholinesterase inhibitors in patients with VaD. We postulate that vascular pathology likely plays a common role in initiating cholinergic neuronal abnormalities in VaD and AD.
Vitamin D, Homocysteine, and Folate in Subcortical Vascular Dementia and Alzheimer Dementia.
Moretti, Rita; Caruso, Paola; Dal Ben, Matteo; Conti, Corrado; Gazzin, Silvia; Tiribelli, Claudio
2017-01-01
Dementia is a worldwide health problem which affects millions of patients; Alzheimer's disease (AD) and subcortical vascular dementia (sVAD) are the two most frequent forms of its presentation. As no definite therapeutic options have been discovered, different risk factors for cognitive impairment have been searched for potential therapies. This report focuses on the possible evidence that vitamin D deficiency and hyper-homocysteinemia can be considered as two important factors for the development or the progression of neurodegenerative or vascular pathologies. To this end, we assessed: the difference in vascular risk factors and vitamin D-OH25 levels among groups of sVAD, AD, and healthy age-matched controls; the association of folate, B12, homocysteine, and vitamin D with sVAD/AD and whether a deficiency of vitamin D and an increment in homocysteine levels may be related to neurodegenerative or vessel damages. The commonly-considered vascular risk factors were collected in 543 patients and compared with those obtained from a healthy old volunteer population. ANOVA group comparison showed that vitamin D deficiency was present in demented cases, as well as low levels of folate and high levels of homocysteine, more pronounced in sVAD cases. The statistical models we employed, with regression models built, and adjustments for biochemical, demographic and neuropsychiatric scores, confirmed the association between the three measures (folate decrease, hyperhomocysteinemia and vitamin D decrease) and dementia, more pronounced in sVAD than in AD.
Ishii, Makoto; Iadecola, Costantino
2016-05-01
Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.
Cancer linked to Alzheimer disease but not vascular dementia
Roe, C M.; Fitzpatrick, A L.; Xiong, C; Sieh, W; Kuller, L; Miller, J P.; Williams, M M.; Kopan, R; Behrens, M I.; Morris, J C.
2010-01-01
Objective: To investigate whether cancer is associated with Alzheimer disease (AD) and vascular dementia (VaD). Methods: Cox proportional hazards models were used to test associations between prevalent dementia and risk of future cancer hospitalization, and associations between prevalent cancer and risk of subsequent dementia. Participants in the Cardiovascular Health Study–Cognition Substudy, a prospective cohort study, aged 65 years or older (n = 3,020) were followed a mean of 5.4 years for dementia and 8.3 years for cancer. Results: The presence of any AD (pure AD + mixed AD/VaD; hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.20–0.84) and pure AD (HR = 0.31, 95% CI = 0.12–0.86) was associated with a reduced risk of future cancer hospitalization, adjusted for demographic factors, smoking, obesity, and physical activity. No significant associations were found between dementia at baseline and rate of cancer hospitalizations for participants with diagnoses of VaD. Prevalent cancer was associated with reduced risk of any AD (HR = 0.72; 95% CI = 0.52–0.997) and pure AD (HR = 0.57; 95% CI = 0.36–0.90) among white subjects after adjustment for demographics, number of APOE ε4 alleles, hypertension, diabetes, and coronary heart disease; the opposite association was found among minorities, but the sample size was too small to provide stable estimates. No significant association was found between cancer and subsequent development of VaD. Conclusions: In white older adults, prevalent Alzheimer disease (AD) was longitudinally associated with a reduced risk of cancer, and a history of cancer was associated with a reduced risk of AD. Together with other work showing associations between cancer and Parkinson disease, these findings suggest the possibility that cancer is linked to neurodegeneration. GLOSSARY 3MSE = modified Mini-Mental State Examination; AD = Alzheimer disease; ADDTC = Alzheimer Disease Diagnostic and Treatment Centers; CHD = coronary heart
Nagahama, Yasuhiro; Okina, Tomoko; Suzuki, Norio
2015-11-01
To examine whether imitation of gestures provided useful information to diagnose early dementia in elderly patients. Imitation of finger and hand gestures was evaluated in patients with mild dementia; 74 patients had dementia with Lewy bodies (DLB), 100 with Alzheimer's disease (AD) and 52 with subcortical vascular dementia (SVaD). Significantly, more patients with DLB (32.4%) compared with patients with AD (5%) or SVaD (11.5%) had an impaired ability to imitate finger gestures bilaterally. Also, significantly, more patients with DLB (36.5%) compared with patients with AD (5%) or SVaD (15.4%) had lower mean scores of both hands. In contrast, impairment of the imitation of bimanual gestures was comparable among the three patient groups (DLB 50%, AD 42%, SVaD 42.3%). Our study revealed that imitation of bimanual gestures was impaired non-specifically in about half of the patients with mild dementia, whereas imitation of finger gestures was significantly more impaired in patients with early DLB than in those with AD or SVaD. Although the sensitivity was not high, the imitation tasks may provide additional information for diagnosis of mild dementia, especially for DLB. 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.
Plasma antioxidant activity and vascular dementia.
Ryglewicz, Danuta; Rodo, Maria; Kunicki, Piotr Krzysztof; Bednarska-Makaruk, Malgorzata; Graban, Alla; Lojkowska, Wanda; Wehr, Hanna
2002-11-15
Little is known about the role of antioxidant activity in the pathogenesis of stroke-associated neuronal damage and impairment following a stroke. Increased free radical formation together with reduced antioxidant defense may increase neuronal injury. A low concentration of antioxidants such as alpha-tocopherol may influence the development of post-stroke dementia. The aim of this study was to evaluate the level of alpha-tocopherol and susceptibility of LDL to oxidation in a group of patients with dementia in comparison to controls. In a group of 68 patients with dementia, according to DSM-IV criteria, 42 with vascular dementia (VaD), 26 with Alzheimer type of dementia (AD) and 46 age-matched persons, with no signs of cognitive disorders (control group), we measured lipids, alpha-tocopherol and the kinetics of LDL oxidation. The levels of triglycerides (TG) and low-density lipoprotein (LDL) were significantly lower in patients with VaD in comparison to AD patients, but the atherogenic index was similar in both groups. alpha-Tocopherol was significantly lower in patients with VaD in comparison to patients with AD and controls: 9.9, 12.6 and 12.6 ng/ml, respectively, p<0.0001. Susceptibility of LDL to oxidation, measured by duration of lag phase did not reveal statistically significant differences between the groups. In patients with VaD, low levels of plasma alpha-tocopherol were observed, which indicate a reduced antioxidant defense in these subjects.
Garriga, Marina; Milà, Marta; Mir, Manzoor; Al-Baradie, Raid; Huertas, Sonia; Castejon, Cesar; Casas, Laura; Badenes, Dolors; Giménez, Nuria; Font, M. Angels; Gonzalez, Jose M.; Ysamat, Maria; Aguilar, Miguel; Slevin, Mark; Krupinski, Jerzy
2015-01-01
Alzheimer’s disease (AD) and vascular dementia (VaD) are the most common cause of dementia. Cerebral ischemia is a major risk factor for development of dementia. 123I-FP-CIT SPECT (DaTScan) is a complementary tool in the differential diagnoses of patients with incomplete or uncertain Parkinsonism. Additional application of DaTScan enables the categorization of Parkinsonian disease with dementia (PDD), and its differentiation from pure AD, and may further contribute to change the therapeutic decision. The aim of this study was to analyze the vascular contribution towards dementia and mild cognitive impairment (MCI). We evaluated the utility of DaTScan for the early diagnosis of dementia in patients with and without a clinical vascular component, and the association between neuropsychological function, vascular component and dopaminergic function on DaTScan. One-hundred and five patients with MCI or the initial phases of dementia were studied prospectively. We developed an initial assessment using neurologic examination, blood tests, cognitive function tests, structural neuroimaging and DaTScan. The vascular component was later quantified in two ways: clinically, according to the Framingham Risk Score (FRS) and by structural neuroimaging using Wahlund Scale Total Score (WSTS). Early diagnosis of dementia was associated with an abnormal DaTScan. A significant association was found between a high WSTS and an abnormal DaTScan (p < 0.01). Mixed AD was the group with the highest vascular component, followed by the VaD group, while MCI and pure AD showed similar WSTS. No significant associations were found between neuropsychological impairment and DaTScan independently of associated vascular component. DaTScan seems to be a good tool to discriminate, in a first clinical assessment, patients with MCI from those with established dementia. There was bigger general vascular affectation observable in MRI or CT in patients with abnormal dopaminergic uptake seen on Da
Neuropsychiatric symptoms in Alzheimer's disease and vascular dementia.
Echávarri, Carmen; Burgmans, Saartje; Uylings, Harry; Cuesta, Manuel J; Peralta, Victor; Kamphorst, Wouter; Rozemuller, Annemieke J M; Verhey, Frans R J
2013-01-01
Neuropsychiatric symptoms (NPSs) have a large impact on the quality of life of patients with dementia. A few studies have compared neuropsychiatric disturbances between dementia subtypes, but the results were conflicting. In the present study, we investigated whether the prevalence of NPSs differs between Alzheimer's disease (AD) and vascular dementia (VaD). The merit of our study is that we used clinical as well as histopathological information to differentiate between dementia subtypes. This retrospective descriptive study comprised 80 brains obtained from donors to the Netherlands Brain Bank between 1984 and 2010. These donors were diagnosed postmortem with AD (n = 40) or VaD (n = 40). We assessed the presence of NPSs by reviewing the information found in the patients' medical files. The most prevalent symptom in the sample as a whole was agitation (45 cases, 57.0%), followed by depression (33, 41.2%) and anxiety (28, 35.4%). Our study tried to contribute to the discussion by including, for the first time in the literature, a sample of AD and VaD patients with neuropathologically confirmed diagnoses. Since no significant differences were found between AD and VaD patients, we suggest that the prevalence of NPSs cannot be predicted from the diagnosis of AD or VaD.
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.
The pathobiology of vascular dementia
Iadecola, Costantino
2013-01-01
Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer’s disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that links inextricably the well being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer’s disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. PMID:24267647
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.
Vascular cognitive impairment and dementia.
Gorelick, Philip B; Counts, Scott E; Nyenhuis, David
2016-05-01
Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now been linked not only to vascular cognitive disorders but also Alzheimer's disease. In this chapter we review 3 related topics that address vascular contributions to cognitive impairment: 1. vascular pathogenesis and mechanisms; 2. neuropsychological and neuroimaging phenotypic manifestations of cerebrovascular disease; and 3. prospects for prevention of cognitive impairment of later life based on cardiovascular and stroke risk modification. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.
Neuropsychiatric Symptoms in Alzheimer Disease, Vascular Dementia, and Mixed Dementia.
Anor, Cassandra J; O'Connor, Sean; Saund, Amardeep; Tang-Wai, David F; Keren, Ron; Tartaglia, Maria Carmela
2017-01-01
Neuropsychiatric symptoms (NPS) are common in Alzheimer disease (AD) and vascular dementia (VaD), and are distressful to patients and caregivers. NPS are likely related to the underlying pathology. Previous studies suggest that frontal lobe lesions and vascular changes such as white matter hyperintensities (WMH) have a significant association with specific NPS. The current study aimed to compare NPS in patients with AD, VaD, and mixed AD/VaD, and to evaluate the differences in the prevalence of NPS in relation to frontal WMH volume. In total, 180 patients with NPS and MRI data (92 probable AD, 51%; 34 probable VaD, 19%; and 54 probable mixed AD/VaD, 30%) were included in the study. Regression analyses were performed to determine the relationships between NPS prevalence and diagnosis, and between NPS and frontal WMH. VaD patients had significantly more agitation (p < 0.05; 40 vs. 14%) and sleep disturbances (p < 0.05; 57 vs. 32%) than AD patients, and significantly more depression (p < 0.05; 48 vs. 20%) and aberrant motor behaviors (p < 0.05; 31 vs. 13%) than mixed AD/VaD patients. AD patients with delusions had significantly greater right frontal WMH volumes than those without (p < 0.05; delusions 1/0 = 314.8/112.6 mm3). Differences in NPS prevalence are likely related to the underlying pathology and warrant further study as they have implications for treatment. © 2017 S. Karger AG, Basel.
Relation of Plasma Lipids to Alzheimer Disease and Vascular Dementia
Reitz, Christiane; Tang, Ming-Xin; Luchsinger, Jose; Mayeux, Richard
2009-01-01
Background The relation between plasma lipid levels and Alzheimer disease (AD) and vascular dementia (VaD), and the impact of drugs to lower lipid levels remains unclear. Objective To investigate the relation between plasma lipid levels and the risk of AD and VaD and the impact of drugs to lower lipid levels on this relationship. Design and Setting Cross-sectional and prospective community-based cohort studies. Participants Random sample of 4316 Medicare recipients, 65 years and older, residing in northern Manhattan, NY. Main Outcome Measures Vascular dementia and AD according to standard criteria. Results Elevated levels of non–high-density lipoprotein (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and decreased levels of HDL-C were weak risk factors for VaD in either cross-sectional or prospective analyses. Higher levels of total cholesterol were associated with a decreased risk of incident AD after adjustment for demographics, apolipoprotein E genotype, and cardiovascular risk factors. Treatment with drugs to lower lipid levels did not change the disease risk of either disorder. Conclusions We found a weak relation between non–HDL-C, LDL-C, and HDL-C levels and the risk of VaD. Lipid levels and the use of agents to lower them do not seem to be associated with the risk of AD. PMID:15148148
Kim, Hee Jin; Cha, Jungho; Lee, Jong-Min; Shin, Ji Soo; Jung, Na-Yeon; Kim, Yeo Jin; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Na, Duk L; Seo, Sang Won
2016-01-01
Recent advances in resting-state functional MRI have revealed altered functional networks in Alzheimer's disease (AD), especially those of the default mode network (DMN) and central executive network (CEN). However, few studies have evaluated whether small vessel disease (SVD) or combined amyloid and SVD burdens affect the DMN or CEN. The aim of this study was to evaluate whether SVD or combined amyloid and SVD burdens affect the DMN or CEN. In this cross-sectional study, we investigated the resting-state functional connectivity within DMN and CEN in 37 Pittsburgh compound-B (PiB)(+) AD, 37 PiB(-) subcortical vascular dementia (SVaD), 13 mixed dementia patients, and 65 normal controls. When the resting-state DMN of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(+) AD patients displayed lower functional connectivity in the inferior parietal lobule while the PiB(-) SVaD patients displayed lower functional connectivity in the medial frontal and superior frontal gyri. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the DMN in the posterior cingulate gyrus. When the resting-state CEN connectivity of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(-) SVaD patients displayed lower functional connectivity in the anterior insular region. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the CEN in the inferior frontal gyrus. Our findings suggest that in PiB(+) AD and PiB(-) SVaD, there is divergent disruptions in resting-state DMN and CEN. Furthermore, patients with combined amyloid and SVD burdens exhibited more disrupted resting-state DMN and CEN than patients with only amyloid or SVD burden.
Financial and health literacy predict incident AD dementia and AD pathology
Yu, Lei; Wilson, Robert S.; Schneider, Julie A.; Bennett, David A.; Boyle, Patricia A.
2017-01-01
Background Domain specific literacy is a multidimensional construct that requires multiple resources including cognitive and non-cognitive factors. Objective We test the hypothesis that domain specific literacy is associated with AD dementia and AD pathology after controlling for cognition. Methods Participants were community based older persons who completed a baseline literacy assessment, underwent annual clinical evaluations for up to 8 years and agreed to organ donation after death. Financial and health literacy was measured using 32 questions and cognition was measured using 19 tests. Annual diagnosis of AD dementia followed standard criteria. AD pathology was examined post-mortem by quantifying plaques and tangles. Cox models examined the association of literacy with incident AD dementia. Performance of model prediction for incident AD dementia was assessed using indices for integrated discrimination improvement and continuous net reclassification improvement. Linear regression models examined the independent association of literacy with AD pathology in autopsied participants. Results All 805 participants were free of dementia at baseline and 102 (12.7%) developed AD dementia during the follow-up. Lower literacy was associated with higher risk for incident AD dementia (p<0.001), and the association persisted after controlling for cognition (Hazard Ratio=1.50, p=0.004). The model including the literacy measure had better predictive performance than the one with demographics and cognition only. Lower literacy also was associated with higher burden of AD pathology after controlling for cognition (β=0.07, p=0.035). Conclusion Literacy predicts incident AD dementia and AD pathology in community-dwelling older persons, and the association is independent of traditional measures of cognition. PMID:28157101
Huperzine A for vascular dementia
Hao, Zilong; Liu, Ming; Liu, Zhiqin; Lu, DongHao
2014-01-01
Background Huperzine A, a form of herbal medicine, has been considered as an alternative treatment for vascular dementia (VaD) in China. Objectives To assess the efficacy and safety of Huperzine A in patients with vascular dementia. Search methods We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register on 10 February 2011 using the terms: chinese, plants, huperzine, HUP, ayapin, scoparon. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), numerous trial registries and grey literature sources. We also searched the following databases in March 2011 using the terms ‘Huperzine A’, ‘Shishanjianjia’, ‘Haboyin’ and ‘Shuangyiping’: The Chinese Biomedical Database (CBM) (1977 to March 2011); Chinese Science and Technique Journals Database (VIP) (1989 to March 2011); China National Knowledge Infrastructure (CNKI) (1979 to March 2011); Google (March 2011). In addition, we searched relevant reference lists. We also contacted researchers to request additional information where necessary. Selection criteria We considered randomized controlled trials comparing Huperzine A with placebo in people with vascular dementia eligible for inclusion. Data collection and analysis Two review authors independently applied the inclusion criteria, assessed trial quality and extracted the data. We resolved any disagreement by discussion. Main results We included only one small trial, involving 14 participants with vascular dementia. No significant effect of Huperzine A on cognitive function measured by MMSE (WMD 2.40; 95% CI −4.78 to 9.58) was observed. There was a significant beneficial effect of Huperzine A on performance of activities of daily living (WMD −13.00; 95% CI −23.24 to −2.76) after six months of treatment. No deaths from any cause at the end of treatment were reported. Behaviour
Huperzine A for vascular dementia.
Hao, Zilong; Liu, Ming; Liu, Zhiqin; Lv, Donghao
2009-04-15
Huperzine A, a form of herbal medicine, has been considered as an alternative treatment for vascular dementia (VaD) in China. To assess the efficacy and safety of Huperzine A in patients with vascular dementia. The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG) was searched on 7 July 2008 using the terms: huperzi* OR ayapin OR scoparon*. The CDCIG Specialized Register contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trials databases and grey literature sources. The review authors searched the following databases in August 2008 using the terms 'Huperzine A', 'Shishanjianjia', 'Haboyin' and 'Shuangyiping': The Chinese Biomedical Database (CBM) (1977 to August 2008); Chinese Science and Technique Journals Database (VIP) (1989 to August 2008); China National Knowledge Infrastructure (CNKI) (1979 to August 2008); The Chinese Clinical Trials Register (ChiCTR, August 2008); Google (August 2008). In addition, the review authors searched reference lists, relevant clinical trials and contacted researchers in an effort to identify further published and unpublished studies. Randomized controlled trials comparing Huperzine A with placebo in patients with vascular dementia were considered eligible for inclusion. Two review authors independently selected trials for inclusion, assessed trial quality, and extracted data. Only one small trial, involving 14 participants, was included. No significant beneficial effect of Huperzine A on the improvement of cognitive function measured by MMSE for VaD (WMD 2.40; 95% CI -4.78 to 9.58) was observed. No death from all causes at the end of treatment were reported. At present, other outcome measures were not available in any of the trials. Although no statistically significant differences were found between the Huperzine A-treated and control groups, the confidence intervals for the treatment effect estimates were
Neuroprotective effect of selective DPP-4 inhibitor in experimental vascular dementia.
Jain, Swati; Sharma, Bhupesh
2015-12-01
Vascular risk factors are associated with a higher incidence of dementia. Diabetes mellitus is considered as a main risk factor for Alzheimer's disease and vascular dementia. Both forms of dementia are posing greater risk to the world population and are increasing at a faster rate. In the past we have reported the induction of vascular dementia by experimental diabetes. This study investigates the role of vildagliptin, a dipeptidyl peptidase-4 inhibitor in the pharmacological interdiction of pancreatectomy diabetes induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. Pancreatectomy diabetes rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with increase in brain inflammation, oxidative stress and calcium. Administration of vildagliptin has significantly attenuated pancreatectomy induced impairment of learning, memory, endothelial function, blood brain barrier permeability and biochemical parameters. It may be concluded that vildagliptin, a dipeptidyl peptidase-4 inhibitor may be considered as potential pharmacological agents for the management of pancreatectomy induced endothelial dysfunction and subsequent vascular dementia. The selective modulators of dipeptidyl peptidase-4 may further be explored for their possible benefits in vascular dementia. Copyright © 2015 Elsevier Inc. All rights reserved.
The pathology and pathophysiology of vascular dementia.
Kalaria, Raj N
2017-12-19
Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on wide-ranging clinical, neuropsychological and neuroimaging measures in life but more importantly pathological confirmation. Factors defining subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes as well as time after the initial vascular event. Atherosclerotic and cardioembolic diseases combined appear the most common subtypes of vascular brain injury. In recent years, cerebral small vessel disease (SVD) has gained prominence worldwide as an important substrate of cognitive impairment. SVD is characterised by arteriolosclerosis, lacunar infarcts and cortical and subcortical microinfarcts and diffuse white matter changes, which involve myelin loss and axonal abnormalities. Global brain atrophy and focal degeneration of the cerebrum including medial temporal lobe atrophy are also features of VaD similar to Alzheimer's disease. Hereditary arteriopathies have provided insights into the mechanisms of dementia particularly how arteriolosclerosis, a major contributor of SVD promotes cognitive impairment. Recently developed and validated neuropathology guidelines indicated that the best predictors of vascular cognitive impairment were small or lacunar infarcts, microinfarcts, perivascular space dilation, myelin loss, arteriolosclerosis and leptomeningeal cerebral amyloid angiopathy. While these substrates do not suggest high specificity, VaD is likely defined by key neuronal and dendro-synaptic changes resulting in executive dysfunction and related cognitive deficits. Greater understanding of the molecular pathology is needed to clearly define microvascular disease and vascular substrates of dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.
Alzheimer and vascular dementia in the elderly patients.
Seetlani, Naresh Kumar; Kumar, Narindar; Imran, Khalid; Ali, Asif; Shams, Nadia; Sheikh, Taha
2016-01-01
To find out the frequency of Alzheimer's and Vascular dementia in the elderly patients. This cross sectional descriptive study was conducted in Department of Medicine, Ziauddin Hospital Karachi from 1 st October 2013 to 31 st March 2014. Patients with symptoms of dementia for more than 6 months duration, and Mini Mental State Examination score <24 were included in this study. Patients who fell in category of dementia were assessed for duration of symptoms. Patients underwent CT scan of brain. Patients with generalized atrophy of brain on CT scanning of brain were labeled as Alzheimer's dementia, while patients with ischemic or hemorrhagic stroke on CT scan of brain were labeled as vascular dementia. Four hundred twenty two patients were included in this study. There were 232 (54.98 %) male and 190 (45.02 %) were female. The mean age ± SD of the patients was 72.58±5.34 years (95% CI: 72.07 to 73.09), similarly average duration of symptoms was 10.14±2.85 months. About 18.96% of patients were illiterate, 32.23% were matric, 28.44% were intermediate and 20.33% were graduate and post graduate. Hypertension and diabetes were the commonest co-morbid i.e. 81.3% and 73.7%, hyperlipedimia and smoking were 38.2% and 45% respectively. Frequency of Alzheimer's disease and vascular dementia in the elderly was observed in 3.79% (16/422) and 2.61% (11/422) cases. A good number of patients, 27 out of 422, in this hospital based study were suffering from Alzheimer's disease and vascular dementia. Early detection and prompt treatment can reduce the burden of the disease in our population.
Depression, insight, and personality changes in Alzheimer's disease and vascular dementia.
Verhey, F R; Ponds, R W; Rozendaal, N; Jolles, J
1995-01-01
Although it is generally believed that depression, retained insight, and preserved personality occur more frequently in vascular dementia than in Alzheimer's disease, there is little empiric evidence for this presumption. Most studies on this subject have been carried out with severely demented inpatients, and confounding factors such as age, sex, and severity of dementia have not been sufficiently taken into account. We compared 48 patients with relatively mild vascular dementia with 48 patients with Alzheimer's disease, matched for age, sex, and stage of dementia, to investigate if depression, lack of insight, and personality changes were related to the cause of dementia. The two groups did not differ regarding the incidence of major depression, the mean depression score, the awareness score, or the sum of scores on the items of the Blessed Dementia Scale concerning personality changes. We conclude that depression, lack of insight, and personality changes do not favor an etiology of vascular dementia over that of Alzheimer's disease. The present findings underscore the notion that the severity of the dementia should be considered in studies on the differences between vascular dementia and Alzheimer's disease.
A meta-analysis of Chinese herbal medicines for vascular dementia.
Qin, Xiude; Liu, Yu; Wu, Yanqing; Wang, Shuo; Wang, Dandan; Zhu, Jinqiang; Ye, Qiaofeng; Mou, Wei; Kang, Liyuan
2013-06-25
To investigate the efficacy and safety of Chinese herbal medicines in the treatment of patients with vascular dementia. We retrieved publications from Cochrane Library (2004 to July 2011), PubMed (1966 to July 2011), the Chinese Science and Technique Journals Database (1977 to July 2011), the China National Knowledge Infrastructure (1979 to July 2011), Google Scholar (July 2011), and the Chinese Biomedical Database (1977 to July 2011) using the key words "Chinese medicine OR Chinese herbal medicine" and "vascular dementia OR mild cognition impair OR multi-infarct dementia OR small-vessel dementia OR strategic infarct dementia OR hypoperfusion dementia OR hemorrhagic dementia OR hereditary vascular dementia". Randomized controlled trials comparing Chinese herbal medicines with placebo/western medicine in the treatment of patients with vascular dementia were included. Diagnostic standards included Diagnostic and Statistical Manual of Mental Disorders-IV, and National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences. Two participants independently conducted literature screening, quality evaluation and data extraction. The quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5.0. Effective rate, Mini-Mental State Examination scores, Hasegawa Dementia Scale scores, and incidence of adverse reactions. We identified 1 143 articles discussing the effects of Chinese medicine on vascular dementia. Thirty-one of these were included in the analysis. These studies involved a total of 2 868 participants (1 605 patients took Chinese medicine decoctions (treatment group); 1 263 patients took western medicine or placebo). The results of our meta-analysis revealed that Chinese herbal remedies in the treatment group were more efficacious than the control intervention (relative risk (RR) = 1.27; 95% confidence interval (CI): 1.18-1.38, P < 0.01). Mini-Mental State Examination
Language Impairment in Alzheimer's Disease and Vascular Dementia.
ERIC Educational Resources Information Center
Lempinen, Maire; And Others
A study of 21 patients with Alzheimer's Disease and 25 with vascular dementia, the two most common forms of dementia, investigated language impairments in the dementia syndrome to see if analysis of language disturbances is helpful in differential diagnosis. Diagnostic assessment included a neurological examination, detailed medical history,…
Corriveau, Roderick A; Bosetti, Francesca; Emr, Marian; Gladman, Jordan T; Koenig, James I; Moy, Claudia S; Pahigiannis, Katherine; Waddy, Salina P; Koroshetz, Walter
2016-03-01
The World Health Organization reports that 47.5 million people are affected by dementia worldwide. With aging populations and 7.7 million new cases each year, the burden of illness due to dementia approaches crisis proportions. Despite significant advances in our understanding of the biology of Alzheimer's disease (AD), the leading dementia diagnosis, the actual causes of dementia in affected individuals are unknown except for rare fully penetrant genetic forms. Evidence from epidemiology and pathology studies indicates that damage to the vascular system is associated with an increased risk of many types of dementia. Both Alzheimer's pathology and cerebrovascular disease increase with age. How AD affects small blood vessel function and how vascular dysfunction contributes to the molecular pathology of Alzheimer's are areas of intense research. The science of vascular contributions to cognitive impairment and dementia (VCID) integrates diverse aspects of biology and incorporates the roles of multiple cell types that support the function of neural tissue. Because of the proven ability to prevent and treat cardiovascular disease and hypertension with population benefits for heart and stroke outcomes, it is proposed that understanding and targeting the biological mechanisms of VCID can have a similarly positive impact on public health.
Dodge, Hiroko H.; Zhu, Jian; Woltjer, Randy; Nelson, Peter T.; Bennett, David A.; Cairns, Nigel J.; Fardo, David W.; Kaye, Jeffrey A.; Lyons, Deniz-Erten; Mattek, Nora; Schneider, Julie A; Silbert, Lisa C.; Xiong, Chengjie; Yu, Lei; Schmitt, Frederick A.; Kryscio, Richard J.; Abner, Erin L.
2016-01-01
Introduction Presence of cerebrovascular pathology may increase the risk of clinical diagnosis of AD. Methods We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modelling of Aging and Risk of Transition (SMART) study, a consortium of longitudinal cohort studies with over 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with lacunes and/or large infarcts). Results The coexistence of lacunes and large infarcts results in higher likelihood of clinical diagnosis of AD only when AD pathology burden is low. Discussion Our results reinforce the diagnostic importance of AD pathology in clinical AD. Further harmonization of assessment approaches for vascular pathologies is required. PMID:28017827
First TV ad for dementia care.
2008-12-10
Last month, viewers saw the first-ever TV advertisement about providing care for people with dementia. Screened as part of Bupa's initiative, bringing the issue of dementia care 'out of the shadows,' the ad features Ernie visiting his sister June, who has dementia, in a Bupa care home and shows the personalised care being delivered by specially trained staff.
Ramirez-Gomez, Liliana; Zheng, Ling; Reed, Bruce; Kramer, Joel; Mungas, Dan; Zarow, Chris; Vinters, Harry; Ringman, John M; Chui, Helena
2017-01-01
The aim of this study was to assess the ability of neuropsychological tests to differentiate autopsy-defined Alzheimer disease (AD) from subcortical ischemic vascular dementia (SIVD). From a sample of 175 cases followed longitudinally that underwent autopsy, we selected 23 normal controls (NC), 20 SIVD, 69 AD, and 10 mixed cases of dementia. Baseline neuropsychological tests, including Memory Assessment Scale word list learning test, control oral word association test, and animal fluency, were compared between the three autopsy-defined groups. The NC, SIVD, and AD groups did not differ by age or education. The SIVD and AD groups did not differ by the Global Clinical Dementia Rating Scale. Subjects with AD performed worse on delayed recall (p < 0.01). A receiver operating characteristics analysis comparing the SIVD and AD groups including age, education, difference between categorical (animals) versus phonemic fluency (letter F), and the first recall from the word learning test distinguished the two groups with a sensitivity of 85%, specificity of 67%, and positive likelihood ratio of 2.57 (AUC = 0.789, 95% CI 0.69-0.88, p < 0.0001). In neuropathologically defined subgroups, neuropsychological profiles have modest ability to distinguish patients with AD from those with SIVD. © 2017 S. Karger AG, Basel.
Ramirez-Gomez, Liliana; Zheng, Ling; Reed, Bruce; Kramer, Joel; Mungas, Dan; Zarow, Chris; Vinters, Harry; Ringman, John M.; Chui, Helena
2018-01-01
Background/Aims The aim of this study was to assess the ability of neuropsychological tests to differentiate autopsy-defined Alzheimer disease (AD) from subcortical ischemic vascular dementia (SIVD). Methods From a sample of 175 cases followed longitudinally that underwent autopsy, we selected 23 normal controls (NC), 20 SIVD, 69 AD, and 10 mixed cases of dementia. Baseline neuropsychological tests, including Memory Assessment Scale word list learning test, control oral word association test, and animal fluency, were compared between the three autopsy-defined groups. Results The NC, SIVD, and AD groups did not differ by age or education. The SIVD and AD groups did not differ by the Global Clinical Dementia Rating Scale. Subjects with AD performed worse on delayed recall (p < 0.01). A receiver operating characteristics analysis comparing the SIVD and AD groups including age, education, difference between categorical (animals) versus phonemic fluency (letter F), and the first recall from the word learning test distinguished the two groups with a sensitivity of 85%, specificity of 67%, and positive likelihood ratio of 2.57 (AUC = 0.789, 95% CI 0.69–0.88, p < 0.0001). Conclusion In neuropathologically defined subgroups, neuropsychological profiles have modest ability to distinguish patients with AD from those with SIVD. PMID:28595184
[Self-consciousness in elderly persons with cognitive impairment and vascular dementia].
Dubinina, E A; Novikova, Yu G; Kalitskaya, A V; Finagentova, N V
2016-01-01
Self-consciousness was compared in 17 elderly (aged 65-89 years old) persons with cognitive impairment without dementia and 17 patients with vascular dementia. Neurocognitive functions and mental health complaints were evaluated. Neuropsychological assessment included evaluation of higher psychological functions, such as attention, memory, conceptualization, gnosis (optic, acoustic), manual skill, speech. Older persons with cognitive impairment assessed their neurocognitive functions adequately. Patients with vascular dementia usually denied cognitive deficit or explained it as a result of aging. Regardless of physical health, older persons with cognitive impairment have active attitude to aging. They could find ways of compensation of cognitive deficits without assistance. Patients with vascular dementia could not compensate their cognitive deficit even with support.
Ballard, C; Patel, A; Oyebode, F; Wilcock, G
1996-05-01
One hundred and twenty-four patients with DSM-III-R dementia were assessed with a standardized battery which included the Geriatric Mental State Schedule, the History and Aetiology Schedule, the Secondary Dementia Schedule and the CAMCOG. Patients with Alzheimer's disease, vascular dementia and senile dementia of Lewy body type (SDLT) all had a similar degree of cognitive impairment at the time of the baseline interview. Patients with Alzheimer's disease and vascular dementia each experienced a mean decline of 27 points in patients with SDLT. Patients with SDLT had a significantly greater decline of verbal fluency than both the other groups. Women were significantly more impaired than men at the time of the baseline assessment but experienced a similar decline during the year of follow-up.
Giebel, Clarissa M; Burns, Alistair; Challis, David
2017-09-01
The literature commonly evaluates those daily activities which are impaired in dementia. However, in the mild stages, people with dementia (PwD) are still able to initiate and perform many of those tasks. With a lack of research exploring variations between different dementia diagnoses, this study sought to investigate those daily activities with modest impairments in the mild stages and how these compare between Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia. Staff from memory assessment services from nine National Health Service trusts across England identified and approached informal carers of people with mild dementia. Carers completed the newly revised Interview for Deteriorations in Daily Living Activities in Dementia 2 assessing the PwD's initiative and performance of instrumental activities of daily living (IADLs). Data were analysed using analysis of variance and Chi-square tests to compare the maintenance of IADL functioning across AD, VaD, and mixed dementia. A total of 160 carers returned the Interview for Deteriorations in Daily Living Activities in Dementia 2, of which 109, 21, and 30 cared for someone with AD, VaD, and mixed dementia, respectively. There were significant variations across subtypes, with AD showing better preserved initiative and performance than VaD for several IADLs. Overall, PwD showed greater preservation of performance than initiative, with tasks such as preparing a hot drink and dressing being best maintained. Findings can help classify dementia better into subtypes in order to receive bespoke support. It suggests that interventions should primarily address initiative to improve overall functioning. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Perri, Roberta; Fadda, Lucia; Caltagirone, Carlo; Carlesimo, Giovanni Augusto
2013-01-01
Different roles have been attributed to mesio-temporal areas and frontal lobes in declarative memory functioning, and qualitative differences have been observed in the amnesic symptoms due to pathological damage of these two portions of the central nervous system. The aim of the present study was to look for memory profiles related to pathological involvement in the temporal and frontal structures in patients with different dementia syndromes on word-list and prose memory tasks. 20 patients with Alzheimer's disease (AD), 20 with frontal variant of FTD (fvFTD), 20 with subcortical ischemic vascular dementia (SIVD), and 20 with Lewy body dementia (LBD) and 34 healthy subjects (NCs) were submitted to word-list and prose memory tasks. All groups performed similarly on both the immediate and delayed recall of the word-list. Conversely, AD patients performed worse than all the other dementia groups on the immediate prose recall. On delayed prose recall, AD patients performed worse than fvFTD and SIVD patients but similar to LBD patients. Differential scores between word-list and prose tests were minimal in the AD group and very pronounced in fvFTD and SIVD groups. The combined use of the prose and word-list tasks evidenced a "mesio-temporal" memory profile in AD patients as opposed to a "frontal" one in fvFTD and SIVD patients and a mixed profile in the LBD patients. In particular, a differential score between the two tests can be useful in differentiating AD patients from patients with other forms of dementia.
Ballard, C; Sauter, M; Scheltens, P; He, Y; Barkhof, F; van Straaten, E C W; van der Flier, W M; Hsu, C; Wu, S; Lane, R
2008-09-01
The aim was to evaluate the efficacy, safety and tolerability of rivastigmine capsules in patients diagnosed with probable vascular dementia (VaD). VantagE (Vascular Dementia trial studying Exelon) was a 24-week, multicentre, double-blind study. VaD patients aged 50-85 years were randomized to rivastigmine capsules (3-12 mg/day) or placebo. Efficacy assessments included global and cognitive performances, activities of daily living and neuropsychiatric symptoms. Adverse events were recorded. Additional exploratory analyses determined whether heterogeneity in pathologies and symptoms extended to differential treatment effects. NCT00099216. 710 patients were randomized. Rivastigmine demonstrated superiority over placebo on three measures of cognitive performance (Vascular Dementia Assessment Scale, Alzheimer's Disease Assessment Scale cognitive subscale, Mini-Mental State Examination; all p< or = 0.05, intent-to-treat population [ITT]), but not other outcomes. Predominant adverse events were nausea and vomiting. Exploratory analyses indicated that older patients (> or =75 years old), assumed more likely to also have Alzheimer's disease (AD) pathology, demonstrated significant cognitive responses to rivastigmine and a safety profile similar to that seen in AD patients. Younger patients, assumed less likely to have concomitant AD pathology, showed no efficacy response and were associated with slight elevations of blood pressure, cerebrovascular accidents and mortality. Rivastigmine-placebo differences in patients with, versus those without, medial temporal atrophy (also suggestive of concomitant AD) showed a numerical difference similar to that seen between the older versus younger patients, but did not attain statistical significance. Consistent with trials evaluating other cholinesterase inhibitors, rivastigmine did not provide consistent efficacy in probable VaD. The efficacy apparent on cognitive outcomes was derived from effects in older patients likely to have
Non-cognitive benefits of galantamine (Reminyl) treatment in vascular dementia.
Kurz, A
2002-01-01
Vascular dementia (VaD) is a condition that involves deterioration in cognitive and non-cognitive areas. Although cognitive impairment is the defining symptom evaluated during clinical trials, changes in non-cognitive areas such as behavior, global functioning and activities of daily living are assessed because they assist in determining quality of life and overall well-being. Therapy has focused traditionally on preventing and controlling risk factors, as no approved treatments are currently available for these patients. Acetylcholinesterase inhibitors (AChEIs), the treatment of choice in patients with Alzheimer's disease (AD), are a potential treatment option for patients with VaD. Galantamine, an AChEI with nicotinic receptor modulation, has demonstrated clinically relevant benefits (cognition, global functioning, functional ability, behavior) in patients with either AD with cerebrovascular disease (AD with CVD) or probable VaD in a 6-month, randomized, double-blind, placebo-controlled study.
Neuroprotective effects of tetrandrine against vascular dementia
Lv, Yan-ling; Wu, Ze-zhi; Chen, Li-xue; Wu, Bai-xue; Chen, Lian-lian; Qin, Guang-cheng; Gui, Bei; Zhou, Ji-ying
2016-01-01
Tetrandrine is one of the major active ingredients in Menispermaceae Stephania tetrandra S. Moore, and has specific therapeutic effects in ischemic cerebrovascular disease. Its use in vascular dementia has not been studied fully. Here, we investigated whether tetrandrine would improve behavioral and cellular impairments in a two-vessel occlusion rat model of chronic vascular dementia. Eight weeks after model establishment, rats were injected intraperitoneally with 10 or 30 mg/kg tetrandrine every other day for 4 weeks. Behavioral assessment in the Morris water maze showed that model rats had longer escape latencies in training trials, and spent less time swimming in the target quadrant in probe trials, than sham-operated rats. However, rats that had received tetrandrine showed shorter escape latencies and longer target quadrant swimming time than untreated model rats. Hematoxylin-eosin and Nissl staining revealed less neuronal necrosis and pathological damage, and more living cells, in the hippocampus of rats treated with tetrandrine than in untreated model rats. Western blot assay showed that interleukin-1β expression, and phosphorylation of the N-methyl-D-aspartate 2B receptor at tyrosine 1472, were lower in model rats that received tetrandrine than in those that did not. The present findings suggest that tetrandrine may be neuroprotective in chronic vascular dementia by reducing interleukin-1β expression, N-methyl-D-aspartate receptor 2B phosphorylation at tyrosine 1472, and neuronal necrosis. PMID:27127485
Vascular Contributions to Cognitive Impairment and Dementia
Gorelick, Philip B.; Scuteri, Angelo; Black, Sandra E.; DeCarli, Charles; Greenberg, Steven M.; Iadecola, Costantino; Launer, Lenore J.; Laurent, Stephane; Lopez, Oscar L.; Nyenhuis, David; Petersen, Ronald C.; Schneider, Julie A.; Tzourio, Christophe; Arnett, Donna K.; Bennett, David A.; Chui, Helena C.; Higashida, Randall T.; Lindquist, Ruth; Nilsson, Peter M.; Roman, Gustavo C.; Sellke, Frank W.; Seshadri, Sudha
2013-01-01
Background and Purpose This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment and dementia of later life are common. Definitions of vascular cognitive impairment (VCI), neuropathology, basic science and pathophysiological aspects, role of neuroimaging and vascular and other associated risk factors, and potential opportunities for prevention and treatment are reviewed. This statement serves as an overall guide for practitioners to gain a better understanding of VCI and dementia, prevention, and treatment. Methods Writing group members were nominated by the writing group co-chairs on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council Scientific Statement Oversight Committee, the Council on Epidemiology and Prevention, and the Manuscript Oversight Committee. The writing group used systematic literature reviews (primarily covering publications from 1990 to May 1, 2010), previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulate recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. After peer review by the American Heart Association, as well as review by the Stroke Council leadership, Council on Epidemiology and Prevention Council, and Scientific Statements Oversight Committee, the statement was approved by the American Heart Association Science Advisory and Coordinating Committee. Results The construct of VCI has been introduced to capture the entire spectrum of cognitive disorders associated with all forms of cerebral vascular brain injury—not solely stroke—ranging from mild cognitive impairment through fully developed
Kandiah, Nagaendran; Pai, Ming-Chyi; Senanarong, Vorapun; Looi, Irene; Ampil, Encarnita; Park, Kyung Won; Karanam, Ananda Krishna; Christopher, Stephen
2017-01-01
Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE-BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations.
Huang, Chi-Wei; Tsai, Meng-Han; Chen, Nai-Ching; Chen, Wei-Hsi; Lu, Yan-Ting; Lui, Chun-Chung; Chang, Ya-Ting; Chang, Wen-Neng; Chang, Alice Y W; Chang, Chiung-Chih
2015-11-25
Endothelial dysfunction leads to worse cognitive performance in Alzheimer's dementia (AD). While both cerebrovascular risk factors and endothelial dysfunction lead to activation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, it is not known whether these biomarkers extend the diagnostic repertoire in reflecting intracerebral structural damage or cognitive performance. A total of 110 AD patients and 50 age-matched controls were enrolled. Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured and correlated with the cognitive performance, white matter macro-structural changes, and major tract-specific fractional anisotropy quantification. The AD patients were further stratified by clinical dementia rating score (mild dementia, n=60; moderate-to-severe dementia, n=50). Compared with the controls, plasma levels of VCAM-1 (p< 0.001), ICAM-1 (p=0.028) and E-selectin (p=0.016) were significantly higher in the patients, but only VCAM-1 levels significantly reflected the severity of dementia (p< 0.001). In addition, only VCAM-1 levels showed an association with macro- and micro- white matter changes especially in the superior longitudinal fasciculus (p< 0.001), posterior thalamic radiation (p=0.002), stria terminalis (p=0.002) and corpus callosum (p=0.009), and were independent of, age and cortical volume. These tracts show significant association with MMSE, short term memory and visuospatial function. Meanwhile, while VCAM-1 level correlated significantly with short-term memory (p=0.026) and drawing (p=0.025) scores in the AD patients after adjusting for age and education, the significance disappeared after adjusting for global FA. Endothelial activation, especially VCAM-1, was of clinical significance in AD that reflects macro- and micro-structural changes and poor short term memory and visuospatial function.
Shah, Ajit; Ellanchenny, Nalini; Suh, Guk-Hee
2005-06-01
There is a paucity of cross-cultural studies of behavioral and psychological symptoms of dementia (BPSD). BPSD were examined in consecutive series of referrals to a psychogeriatric service in Korea and the U.K. using the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale and the Cornell Scale for Depression in Dementia (CSDD). Results were analyzed separately for Alzheimer's disease and vascular dementia. Koreans in both diagnostic groups had lower Mini-mental State Examination (MMSE) scores and higher BEHAVE-AD total and subscale scores for most subscales. In both countries, for both diagnostic groups, the total BEHAVE-AD score and several subscale scores were negatively correlated with the MMSE scores. Logistic regression analysis for Alzheimer's disease revealed that BEHAVE-AD total and most subscale scores independently predicted the country of origin in addition to the MMSE scores predicting the same. These differences in BPSD are most likely explained by the lower MMSE scores in the Korean sample. However, genuine differences in BPSD between the two countries can only be critically examined in a cross-cultural population-based epidemiological study for both diagnostic categories using validated instruments to measure BPSD and controlling for the influence of MMSE score.
Bruandet, A; Richard, F; Bombois, S; Maurage, C A; Deramecourt, V; Lebert, F; Amouyel, P; Pasquier, F
2009-02-01
Vascular dementia (VaD) and Alzheimer disease with cerebrovascular disease (AD+CVD) are the leading causes of dementia after Alzheimer disease alone (AD). Little is known about the progression of either VaD or AD+CVD. The aim of this study was to compare demographic features, cognitive decline and survival of patients with VaD, AD+CVD and AD alone attending a memory clinic. This study included 970 patients who were followed at the Lille-Bailleul memory clinic, France. Cognitive functions were measured with the Mini Mental State Examination (MMSE) and the Dementia Rating Scale (DRS). Survival rate was analysed with a left-truncated Cox model. Analyses were adjusted for age, sex, education, hypertension, diabetes and baseline MMSE and DRS. Of 970 patients, 141 had VaD, 663 AD alone and 166 AD+CVD. The latter were significantly older than AD or VaD patients at onset (71 (SD 7) vs 69 (9) and 68 (9) years, p = 0.01) and at first visit (75 (6) vs 73 (8) and 72 (8) years, p = 0.0002). Baseline MMSE and DRS evaluations were highest for VaD compared with AD alone or AD+CVD patients (p<0.006). Cognitive decline during follow-up was slowest for VaD, intermediate for AD+CVD and fastest for AD alone (p = 0.03). After adjustment, compared with AD patients, mortality risk was similar for those with VaD (relative mortality risk (RR) = 0.7 (0.5 to 1.1)) and tended to be lower for AD+CVD (RR = 0.7 (0.5 to 1.0)). The shorter the delay between first symptoms and first visit, the longer patients survived. This clinical cohort study shows that patients with VaD, AD+CVD and AD present different characteristics at baseline and during follow-up, and underlines the need to distinguish between them.
Quinlan, Patrick; Horvath, Alexandra; Nordlund, Arto; Wallin, Anders; Svensson, Johan
2017-12-01
Insulin-like growth factor-I (IGF-I) is important for the adult brain, but little is known of the role of IGF-I in Alzheimeŕs disease (AD) or vascular dementia (VaD). A prospective study of 342 patients with subjective or objective mild cognitive impairment recruited at a single memory clinic. We determined whether serum IGF-I concentrations at baseline were associated with the risk of all-cause dementia, AD, or VaD. Patients developing mixed forms of AD and VaD were defined as suffering from VaD. The statistical analyses included Cox proportional hazards regression analysis. During the follow-up (mean 3.6 years), 95 (28%) of the patients developed all-cause dementia [AD, n=37 (11%) and VaD, n=42 (12%)]. Low as well as high serum IGF-I (quartile 1 or 4 vs. quartiles 2-3) did not associate with all-cause dementia [crude hazard ratio (HR) 1.30, 95% confidence interval (CI): 0.81-2.08 and crude HR 1.05, 95% CI: 0.63-1.75, respectively] or AD (crude HR 0.79, 95% CI: 0.35-1.79 and crude HR 0.94, 95% CI: 0.43-2.06, respectively]. In contrast, low serum IGF-I concentrations were associated with increased risk of VaD (quartile 1 vs. quartiles 2-3, crude HR 2.22, 95% CI: 1.13-4.36). The latter association remained significant also after adjustment for multiple covariates. In a memory clinic population, low serum IGF-I was a risk marker for subsequent VaD whereas low IGF-I did not associate with the risk of AD. High serum IGF-I was not related to the risk of conversion to dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.
Cerciello, Milena; Isella, Valeria; Proserpi, Alice; Papagno, Costanza
2017-01-01
Alzheimer's disease (AD), vascular dementia (VaD) and frontotemporal dementia (FTD) are the most common forms of dementia. It is well known that memory deficits in AD are different from those in VaD and FTD, especially with respect to cued recall. The aim of this clinical study was to compare the memory performance in 15 AD, 10 VaD and 9 FTD patients and 20 normal controls by means of a 24-item Grober-Buschke test [8]. The patients' groups were comparable in terms of severity of dementia. We considered free and total recall (free plus cued) both in immediate and delayed recall and computed an Index of Sensitivity to Cueing (ISC) [8] for immediate and delayed trials. We assessed whether cued recall predicted the subsequent free recall across our patients' groups. We found that AD patients recalled fewer items from the beginning and were less sensitive to cueing supporting the hypothesis that memory disorders in AD depend on encoding and storage deficit. In immediate recall VaD and FTD showed a similar memory performance and a stronger sensitivity to cueing than AD, suggesting that memory disorders in these patients are due to a difficulty in spontaneously implementing efficient retrieval strategies. However, we found a lower ISC in the delayed recall compared to the immediate trials in VaD than FTD due to a higher forgetting in VaD.
Vascular cognitive impairment, dementia, aging and energy demand. A vicious cycle.
Popa-Wagner, A; Buga, Ana-Maria; Popescu, B; Muresanu, D
2015-08-01
To a great extent, cognitive health depends on cerebrovascular health and a deeper understanding of the subtle interactions between cerebrovascular function and cognition is needed to protect humans from one of the most devastating affliction, dementia. However, the underlying biological mechanisms are still not completely clear. Many studies demonstrated that the neurovascular unit is compromised in cerebrovascular diseases and also in other types of dementia. The hemodynamic neurovascular coupling ensures a strong increase of the cerebral blood flow (CBF) and an acute increase in neuronal glucose uptake upon increased neural activity. Dysfunction of cerebral autoregulation with increasing age along with age-related structural and functional alterations in cerebral blood vessels including accumulation of amyloid-beta (Aβ) in the media of cortical arterioles, neurovascular uncoupling due to astrocyte endfeet retraction, impairs the CBF and increases the neuronal degeneration and susceptibility to hypoxia and ischemia. A decreased cerebral glucose metabolism is an early event in Alzheimer's disease (AD) pathology and may precede the neuropathological Aβ deposition associated with AD. Aβ accumulation in turn leads to further decreases in the CBF closing the vicious cycle. Alzheimer, aging and diabetes are also influenced by insulin/insulin-like growth factor-1 signaling, and accumulated evidence indicates sporadic AD is associated with disturbed brain insulin metabolism. Understanding how vascular and metabolic factors interfere with progressive loss of functional neuronal networks becomes essential to develop efficient drugs to prevent cognitive decline in elderly.
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
Kandiah, Nagaendran; Pai, Ming-Chyi; Senanarong, Vorapun; Looi, Irene; Ampil, Encarnita; Park, Kyung Won; Karanam, Ananda Krishna; Christopher, Stephen
2017-01-01
Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE−BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations. PMID:28458525
Li, C; Zheng, J; Wang, J; Gui, L
2011-01-01
Blood oxygen level dependent functional magnetic resonance imaging (fMRI) and the Stroop test were used to assess attentional cortex activation in patients with Alzheimer's disease, subcortical vascular dementia, and normal control subjects. Patients with Alzheimer's disease and subcortical vascular dementia demonstrated similar locations of cortical activation, including the bilateral middle and inferior frontal gyri, anterior cingulate and inferior parietal lobule in response to Stroop colour word stimuli. This activation was distinctly decreased in patients with dementia compared with normal control subjects. Different regions of the brain were activated in patients with Alzheimer's disease and subcortical vascular dementia compared with normal controls. fMRI is a useful tool for the study of dementia in humans and has some potential diagnostic value. Further studies with larger numbers of participants are required.
Senile dementia of the Binswanger type: a vascular form of dementia in the elderly
DOE Office of Scientific and Technical Information (OSTI.GOV)
Roman, G.C.
1987-10-02
Computed tomography and magnetic resonance imaging in the elderly have demonstrated the common occurrence of deep white-matter lesions in the aging brain. These radiologic lesions (leukoaraiosis) may represent an early marker of dementia. At autopsy, an ischemic periventricular leukoencephalopathy (Binswanger's disease) has been found in most cases. The clinical spectrum of Binswanger's disease appears to range from asymptomatic radiologic lesions to dementia with focal deficits, frontal signs, pseudobulbar palsy, gait difficulties, and urinary incontinence. The name senile dementia of the Binswanger type (SDBT) is proposed for this poorly recognized, vascular form of subcortical dementia. The SDBT probably results from corticalmore » disconnections most likely caused by hypoperfusion. In contrast, multi-infarct dementia is correlated with multiple large and small strokes that cause a loss of over 50 to 100 mL of brain volume. The periventricular white matter is a watershed area irrigated by long, penetrating medullary arteries. Risk factors for SDBT are small-artery diseases, such as hypertension and amyloid angiopathy, impaired autoregulation of cerebral blood flow in the elderly, and periventricular hypoperfusion due to cardiac failure, arrhythmias, and hypotension. The SDBT may be a potentially preventable and treatable form of dementia.« less
Poor Gait Performance and Prediction of Dementia: Results From a Meta-Analysis.
Beauchet, Olivier; Annweiler, Cédric; Callisaya, Michele L; De Cock, Anne-Marie; Helbostad, Jorunn L; Kressig, Reto W; Srikanth, Velandai; Steinmetz, Jean-Paul; Blumen, Helena M; Verghese, Joe; Allali, Gilles
2016-06-01
Poor gait performance predicts risk of developing dementia. No structured critical evaluation has been conducted to study this association yet. The aim of this meta-analysis was to systematically examine the association of poor gait performance with incidence of dementia. An English and French Medline search was conducted in June 2015, with no limit of date, using the medical subject headings terms "Gait" OR "Gait Disorders, Neurologic" OR "Gait Apraxia" OR "Gait Ataxia" AND "Dementia" OR "Frontotemporal Dementia" OR "Dementia, Multi-Infarct" OR "Dementia, Vascular" OR "Alzheimer Disease" OR "Lewy Body Disease" OR "Frontotemporal Dementia With Motor Neuron Disease" (Supplementary Concept). Poor gait performance was defined by standardized tests of walking, and dementia was diagnosed according to international consensus criteria. Four etiologies of dementia were identified: any dementia, Alzheimer disease (AD), vascular dementia (VaD), and non-AD (ie, pooling VaD, mixed dementias, and other dementias). Fixed effects meta-analyses were performed on the estimates in order to generate summary values. Of the 796 identified abstracts, 12 (1.5%) were included in this systematic review and meta-analysis. Poor gait performance predicted dementia [pooled hazard ratio (HR) combined with relative risk and odds ratio = 1.53 with P < .001 for any dementia, pooled HR = 1.79 with P < .001 for VaD, HR = 1.89 with P value < .001 for non-AD]. Findings were weaker for predicting AD (HR = 1.03 with P value = .004). This meta-analysis provides evidence that poor gait performance predicts dementia. This association depends on the type of dementia; poor gait performance is a stronger predictor of non-AD dementias than AD. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.
Suto, Teiko; Meguro, Kenichi; Nakatsuka, Masahiro; Kato, Yuriko; Tezuka, Kimihiro; Yamaguchi, Satoshi; Tashiro, Manabu
2014-07-01
In dementia patients, dietary intake problems may occur despite the absence of swallowing problems. We investigated cognitive functions on food and taste in Alzheimer's disease (AD) and vascular dementia (VaD) patients. Participants included 15 healthy controls (HC), 30 AD and 20 VaD patients. Food Cognition Test: Replicas of three popular foods in Japan with no odors were presented visually to each participant, with the instruction to respond with the name of each food. Replicas of food materials were subsequently presented to ask whether they were included in these foods. Taste Cognition Test: Replicas of 12 kinds of foods were presented to describe their expected tastes. The AD/VaD groups exhibited significantly lower scores on Food/Taste Cognition Tests compared with the HC group. These scores correlated inversely with Mini-Mental State Examination (MMSE) scores in the AD group. Decreased dietary intake was observed in 12 of the 50 patients; 8 of the 12 exhibited decreased Taste Cognition Test scores, higher than that of the normal-intake patients. There was no difference in the filter paper taste disc test between HC/AD/VaD groups. To test the hypothesis that the insula is associated with taste cognition, two MMSE-matched AD subgroups (n = 10 vs. 10) underwent positron emission tomography. Glucose metabolism in the right insula was lower in the low taste cognition subgroup. The VaD patients with insular lesions exhibited impaired Taste Cognition Test findings. It is important to consider the cognitive aspect of dietary intake when we care for dementia patients.
The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged.
Craft, Suzanne
2009-03-01
In recent years a rapidly increasing number of studies has focused on the relationship between dementia and metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. Etiological heterogeneity and comorbidity pose challenges for determining relationships among metabolic disorders. The independent and interactive effects of brain vascular injury and classic pathological agents such as beta-amyloid have also proved difficult to distinguish in human patients, blurring the lines between Alzheimer disease and vascular dementia. This review highlights recent work aimed at identifying convergent mechanisms such as insulin resistance that may underlie comorbid metabolic disorders and thereby increase dementia risk. Identification of such convergent factors will not only provide important insight into the causes and interdependencies of late-life dementias but will also inspire novel strategies for treating and preventing these disorders.
The Role of Metabolic Disorders in Alzheimer's Disease and Vascular Dementia: Two Roads Converged?
Craft, Suzanne
2009-01-01
In recent years, there has been a rapidly increasing number of studies focused on the relationship between dementia and metabolic disorders such as diabetes, obesity, hypertension and dyslipidemia. Etiological heterogeneity and co-morbidity pose challenges for determining relationships among metabolic disorders. The independent and interactive effects of brain vascular injury and classic pathological agents such as Aβ have also proved difficult to untangle in human patients, blurring the lines between Alzheimer's disease and vascular dementia. This review highlights recent work aimed at identifying convergent mechanisms such as insulin resistance that may underlie co-morbid metabolic disorders and thereby increase dementia risk. Identification of such convergent factors will not only provide important insights into the causes and interdependencies of late-life dementias, but will also inspire novel strategies for treating and preventing these disorders. PMID:19273747
Zhu, Yanzhen; Zeng, Yanjun; Wang, Xuan; Ye, Xiaobao
2013-07-01
Clinically, electroacupuncture is proved to be an effective therapy for vascular dementia; however, their mechanisms remain uncertain. The aim of the current study was to investigate the mechanism of electroacupuncture therapy for vascular dementia. One month after a vascular dementia animal model was established by bilateral occlusion of common carotid arteries, electroacupuncture treatment was given at "Baihui" (DU20), "Dazhui" (DU14), and "Shenshu" (BL23). Morris water maze was used to assess the learning and memory ability of rats. Western blot assay was performed to detect the expression of mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E (eIF4E) in hippocampus of rats. Morris water maze test showed that electroacupuncture improved the learning ability of vascular dementia rats. Western blot assay revealed that the expression level of mTOR and eIF4E in the electroacupuncture group and sham-operated group was higher than that in the vascular dementia group (P < 0.05). In conclusion, the decreasing expression of mTOR and eIF4E plays important roles in the pathogenesis of vascular dementia. Electroacupuncture improves learning and memory ability by up-regulating expression of mTOR and eIF4E in the hippocampus of vascular dementia rats.
Niemantsverdriet, Ellis; Feyen, Bart F E; Le Bastard, Nathalie; Martin, Jean-Jacques; Goeman, Johan; De Deyn, Peter Paul; Bjerke, Maria; Engelborghs, Sebastiaan
2018-01-01
Differential dementia diagnosis remains a challenge due to overlap of clinical profiles, which often results in diagnostic doubt. Determine the added diagnostic value of cerebrospinal fluid (CSF) biomarkers for differential dementia diagnosis as compared to autopsy-confirmed diagnosis. Seventy-one dementia patients with autopsy-confirmed diagnoses were included in this study. All neuropathological diagnoses were established according to standard neuropathological criteria and consisted of Alzheimer's disease (AD) or other dementias (NONAD). CSF levels of Aβ1 - 42, T-tau, and P-tau181 were determined and interpreted based on the IWG-2 and NIA-AA criteria, separately. A panel of three neurologists experienced with dementia made clinical consensus dementia diagnoses. Clinical and CSF biomarker diagnoses were compared to the autopsy-confirmed diagnoses. Forty-two patients (59%) had autopsy-confirmed AD, whereas 29 patients (41%) had autopsy-confirmed NONAD. Of the 24 patients with an ambiguous clinical dementia diagnosis, a correct diagnosis would have been established in 67% of the cases applying CSF biomarkers in the context of the IWG-2 or the NIA-AA criteria respectively. AD CSF biomarkers have an added diagnostic value in differential dementia diagnosis and can help establishing a correct dementia diagnosis in case of ambiguous clinical dementia diagnoses.
Genomics of Dementia: APOE- and CYP2D6-Related Pharmacogenetics
Cacabelos, Ramón; Martínez, Rocío; Fernández-Novoa, Lucía; Carril, Juan C.; Lombardi, Valter; Carrera, Iván; Corzo, Lola; Tellado, Iván; Leszek, Jerzy; McKay, Adam; Takeda, Masatoshi
2012-01-01
Dementia is a major problem of health in developed societies. Alzheimer's disease (AD), vascular dementia, and mixed dementia account for over 90% of the most prevalent forms of dementia. Both genetic and environmental factors are determinant for the phenotypic expression of dementia. AD is a complex disorder in which many different gene clusters may be involved. Most genes screened to date belong to different proteomic and metabolomic pathways potentially affecting AD pathogenesis. The ε4 variant of the APOE gene seems to be a major risk factor for both degenerative and vascular dementia. Metabolic factors, cerebrovascular disorders, and epigenetic phenomena also contribute to neurodegeneration. Five categories of genes are mainly involved in pharmacogenomics: genes associated with disease pathogenesis, genes associated with the mechanism of action of a particular drug, genes associated with phase I and phase II metabolic reactions, genes associated with transporters, and pleiotropic genes and/or genes associated with concomitant pathologies. The APOE and CYP2D6 genes have been extensively studied in AD. The therapeutic response to conventional drugs in patients with AD is genotype specific, with CYP2D6-PMs, CYP2D6-UMs, and APOE-4/4 carriers acting as the worst responders. APOE and CYP2D6 may cooperate, as pleiotropic genes, in the metabolism of drugs and hepatic function. The introduction of pharmacogenetic procedures into AD pharmacological treatment may help to optimize therapeutics. PMID:22482072
Jinnouchi, Hiroshige; Kitamura, Akihiko; Yamagishi, Kazumasa; Kiyama, Masahiko; Imano, Hironori; Okada, Takeo; Cui, Renzhe; Umesawa, Mitsumasa; Muraki, Isao; Hayama-Terada, Mina; Kawasaki, Ryo; Sankai, Tomoko; Ohira, Tetsuya
2017-01-01
Aim: To investigate the association of retinal vascular changes with a risk of dementia in longitudinal population-based study. Methods: We performed a nested case-control study of 3,718 persons, aged 40–89 years, enrolled between 1983 and 2004. Retinal vascular changes were observed in 351 cases with disabling dementia (average period before the onset, 11.2 years) and in 702 controls matched for sex, age, and baseline year. Incidence of disabling dementia was defined as individuals who received cares for disabilities including dementia-related symptoms and/or behavioral disturbance. Conditional logistic regression analysis was used to calculate odds ratio (OR) and multivariable adjusted OR (Models 1 and 2) for incidence of disabling dementia according to each retinal vascular change. Regarding confounding variables, Model 1 included overweight status, hypertension, hyperglycemia, dyslipidemia, and smoking status, whereas Model 2 also included incidence of stroke prior to disabling dementia for further analysis. Results: The proportion of cases (controls) with retinal vascular changes was 23.1 (15.7)% for generalized arteriolar narrowing, 7.7 (7.5)% for focal arteriolar narrowing, 15.7 (11.8)% for arteriovenous nicking, 10.5 (9.3)% for increased arteriolar wall reflex, and 11.4 (9.8)% for any other retinopathy. Generalized arteriolar narrowing was associated with an increased risk of disabling dementia: crude OR, 1.66 (95% confidence interval, 1.19–2.31); Model 1: OR, 1.58 (1.12–2.23); Model 2: OR, 1.48 (1.04–2.10). The number of retinal abnormalities was associated in a dose–response manner with the risk. Conclusion: Generalized arteriolar narrowing and total number of retinal abnormalities may be useful markers for identifying persons at higher risks of disabling dementia. PMID:27904027
Decline in Literacy and Incident AD Dementia Among Community-Dwelling Older Persons.
Yu, Lei; Wilson, Robert S; Han, S Duke; Leurgans, Sue; Bennett, David A; Boyle, Patricia A
2017-06-01
To quantify longitudinal change in financial and health literacy and examine the associations of declining literacy with incident Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI). Data came from 799 participants of an ongoing cohort study. Literacy was measured using a battery of 32 questions. Clinical diagnoses were made annually following uniform structured procedures. The associations of declining literacy with incident AD dementia and MCI were tested using a joint model for longitudinal and time-to-event data. We observed an overall decline in total literacy score over up to 6 years of follow-up ( p < .001). Faster decline in literacy was associated with higher risks for incident AD dementia (hazard ratio = 4.526, 95% confidence interval = [2.993, 6.843], p < .001) and incident MCI (hazard ratio = 2.971, 95% confidence interval = [1.509, 5.849], p = .002). Declining literacy among community-dwelling older persons predicts adverse cognitive outcomes and serves as an early indicator of impending dementia.
Cardiovascular risk factors and dementia.
Fillit, Howard; Nash, David T; Rundek, Tatjana; Zuckerman, Andrea
2008-06-01
Dementias, such as Alzheimer's disease (AD) and vascular dementia, are disorders of aging populations and represent a significant economic burden. Evidence is accumulating to suggest that cardiovascular disease (CVD) risk factors may be instrumental in the development of dementia. The goal of this review was to discuss the relationship between specific CVD risk factors and dementia and how current treatment strategies for dementia should focus on reducing CVD risks. We conducted a review of the literature for the simultaneous presence of 2 major topics, cardiovascular risk factors and dementia (eg, AD). Special emphasis was placed on clinical outcome studies examining the effects of treatments of pharmacologically modifiable CVD risk factors on dementia and cognitive impairment. Lifestyle risk factors for CVD, such as obesity, lack of exercise, smoking, and certain psychosocial factors, have been associated with an increased risk of cognitive decline and dementia. Some evidence suggests that effectively managing these factors may prevent cognitive decline/dementia. Randomized, placebo-controlled trials of antihypertensive medications have found that such therapy may reduce the risk of cognitive decline, and limited data suggest a benefit for patients with AD. Some small open-label and randomized clinical trials of statins have observed positive effects on cognitive function; larger studies of statins in patients with AD are ongoing. Although more research is needed, current evidence indicates an association between CVD risk factors--such as hypertension, dyslipidemia, and diabetes mellitus--and cognitive decline/dementia. From a clinical perspective, these data further support the rationale for physicians to provide effective management of CVD risk factors and for patients to be compliant with such recommendations to possibly prevent cognitive decline/dementia.
Gao, Yong-Zhe; Zhang, Jun-Jian; Liu, Hui; Wu, Guang-Yao; Xiong, Li; Shu, Min
2013-02-01
Hemodynamic disturbance in cerebral blood flow (CBF) is common in both Alzheimer's disease (AD) and vascular dementia (VaD).The aim of this study is to investigate the different patterns of regional cerebral blood flow (rCBF) change and cerebrovascular reactivity (CVR) in these two types of dementia. Mean flow velocity (MFV) of middle cerebral artery and rCBF were measured by Transcranial Doppler ultrasound (TCD) and arterial spin-labeling (ASL) magnetic resonance, separately. CVR was evaluated by MFV or rCBF change in response to 5% CO2 inhalation. The ASL results showed that, rCBF was significantly lower in both the bilateral frontal and temporal lobes in AD group and lower in left frontal and temporal white matter in patients with VaD. CVR calculated by rCBF was impaired more severely in bilateral frontal cortices in AD. Conversely, TCD tests failed to demonstrate significant difference in MFV and CVR between the two groups. It is concluded that the different patterns detected by ASL in resting rCBF change and cerebrovascular reactivity in response to carbogen inhalation may serve as a potential marker to distinguish AD and VaD.
Fully automated structural MRI of the brain in clinical dementia workup.
Persson, Karin; Selbæk, Geir; Brækhus, Anne; Beyer, Mona; Barca, Maria; Engedal, Knut
2017-06-01
Background The dementia syndrome has been regarded a clinical diagnosis but the focus on supplemental biomarkers is increasing. An automatic magnetic resonance imaging (MRI) volumetry method, NeuroQuant® (NQ), has been developed for use in clinical settings. Purpose To evaluate the clinical usefulness of NQ in distinguishing Alzheimer's disease dementia (AD) from non-dementia and non-AD dementia. Material and Methods NQ was performed in 275 patients diagnosed according to the criteria of ICD-10 for AD, vascular dementia and Parkinson's disease dementia (PDD); the Winblad criteria for mild cognitive impairment; the Lund-Manchester criteria for frontotemporal dementia; and the revised consensus criteria for Lewy body dementia (LBD). Receiver operating curve (ROC) analyses with calculation of area under the curve (AUC) and regression analyses were carried out. Results Forebrain parenchyma (AUC 0.82), hippocampus (AUC 0.80), and inferior lateral ventricles (AUC 0.78) yielded the highest AUCs for AD/non-dementia discrimination. Only hippocampus (AUC 0.62) and cerebellum (AUC 0.67) separated AD from non-AD dementia. Cerebellum separated AD from PDD-LBD (AUC 0.83). Separate multiple regression analyses adjusted for age and gender, showed that memory (CERAD 10-word delayed recall) (beta 0.502, P < 0.001) was more strongly associated to the hippocampus volume than the diagnostic distinction of AD versus non-dementia (beta -0.392, P < 0.001). Conclusion NQ measures could separate AD from non-dementia fairly well but generally poorer from non-AD dementia. Degree of memory impairment, age, and gender, but not diagnostic distinction, were associated to the hippocampus volume in adjusted analyses. Surprisingly, cerebellum was found relevant in separating AD from PDD-LBD.
Vascular dementia: Pharmacological treatment approaches and perspectives
Baskys, Andrius; Hou, Anthony C
2007-01-01
Vascular dementia is a common condition for which there are no effective approved pharmacological treatments available. Absence of effective treatments creates a difficult situation for those suffering from the disease, their caregivers, and healthcare providers. This review will address our current understanding of the mechanisms of nerve cell damage due to ischemia and summarize available clinical trial data on several commonly used compounds including memantine, donepezil, galantamine, rivastigmine, nimodipine, hydergine, nicergoline, CDP-choline, folic acid, as well as such nonpharmacological approaches as validation therapy. PMID:18044183
Jessen, Frank; Wiese, Birgitt; Bachmann, Cadja; Eifflaender-Gorfer, Sandra; Haller, Franziska; Kölsch, Heike; Luck, Tobias; Mösch, Edelgard; van den Bussche, Hendrik; Wagner, Michael; Wollny, Anja; Zimmermann, Thomas; Pentzek, Michael; Riedel-Heller, Steffi G; Romberg, Heinz-Peter; Weyerer, Siegfried; Kaduszkiewicz, Hanna; Maier, Wolfgang; Bickel, Horst
2010-04-01
Subjective memory impairment (SMI) is receiving increasing attention as a pre-mild cognitive impairment (MCI) condition in the course of the clinical manifestation of Alzheimer disease (AD). To determine the risk for conversion to any dementia, dementia in AD, or vascular dementia by SMI, graded by the level of SMI-related worry and by the temporal association of SMI and subsequent MCI. Longitudinal cohort study with follow-up examinations at 1(1/2) and 3 years after baseline. Primary care medical record registry sample. A total of 2415 subjects without cognitive impairment 75 years or older in the German Study on Aging, Cognition and Dementia in Primary Care Patients. Conversion to any dementia, dementia in AD, or vascular dementia at follow-up 1 or follow-up 2 predicted by SMI with or without worry at baseline and at follow-up 2 predicted by different courses of SMI at baseline and MCI at follow-up 1. In the first analysis, SMI with worry at baseline was associated with greatest risk for conversion to any dementia (hazard ratio [HR], 3.53; 95% confidence interval [CI], 2.07-6.03) or dementia in AD (6.54; 2.82-15.20) at follow-up 1 or follow-up 2. The sensitivity was 69.0% and the specificity was 74.3% conversion to dementia in AD. In the second analysis, SMI at baseline and MCI at follow-up 1 were associated with greatest risk for conversion to any dementia (odds ratio [OR], 8.92; 95% CI, 3.69-21.60) or dementia in AD (19.33; 5.29-70.81) at follow-up 2. Furthermore, SMI at baseline and amnestic MCI at follow-up 1 increased the risk for conversion to any dementia (OR, 29.24; 95% CI, 8.75-97.78) or dementia in AD (60.28; 12.23-297.10), with a sensitivity of 66.7% and a specificity of 98.3% for conversion to dementia in AD. The prediction of dementia in AD by SMI with subsequent amnestic MCI supports the model of a consecutive 3-stage clinical manifestation of AD from SMI via MCI to dementia.
Garcia-Ptacek, Sara; Kåreholt, Ingemar; Cermakova, Pavla; Rizzuto, Debora; Religa, Dorota; Eriksdotter, Maria
2016-11-01
The causes of death in dementia are not established, particularly in rarer dementias. The aim of this study is to calculate risk of death from specific causes for a broader spectrum of dementia diagnoses. Cohort study. Swedish Dementia Registry (SveDem), 2007-2012. Individuals with incident dementia registered in SveDem (N = 28,609); median follow-up 741 days. Observed deaths were 5,368 (19%). Information on number of deaths and causes of mortality was obtained from death certificates. Odds ratios for the presence of dementia on death certificates were calculated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox hazards regression for cause-specific mortality, using Alzheimer's dementia (AD) as reference. Hazard ratios for death for each specific cause of death were compared with hazard ratios of death from all causes (P-values from t-tests). The most frequent underlying cause of death in this cohort was cardiovascular (37%), followed by dementia (30%). Dementia and cardiovascular causes appeared as main or contributory causes on 63% of certificates, followed by respiratory (26%). Dementia was mentioned less in vascular dementia (VaD; 57%). Compared to AD, cardiovascular mortality was higher in individuals with VaD than in those with AD (HR = 1.82, 95% CI = 1.64-2.02). Respiratory death was higher in individuals with Lewy body dementia (LBD, including Parkinson's disease dementia and dementia with Lewy bodies, HR = 2.16, 95% CI = 1.71-2.71), and the risk of respiratory death was higher than expected from the risk for all-cause mortality. Participants with frontotemporal dementia were more likely to die from external causes of death than those with AD (HR = 2.86, 95% CI = 1.53-5.32). Dementia is underreported on death certificates as main and contributory causes. Individuals with LBD had a higher risk of respiratory death than those with AD. © 2016 The Authors. The Journal of the American Geriatrics Society published by Wiley
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.
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
Vascular risk factors and neuropsychiatric symptoms in Alzheimer's disease: the Cache County Study.
Steinberg, Martin; Hess, Kyle; Corcoran, Chris; Mielke, Michelle M; Norton, Maria; Breitner, John; Green, Robert; Leoutsakos, Jeannie; Welsh-Bohmer, Kathleen; Lyketsos, Constantine; Tschanz, Joann
2014-02-01
Knowledge of potentially modifiable risk factors for neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) is important. This study longitudinally explores modifiable vascular risk factors for NPS in AD. Participants enrolled in the Cache County Study on Memory in Aging with no dementia at baseline were subsequently assessed over three additional waves, and those with incident (new onset) dementia were invited to join the Dementia Progression Study for longitudinal follow-up. A total of 327 participants with incident AD were identified and assessed for the following vascular factors: atrial fibrillation, hypertension, diabetes mellitus, angina, coronary artery bypass surgery, myocardial infarction, cerebrovascular accident, and use of antihypertensive or diabetes medicines. A vascular index (VI) was also calculated. NPS were assessed over time using the Neuropsychiatric Inventory (NPI). Affective and Psychotic symptom clusters were assessed separately. The association between vascular factors and change in NPI total score was analyzed using linear mixed model and in symptom clusters using a random effects model. No individual vascular risk factors or the VI significantly predicted change in any individual NPS. The use of antihypertensive medications more than four times per week was associated with higher total NPI and Affective cluster scores. Use of antihypertensive medication was associated with higher total NPI and Affective cluster scores. The results of this study do not otherwise support vascular risk factors as modifiers of longitudinal change in NPS in AD. Copyright © 2013 John Wiley & Sons, Ltd.
Physical activity and dementia risk in the elderly: findings from a prospective Italian study.
Ravaglia, G; Forti, P; Lucicesare, A; Pisacane, N; Rietti, E; Bianchin, M; Dalmonte, E
2008-05-06
To examine the effect of physical activity on risk of developing Alzheimer disease (AD) and vascular dementia (VaD) in the elderly. Data are from a prospective population-based cohort of 749 Italian subjects aged 65 and older who, in 1999/2000, were cognitively normal at an extensive assessment for clinically overt and preclinical dementia and, in 2003/2004, underwent follow-up for incident dementia. Baseline physical activity was measured as energy expenditure on activities of different intensity (walking, stair climbing, moderate activities, vigorous activities, and total physical activity). Over 3.9 +/- 0.7 years of follow-up there were 86 incident dementia cases (54 AD, 27 VaD). After adjustment for sociodemographic and genetic confounders, VaD risk was significantly lower for the upper tertiles of walking (hazard ratio [HR] 0.27, 95% CI 0.12 to 0.63), moderate (HR 0.29, 95% CI 0.12 to 0.66), and total physical activity (HR 0.24, 95% 0.11 to 0.56) compared to the corresponding lowest tertile. The association persisted after accounting for vascular risk factors and overall health status. After adjustment for sociodemographic and genetic confounders, AD risk was not associated with measures of physical activity and results did not change after further adjustment for vascular risk factors and overall health and functional status. In this cohort, physical activity is associated with a lower risk of vascular dementia but not of Alzheimer disease. Further research is needed about the biologic mechanisms operating between physical activity and cognition.
CSF/serum albumin ratio in dementias: a cross-sectional study on 1861 patients.
Skillbäck, Tobias; Delsing, Louise; Synnergren, Jane; Mattsson, Niklas; Janelidze, Shorena; Nägga, Katarina; Kilander, Lena; Hicks, Ryan; Wimo, Anders; Winblad, Bengt; Hansson, Oskar; Blennow, Kaj; Eriksdotter, Maria; Zetterberg, Henrik
2017-11-01
A connection between dementias and blood-brain barrier (BBB) dysfunction has been suggested, but previous studies have yielded conflicting results. We examined cerebrospinal fluid (CSF)/serum albumin ratio in a large cohort of patients diagnosed with Alzheimer's disease (AD, early onset [EAD, n = 130], late onset AD [LAD, n = 666]), vascular dementia (VaD, n = 255), mixed AD and VaD (MIX, n = 362), Lewy body dementia (DLB, n = 50), frontotemporal dementia (FTD, n = 56), Parkinson's disease dementia (PDD, n = 23), other dementias (other, n = 48), and dementia not otherwise specified (NOS, n = 271). We compared CSF/serum albumin ratio to 2 healthy control groups (n = 292, n = 20), between dementia diagnoses, and tested biomarker associations. Patients in DLB, LAD, VaD, MIX, other, and NOS groups had higher CSF/serum albumin ratio than controls. CSF/serum albumin ratio correlated with CSF neurofilament light in LAD, MIX, VaD, and other groups but not with AD biomarkers. Our data show that BBB leakage is common in dementias. The lack of association between CSF/serum albumin ratio and AD biomarkers suggests that BBB dysfunction is not inherent to AD but might represent concomitant cerebrovascular pathology. Copyright © 2017 Elsevier Inc. All rights reserved.
Barca, Maria Lage; Engedal, Knut; Laks, Jerson; Selbaek, Geir
2012-01-01
This study explores factors associated with depression in Alzheimer's disease (AD) compared with mild cognitive impairment (MCI) and other dementia disorders. In a prospective study we included 195 patients: 31 with MCI, 112 with AD and 52 with other dementias. According to the ICD-10 and the DSM-IV criteria, 88 (44.1%) and 59 (30.3%), respectively, had a depressive disorder. An adjusted multiple regression analysis showed that previous depression (p < 0.05) was significantly associated with depression in AD patients. Severity of dementia (p < 0.05) was significantly associated with a depressive disorder in a group of patients with frontotemporal dementia, vascular dementia, or dementia due to Lewy Body disease or Parkinson's disease. We found different factors associated with a depressive disorder in AD compared to those found for other dementia disorders.
Areosa Sastre, A; McShane, R; Sherriff, F
2004-10-18
function is not translated into clinically detectable changes. :Memantine 20 mg/day caused a clinically noticeable reduction in deterioration over 28 weeks in patients with moderate to severe Alzheimer disease. This was supported by less functional and cognitive deterioration. Patients taking memantine were less likely to become agitated. The effect in mild to moderate AD is unknown. Patients with mild to moderate vascular dementia receiving memantine 20 mg/day had less cognitive deterioration at 28 weeks but the effects were not clinically discernible. There is an early beneficial effect on cognition, mood, behaviour and clinical impression for memantine at 6 weeks. The drug is well tolerated in general and the incidence of adverse effects is low.
Diagnosis and treatment of vascular damage in dementia.
Biessels, Geert Jan
2016-05-01
This paper provides an overview of cognitive impairment due to vascular brain damage, which is referred to as vascular cognitive impairment (VCI). Over the past decades, we have seen marked progress in detecting VCI, both through maturation of diagnostic concepts and through advances in brain imaging, especially MRI. Yet in daily practice, it is often challenging to establish the diagnosis, particularly in patients where there is no evident temporal relation between a cerebrovascular event and cognitive dysfunction. Because vascular damage is such a common cause of cognitive dysfunction, it provides an obvious target for treatment. In patients whose cognitive dysfunction follows directly after a stroke, the etiological classification of this stroke will direct treatment. In many patients however, VCI develops due to so-called "silent vascular damage," without evident cerebrovascular events. In these patients, small vessel diseases (SVDs) are the most common cause. Yet no SVD-specific treatments currently exist, which is due to incomplete understanding of the pathophysiology. This review addresses developments in this field. It offers a framework to translate diagnostic criteria to daily practice, addresses treatment, and highlights some future perspectives. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau, and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.
ERIC Educational Resources Information Center
DenBesten, Nicholas P.
2009-01-01
This research involves an examination of the relationship between education and age on a wide array of neuropsychological test measures among patients diagnosed with Alzheimer's and vascular dementia. The purpose of this study was to investigate the role of education as an attenuating factor to neurocognitive decline in dementia. Although numerous…
Post-stroke dementia: the contribution of thalamus and basal ganglia changes.
Lopes, Marcos Antonio; Firbank, Michael J; Widdrington, Michelle; Blamire, Andrew M; Kalaria, Raj N; O'Brien, John T
2012-04-01
The neurobiological basis of increased risk of dementia in stroke patients is unclear, though there are several related pathological changes, including white matter hyperintensities (WMH), and medial temporal atrophy. Subcortical gray matter structures have also been implicated in dementia resulting from vascular pathology, particularly vascular dementia. This study aimed to investigate the contribution of changes in subcortical gray matter structures to post-stroke dementia (PSD). T1- and T2-weighted images and T2-weighted fluid-attenuated inversion recovery (FLAIR) images were obtained on a 3-Tesla magnetic resonance (MR) system, in four groups aged over 75 years: post-stroke with dementia (PSD; 8), post-stroke no dementia (PSnoD; 33), Alzheimer's disease (AD; 26) and controls (30). Automated software was used to measure the volume of thalamus, putamen, caudate nucleus, and hippocampus as well as total WMH volume. The number of subcortical lacunes was also counted. The number of caudate lacunes was higher in the PSnoD group, compared with AD (p = 0.029) and controls (p = 0.019). The putamen volume was smaller in the stroke and AD groups, when compared with controls. In the whole stroke group, putamen lacunes were correlated with impairment in memory (Rey test; ρ = -0.365; p = 0.031), while WMH and hippocampal volume both correlated with global dysfunction. Our findings implicate a variety of neurobiological substrates of dementia, such as small vessel disease and Alzheimer pathology, which develop after stroke in an old older population, with a contribution from subcortical brain structures.
Barca, Maria Lage; Engedal, Knut; Laks, Jerson; Selbaek, Geir
2012-01-01
Background This study explores factors associated with depression in Alzheimer's disease (AD) compared with mild cognitive impairment (MCI) and other dementia disorders. Method In a prospective study we included 195 patients: 31 with MCI, 112 with AD and 52 with other dementias. Results According to the ICD-10 and the DSM-IV criteria, 88 (44.1%) and 59 (30.3%), respectively, had a depressive disorder. An adjusted multiple regression analysis showed that previous depression (p < 0.05) was significantly associated with depression in AD patients. Severity of dementia (p < 0.05) was significantly associated with a depressive disorder in a group of patients with frontotemporal dementia, vascular dementia, or dementia due to Lewy Body disease or Parkinson's disease. Conclusion We found different factors associated with a depressive disorder in AD compared to those found for other dementia disorders. PMID:22479262
Saul, Anika; Lashley, Tammaryn; Revesz, Tamas; Holton, Janice; Ghiso, Jorge A.; Coomaraswamy, Janaky; Wirths, Oliver
2013-01-01
Familial British (FBD) and familial Danish dementia (FDD) are progressive neurodegenerative disorders characterized by cerebral deposition of the amyloidogenic peptides ABri and ADan. These amyloid peptides start with an N-terminal glutamate residue, which can be posttranslationally converted into a pyroglutamate (pGlu-) modified form, a mechanism which has been extensively described to be relevant for Aβ peptides in Alzheimer’s disease (AD). Like pGlu-Aβ peptides, pGlu-ABri peptides have an increased aggregation propensity and show higher toxicity on human neuroblastoma cells as their non-modified counterparts. We have generated novel N-terminal specific antibodies detecting the pGlu-modified forms of ABri and ADan peptides. With these antibodies we were able to identify abundant extracellular amyloid plaques, vascular and parenchymal deposits in human FBD and FDD brain tissue, as well as in a mouse model for FDD. Double-stainings using C-terminal specific antibodies in human samples revealed that highly aggregated pGlu-ABri and pGlu-ADan peptides are mainly present in plaque cores and central vascular deposits, leading to the assumption that these peptides have seeding properties. Furthermore, in an FDD-mouse model ADan peptides were detected in pre-synaptic terminals of the hippocampus where they might contribute to impaired synaptic transmission. These similarities of ABri and ADan to Aβ in AD suggest that the posttranslational pGlu-modification of amyloid peptides might represent a general pathological mechanism leading to increased aggregation and toxicity in these forms of degenerative dementias. PMID:23261769
MTHFR and ACE Gene Polymorphisms and Risk of Vascular and Degenerative Dementias in the Elderly
ERIC Educational Resources Information Center
Pandey, Pratima; Pradhan, Sunil; Modi, Dinesh Raj; Mittal, Balraj
2009-01-01
Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as…
The borderland between normal aging and dementia.
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
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
Type 2 diabetes aggravates Alzheimer's disease-associated vascular alterations of the aorta in mice.
Sena, Cristina M; Pereira, Ana M; Carvalho, Cristina; Fernandes, Rosa; Seiça, Raquel M; Oliveira, Catarina R; Moreira, Paula I
2015-01-01
Vascular risk factors are associated with a higher incidence of dementia. In fact, diabetes mellitus is considered a main risk factor for Alzheimer's disease (AD) and both diseases are characterized by vascular dysfunction. However, the underlying mechanisms remain largely unknown. Here, the effects of high-sucrose-induced type 2 diabetes (T2D) in the aorta of wild type (WT) and triple-transgenic AD (3xTg-AD) mice were investigated. 3xTg-AD mice showed a significant decrease in body weight and an increase in postprandial glycemia, glycated hemoglobin (HbA1c), and vascular nitrotyrosine, superoxide anion (O2•-), receptor for the advanced glycation end products (RAGE) protein, and monocyte chemoattractant protein-1 (MCP-1) levels when compared to WT mice. High-sucrose intake caused a significant increase in body weight, postprandial glycemia, HbA1c, triglycerides, plasma vascular cell adhesion molecule 1 (VCAM-1), and vascular nitrotyrosine, O2•-, RAGE, and MCP-1 levels in both WT and 3xTg-AD mice when compared to the respective control group. Also, a significant decrease in nitric oxide-dependent vasorelaxation was observed in 3xTg-AD and sucrose-treated WT mice. In conclusion, AD and T2D promote similar vascular dysfunction of the aorta, this effect being associated with elevated oxidative and nitrosative stress and inflammation. Also, AD-associated vascular alterations are potentiated by T2D. These findings support the idea that metabolic alterations predispose to the onset and progression of dementia.
Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease.
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.
Brucki, Sonia Maria Dozzi; Ferraz, Ana Cláudia; de Freitas, Gabriel R.; Massaro, Ayrton Roberto; Radanovic, Márcia; Schultz, Rodrigo Rizek
2011-01-01
Scientific Department of Cognitive Neurology and Aging of ABN had a consensus meeting to write recommendations on treatment of vascular dementia, there was no previous issue. This disease has numerous particularities and can be considered a preventable dementia. Prevention treatment is primary care of vascular risk factors or a secondary prevention of factors that could cause recurrence of ischemic or hemorrhagic brain modifications. In these guidelines we suggested only symptomatic treatment, pharmacologic or non-pharmacologic. We have reviewed current publications on MEDLINE (PubMed), LILACS e Cochrane Library databases. Recommendations are concern to the following factors and their prevention evidences, association, or treatment of vascular dementia: physical activity, tobacco use, diet and food supplements, arterial hypertension, diabetes mellitus, obesity, statins, cardiac failure, atrial fibrillation, antithrombotics, sleep apnea, carotid revascularization, symptomatic pharmacological treatment. PMID:29213754
Kojima, Gotaro; Taniguchi, Yu; Iliffe, Steve; Walters, Kate
2016-10-01
To perform a systematic search of the literature for currently available evidence on frailty as a predictor of dementia and to conduct a meta-analysis to synthesize the pooled risk estimates among community-dwelling older people. A systematic review and meta-analysis. Embase, MEDLINE, CINAHL Plus, PsycINFO, and the Cochrane Library from 2000 to January 2016, and reference lists of relevant articles. Any studies that prospectively examined the incident risks of dementia with frailty among community-dwelling older people without language restriction. Of 2565 studies identified through the systematic review, 7 studies were included in this review. Of these, 4 studies reported hazard ratios (HR) of incident dementia for physical frailty defined by Cardiovascular Health Study criteria and were included in a meta-analysis. Frailty was a significant predictor of incident Alzheimer disease (4 studies: pooled HR = 1.28, 95% confidence interval (95% CI) = 1.00-1.63, P = .05), vascular dementia (2 studies: pooled HR 2.70, 95% CI 1.40-5.23, P = .003), and all dementia (3 studies: pooled HR 1.33, 95% CI 1.07-1.67, P = .01). Heterogeneity across the studies was low to modest (I(2) = 0%-51%). A random-effects meta-regression analysis showed that the female proportion of the cohort primarily mediated the association of frailty with Alzheimer disease (female proportion coefficient = 0.04, 95%CI = 0.01-0.08, P = .01). This systematic review and meta-analysis suggests that frailty was a significant predictor of Alzheimer disease, vascular dementia, and all dementia among community-dwelling older people. Frail women may have a higher risk of incident Alzheimer disease than frail men. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.
Vascular Cognitive Impairment.
Dichgans, Martin; Leys, Didier
2017-02-03
Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts. © 2017 American Heart Association, Inc.
... Alzheimer's Disease, and Dementia . 2nd ed. Philadelphia, PA: Elsevier; 2016:chap 6. Gorelick PB, Scuteri A, Black ... eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 402. Peterson R, Graff-Radford ...
Lokomat training in vascular dementia: motor improvement and beyond!
Calabrò, Rocco Salvatore; De Luca, Rosaria; Leo, Antonino; Balletta, Tina; Marra, Angela; Bramanti, Placido
2015-12-01
Vascular dementia (VaD) is a general term describing problems with reasoning, planning, judgment, memory, and other thought processes caused by brain damage from impaired blood flow to the brain. Cognitive rehabilitation and physical therapy are the mainstays of dementia treatment, although often ineffective because of the scarce collaboration of the patients. However, emerging data suggest that physical activity may reduce the risk of cognitive impairment, mainly VaD, in older people living independently. Herein, we describe a 72-year-old male affected by VaD, in which traditional cognitive training in addition to intensive gait robotic rehabilitation (by using Lokomat device) led to a significant improvement in the motor and cognitive function. This promising finding may be related either to the intensive and repetitive aerobic exercises or to the task-oriented training with computerized visual feedback, which can be considered as a relevant tool to increase patients' motor output, involvement, and motivation during robotic training.
Mayer, Flavia; Di Pucchio, Alessandra; Lacorte, Eleonora; Bacigalupo, Ilaria; Marzolini, Fabrizio; Ferrante, Gianluigi; Minardi, Valentina; Masocco, Maria; Canevelli, Marco; Di Fiandra, Teresa; Vanacore, Nicola
2018-01-01
Up to 53.7% of all cases of dementia are assumed to be due to Alzheimer disease (AD), while 15.8% are considered to be due to vascular dementia (VaD). In Europe, about 3 million cases of AD could be due to 7 potentially modifiable risk factors: diabetes, midlife hypertension and/or obesity, physical inactivity, depression, smoking, and low educational level. To estimate the number of VaD cases in Europe and the number of AD and VaD cases in Italy attributable to these 7 potentially modifiable risk factors. Assuming the nonindependence of the 7 risk factors, the adjusted combined population attributable risk (PAR) was estimated for AD and VaD. In Europe, adjusted combined PAR was 31.4% for AD and 37.8% for VaD. The total number of attributable cases was 3,033,000 for AD and 873,000 for VaD. In Italy, assuming a 20% reduction of the prevalence of each risk factor, adjusted combined PAR decreased from 45.2 to 38.9% for AD and from 53.1 to 46.6% for VaD, implying a 6.4 and 6.5% reduction in the prevalence of AD and VaD, respectively. A relevant reduction of AD and VaD cases in Europe and Italy could be obtained through primary prevention.
[Effects of Total Alkaloids of Harmaline on Learning and Memory in Vascular Dementia Rats].
Zhang, Xiao-shuang; Sun, Jian-ning; Yu, Hui-ling
2015-11-01
To investigate the effects of total alkaloids of harmaline on learning and memory in vascular dementia rats, and its mechanism. The model rats of vascular dementia were established with bilateral carotid artery ligation. After 30 days, the model rats were randomly divided into six groups: sham group, model group, nicergoline tablets 7 mg/kg group, and 25, 12.5 and 6.25 mg/kg dose groups of total alkaloids of harmaline, the rats were given medicine for 30 days. Learning and memory abilities were tested by Morris water maze, histomorphology in hippocampal CA1 area were observed by HE staining, BAX and BCL-2 protein expression in hippocampal CA1 area were detected by immunohistochemistry. Compared with model group, 25 mg/kg group of total alkaloids of harmaline shortened the incubation period in the third and fourth day significantly, 12.5 mg/kg group of total alkaloids of harmaline shortened the incubation period in the fourth day. 25 and 12.5 mg/kg groups of total alkaloids of harmaline significantly increased the times crossing the target. Total alkaloids of harmaline improved the neurons pathological changes of rat in the hippocampus CA1 area, 25 and 12.5 mg/kg of total alkaloids of harmaline downregulated the expression of apoptosis proteins BAX, upregulated the protein expression of BCL-2. Total alkaloids of harmaline can improve the learning and memory abilities in vascular dementia rats, which probably is related to inhibiting apoptosis of hippocampus cell.
Goossens, Joery; Bjerke, Maria; Struyfs, Hanne; Niemantsverdriet, Ellis; Somers, Charisse; Van den Bossche, Tobi; Van Mossevelde, Sara; De Vil, Bart; Sieben, Anne; Martin, Jean-Jacques; Cras, Patrick; Goeman, Johan; De Deyn, Peter Paul; Van Broeckhoven, Christine; van der Zee, Julie; Engelborghs, Sebastiaan
2017-07-14
The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ 1-42 , t-tau, and p-tau 181 overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-tau rel ), may improve differential dementia diagnosis. The goal of this study is to investigate if p-tau rel can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis. The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls. A substantial subset of the patients was pathology-confirmed. CSF levels of Aβ 1-42 , t-tau, p-tau 181 , and p-tau rel were determined with commercially available single-analyte enzyme-linked immunosorbent assay (ELISA) kits. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analyses, and area under the curve (AUC) values were compared using DeLong tests. The diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. The addition of p-tau rel to the AD biomarker panel decreased its diagnostic performance when discriminating non-AD, FTLD, and DLB from AD. As a single marker, p-tau rel increased the diagnostic performance for CJD. No significant difference was found in AUC values with the addition of p-tau rel when differentiating between AD or non-AD dementias and controls. The addition of p-tau rel to the AD CSF biomarker panel failed to improve differentiation between AD and non-AD dementias.
Cognitive decline and dementia in the oldest-old.
Kravitz, Efrat; Schmeidler, James; Beeri, Michal Schnaider
2012-10-01
The oldest-old are the fastest growing segment of the Western population. Over half of the oldest-old will have dementia, but the etiology is yet unknown. Age is the only risk factor consistently associated with dementia in the oldest-old. Many of the risk and protective factors for dementia in the young elderly, such as ApoE genotype, physical activity, and healthy lifestyle, are not relevant for the oldest-old. Neuropathology is abundant in the oldest-old brains, but specific pathologies of Alzheimer's disease (AD) or vascular dementia are not necessarily correlated with cognition, as in younger persons. It has been suggested that accumulation of both AD-like and vascular pathologies, loss of synaptic proteins, and neuronal loss contribute to the cognitive decline observed in the oldest-old. Several characteristics of the oldest-old may confound the diagnosis of dementia in this age group. A gradual age-related cognitive decline, particularly in executive function and mental speed, is evident even in non-demented oldest-old. Hearing and vision losses, which are also prevalent in the oldest-old and found in some cases to precede/predict cognitive decline, may mechanically interfere in neuropsychological evaluations. Difficulties in carrying out everyday activities, observed in the majority of the oldest-old, may be the result of motor or physical dysfunction and of neurodegenerative processes. The oldest-old appear to be a select population, who escapes major illnesses or delays their onset and duration toward the end of life. Dementia in the oldest-old may be manifested when a substantial amount of pathology is accumulated, or with a composition of a variety of pathologies. Investigating the clinical and pathological features of dementia in the oldest-old is of great importance in order to develop therapeutic strategies and to provide the most elderly of our population with good quality of life.
Cognitive Decline and Dementia in the Oldest-Old
Kravitz, Efrat; Schmeidler, James; Beeri, Michal Schnaider
2012-01-01
The oldest-old are the fastest growing segment of the Western population. Over half of the oldest-old will have dementia, but the etiology is yet unknown. Age is the only risk factor consistently associated with dementia in the oldest-old. Many of the risk and protective factors for dementia in the young elderly, such as ApoE genotype, physical activity, and healthy lifestyle, are not relevant for the oldest-old. Neuropathology is abundant in the oldest-old brains, but specific pathologies of Alzheimer’s disease (AD) or vascular dementia are not necessarily correlated with cognition, as in younger persons. It has been suggested that accumulation of both AD-like and vascular pathologies, loss of synaptic proteins, and neuronal loss contribute to the cognitive decline observed in the oldest-old. Several characteristics of the oldest-old may confound the diagnosis of dementia in this age group. A gradual age-related cognitive decline, particularly in executive function and mental speed, is evident even in non-demented oldest-old. Hearing and vision losses, which are also prevalent in the oldest-old and found in some cases to precede/predict cognitive decline, may mechanically interfere in neuropsychological evaluations. Difficulties in carrying out everyday activities, observed in the majority of the oldest-old, may be the result of motor or physical dysfunction and of neurodegenerative processes. The oldest-old appear to be a select population, who escapes major illnesses or delays their onset and duration toward the end of life. Dementia in the oldest-old may be manifested when a substantial amount of pathology is accumulated, or with a composition of a variety of pathologies. Investigating the clinical and pathological features of dementia in the oldest-old is of great importance in order to develop therapeutic strategies and to provide the most elderly of our population with good quality of life. PMID:23908850
Struyfs, Hanne; Van Broeck, Bianca; Timmers, Maarten; Fransen, Erik; Sleegers, Kristel; Van Broeckhoven, Christine; De Deyn, Peter P; Streffer, Johannes R; Mercken, Marc; Engelborghs, Sebastiaan
2015-01-01
Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-β (Aβ) isoforms might improve the AD versus non-AD differential diagnosis. To determine the added diagnostic value of Aβ isoforms, Aβ(1-37), Aβ(1-38), and Aβ(1-40), as compared to the AD CSF biomarkers Aβ(1-42), T-tau, and P-tau(181P). CSF from patients with dementia due to AD (n = 50), non-AD dementias (n = 50), mild cognitive impairment due to AD (n = 50) and non-demented controls (n = 50) was analyzed with a prototype multiplex assay using MSD detection technology. The non-AD group consisted of frontotemporal dementia (FTD; n = 17), dementia with Lewy bodies (DLB; n = 17), and vascular dementia (n = 16). Aβ(1-37) and Aβ(1-38) increased accuracy to differentiate AD from FTD or DLB. Aβ(1-37), Aβ(1-38), and Aβ(1-40) levels correlated with Mini-Mental State Examination scores and disease duration in dementia due to AD. The Aβ(1-42)/Aβ(1-40) ratio improved diagnostic performance of Aβ(1-42) in most differential diagnostic situations. Aβ(1-42) levels were lower in APOE ε4 carriers compared to non-carriers. Aβ isoforms help to differentiate AD from FTD and DLB. Aβ isoforms increase diagnostic performance of Aβ(1-42). In contrast to Aβ1-42, Aβ isoforms seem to be correlated with disease severity in AD. Adding the Aβ isoforms to the current biomarker panel could enhance diagnostic accuracy.
Nguyen, Kim-Huong; Mulhern, Brendan; Kularatna, Sanjeewa; Byrnes, Joshua; Moyle, Wendy; Comans, Tracy
2017-01-25
With an ageing population, the number of people with dementia is rising. The economic impact on the health care system is considerable and new treatment methods and approaches to dementia care must be cost effective. Economic evaluation requires valid patient reported outcome measures, and this study aims to develop a dementia-specific health state classification system based on the Quality of Life for Alzheimer's disease (QOL-AD) instrument (nursing home version). This classification system will subsequently be valued to generate a preference-based measure for use in the economic evaluation of interventions for people with dementia. We assessed the dimensionality of the QOL-AD to develop a new classification system. This was done using exploratory and confirmatory factor analysis and further assessment of the structure of the measure to ensure coverage of the key areas of quality of life. Secondly, we used Rasch analysis to test the psychometric performance of the items, and select item(s) to describe each dimension. This was done on 13 items of the QOL-AD (excluding two general health items) using a sample of 284 residents living in long-term care facilities in Australia who had a diagnosis of dementia. A five dimension classification system is proposed resulting from the three factor structure (defined as 'interpersonal environment', 'physical health' and 'self-functioning') derived from the factor analysis and two factors ('memory' and 'mood') from the accompanying review. For the first three dimensions, Rasch analysis selected three questions of the QOL-AD ('living situation', 'physical health', and 'do fun things') with memory and mood questions representing their own dimensions. The resulting classification system (AD-5D) includes many of the health-related quality of life dimensions considered important to people with dementia, including mood, global function and skill in daily living. The development of the AD-5D classification system is an important step
Jiang, Shixiang; Yan, Chang; Qiao, Zhengxue; Yao, Haiqian; Jiang, Shiquan; Qiu, Xiaohui; Yang, Xiuxian; Fang, Deyu; Yang, Yanjie; Zhang, Limei; Wang, Lina; Zhang, Liming
2017-04-24
Alzheimer's disease (AD) and vascular dementia (VD) are serious, irreversible forms of cognitive impairment, which means that an early diagnosis is essential to slow down their progression. One potential neurophysiological biomarker of these diseases is the mismatch negativity (MMN) event-related potentials (ERP) component, which reflects an automatic detection mechanism at the pre-attentive stages of information processing. We evaluated the auditory MMN response in individuals from two patient groups: those in the prodromal stages of AD (P-AD) and those in the prodromal stages of VD (P-VD). Thirty patients (15 P-AD patients and 15 P-VD patients) and 30 age-matched controls were recruited to undergo electrophysiological recordings during the presentation of an auditory deviant-standard-reverse oddball paradigm that was used to elicit genuine MMN responses. We show that over the frontal-central area, the mean amplitude of the MMN was significantly reduced in both the P-AD (p=0.017) and P-VD groups (p=0.013) compared with controls. The MMN peak latency in P-VD patients was significantly shorter than in controls (p=0.027). No MMN response differences between the P-AD and P-VD were found in either the frontal-central or the temporal areas. These results indicate that P-AD and P-VD patients exhibit impaired pre-attentive information processing mechanisms as revealed by the frontal-central area MMN response, which is associated with sensory memory and cognitive deficits. Copyright © 2017 Elsevier B.V. All rights reserved.
Garre-Olmo, Josep; Garcia-Ptacek, Sara; Calvó-Perxas, Laia; Turró-Garriga, Oriol; López-Pousa, Secundino; Eriksdotter, Maria
2016-01-01
The aim of this study was to compare the frequency of dementia diagnoses from two dementia registries in Europe. Patients registered between 2007 and 2013 in the Swedish Dementia Registry (SveDem; Sweden) and in the Registry of Dementias of Girona (ReDeGi; North-East of Spain) were selected. We compared sociodemographic data, Mini-Mental State Examination (MMSE) scores, dementia subtype, and medication consumption of 22,384 cases from SveDem and 5,032 cases from ReDeGi. The average age (78.1 years SveDem versus 79.7 years ReDeGi) and the gender (female 58.2% SveDem versus 61.5% ReDeGi) did not greatly differ. MMSE score at diagnosis was higher for SveDem cases (22.1 versus 17.8). Alzheimer’s disease (AD) accounted for the main dementia subtype (36.6% SveDem versus 55.6% ReDeGi). The proportion of vascular dementia (VaD) and mixed dementia was higher in SveDem (18.8% versus 6.4% and 24.9 versus 13.4%), with an odds ratio (OR) and 95% confidence interval (CI) for SveDem relative to the ReDeGi of 3.41 (3.03–3.84) for VaD, and 2.15 (1.97–2.35) for mixed dementia. This was at the expense of a lower frequency of AD in SveDem (OR 0.41; 95% CI 0.39–0.44). Other dementia diagnoses such as frontotemporal dementia or dementia with Lewy bodies did not significantly differ between registries (2.3% versus 2.9%; 1.9 versus 3.1%). Large differences in medication consumption at the time of dementia diagnosis were detected (4.7 treatments SveDem versus 6.8 ReDeGi). Northern and southern European dementia cohorts differ in demographic characteristics, MMSE score at diagnosis, and drug treatment profile. PMID:27392854
Engelhardt, Eliasz; Tocquer, Carla; André, Charles; Moreira, Denise Madeira; Okamoto, Ivan Hideyo; Cavalcanti, José Luiz de Sá
2011-01-01
Vascular dementia (VaD) is the most prevalent form of secondary dementia and the second most common of all dementias. The present paper aims to define guidelines on the basic principles for treating patients with suspected VaD (and vascular cognitive impairment - no dementia) using an evidence-based approach. The material was retrieved and selected from searches of databases (Medline, Scielo, Lilacs), preferentially from the last 15 years, to propose a systematic way to assess cognition, function and behavior, and disease severity staging, with instruments adapted for our milieu, and diagnosis disclosure. The present proposal contributes to the definition of standard diagnostic criteria for VaD based on various levels of evidence. It is noteworthy that only around half of the population of patients with vascular cognitive impairment present with dementia, which calls for future proposals defining diagnostic criteria and procedures for this condition. PMID:29213753
Intracranial stenosis in cognitive impairment and dementia.
Hilal, Saima; Xu, Xin; Ikram, M Kamran; Vrooman, Henri; Venketasubramanian, Narayanaswamy; Chen, Christopher
2017-06-01
Intracranial stenosis is a common vascular lesion observed in Asian and other non-Caucasian stroke populations. However, its role in cognitive impairment and dementia has been under-studied. We, therefore, examined the association of intracranial stenosis with cognitive impairment, dementia and their subtypes in a memory clinic case-control study, where all subjects underwent detailed neuropsychological assessment and 3 T neuroimaging including three-dimensional time-of-flight magnetic resonance angiography. Intracranial stenosis was defined as ≥50% narrowing in any of the intracranial arteries. A total of 424 subjects were recruited of whom 97 were classified as no cognitive impairment, 107 as cognitive impairment no dementia, 70 vascular cognitive impairment no dementia, 121 Alzheimer's Disease, and 30 vascular dementia. Intracranial stenosis was associated with dementia (age/gender/education - adjusted odds ratios (OR): 4.73, 95% confidence interval (CI): 1.93-11.60) and vascular cognitive impairment no dementia (OR: 3.98, 95% CI: 1.59-9.93). These associations were independent of cardiovascular risk factors and MRI markers. However, the association with Alzheimer's Disease and vascular dementia became attenuated in the presence of white matter hyperintensities. Intracranial stenosis is associated with vascular cognitive impairment no dementia independent of MRI markers. In Alzheimer's Disease and vascular dementia, this association is mediated by cerebrovascular disease. Future studies focusing on perfusion and functional markers are needed to determine the pathophysiological mechanism(s) linking intracranial stenosis and cognition so as to identify treatment strategies.
Epidemiology of early-onset dementia: a review of the literature
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
On the history of lacunes, etat criblé, and the white matter lesions of vascular dementia.
Román, Gustavo C
2002-01-01
The history of lesions associated with vascular dementia (17th to 19th century) is reviewed. Recognition of ischemic and hemorrhagic stroke types dates back to the 17th century; however, at that time a third type ('cerebral congestion') emerged as the most common form of apoplexy. This entity vanished as arterial hypertension became established with the introduction of the sphygmomanometer (1905). Before the 19th century, apoplexy was considered a uniformly fatal disease, although Willis first recognized post-stroke dementia in 1672. Dechambre (1838) first reported 'lacunes' in stroke survivors with small cerebral softenings. Durand-Fardel (1842) described interstitial atrophy of the brain (leukoaraiosis) and état criblé (cribriform state) reflecting chronic cerebral congestion. In 1894, Alzheimer and Binswanger identified 'arteriosclerotic brain atrophy,' a form of vascular dementia characterized by 'miliary apoplexies' (lacunes). Also in 1894, Binswanger described the disease that now bears his name. In 1901, Pierre Marie coined the name état lacunaire (lacunar state) for the clinical syndrome of elderly patients with multiple lacunes. Copyright 2002 S. Karger AG, Basel
Bergem, A L; Lannfelt, L
1997-11-01
The apolipoprotein E (APOE) epsilon4 allele is a risk factor in Alzheimer disease (AD), but not in vascular dementia (VaD). We have investigated whether the epsilon4 allele is more common in twin pairs concordant for AD, compared with those discordant for AD, and whether the epsilon4 allele is more common in AD twins than in VaD twins. In addition, we have investigated the relationship of the epsilon4 allele and the age at onset in AD and VaD. APOE genotype was analysed in 29 senile demented twin pairs. The epsilon4 allele was associated with AD and not with VaD. However, there was no difference in the frequency of the APOE epsilon4 allele in concordant (33.3%) and discordant (31.3%) AD dizygotic twin pairs. Age at onset in AD was significantly lower in epsilon4 homozygotes than in individuals with one or no copies of epsilon4 (62.4 vs. 73.5, p<0.01). In concordant AD twin pairs, the epsilon4 allele frequency was somewhat higher in the twins with earlier onset (41.7% vs. 25%), but the difference was not statistically significant. In the VaD group the age at onset was not significantly different between individuals with or without epsilon4 in their genotypes.
Lin, Ai-Ling; Zheng, Wei; Halloran, Jonathan J; Burbank, Raquel R; Hussong, Stacy A; Hart, Matthew J; Javors, Martin; Shih, Yen-Yu Ian; Muir, Eric; Solano Fonseca, Rene; Strong, Randy; Richardson, Arlan G; Lechleiter, James D; Fox, Peter T; Galvan, Veronica
2013-01-01
Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias. PMID:23801246
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.
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
Gao, Yuan; Huang, Changquan; Zhao, Kexiang; Ma, Louyan; Qiu, Xuan; Zhang, Lei; Xiu, Yun; Chen, Lin; Lu, Wei; Huang, Chunxia; Tang, Yong; Xiao, Qian
2013-05-01
This study examined whether depression was a risk factor for onset of dementia including Alzheimer's disease (AD), vascular dementia (VD) and any dementia, and mild cognitive impairment (MCI) by using a quantitative meta-analysis of longitudinal studies. EMBASE and MEDLINE were searched for articles published up to February 2011. All studies that examined the relationship between depression and the onset of dementia or MCI were included. Pooled relative risk was calculated using fixed-effects models. Twelve studies met our inclusion criteria for this meta-analysis. All subjects were without dementia or MCI at baseline. Four, two, five, and four studies compared the incidence of AD, VD, any dementia, and MCI between subjects with or without depression, respectively. After pooling all the studies, subjects with depression had higher incidence of AD (relative risk (RR):1.66, 95% confidence interval (CI): 1.29-2.14), VD (RR: 1.89, 95% CI: 1.19-3.01), any dementia (RR: 1.55, 95% CI: 1.31-2.83), and MCI (RR: 1.97, 95% CI: 1.53-2.54) than those without depression. The quantitative meta-analysis showed that depression was a major risk factor for incidence of dementia (including AD, VD, and any dementia) and MCI. Copyright © 2012 John Wiley & Sons, Ltd.
COMPARATIVE EFFECTIVENESS OF MCI and DEMENTIA TREATMENTS IN A COMMUNITY-BASED DEMENTIA PRACTICE
2016-08-04
Mild Cognitive Impairment; Dementia; Hypoxia; Hyperhomocysteinemia; Vitamin B 12 Deficiency; Iron Deficiency; Anemia; TBI; Neurodegenerative Disorders; Alzheimer's Disease; Vascular Dementia; Brain Injuries; Tauopathies; Parkinson's Disease; Lewy Body Dementia; Frontotemporal Dementia; TDP-43 Proteinopathies
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The usefulness of monitoring sleep talking for the diagnosis of Dementia with Lewy bodies.
Honda, Kazuki; Hashimoto, Mamoru; Yatabe, Yusuke; Kaneda, Keiichiro; Yuki, Seiji; Ogawa, Yusuke; Matsuzaki, Shiho; Tsuyuguchi, Atsuko; Tanaka, Hibiki; Kashiwagi, Hiroko; Hasegawa, Noriko; Ishikawa, Tomohisa; Ikeda, Manabu
2013-05-01
Dementia with Lewy bodies (DLB) is the second most common type of neurodegenerative dementia. It is frequently difficult to differentiate DLB from Alzheimer's disease (AD) and other types of dementia. This study examined the usefulness of monitoring sleep talking for the diagnosis of DLB. A total of 317 patients with dementia were selected from a consecutive series at the Dementia Clinic of Kumamoto University Hospital. Diagnostic categories consisted of probable DLB (n = 55), probable AD (n = 191), frontotemporal lobar degeneration (FTLD) (n = 16), vascular dementia (VaD) (n = 18), and other/unspecified dementia (n = 37). We evaluated sleep talking in all dementia patients and normal elderly subjects (n = 32) using an originally designed sleep talking questionnaire. Sleep talking occurred most frequently in the DLB group (61.8%), followed by the VaD group (33.3%), other/unspecified dementia group (27.0%), AD group (18.8%), FTLD group (12.5%), and normal elderly subjects group (6.3%). The prevalence of sleep talking in the DLB group was significantly higher than in other groups, except in the VaD group. The sleep talking yielded high specificity (81.2%) and some sensitivity (61.8%) for the differential diagnosis of DLB from AD. Furthermore, loud sleep talking may improve the specificity (96.9%). For the differentiation of DLB from all other dementia types, the specificity of sleep talking and loud sleep talking was also high (79.4% and 95.8% respectively). Assessing sleep talking, especially the volume of sleep talking, may be useful in the clinical discrimination of DLB from not only AD but also from all other types of dementia.
Biomarkers of aggression in dementia.
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.
Extracellular matrix inflammation in vascular cognitive impairment and dementia.
Rosenberg, Gary A
2017-03-01
Vascular cognitive impairment and dementia (VCID) include a wide spectrum of chronic manifestations of vascular disease related to large vessel strokes and small vessel disease (SVD). Lacunar strokes and white matter (WM) injury are consequences of SVD. The main vascular risk factor for SVD is brain hypoperfusion from cerebral blood vessel narrowing due to chronic hypertension. The hypoperfusion leads to activation and degeneration of astrocytes with the resulting fibrosis of the extracellular matrix (ECM). Elasticity is lost in fibrotic cerebral vessels, reducing the response of stiffened blood vessels in times of increased metabolic need. Intermittent hypoxia/ischaemia activates a molecular injury cascade, producing an incomplete infarction that is most damaging to the deep WM, which is a watershed region for cerebral blood flow. Neuroinflammation caused by hypoxia activates microglia/macrophages to release proteases and free radicals that perpetuate the damage over time to molecules in the ECM and the neurovascular unit (NVU). Matrix metalloproteinases (MMPs) secreted in an attempt to remodel the blood vessel wall have the undesired consequences of opening the blood-brain barrier (BBB) and attacking myelinated fibres. This dual effect of the MMPs causes vasogenic oedema in WM and vascular demyelination, which are the hallmarks of the subcortical ischaemic vascular disease (SIVD), which is the SVD form of VCID also called Binswanger's disease (BD). Unravelling the complex pathophysiology of the WM injury-related inflammation in the small vessel form of VCID could lead to novel therapeutic strategies to reduce damage to the ECM, preventing the progressive damage to the WM. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.
MRI-leukoaraiosis thresholds and the phenotypic expression of dementia
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
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.
Lifestyle-related factors in predementia and dementia syndromes.
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
Gupta, Surbhi; Singh, Prabhat; Sharma, Brij Mohan; Sharma, Bhupesh
2015-01-01
Chronic cerebral hypoperfusion (CCH) has been considered as a critical cause for the development of cognitive decline and dementia of vascular origin. Melatonin receptors have been reported to be beneficial in improving memory deterioration. Phosphodiesterase-1 (PDE1) enzyme offers protection against cognitive impairments and cerebrovascular disorders. Aim of this study is to explore the role of agomelatine (a dual MT1 and MT2 melatonin receptor agonist) and vinpocetine (selective PDE1 inhibitor) in CCH induced vascular dementia (VaD). Two vessel occlusion (2VO) or bilateral common carotid arteries ligation method was performed to initiate a phase of chronic hypoperfusion in mice. 2VO animals have shown significant cognitive deficits (Morris water maze), cholinergic dysfunction (increased acetyl cholinesterase -AChE) activity alongwith increased brain oxidative stress (decreased brain catalase, glutathione, as well as superoxide dismutase with an increase in malondialdehyde levels), and significant increase in brain infarct size (2,3,5- triphenylterazolium chloride-TTC staining). Treatment of agomelatine and vinpocetine reduced CCH induced learning and memory deficits and limited cholinergic dysfunction, oxidative stress, and tissue damage, suggesting that agomelatine and vinpocetine may provide benefits in CCH induced VaD.
Wimo, Anders; Winblad, Bengt
2003-01-01
Knowledge about the health economic implications of vascular dementia (VaD) is insufficient. The impact of cardiovascular comorbidities must also be taken into consideration when resource utilization and costs in patients with VaD are analyzed. It is also of great importance that the analysis be done from a societal perspective. In the rural Nordanstig cohort of the Kungsholmen project in Sweden, the major cost drivers in the RUD (Resource Utilization in Dementia) instrument were used. The cost from a societal perspective was 23% higher for patients with VaD compared with patients with Alzheimer's disease ( p = .02).
Choto-san in the treatment of vascular dementia: a double-blind, placebo-controlled study.
Terasawa, K; Shimada, Y; Kita, T; Yamamoto, T; Tosa, H; Tanaka, N; Saito, Y; Kanaki, E; Goto, S; Mizushima, N; Fujioka, M; Takase, S; Seki, H; Kimura, I; Ogawa, T; Nakamura, S; Araki, G; Maruyama, I; Maruyama, Y; Takaori, S
1997-03-01
In an earlier placebo-controlled study, we demonstrated that a kampo (Japanese herbal) medicine called Choto-san (Diao-Teng-San in Chinese) was effective in treating vascular dementia. To evaluate its efficacy using more objective criteria, we carried out a multi-center, double-blind study of Choto-san extract (7.5 g/day) and a placebo, each given three times a day for 12 weeks to patients suffering from this condition. The study enrolled and analyzed 139 patients, 50 males and 89 females, with a mean age of 76.6 years. Choto-san was statistically superior to the placebo in global improvement rating, utility rating, global improvement rating of subjective symptoms, global improvement rating of psychiatric symptoms and global improvement rating of disturbance in daily living activities. Such items as spontaneity of conversation, lack of facial expression, decline in simple mathematical ability, global intellectual ability, nocturnal delirium, sleep disturbance, hallucination or delusion, and putting on and taking off clothes were significantly improved at one or more evaluation points in those taking Choto-san compared to those taking the placebo. Furthermore, the change in revised version of Hasegawa's dementia scale from the beginning point in Choto-san group was tended to be higher than that in placebo group with no statistical significance. These results suggest that Choto-san is effective in the treatment of vascular dementia. Copyright © 1997 Gustav Fischer Verlag. Published by Elsevier GmbH.. All rights reserved.
Beecham, Gary W; Hamilton, Kara; Naj, Adam C; Martin, Eden R; Huentelman, Matt; Myers, Amanda J; Corneveaux, Jason J; Hardy, John; Vonsattel, Jean-Paul; Younkin, Steven G; Bennett, David A; De Jager, Philip L; Larson, Eric B; Crane, Paul K; Kamboh, M Ilyas; Kofler, Julia K; Mash, Deborah C; Duque, Linda; Gilbert, John R; Gwirtsman, Harry; Buxbaum, Joseph D; Kramer, Patricia; Dickson, Dennis W; Farrer, Lindsay A; Frosch, Matthew P; Ghetti, Bernardino; Haines, Jonathan L; Hyman, Bradley T; Kukull, Walter A; Mayeux, Richard P; Pericak-Vance, Margaret A; Schneider, Julie A; Trojanowski, John Q; Reiman, Eric M; Schellenberg, Gerard D; Montine, Thomas J
2014-09-01
Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs), and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), hippocampal sclerosis of the elderly (HS), and vascular brain injury (VBI). Genome-wide significance was observed for clinico-pathologic AD dementia, NPs, NFTs, CAA, and LBD with a number of variants in and around the apolipoprotein E gene (APOE). GalNAc transferase 7 (GALNT7), ATP-Binding Cassette, Sub-Family G (WHITE), Member 1 (ABCG1), and an intergenic region on chromosome 9 were associated with NP score; and Potassium Large Conductance Calcium-Activated Channel, Subfamily M, Beta Member 2 (KCNMB2) was strongly associated with HS. Twelve of the 21 non-APOE genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample: CR1, BIN1, CLU, MS4A6A, PICALM, ABCA7, CD33, PTK2B, SORL1, MEF2C, ZCWPW1, and CASS4 with 9 of these 12 loci showing larger odds ratio in the clinico-pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for NFTs or NPs showed positive correlation, while those for risk of VBI showed a moderate negative correlation. The other co-morbid neuropathologic features showed only nominal association with the known AD loci. Our results discovered new genetic associations with specific neuropathologic features and aligned known genetic risk for AD dementia with specific neuropathologic changes in the largest brain autopsy study of AD and related dementias.
Comans, Tracy A; Nguyen, Kim-Huong; Mulhern, Brendan; Corlis, Megan; Li, Li; Welch, Alyssa; Kurrle, Susan E; Rowen, Donna; Moyle, Wendy; Kularatna, Sanjeewa; Ratcliffe, Julie
2018-01-21
Generic instruments for assessing health-related quality of life may lack the sensitivity to detect changes in health specific to certain conditions, such as dementia. The Quality of Life in Alzheimer's Disease (QOL-AD) is a widely used and well-validated condition-specific instrument for assessing health-related quality of life for people living with dementia, but it does not enable the calculation of quality-adjusted life years, the basis of cost utility analysis. This study will generate a preference-based scoring algorithm for a health state classification system -the Alzheimer's Disease Five Dimensions (AD-5D) derived from the QOL-AD. Discrete choice experiments with duration (DCE TTO ) and best-worst scaling health state valuation tasks will be administered to a representative sample of 2000 members of the Australian general population via an online survey and to 250 dementia dyads (250 people with dementia and their carers) via face-to-face interview. A multinomial (conditional) logistic framework will be used to analyse responses and produce the utility algorithm for the AD-5D. The algorithms developed will enable prospective and retrospective economic evaluation of any treatment or intervention targeting people with dementia where the QOL-AD has been administered and will be available online. Results will be disseminated through journals that publish health economics articles and through professional conferences. This study has ethical approval. © 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.
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
High normal fasting blood glucose is associated with dementia in Chinese elders
Mortimer, J.A.; Borenstein, A.R.; Ding, D.; DeCarli, C.; Zhao, Q.; Copenhaver, C.; Guo, Q.; Chu, S.; Galasko, D.; Salmon, D.P.; Dai, Q.; Wu, Y.; Petersen, R.; Hong, Z.
2010-01-01
Background Diabetes is a risk factor for MCI and dementia. However, the association between high normal fasting blood glucose (FBG) and dementia has not been studied. Methods Polytomous logistic regression was used to assess the association of dementia and MCI with FBG in an age- and sex-matched sample of 32 dementia patients, 27 amnestic MCI (aMCI) patients and 31 normal controls (NC). Analyses were repeated for those with normal FBG. Correlations between FBG and cognitive test scores were obtained. Results Controlling for age, sex, education, body mass index, Hachinski Ischemic Score, MRI stroke, and normalized brain, hippocampal and white matter hyperintensity MRI volumes; higher FBG was associated with dementia vs. aMCI status (OR= 3.13; 95% CI:1.28–7.69). This association remained (OR= 7.75; 95% CI:1.10–55.56) when analyses were restricted to subjects with normal FBG. When dementia patients were compared with NC adjusting for age, sex and education a significant association with FBG also was seen (OR=1.83; 95%CI:1.09–3.08), but the association was lost when vascular covariates were added to the model. FBG was not associated with aMCI status vs. NC. Higher FBG was correlated with poorer performance on the Trailmaking Test Part B (p=0.003). The percentage of dementia patients with high normal FBG (90%) was significantly higher than that of aMCI patients with high normal FBG (32.9%) (χ2=13.9, p<0.001). Conclusions Higher FBG was associated with dementia (vs. aMCI) independent of vascular risk factors and MRI indicators of vascular disease, and remained a significant risk factor when analyses were restricted to subjects with normal FBG. The results of this cross-sectional study suggest that a high normal level of FBG may be a risk factor for dementia. PMID:21044774
Endo, Arisa; Suzuki, Makoto; Akagi, Atsumi; Chiba, Naoyuki; Ishizaka, Ikuyo; Matsunaga, Atsuhiko; Fukuda, Michinari
2015-03-01
The purpose of this study was to examine the reliability and validity of the Upper-body Dressing Scale (UBDS) for buttoned shirt dressing, which evaluates the learning process of new component actions of upper-body dressing in patients diagnosed with dementia and hemiparesis. This was a preliminary correlational study of concurrent validity and reliability in which 10 vascular dementia patients with hemiparesis were enrolled and assessed repeatedly by six occupational therapists by means of the UBDS and the dressing item of the Functional Independence Measure (FIM). Intraclass correlation coefficient was 0.97 for intra-rater reliability and 0.99 for inter-rater reliability. The level of correlation between UBDS score and FIM dressing item scores was -0.93. UBDS scores for paralytic hand passed into the sleeve and sleeve pulled up beyond the shoulder joint were worse than the scores for the other components of the task. The UBDS has good reliability and validity for vascular dementia patients with hemiparesis. Further research is needed to investigate the relation between UBDS score and the effect of intervention and to clarify sensitivity or responsiveness of the scale to clinical change. Copyright © 2014 John Wiley & Sons, Ltd.
Prevalence of Dementia and Main Subtypes in Rural Northern China
Ji, Yong; Shi, Zhihong; Zhang, Ying; Liu, Shuling; Liu, Shuai; Yue, Wei; Liu, Mengyuan; Huo, Ya Ruth; Wang, Jinhuan; Wisniewski, Thomas
2016-01-01
Background/Aims The aim of this article was to estimate the prevalence of and to determine the sociodemographic risk factors for dementia, Alzheimer’s disease (AD) and vascular dementia (VaD) among individuals residing in rural northern China. Methods Between 2011 and 2012, residents aged ≥ 60 years and residing in rural areas of northern China were clinically assessed for symptoms of dementia, AD and VaD. Diagnoses were made using established criteria and standard procedures. Results Among 5,578 enrolled study participants aged ≥ 60 years, the prevalence rates of dementia, AD and VaD were 7.7, 5.4 and 1.7%, respectively. Older age (OR = 1.17; 95% CI: 1.14–1.19) and female gender (OR = 2.13; 95% CI: 1.51–3.00) were identified as independent risk factors for AD. In turn, a higher educational level (OR = 0.36; 95% CI: 0.21–0.60) and engagement in social activities (OR = 0.219; 95% CI: 0.163–0.295) were protective factors. Risk factors associated with VaD were older age (OR = 1.11; 95% CI: 1.1– 1.12) and hypertension (OR = 1.83; 95% CI: 1.18–2.86), while a higher educational level (OR = 0.53, 95% CI: 0.44–0.65) and engagement in social activities (OR = 0.34; 95% CI: 0.29–0.41) were protective factors. Conclusion High rates of dementia (7.7%) and AD (5.4%) were found in the rural areas of northern China. Older age and female gender were identified as risk factors for AD, while older age and hypertension were risk factors for VaD. A higher educational level and engagement in social activities were identified as protective factors against both AD and VaD. PMID:25792116
Alvarado-Esquivel, Cosme; Hernández-Alvarado, Ana Berthina; Tapia-Rodríguez, Rosa Oralia; Guerrero-Iturbe, Angel; Rodríguez-Corral, Karina; Martínez, Sergio Estrada
2004-02-18
Epidemiological reports about dementia and Alzheimer's disease (AD) in elderly people from developing countries are scarce. Therefore, we sought to determine the prevalences of dementia and AD in a population of nursing home residents and senior center attendees of Durango City, Mexico, and to determine whether any socio-demographic characteristics from the subjects associated with dementia or AD exist. One hundred and fifty-five residents of two nursing homes and 125 attendees of a senior center were examined for dementia and Alzheimer's disease. All subjects were tested by the mini-mental state examination, and those who scored twenty-four or less underwent psychiatric and neurological evaluations. Diagnosis of dementia, AD and vascular dementia (VaD) was based on the DSM-IV criteria. Socio-demographic characteristics from each participant were also obtained. Residents of nursing homes found to suffer from dementia were 25 out of 155 (16.1%). Eighteen of them (11.6%) had AD, and seven (4.5%) had VaD. None of the attendees of the senior center suffered from dementia. Dementia (pooled AD and VaD cases) correlated with white ethnicity (OR = 3.2; 95%CI = 1.28-8.31), and a history of unemployment (OR = 6.46; 95%CI = 1.42-25.97), while AD correlated with journeymen occupations (OR = 4.55; 95%CI = 1.00-19.29). Prevalence of dementia in residents of nursing homes found in this study is much lower than reported from more industrialized countries. AD was more frequent than VaD. Ethnicity and occupation showed effects on the prevalence figures. The prevalence of dementia found has implications for the optimum kind of health care that nursing homes should provide to their residents.
Identification of VaD and AD prodromes: the Cache County Study.
Hayden, K M; Warren, L H; Pieper, C F; Østbye, T; Tschanz, J T; Norton, M C; Breitner, J C S; Welsh-Bohmer, K A
2005-07-01
It is unclear whether vascular dementia (VaD) has a cognitive prodrome, akin to the mild cognitive impairment (MCI) prodrome to Alzheimer's dementia (AD). To evaluate whether VaD has a cognitive prodrome, and if it can be differentiated from prodromal AD, we examined neuropsychological test performance of participants in a nested case-control study within a population-based cohort aged 65 or older. Participants (n = 485) were identified from the Cache County Study, a large population-based study of aging and dementia. After an average of 3 years of follow-up, a total of 62 incident dementia cases were identified (14 VaD, 48 AD). We identified a number of neuropsychological tests (executive and memory) that discriminated between diagnosed VaD and AD cases. Multivariate analyses sought to differentiate between these same groups 3 years before clinical diagnosis. The Consortium to Establish a Registry for Alzheimer's Disease Word List Recognition Test correct recognition of foils (mean difference, 1.25; 95% confidence interval [CI], 0.42 to 2.07; p < 0.01), Logical Memory I (mean difference, 7.16; 95% CI, 0.78 to 13.55, p < 0.05), Logical Memory II delayed recall (mean difference, 8.67; 95% CI, 1.59 to 15.74, p < 0.05), and percent savings (mean difference, 51.07; 95% CI, 32.58 to 69.56, p < 0.0001) differentiated VaD from AD cases after adjustment for age, sex, education, and dementia severity. Three years before dementia diagnosis, word list recognition ("no" responses mean difference, 1.40; 95% CI, 0.64 to 2.17; p < 0.001, and "yes" responses mean difference, -1.14; 95% CI, -2.14 to -0.13; p < 0.03) discriminated between prodromal VaD and AD. These results suggest that VaD has a prodromal syndrome, the cognitive features of which are distinguishable from the cognitive prodrome of AD.
Comans, Tracy A; Nguyen, Kim-Huong; Mulhern, Brendan; Corlis, Megan; Li, Li; Welch, Alyssa; Kurrle, Susan E; Rowen, Donna; Moyle, Wendy; Kularatna, Sanjeewa; Ratcliffe, Julie
2018-01-01
Introduction Generic instruments for assessing health-related quality of life may lack the sensitivity to detect changes in health specific to certain conditions, such as dementia. The Quality of Life in Alzheimer’s Disease (QOL-AD) is a widely used and well-validated condition-specific instrument for assessing health-related quality of life for people living with dementia, but it does not enable the calculation of quality-adjusted life years, the basis of cost utility analysis. This study will generate a preference-based scoring algorithm for a health state classification system -the Alzheimer’s Disease Five Dimensions (AD-5D) derived from the QOL-AD. Methods and analysis Discrete choice experiments with duration (DCETTO) and best–worst scaling health state valuation tasks will be administered to a representative sample of 2000 members of the Australian general population via an online survey and to 250 dementia dyads (250 people with dementia and their carers) via face-to-face interview. A multinomial (conditional) logistic framework will be used to analyse responses and produce the utility algorithm for the AD-5D. Ethics and dissemination The algorithms developed will enable prospective and retrospective economic evaluation of any treatment or intervention targeting people with dementia where the QOL-AD has been administered and will be available online. Results will be disseminated through journals that publish health economics articles and through professional conferences. This study has ethical approval. PMID:29358437
Harrington, C R; Louwagie, J; Rossau, R; Vanmechelen, E; Perry, R H; Perry, E K; Xuereb, J H; Roth, M; Wischik, C M
1994-12-01
Alzheimer's disease (AD) is associated with an increased frequency of the apolipoprotein E type epsilon 4 allele. To address both the disease and the allele specificity of this association, we have examined the apolipoprotein E allele distribution in 255 elderly persons including those with autopsy-confirmed AD, senile dementia of the Lewy body type (SDLT), vascular dementia, Parkinson's disease (PD) or Huntington's disease and in nondemented controls either with or without coronary complications. The epsilon 4 allele frequency was increased in SDLT (0.365) and AD (0.328) as compared with controls (0.147), PD (0.098), or Huntington's chorea (0.171). Coronary disease and vascular dementia were associated with marginally higher epsilon 4 allele frequencies than in controls. In PD, amyloid beta-protein accumulated to a greater extent in those cases possessing an epsilon 4 allele than in those without. Those PD cases with dementia were not distinguished from either controls or PD cases without dementia, whether tested biochemically or by apolipoprotein E genotype. It is the comparison of the results in AD and SDLT that yielded the most significant findings. There was a 1.8-fold excess of amyloid beta-protein in AD as compared with controls, and the levels in SDLT were intermediate between those in AD and controls. In contrast, AD was discriminated from both controls and SDLT by the substantial accumulation of paired helical filament tau and phosphorylated tau (both increased more than 20-fold as compared with controls). SDLT was nevertheless characterized by an increased epsilon 4 allele frequency in the absence of significant tau pathology (at least 10-fold less than that in AD). These findings indicate that tau processing is more specifically associated with AD than is amyloid beta-protein accumulation and that presence of the epsilon 4 allele is not an etiological factor that accounts for tau pathology.
Harrington, C. R.; Louwagie, J.; Rossau, R.; Vanmechelen, E.; Perry, R. H.; Perry, E. K.; Xuereb, J. H.; Roth, M.; Wischik, C. M.
1994-01-01
Alzheimer's disease (AD) is associated with an increased frequency of the apolipoprotein E type epsilon 4 allele. To address both the disease and the allele specificity of this association, we have examined the apolipoprotein E allele distribution in 255 elderly persons including those with autopsy-confirmed AD, senile dementia of the Lewy body type (SDLT), vascular dementia, Parkinson's disease (PD) or Huntington's disease and in nondemented controls either with or without coronary complications. The epsilon 4 allele frequency was increased in SDLT (0.365) and AD (0.328) as compared with controls (0.147), PD (0.098), or Huntington's chorea (0.171). Coronary disease and vascular dementia were associated with marginally higher epsilon 4 allele frequencies than in controls. In PD, amyloid beta-protein accumulated to a greater extent in those cases possessing an epsilon 4 allele than in those without. Those PD cases with dementia were not distinguished from either controls or PD cases without dementia, whether tested biochemically or by apolipoprotein E genotype. It is the comparison of the results in AD and SDLT that yielded the most significant findings. There was a 1.8-fold excess of amyloid beta-protein in AD as compared with controls, and the levels in SDLT were intermediate between those in AD and controls. In contrast, AD was discriminated from both controls and SDLT by the substantial accumulation of paired helical filament tau and phosphorylated tau (both increased more than 20-fold as compared with controls). SDLT was nevertheless characterized by an increased epsilon 4 allele frequency in the absence of significant tau pathology (at least 10-fold less than that in AD). These findings indicate that tau processing is more specifically associated with AD than is amyloid beta-protein accumulation and that presence of the epsilon 4 allele is not an etiological factor that accounts for tau pathology. PMID:7992850
Hypertension and vascular dementia in the elderly: the potential role of anti-hypertensive agents.
Coca, Antonio
2013-09-01
Vascular dementia (VaD) - a severe form of vascular cognitive impairment - and cognitive decline are associated with hypertension and therefore it seems logical to consider that reducing BP with anti-hypertensive therapy may protect against the development/onset of cognitive function impairment or dementia. This narrative, non-systematic review discusses the available evidence on the potential correlation between the use of anti-hypertensive agents and the risk of VaD and cognitive decline. MEDLINE was searched for inclusion of relevant studies. No limitations in time were considered. A consensus on the potential effects of anti-hypertensive treatment in the reduction of VaD and associated cognitive decline has not been reached. A protective effect of anti-hypertensive agents has been observed in a number of studies although it is still unclear whether different classes of anti-hypertensive agents have a different effect on the development of VaD. The protective effect of anti-hypertensive agents appears to depend on the specific drug used - positive effects have been observed with calcium channel blockers (CCBs), such as lercanidipine and nitrendipine, the combination perindopril-indapamide and telmisartan.
Cannabinoids and Dementia: A Review of Clinical and Preclinical Data
Walther, Sebastian; Halpern, Michael
2010-01-01
The endocannabinoid system has been shown to be associated with neurodegenerative diseases and dementia. We review the preclinical and clinical data on cannabinoids and four neurodegenerative diseases: Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD) and vascular dementia (VD). Numerous studies have demonstrated an involvement of the cannabinoid system in neurotransmission, neuropathology and neurobiology of dementias. In addition, several candidate compounds have demonstrated efficacy in vitro. However, some of the substances produced inconclusive results in vivo. Therefore, only few trials have aimed to replicate the effects seen in animal studies in patients. Indeed, the literature on cannabinoid administration in patients is scarce. While preclinical findings suggest causal treatment strategies involving cannabinoids, clinical trials have only assessed the suitability of cannabinoid receptor agonists, antagonists and cannabidiol for the symptomatic treatment of dementia. Further research is needed, including in vivo models of dementia and human studies. PMID:27713372
Assessment of risk factors for earlier onset of sporadic Alzheimer's disease dementia.
de Oliveira, Fabricio Ferreira; Bertolucci, Paulo Henrique Ferreira; Chen, Elizabeth Suchi; Smith, Marilia Cardoso
2014-01-01
Pharmacological treatment has mild effects for patients with Alzheimer's disease dementia (AD); therefore, the search for modifiable risk factors is an important challenge. Though risk factors for AD are widely recognized, elements that influence the time of dementia onset have not been comprehensively reported. We aimed to investigate which risk factors might be related to the age of onset of AD in a sample of patients with highly variable educational levels, taking into account the Framingham risk scoring as the sole measure of vascular risk. We included 209 consecutive late-onset AD patients to find out which factors among educational levels, coronary heart disease risk estimated by way of Framingham risk scores, history of head trauma or depression, surgical procedures under general anesthesia, family history of neurodegenerative diseases, gender, marital status and APOE haplotypes might be related to the age of dementia onset in this sample of patients with low mean schooling. Mean age of AD onset was 73.38±6.5 years old, unaffected by schooling or family history of neurodegenerative diseases. Patients who were APOE-ε4 carriers, married, or with history of depression, had earlier onset of AD, particularly when they were women. Coronary heart disease risk was marginally significant for later onset of AD. APOE haplotypes, marital status and history of depression were the most important factors to influence the age of AD onset in this sample. While midlife cerebrovascular risk factors may increase incidence of AD, they may lead to later dementia onset when present in late life.
Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview.
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.
Zhu, Jun-De; Wang, Jun-Jie; Zhang, Xian-Hu; Yu, Yan; Kang, Zhao-Sheng
2018-04-01
Panax ginseng is a slow-growing perennial plant. Panax ginseng extract has numerous biological activities, including antitumor, anti-inflammatory and antistress activities. Panax ginseng extract also has a cognition-enhancing effect in rats with alcohol-induced memory impairment. In this study, we partially occluded the bilateral carotid arteries in the rat to induce chronic cerebral hypoperfusion, a well-known model of vascular dementia. The rats were then intragastrically administered 50 or 100 mg/kg Panax ginseng extract. Morris water maze and balance beam tests were used to evaluate memory deficits and motor function, respectively. Protein quantity was used to evaluate cholinergic neurons. Immunofluorescence staining was used to assess the number of glial fibrillary acidic protein-positive cells. Western blot assay was used to evaluate protein levels of vascular endothelial growth factor, basic fibroblast growth factor, Bcl-2 and Bax. Treatment with Panax ginseng extract for 8 weeks significantly improved behavioral function and increased neuronal density and VEGF and bFGF protein expression in the hippocampal CA3 area. Furthermore, Panax ginseng extract reduced the number of glial fibrillary acidic protein-immunoreactive cells, and it decreased apoptosis by upregulating Bcl-2 and downregulating Bax protein expression. The effect of Panax ginseng extract was dose-dependent and similar to that of nimodipine, a commonly used drug for the treatment of vascular dementia. These findings suggest that Panax ginseng extract is neuroprotective against vascular dementia induced by chronic cerebral hypoperfusion, and therefore might have therapeutic potential for preventing and treating the disease.
Stroke injury, cognitive impairment and vascular dementia☆
Kalaria, Raj N.; Akinyemi, Rufus; Ihara, Masafumi
2016-01-01
The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25–30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood–brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26806700
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
Systematic review of quantitative clinical gait analysis in patients with dementia.
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.
Pharmacogenomics and therapeutic prospects in dementia.
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
Population-based Study of Risk Polymorphisms Associated with Vascular Disorders and Dementia
Teijido, Óscar; Carril, Juan Carlos; Cacabelos, Ramón
2017-01-01
Introduction: Cardiovascular and neurodegenerative disorders are among the major causes of mortality in the developed countries. Population studies evaluate the genetic risk, i.e. the probability of an individual carrying a specific disease-associated polymorphism. Identification of risk polymorphisms is essential for an accurate diagnosis or prognosis of a number of pathologies. Aims: The aim of this study was to characterize the influence of risk polymorphisms associated with lipid metabolism, hypertension, thrombosis, and dementia, in a large population of Spanish individuals affected by a variety of brain and vascular disorders as well as metabolic syndrome. Material & Method: We performed a cross-sectional study on 4415 individuals from a widespread regional distribution in Spain (48.15% males and 51.85% females), with mental, neurodegenerative, cerebrovascular, and metabolic disorders. We evaluated polymorphisms in 20 genes involved in obesity, vascular and cardiovascular risk, and dementia in our population and compared it with representative Spanish and European populations. Risk polymorphisms in ACE, AGT(235), IL6(573), PSEN1, and APOE (specially the APOE-ε4 allele) are representative of our population as compared to the reference data of Spanish and European individuals. Conclusion: The significantly higher distribution of risk polymorphisms in PSEN1 and APOE-ε4 is characteristic of a representative number of patients with Alzheimer’s disease; whereas polymorphisms in ACE, AGT(235), and IL6(573), are most probably related with the high number of patients with metabolic syndrome or cerebrovascular damage. PMID:29081698
Happich, Michael; Kirson, Noam Y.; Desai, Urvi; King, Sarah; Birnbaum, Howard G.; Reed, Catherine; Belger, Mark; Lenox-Smith, Alan; Price, David
2016-01-01
Background: Prior diagnosis of Alzheimer’s disease (AD) among patients later diagnosed with vascular dementia (VaD) has been associated with excess costs, suggesting potential benefits of earlier rule-out of AD diagnosis. Objective: To investigate whether prior diagnosis with AD among patients with VaD is associated with excess costs in the UK. Methods: Patients with a final VaD diagnosis, continuous data visibility for≥6 months prior to index date, and linkage to Hospital Episode Statistics data were retrospectively selected from de-identified Clinical Practice Research Datalink data. Patients with AD diagnosis before a final VaD diagnosis were matched to similar patients with no prior AD diagnosis using propensity score methods. Annual excess healthcare costs were calculated for 5 years post-index, stratified by time to final diagnosis. Results: Of 9,311 patients with VaD, 508 (6%) had prior AD diagnosis with a median time to VaD diagnosis exceeding 2 years from index date. Over the entire follow-up period, patients with prior AD diagnosis had accumulated healthcare costs that were approximately GBP2,000 higher than those for matched counterparts (mostly due to higher hospitalization costs). Cost differentials peaked particularly in the period including the final VaD diagnosis, with excess costs quickly declining thereafter. Conclusion: Potential misdiagnosis of AD among UK patients with VaD resulted in substantial excess costs. The decline in excess costs following a final VaD diagnosis suggests potential benefits from earlier rule-out of AD. PMID:27163798
Risk of Dementia Associated with Elevated Plasma Homocysteine in a Latin American Population
Chacón, Inara J.; Molero, Aldrín E.; Pino-Ramírez, Gloria; Luchsinger, José A.; Lee, Joseph H.; Maestre, Gladys E.
2009-01-01
The relationship between total homocysteine (tHcy) and dementia risk remains controversial, as the association varies among populations and dementia subtypes. We studied a Venezuelan population that has high prevalence of both elevated tHcy and dementia. We tested the hypotheses that (1) elevated tHcy is associated with increased dementia risk, (2) the risk is greater for vascular dementia (VaD) than for Alzheimer's disease (AD), and (3) a history of stroke may partly explain this association. 2100 participants (≥55 years old) of the Maracaibo Aging Study underwent standardized neurological, neuropsychiatric, and cardiovascular assessments. Elevated tHcy was significantly associated with dementia, primarily VaD. When history of stroke and other confounding factors were taken into account, elevated tHcy remained a significant risk factor in older (>66 years), but not in younger (55–66 years) subjects. Ongoing studies of this population may provide insight into the mechanism by which tHcy increases risk for dementia. PMID:20798752
Rivastigmine for vascular cognitive impairment.
Birks, Jacqueline; McGuinness, Bernadette; Craig, David
2013-05-31
Vascular dementia represents the second most common type of dementia after Alzheimer's disease. In older patients, in particular, the combination of vascular dementia and Alzheimer's disease is common, and is referred to as mixed dementia. The classification of vascular dementia broadly follows three clinico-pathological processes: multi-infarct dementia, single strategic infarct dementia and subcortical dementia. Not all victims fulfil strict criteria for dementia and may be significantly cognitively impaired without memory loss, when the term vascular cognitive impairment (VCI) is more useful. Currently, no established standard treatment for VCI exists. Reductions in acetylcholine and acetyltransferase activity are common to both Alzheimer's disease and VCI, raising the possibility that cholinesterase inhibitors - such as rivastigmine - which are beneficial in Alzheimer's disease, may also be beneficial for VCI. To assess the efficacy of rivastigmine compared with placebo in the treatment of people with vascular cognitive impairment (VCI), vascular dementia or mixed dementia. We searched ALOIS (the Cochrane Dementia and Cognitive Improvement Group's Specialized Register) on 12 February 2013 using the terms: rivastigmine, exelon, "SDZ ENA 713". ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS), numerous trial registries and grey literature sources. All unconfounded randomized double-blind trials comparing rivastigmine with placebo in the treatment of people with VCI, vascular dementia or mixed dementia were eligible for inclusion. Two reviewers extracted and assessed data independently, and agreement was reached after discussion. They noted results concerning adverse effects. Three trials, with a total of 800 participants, were identified for inclusion. The participants in one trial did not have dementia, while the other two studies
A comparative study to screen dementia and APOE genotypes in an ageing East African population
Chen, Chien-Hsiun; Mizuno, Toshiki; Elston, Robert; Kariuki, Monica M.; Hall, Kathleen; Unverzagt, Fred; Hendrie, Hugh; Gatere, Samuel; Kioy, Paul; Patel, Nilesh B.; Friedland, Robert P.; Kalaria, Raj N.
2010-01-01
Previous studies have established cross-cultural methods to screen for ageing- related dementia and susceptibility genes, in particular Alzheimer’s disease (AD) among the Canadian Cree, African Americans and Yoruba in Nigeria. We determined whether the Community Screening Interview for Dementia (CSID), translated into Kikuyu, a major language of Kenya, could be used to evaluate dementia of the Alzheimer type. Using two sets of coefficients of cognitive and informant scores, two discriminant function (DF) scores were calculated for each of 100 elderly (>65 years) Nyeri Kenyans. When the cut-off points were selected for 100% sensitivities, the specificities of the DF scores were remarkably similar (93.75%) in the Kenyan sample. We propose the adapted CSID can be utilised to detect dementia among East Africans. We also show that apolipoprotein E ε4 allele frequencies were high (∼30%) and not different between normal subjects and those with probable AD. There was no evidence to suggest years of education or vascular factors were associated with dementia status. PMID:18703255
Scrascia, Federica; Quattrocchi, Carlo Cosimo; Errante, Yuri; Gangemi, Emma; Curcio, Giuseppe; Ursini, Francesca; Silvestrini, Mauro; Maggio, Paola; Beomonte Zobel, Bruno; Rossini, Paolo Maria; Pasqualetti, Patrizio; Falsetti, Lorenzo; Vernieri, Fabrizio
2016-01-01
Background and Purpose An increase in brain water diffusivity as measured using magnetic resonance imaging (MRI) has been recently reported in normal-appearing white matter (NAWM) in patients affected by cognitive impairment. However, it remains to be clarified if this reflects an overt neuronal tissue disruption that leads to degenerative or microvascular lesions. This question was addressed by comparing the regional MRI apparent diffusion coefficients (ADCs) of NAWM in patients affected by Alzheimer's disease (AD) or vascular dementia (VaD). The relationships of ADCs with the white-matter hyperintensity (WMH) burden, carotid atherosclerosis, and cognitive performance were also investigated. Methods Forty-nine AD and 31 VaD patients underwent brain MRI to assess the WMH volume and regional NAWM ADCs, neuropsychological evaluations, and carotid ultrasound to assess the plaque severity and intima-media thickness (IMT). Results Regional ADCs in NAWM did not differ between VaD and AD patients, while the WMH volume was greater in VaD than in AD patients. The ADC in the anterior corpus callosum was related to the WMH volume, while a greater carotid IMT was positively correlated with the temporal ADC and WMH volume. The memory performance was worse in patients with higher temporal ADCs. Constructional praxis scores were related to ADCs in the frontal, and occipital lobes, in the anterior and posterior corpus callosum as well as to the WMH volume. Abstract reasoning was related to frontal, parietal, and temporal ADCs. Conclusions Our data show that higher regional ADCs in NAWM are associated with microcirculatory impairment, as depicted by the WMH volume. Moreover, regional ADCs in NAWM are differently associated with the neuropsychological performances in memory, constructional praxia, and abstract reasoning domains. PMID:27074295
Zhao, Ran-Ran; Xu, Fei; Xu, Xiao-Chen; Tan, Guo-Jun; Liu, Liang-Min; Wu, Ning; Zhang, Wen-Zhong; Liu, Ji-Xiang
2015-02-05
Brain oxidative stress due to chronic cerebral hypoperfusion was considered to be the major risk factor in the pathogenesis of vascular dementia. In this study, we investigated the protective efficacy of alpha-lipoic acid, an antioxidant, against vascular dementia in rats, as well as the potential mechanism. Bilateral common carotid arteries occlusion (BCCAO) induced severe cognitive deficits tested by Morris water maze (MWM), along with oxidative stress and disturbance of central cholinergic system. However, administration of alpha-lipoic acid (50mg/kg, i.p.) for 28 days significantly restored cognitive deficits induced by BCCAO. Biochemical determination revealed that alpha-lipoic acid markedly decreased the production of malondialdehyde (MDA) and the generation of reactive oxidative species (ROS), and increased the level of reduced glutathione (GSH) in the hippocampal tissue. Additionally, alpha-lipoic acid raised the level of acetylcholine (ACh) and choline acetyltransferase (ChAT) and decreased the activity of acetycholinesterase (AChE) in the hippocampus. These results indicated that treatment with alpha-lipoic acid significantly improved behavioral alterations, protected against oxidative stress, and restored central cholinergic system in the rat model of vascular dementia induced by BCCAO. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Cerebral Perfusion Enhancing Interventions: A New Strategy for the Prevention of Alzheimer Dementia.
de la Torre, Jack C
2016-09-01
Cardiovascular and cerebrovascular diseases are major risk factors in the development of cognitive impairment and Alzheimer's disease (AD). These cardio-cerebral disorders promote a variety of vascular risk factors which in the presence of advancing age are prone to markedly reduce cerebral perfusion and create a neuronal energy crisis. Long-term hypoperfusion of the brain evolves mainly from cardiac structural pathology and brain vascular insufficiency. Brain hypoperfusion in the elderly is strongly associated with the development of mild cognitive impairment (MCI) and both conditions are presumed to be precursors of Alzheimer dementia. A therapeutic target to prevent or treat MCI and consequently reduce the incidence of AD aims to elevate cerebral perfusion using novel pharmacological agents. As reviewed here, the experimental pharmaca include the use of Rho kinase inhibitors, neurometabolic energy boosters, sirtuins and vascular growth factors. In addition, a compelling new technique in laser medicine called photobiomodulation is reviewed. Photobiomodulation is based on the use of low level laser therapy to stimulate mitochondrial energy production non-invasively in nerve cells. The use of novel pharmaca and photobiomodulation may become important tools in the treatment or prevention of cognitive decline that can lead to dementia. © 2016 International Society of Neuropathology.
Engelhardt, Eliasz; Tocquer, Carla; André, Charles; Moreira, Denise Madeira; Okamoto, Ivan Hideyo; Cavalcanti, José Luiz de Sá
2011-01-01
Vascular dementia (VaD) is the most prevalent form of secondary dementia and the second most common of all dementias. The present paper aims to define guidelines on the basic principles for treating patients with suspected VaD (and vascular cognitive impairment - no dementia) using an evidence-based, systematized approach. The knowledge used to define these guidelines was retrieved from searches of several databases (Medline, Scielo, Lilacs) containing scientific articles, systematic reviews, meta-analyses, largely published within the last 15 years or earlier when pertinent. Information retrieved and selected for relevance was used to analyze diagnostic criteria and to propose a diagnostic system encompassing diagnostic criteria, anamnesis, as well as supplementary and clinical exams (neuroimaging and laboratory). Wherever possible, instruments were selected that had versions previously adapted and validated for use in Brazil that take into account both schooling and age. This task led to proposed protocols for supplementary exams based on degree of priority, for application in clinical practice and research settings. PMID:29213752
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.
Kaewkaen, Pratchaya; Tong-un, Terdthai; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Kaewrueng, Wiroje; Wongcharoenwanakit, Sathaporn
2012-01-01
Nowadays, the preventive strategy of vascular dementia, one of the challenge problems of elderly, has received attention due to the limitation of therapeutic efficacy. In this study, we aimed to determine the protective effect and possible mechanism of action of mulberry fruit extract on memory impairment and brain damage in animal model of vascular dementia. Male Wistar rats, weighing 300–350 g, were orally given mulberry extract at doses of 2, 10 and 50 mg/kg at a period of 7 days before and 21 days after the occlusion of right middle cerebral artery (Rt.MCAO). It was found that rats subjected to mulberry fruits plus Rt.MCAO showed the enhanced memory, the increased densities of neuron, cholinergic neuron, Bcl-2-immunopositive neuron together with the decreased oxidative stress in hippocampus. Taken all data together, the cognitive enhancing effect of mulberry fruit extract observed in this study might be partly associated with the increased cholinergic function and its neuroprotective effect in turn occurs partly via the decreased oxidative stress and apoptosis. Therefore, mulberry fruit is the potential natural cognitive enhancer and neuroprotectant. However, further researches are essential to elucidate the possible active ingredient. PMID:22952555
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
Honda, Yukiko; Meguro, Kenichi; Meguro, Mitsue; Akanuma, Kyoko
2013-01-01
Patients with vascular dementia (VaD) are often isolated, withdrawn from society because of negative symptoms and functional disabilities. The aim of this study was to detect factors associated with social withdrawal in patients with VaD. The participants were 36 institutionalized patients with VaD. Social withdrawal was assessed with the social withdrawal of the Multidimensional Observation Scale for Elderly Subjects (MOSES). Possible explanatory variables were the MOSES items depression and self-care, Cognitive Abilities Screening Instrument (CASI), apathy evaluation scale (AES), and Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW). Multiple regression analyses were conducted for two groups: Analysis 1 was performed in all patients (N = 36) and Analysis 2 was performed in the patients with the ability to move by themselves (i.e., independent walking or independent movement with a cane or a wheelchair; n = 28). In Analysis 1, MOSES item social withdrawal was correlated with AES and MOSES item self-care. In Analysis 2, MOSES item social withdrawal was correlated with AES and CASI domain abstraction and judgment. Decreased social activities of VaD were not related to general cognitive function or depression. Disturbed activities of daily living (ADLs) for self-care may involve decreased frontal lobe function, indicating that comprehensive rehabilitation for both ADL and dementia are needed to improve the social activities of patients with VaD.
Matsumoto, Kinzo; Zhao, Qi; Niu, Yimin; Fujiwara, Hironori; Tanaka, Ken; Sasaki-Hamada, Sachie; Oka, Jun-Ichiro
2013-01-01
Cognitive deficits and behavioral and psychological symptoms of dementia (BPSD) are typical features of patients with dementia such as Alzheimer's disease (AD), vascular dementia (VD), and other forms of senile dementia. Clinical evidence has demonstrated the potential usefulness of chotosan (CTS) and yokukansan (YKS), traditional herbal formulations called Kampo medicines, in the treatment of cognitive disturbance and BPSD in dementia patients, although the indications targeted by CTS and YKS in Kampo medicine differ. The availability of CTS and YKS for treating dementia patients is supported by preclinical studies using animal models of dementia that include cognitive/emotional deficits caused by aging and diabetes, dementia risk factors. These studies have led not only to the concept of a neuronal basis for the CTS- and YKS-induced amelioration of cognitive function and emotional/psychiatric symptom-related behavior in animal models, but also to a proposal that ingredient(s) of Uncariae Uncis cum Ramulus, a medicinal herb included in CTS and YKS, may play an important role in the actions of these formulae in dementia patients. Further studies are needed to clarify the active ingredients of these formulae and their target endogenous molecules implicated in the anti-dementia drug-like actions.
Paraoxonase activity and dementia.
Wehr, Hanna; Bednarska-Makaruk, Małgorzata; Graban, Ałła; Lipczyńska-Łojkowska, Wanda; Rodo, Maria; Bochyńska, Anna; Ryglewicz, Danuta
2009-08-15
Paraoxonase activity, homocysteine level and lipids were determined in 120 patients with dementia (51 with Alzheimer disease, 28 with dementia of vascular origin, 41 with mixed dementia), 45 with mild cognitive impairment and in 61 age and sex matched controls without dementia. Paraoxonase activity was decreased in Alzheimer disease and in mixed dementia as compared with control group. In the same forms of dementia homocysteine levels were increased. In Alzheimer disease paraoxonase activity was negatively correlated with homocysteine levels. Minimental State Examination results showed positive correlation with paraoxonase activity. The results suggest an important role of oxidative stress in the development of the forms of dementia with prevailing neurodegeneration.
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…
Gorelick, Philip B; Scuteri, Angelo; Black, Sandra E; Decarli, Charles; Greenberg, Steven M; Iadecola, Costantino; Launer, Lenore J; Laurent, Stephane; Lopez, Oscar L; Nyenhuis, David; Petersen, Ronald C; Schneider, Julie A; Tzourio, Christophe; Arnett, Donna K; Bennett, David A; Chui, Helena C; Higashida, Randall T; Lindquist, Ruth; Nilsson, Peter M; Roman, Gustavo C; Sellke, Frank W; Seshadri, Sudha
2011-09-01
This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment and dementia of later life are common. Definitions of vascular cognitive impairment (VCI), neuropathology, basic science and pathophysiological aspects, role of neuroimaging and vascular and other associated risk factors, and potential opportunities for prevention and treatment are reviewed. This statement serves as an overall guide for practitioners to gain a better understanding of VCI and dementia, prevention, and treatment. Writing group members were nominated by the writing group co-chairs on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council Scientific Statement Oversight Committee, the Council on Epidemiology and Prevention, and the Manuscript Oversight Committee. The writing group used systematic literature reviews (primarily covering publications from 1990 to May 1, 2010), previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulate recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. After peer review by the American Heart Association, as well as review by the Stroke Council leadership, Council on Epidemiology and Prevention Council, and Scientific Statements Oversight Committee, the statement was approved by the American Heart Association Science Advisory and Coordinating Committee. The construct of VCI has been introduced to capture the entire spectrum of cognitive disorders associated with all forms of cerebral vascular brain injury-not solely stroke-ranging from mild cognitive impairment through fully developed dementia. Dysfunction of the neurovascular
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
Martyr, Anthony; Clare, Linda; Nelis, Sharon M; Roberts, Judith L; Robinson, Julia U; Roth, Ilona; Markova, Ivana S; Woods, Robert T; Whitaker, Christopher J; Morris, Robin G
2011-01-01
To determine whether people with dementia (PwD), and carers of PwD, show a processing bias to dementia-related words in an emotional Stroop task, and if so, whether the presence of such a bias is related to level of explicit awareness of the condition. Seventy-nine people with early stage Alzheimer's disease (AD), vascular or mixed dementia, and their carers, completed an emotional Stroop task. Time taken to colour-name dementia-related and neutral words was compared within and between groups. Additionally, as a comparison, ratings of the awareness of the condition shown by PwD were made on the basis of a detailed interview with each PwD and his/her carer. PwD and carers showed the same level of increase in response times to salient compared to neutral words. In the PwD this effect was unrelated to the degree of awareness that they demonstrated regarding the condition. The emotional Stroop effect in response to dementia-related words in PwD indicates that preserved implicit awareness of the condition can be elicited even where there is reduced explicit awareness. Copyright © 2010 John Wiley & Sons, Ltd.
Increased CAIDE dementia risk, cognition, CSF biomarkers, and vascular burden in healthy adults.
Ecay-Torres, Mirian; Estanga, Ainara; Tainta, Mikel; Izagirre, Andrea; Garcia-Sebastian, Maite; Villanua, Jorge; Clerigue, Montserrat; Iriondo, Ane; Urreta, Iratxe; Arrospide, Arantzazu; Díaz-Mardomingo, Carmen; Kivipelto, Miia; Martinez-Lage, Pablo
2018-06-13
To investigate the cognitive profile of healthy individuals with increased Cardiovascular Risk Factors, Aging and Dementia (CAIDE) dementia risk score and to explore whether this association is related to vascular burden and CSF biomarkers of amyloidosis and neurodegeneration. Cognitively normal participants (mean age 57.6 years) from the Gipuzkoa Alzheimer Project study were classified as having high risk (HR; n = 82) or low risk (LR; n = 293) for dementia according to a CAIDE score cutoff of 9. Cognitive composites were compared between groups. We explored using generalized linear models the role of APOE genotype, MRI white matter hyperintensities (WMH), and CSF (n = 218) levels of β-amyloid 1-42 (Aβ 1-42 ), total tau (t-tau), and phosphorylated tau (p-tau) in the association between CAIDE score and cognition. HR participants obtained lower scores on executive function (EF) ( p = 0.001) and visual perception and construction (VPC) ( p < 0.001) composites. EF composite was associated with CAIDE score × p-tau ( p = 0.001), CAIDE score × t-tau ( p = 0.001), and WMH ( p = 0.003). VPC composite was associated with APOE ( p = 0.001), Aβ 1-42 ( p = 0.004), the interaction APOE × Aβ 1-42 ( p = 0.003), and WMH ( p = 0.004). Performance on global memory was associated with Aβ 1-42 ( p = 0.006), APOE ( p = 0.008), and their interaction ( p = 0.006). Analyses were adjusted for age, education, sex, premorbid intelligence, and stress. Healthy participants at increased dementia risk based on CAIDE scores show lower performance in EF and VPC. This difference is related to APOE , WMH, and Alzheimer biomarkers. © 2018 American Academy of Neurology.
Wang, Hu-Qing; Zhang, Meng; Zhao, Jia-Xin; Wu, Hai-Qin; Gao, Zhen; Zhang, Gui-Lian; Zhang, Ru
2018-05-01
To observe the effect of puerarin on methyl-CpG binding protein 2 (MeCP2) phosphorylation (pMeCP2) in the hippocampus of a rat model of vascular dementia (VD). Thirty-six healthy Sprague-Dawley rats were randomly assigned to the sham-operated group, dementia group and puerarintreated group using a random number table (n=12 per group). The modifified permanent bilateral common carotid artery occlusion method was used to establish the VD model. The sham-operated and dementia groups were given 2 mL/d of saline, while the puerarin-treated group was given 100 mg/(kg•d) of puerarin for 17 days. The learning and memory abilities were evaluated by the Morris water maze test. Hematoxylin-eosin staining, immunohistochemical (IHC) staining and Western blot analysis were carried out to observe changes in neuron morphology and in level of pMeCP2 in the hippocampus, respectively. The morphologies of rat hippocampal neurons in the puerarintreated group were markedly improved compared with the dementia group. The escape latency of the dementia group was significantly longer than the sham-operated group (P<0.05), while the puerarin-treated group was obviously shorter than the dementia group (P<0.05). Cross-platform times of the dementia group were signifificantly decreased compared with the sham-operated group (P<0.05), while the puerarin-treated group was obviously increased compared with the dementia group (P<0.05). IHC staining showed no significant difference in the number of MeCP2 positive cells among 3 groups (P>0.05). The number of pMeCP2 positive cells in the CA1 region of hippocampus in the dementia group was signifificantly increased compared with the sham-operated group, and the puerarin-treated group was signifificantly increased compared with the dementia group (both P<0.05). Western blot analysis showed no signifificant difference of MeCP2 expression among 3 groups (P>0.05). The expression of pMeCP2 in the dementia group was signifificantly increased compared with
Wang, Qing-Hua; Wang, Xin; Bu, Xian-Le; Lian, Yan; Xiang, Yang; Luo, Hong-Bo; Zou, Hai-Qiang; Pu, Jie; Zhou, Zhong-He; Cui, Xiao-Ping; Wang, Qing-Song; Shi, Xiang-Qun; Han, Wei; Wu, Qiang; Chen, Hui-Sheng; Lin, Hang; Gao, Chang-Yue; Zhang, Li-Li; Xu, Zhi-Qiang; Zhang, Meng; Zhou, Hua-Dong; Wang, Yan-Jiang
2017-12-01
Dementia is increasing dramatically and imposes a huge burden on society. To date, there is a lack of data on the health status of patients with dementia in China. In an attempt to investigate the comorbidity burden of dementia patients in China at the national level, we enrolled 2,938 patients with Alzheimer's disease (AD), vascular dementia (VaD), or other types of dementia, who were admitted to tertiary hospitals in seven regions of China from January 2003 to December 2012. The Charlson Comorbidity Index (CCI) was used to evaluate the comorbidity burden of the patients with dementia. Among these patients, 53.4% had AD, 26.3% had VaD, and 20.3% had other types of dementia. The CCI was 3.0 ± 1.9 for all patients, 3.4 ± 1.8 for those with VaD, and 3.0 ± 2.1 for those with AD. The CCI increased with age in all patients, and the length of hospital stay and daily expenses rose with age and CCI. Males had a higher CCI and a longer stay than females. Moreover, patients admitted in the last 5 years of the study had a higher CCI than those admitted in the first 5 years. We found that the comorbidity burden of patients with dementia is heavy. These findings provide a better understanding of the overall health status of dementia patients, and help to increase the awareness of clinicians and policy-makers to improve medical care for patients.
Patterns of anti-inflammatory drug use and risk of dementia: a matched case-control study.
Dregan, A; Chowienczyk, P; Armstrong, D
2015-11-01
There is limited primary-care-based evidence about a potential association between anti-inflammatory therapy and dementia subtypes. The present study addressed this limitation by using electronic health records from a large primary care database. A case-control study was implemented using electronic medical records. Cases had a diagnosis of dementia between 1992 and 2014. Up to four controls matched on age, gender, family practice and index date were selected for each case. Use of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoid drugs represented the exposure variables. Primary outcome measures included all-cause dementia and main dementia subtypes, including Alzheimer disease (AD), vascular dementia (VaD) and Lewy body dementia (LBD). Data were analysed using conditional logistic regression. The study identified 31,083 patients with AD, 23,465 with VaD and 1694 with LBD. Ever-used NSAIDs were associated with a modest increase in the risk of all-cause dementia (odds ratio 1.04, 95% confidence interval 1.02-1.05, P < 0.006), whilst no association was apparent for ever-used glucocorticoids (0.98, 0.96-1.01, P = 0.152). There was no evidence for an association between NSAIDs and AD (1.03, 0.99-1.06, P = 0.07) or LBD (1.13, 0.99-1.29, P = 0.08). However, a significant increase in the risk for VaD (1.33, 1.29-1.38, P < 0.001) was observed. Similar patterns emerged for glucocorticoid therapy. In a large primary care population, there was no robust evidence for a potential association between anti-inflammatory drugs and risk of AD or LBD. NSAIDs and glucocorticoid drugs were associated with higher risk of VaD. © 2015 EAN.
Midlife use of written Japanese and protection from late life dementia
Crane, Paul K.; Gibbons, Laura E.; Arani, Keerthi; Nguyen, Viet; Rhoads, Kristoffer; McCurry, Susan M.; Launer, Lenore; Masaki, Kamal; White, Lon
2011-01-01
Background The cognitive reserve hypothesis would predict that use of written Japanese should confer protection against dementia because of the complexity of its ideograms compared with written English. We sought to test this hypothesis in analyses from a longitudinal study of Japanese-American men. Methods Participants were second-generation Japanese-American men (Nisei) on the island of Oahu, Hawaii, who were seen in 1965 and in subsequent examinations to detect dementia beginning in 1991-1993. Use of spoken and written Japanese was self-reported in 1965 (Analyses 1 and 2), and mid-life use of written Japanese and written English was self-reported in 1994-1996 (Analysis 3). We analyzed prevalent dementia outcomes in 1991-1993 (Analysis 1, n=3,139) using logistic regression, and incident dementia outcomes in 1994-2002 (Analysis 2, n=2,299) and in 1997-2002 (Analysis 3, n=1,655) using Cox proportional hazards regression. Dementia outcomes included all-cause dementia, probable and possible Alzheimer disease, and probable vascular dementia. We adjusted models for probable and possible confounders. Results Participants who reported proficiency with written Japanese were older and had lower incomes. For Analysis 1, there were 154 prevalent cases of dementia, 74 of Alzheimer disease, and 43 of vascular dementia; for Analysis 2, 236 incident cases of dementia, 138 of Alzheimer disease, and 45 of vascular dementia; and for Analysis 3, 125 incident cases of dementia, 80 of Alzheimer disease, and 20 of vascular dementia. There was no relationship in adjusted models between self-reported proficiency with written Japanese and any dementia outcomes. Conclusions Proficiency with written Japanese does not appear to be protective for dementia. PMID:19593152
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
Agogo, George O; Ramsey, Christine M; Gnjidic, Danijela; Moga, Daniela C; Allore, Heather
2018-04-18
ABSTRACTBackground:Longitudinal studies of older adults are characterized by high dropout rates, multimorbid conditions, and multiple medication use, especially proximal to death. We studied the association between multiple medication use and incident dementia diagnoses including Alzheimer's disease (AD), vascular dementia (VD), and Lewy-body dementia (LBD), simultaneously accounting for dropout. Using the National Alzheimer's Coordinating Center data with three years of follow-up, a set of covariate-adjusted models that ignore dropout was fit to complete-case data, and to the whole-cohort data. Additionally, covariate-adjusted joint models with shared random effects accounting for dropout were fit to the whole-cohort data. Multiple medication use was defined as polypharmacy (⩾ five medications), hyperpolypharmacy (⩾ ten medications), and total number of medications. Incident diagnoses were 2,032 for AD, 135 for VD, and 139 for LBD. Percentages of dropout at the end of follow-up were as follows: 71.8% for AD, 81.5% for VD, and 77.7% for LBD. The odds ratio (OR) estimate for hyperpolypharmacy among those with LBD versus AD was 2.19 (0.78, 6.15) when estimated using complete-case data and 3.00 (1.66, 5.40) using whole-cohort data. The OR reduced to 1.41 (0.76, 2.64) when estimated from the joint model accounting for dropout. The OR for polypharmacy using complete-case data differed from the estimates using whole-cohort data. The OR for dementia diagnoses on total number of medications was similar, but non-significant when estimated using complete-case data. Reasons for dropout should be investigated and appropriate statistical methods should be applied to reduce bias in longitudinal studies among high-risk dementia cohorts.
Hemanth Kumar, Boyina; Arun Reddy, Ravula; Mahesh Kumar, Jerald; Dinesh Kumar, B; Diwan, Prakash V
2017-01-01
This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.
Beishuizen, Cathrien R L; Coley, Nicola; Moll van Charante, Eric P; van Gool, Willem A; Richard, Edo; Andrieu, Sandrine
2017-07-01
To explore and compare sociodemographic, clinical, and neuropsychiatric determinants of dropout and nonadherence in older people participating in an open-label cluster-randomized controlled trial-the Prevention of Dementia by Intensive Vascular care (preDIVA) trial-over 6 years. Secondary analysis. One hundred sixteen general practices in the Netherlands. Community-dwelling individuals aged 70 to 78 (N = 2,994). Nurse-led multidomain intervention targeting cardiovascular risk factors to prevent dementia. The associations between participant baseline sociodemographic (age, sex, education), clinical (medical history, disability, cardiovascular risk), neuropsychiatric (depressive symptoms (Geriatric Depression Scale-15), and cognitive (Mini-Mental State Examination)) characteristics and dropout from the trial and nonadherence to the trial intervention were explored using multilevel logistic regression models. Older age, poorer cognitive function, more symptoms of depression, and greater disability were the most important determinants of dropout of older people. The presence of cardiovascular risk factors was not associated with dropout but was associated with nonadherence. Being overweight was a risk factor for nonadherence, whereas people with high blood pressure or a low level of physical exercise adhered better to the intervention. The association between poorer cognitive function and symptoms of depression and dropout was stronger in the control group than in the intervention group, and vice versa for increased disability. In a large dementia prevention trial with 6-year follow-up, dropout was associated with older age, poorer cognitive function, symptoms of depression, and disability at baseline. These findings can help to guide the design of future dementia prevention trials in older adults. The associations found between cardiovascular risk factors and nonadherence need to be confirmed in other older populations receiving cardiovascular prevention interventions
Olivares, David; Deshpande, Varun K.; Shi, Ying; Lahiri, Debomoy K.; Greig, Nigel H.; Rogers, Jack T.; Huang, Xudong
2016-01-01
Memantine, a partial antagonist of N-methyl-D-aspartate receptor (NMDAR), approved for moderate to severe Alzheimer’s disease (AD) treatment within the US and Europe under brand name Namenda (Forest), Axura and Akatinol (Merz), and Ebixa and Abixa (Lundbeck), may have potential in alleviating additional neurological conditions, such as vascular dementia (VD) and Parkinson’s disease (PD). In various animal models, memantine has been reported to be a neuroprotective agent that positively impacts both neurodegenerative and vascular processes. While excessive levels of glutamate result in neurotoxicity, in part through the over-activation of NMDARs, memantine—as a partial NMDAR antagonist, blocks the NMDA glutamate receptors to normalize the glutamatergic system and ameliorate cognitive and memory deficits. The key to memantine’s therapeutic action lies in its uncompetitive binding to the NMDAR through which low affinity and rapid off-rate kinetics of memantine at the level of the NMDAR-channel preserves the physiological function of the receptor, underpinning memantine’s tolerability and low adverse event profile. As the biochemical pathways evoked by NMDAR antagonism also play a role in PD and since no other drug is sufficiently effective to substitute for the first-line treatment of L-dopa despite its side effects, memantine may be useful in PD treatment with possibly fewer side effects. In spite of the relative modest nature of its adverse effects, memantine has been shown to provide only a moderate decrease in clinical deterioration in AD and VD, and hence efforts are being undertaken in the design of new and more potent memantine-based drugs to hopefully provide greater efficacy. PMID:21875407
Anstey, Kaarin J; Ashby-Mitchell, Kimberly; Peters, Ruth
2017-01-01
Cohort studies have reported that midlife high total serum cholesterol (TC) is associated with increased risk of Alzheimer's disease (AD) in late-life but findings have been based on few studies and previous reviews have been limited by a lack of compatible data. We synthesized all high quality data from cohort studies reporting on the association between total serum cholesterol measured and late-life cognitive outcomes including Alzheimer's disease (AD), vascular dementia (VaD), any dementia, mild cognitive impairment (MCI), and cognitive decline. The literature was searched up to October 2016 using a registered protocol. Thirty-four articles meeting study criteria were identified. Seventeen studies published from 1996 to 2014, including 23,338 participants were included in meta-analyses. Relative risk of developing AD for adults with high TC in midlife was 2.14 (95% CI 1.33-3.44) compared with normal cholesterol. Individual studies that could not be pooled also reported high TC in midlife increased the risk of MCI and cognitive decline in late-life. High TC in late-life was not associated with MCI, AD, VaD, any dementia, or cognitive decline. Late-life measured HDL cholesterol and triglycerides were not associated with increased risk of VaD, and HDL was not associated with risk of MCI, AD, or any dementia. There were insufficient data to examine other cholesterol sub-fractions, sex differences, or APOE interactions. Significant gaps in the literature regarding TC and late-life dementia remain. Evidence suggests that high midlife TC increases risk of late-life AD, and may correlate with the onset of AD pathology.
Pain in dementia: prevalence and associated factors: protocol of a multidisciplinary study.
van Kooten, Janine; Delwel, Suzanne; Binnekade, Tarik T; Smalbrugge, Martin; van der Wouden, Johannes C; Perez, Roberto S G M; Rhebergen, Didi; Zuurmond, Wouter W A; Stek, Max L; Lobbezoo, Frank; Hertogh, Cees M P M; Scherder, Erik J A
2015-03-21
Pain is a common problem in people with dementia, however the exact prevalence of pain in dementia subtypes, e.g. Alzheimer's Disease (AD), Vascular Dementia (VaD), Frontotemporal Dementia (FTD) and dementia with Lewy Bodies (DLB), is unknown, as is the relation between pain and the different subtypes of dementia. In this study, the prevalence of pain in people with dementia will be investigated per dementia subtype and the relationship between the various subtypes of dementia and the presence of specific types of pain (i.e. musculoskeletal pain, neuropathic pain and orofacial pain) will be examined. Secondly, associations between various types of pain, cognitive functioning, neuropsychiatric symptoms and quality of life in people with dementia will be examined. A third purpose is to study the value of the assessment of autonomic responses in assessing pain in people with dementia. Finally, the effect of feedback to the attending physician on the presence of pain, based on examination by investigators with backgrounds in neuropsychology, geriatric dentistry and elderly care medicine, will be evaluated. A cross-sectional, partially longitudinal observational study in 400 participants with dementia, aged 60 years and older. Participants will be recruited from an outpatient memory clinic and dementia special care units. All participants will be examined by an elderly care medicine trainee, a dentist with experience in geriatric dentistry, and a neuropsychologist. The primary outcome is presence of pain. Secondary outcomes will include oral health, autonomic responses to pain stimulus, vital sensibility and gnostic sensibility, musculoskeletal examination, cognitive functioning, neuropsychiatric symptoms, and quality of life. This study will help to enhance our knowledge regarding the prevalence of different types of pain in different dementia subtypes i.e. AD, VaD, FTD and DLB. This study also aims to contribute to a better understanding of oral health status in
Validation and diagnostic utility of the dementia rating scale in a mixed dementia population.
McCulloch, Katie; Collins, Robert L; Maestas, Kacey L; LeMaire, Ashley W; Pacheco, Vitor
2014-01-01
The Dementia Severity Rating Scale (DSRS), a previously validated caregiver-based measure assessing dementia severity, was recently revised to improve clarity. Our study aims included: (1) identifying the DSRS factor structure, (2) examining the relation between neuropsychological measures, the Mini-Mental State Examination, and clinical diagnoses with the DSRS, and (3) determining the clinical utility of the DSRS in a mixed clinical sample. A total of 270 veterans were referred to a cognitive disorders clinic at a VA medical center and completed neuropsychological, affective, and cognitive screening measures. Caregivers completed the DSRS. Principal components analysis identified a 2-factor solution. After controlling for age and education, memory and language were related to the Cognitive factor, whereas attention, processing speed, visuospatial processing, and executive functioning were related to both Cognitive and Self-Care factors. Neither factors correlated with depression. The total DSRS score was able to differentiate patients by the Mini-Mental State Examination scores and diagnoses of mild cognitive impairment and dementia (mixed vascular Alzheimer, vascular dementia, and Alzheimer disease). A cut-score >15 was optimal for detecting dementia in a mixed clinical sample (sensitivity=0.41, specificity=0.79), with a posttest probability of 74%. This study suggests that the DSRS improves detection of dementia and requires minimal effort to implement.
Atri, Alireza
2016-01-01
This chapter reviews clinical applications and imaging findings useful in medical practice relating to neurodegenerative cognitive/dementing disorders. The preponderance of evidence and consensus guidelines support an essential role of multitiered neuroimaging in the evaluation and management of neurodegenerative cognitive/dementia syndrome that range in severity from mild impairments to frank dementia. Additionally, imaging features are incorporated in updated clinical and research diagnostic criteria for most dementias, including Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), Frontotemporal Lobar Degenerations/Frontotemporal Dementia (FTD), and Vascular Cognitive Impairment (VCI). Best clinical practices dictate that structural imaging, preferably with magnetic resonance imaging (MRI) when possible and computed tomography when not, be obtained as a first-tier approach during the course of a thorough clinical evaluation to improve diagnostic confidence and assess for nonneurodegenerative treatable conditions that may cause or substantially contribute to cognitive/behavioral symptoms or which may dictate a substantial change in management. These conditions include less common structural (e.g., mass lesions such as tumors and hematomas; normal-pressure hydrocephalus), inflammatory, autoimmune and infectious conditions, and more common comorbid contributing conditions (e.g., vascular cerebral injury causing leukoaraiosis, infarcts, or microhemorrhages) that can produce a mixed dementia syndrome. When, after appropriate clinical, cognitive/neuropsychologic, and structural neuroimaging assessment, a dementia specialist remains in doubt regarding etiology and appropriate management, second-tier imaging with molecular methods, preferably with fluorodexoyglucose positron emission tomography (PET) (or single-photon emission computed tomography if PET is unavailable) can provide more diagnostic specificity (e.g., help differentiate between atypical AD and FTD as
Oztürk, Candan; Ozge, Aynur; Yalin, Osman Ozgür; Yilmaz, I Arda; Delialioglu, Nuran; Yildiz, Cilem; Tesdelen, Bahar; Kudiaki, Cigdem
2007-01-01
In the past years, the possible involvement of inflammation in the pathogenesis of dementia has been the subject of several investigations. However there are restricted data about the profile of the inflammatory and soluble proteins in well evaluated Alzheimer's disease (AD), vascular dementia (VD), mild cognitive impairment (MCI) and healthy controls. There are also no reliable data regarding the relationship between the overlapping protein levels and cognitive or functional decline. We measured levels of IL-1beta, IL-2, IL-6, IL-18, TNF-alpha, beta-Amlyloid 1-40 and alpha1-antichymotrypsin levels in plasma in groups of total 82 subjects with AD, MCI, VD and controls using enzyme-linked immunosorbent assay (ELISA) method. Our study samples showed high levels of proinflammatory cytokine levels (especially IL-18) in all patient groups but only high levels of alpha1-antichymotrypsine in VD patients compared to controls. There is no significant correlation between the laboratory and clinical variables except for a link between IL-1beta and NPI scores of AD. In conclusion, this study yielded evidence of some shared mechanisms underlying AD and VD and thus motivates further studies of inflammatory markers in various types of dementia and MCI.
Al-Qazzaz, Noor Kamal; Ali, Sawal Hamid Bin Mohd; Ahmad, Siti Anom; Islam, Mohd Shabiul; Escudero, Javier
2018-01-01
Stroke survivors are more prone to developing cognitive impairment and dementia. Dementia detection is a challenge for supporting personalized healthcare. This study analyzes the electroencephalogram (EEG) background activity of 5 vascular dementia (VaD) patients, 15 stroke-related patients with mild cognitive impairment (MCI), and 15 control healthy subjects during a working memory (WM) task. The objective of this study is twofold. First, it aims to enhance the discrimination of VaD, stroke-related MCI patients, and control subjects using fuzzy neighborhood preserving analysis with QR-decomposition (FNPAQR); second, it aims to extract and investigate the spectral features that characterize the post-stroke dementia patients compared to the control subjects. Nineteen channels were recorded and analyzed using the independent component analysis and wavelet analysis (ICA-WT) denoising technique. Using ANOVA, linear spectral power including relative powers (RP) and power ratio were calculated to test whether the EEG dominant frequencies were slowed down in VaD and stroke-related MCI patients. Non-linear features including permutation entropy (PerEn) and fractal dimension (FD) were used to test the degree of irregularity and complexity, which was significantly lower in patients with VaD and stroke-related MCI than that in control subjects (ANOVA; p ˂ 0.05). This study is the first to use fuzzy neighborhood preserving analysis with QR-decomposition (FNPAQR) dimensionality reduction technique with EEG background activity of dementia patients. The impairment of post-stroke patients was detected using support vector machine (SVM) and k-nearest neighbors (kNN) classifiers. A comparative study has been performed to check the effectiveness of using FNPAQR dimensionality reduction technique with the SVM and kNN classifiers. FNPAQR with SVM and kNN obtained 91.48 and 89.63% accuracy, respectively, whereas without using the FNPAQR exhibited 70 and 67.78% accuracy for SVM and k
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.
Proton Pump Inhibitors and Risk of Mild Cognitive Impairment and Dementia.
Goldstein, Felicia C; Steenland, Kyle; Zhao, Liping; Wharton, Whitney; Levey, Allan I; Hajjar, Ihab
2017-09-01
To examine the risk associated with the use of proton pump inhibitors (PPIs) of conversion to mild cognitive impairment (MCI), dementia, and specifically Alzheimer's disease (AD). Observational, longitudinal study. Tertiary academic Alzheimer's Disease Centers funded by the National Institute on Aging. Research volunteers aged 50 and older with two to six annual visits; 884 were taking PPIs at every visit, 1,925 took PPIs intermittently, and 7,677 never reported taking PPIs. All had baseline normal cognition or MCI. Multivariable Cox regression analyses evaluated the association between PPI use and annual conversion of baseline normal cognition to MCI or dementia or annual conversion of baseline MCI to dementia, controlling for demographic characteristics, vascular comorbidities, mood, and use of anticholinergics and histamine-2 receptor antagonists. Continuous (always vs never) PPI use was associated with lower risk of decline in cognitive function (hazard ratio (HR) = 0.78, 95% confidence interval (CI) =0.66-0.93, P = .005) and lower risk of conversion to MCI or AD (HR = 0.82, 95% CI = 0.69-0.98, P = .03). Intermittent use was also associated with lower risk of decline in cognitive function (HR = 0.84, 95% CI = 0.76-0.93, P = .001) and risk of conversion to MCI or AD (HR = 0.82, 95% CI = 0.74-0.91, P = .001). This lower risk was found for persons with normal cognition or MCI. Proton pump inhibitors were not associated with greater risk of dementia or of AD, in contrast to recent reports. Study limitations include reliance on self-reported PPI use and lack of dispensing data. Prospective studies are needed to confirm these results to guide empirically based clinical treatment recommendations. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.
Hainsworth, Atticus H; Yeo, Natalie E; Weekman, Erica M; Wilcock, Donna M
2016-01-01
Homocysteine is produced physiologically in all cells, and is present in plasma of healthy individuals (plasma [HCy]: 3–10µM). While rare genetic mutations (CBS, MTHFR) cause severe hyperhomocysteinemia ([HCy]: 100–200µM), mild-moderate hyperhomocysteinemia ([HCy]: 10–100µM) is common in older people, and is an independent risk factor for stroke and cognitive impairment. As B-vitamin supplementation (B6, B12 and folate) has well-validated homocysteine-lowering efficacy, this may be a readily-modifiable risk factor in vascular contributions to cognitive impairment and dementia (VCID). Here we review the biochemical and cellular actions of HCy related to VCID. Neuronal actions of HCy were at concentrations above the clinically-relevant range. Effects of HCy <100 µM were primarily vascular, including myocyte proliferation, vessel wall fibrosis, impaired nitric oxide signalling, superoxide generation and pro-coagulant actions. HCy-lowering clinical trials relevant to VCID are discussed. Extensive clinical and preclinical data support Hcy as a mediator for VCID. In our view further trails of combined B-vitamin supplementation are called for, incorporating lessons from previous trails and from recent experimental work. To maximise likelihood of treatment effect, a future trial should: supply a high-dose, combination supplement (B6, B12 and folate); target the at-risk age range; target cohorts with low baseline B-vitamin status. PMID:26689889
Vascular Factors and Cognitive Dysfunction in Alzheimer Disease.
Pąchalska, Maria; Bidzan, Leszek; Bidzan, Mariola; Góral-Półrola, Jolanta
2015-11-12
The purpose of the present study was to assess the influence of vascular factors on the degree of intensity and rate of progression of cognitive disorders in the course of Alzheimer Disease (AD). The research group consisted of 39 persons, all of whom were diagnosed with AD according to the NINCDS/ADRDA criteria. We divided these patients into 2 subgroups, based on the vascular factors measured by the modified Hachinski Ischemic Scale (Ha-mod): group A, without the vascular component (HA-mod score of 0-1 point), and group B, with the vascular component (a score over 1 point). Cognitive functions were evaluated at baseline and again 2 years later, using the Cognitive Part of the Alzheimer Disease Assessment Scale (ADAS-cog). We found that the patients from subgroup B, with the stronger vascular component, demonstrated the highest intensity of cognitive disorders at baseline, both in terms of the overall ADAS-cog score, and in the subscores for ideational praxis, orientation, spoken language ability, comprehension of spoken language, and word-finding difficulty in spontaneous speech. Another variable which was connected with the intensity of dementia was age. After 2 years, however, the rate of progression of cognitive disorders was not significantly different between the 2 groups. The severity of vascular factors correlates directly with the intensity of cognitive disturbances. At the 2-year follow-up examination, however, no correlation was observed in the research group between greater vascular involvement and more rapid progression of cognitive disorders, as measured by the ADAS-cog scale.
Saul, Anika; Lashley, Tammaryn; Revesz, Tamas; Holton, Janice; Ghiso, Jorge A; Coomaraswamy, Janaky; Wirths, Oliver
2013-05-01
Familial British and familial Danish dementia (FDD) are progressive neurodegenerative disorders characterized by cerebral deposition of the amyloidogenic peptides ABri and ADan, respectively. These amyloid peptides start with an N-terminal glutamate residue, which can be posttranslationally converted into a pyroglutamate (pGlu) modified form, a mechanism which has been extensively described to be relevant for amyloid-beta (Aβ) peptides in Alzheimer's disease. Like pGlu-Aβ peptides, pGlu-ABri peptides have an increased aggregation propensity and show higher toxicity on human neuroblastoma cells as their nonmodified counterparts. We have generated novel N-terminal specific antibodies detecting the pGlu-modified forms of ABri and ADan peptides. With these antibodies we were able to identify abundant extracellular amyloid plaques, vascular, and parenchymal deposits in human familial British dementia and FDD brain tissue, and in a mouse model for FDD. Double-stainings using C-terminal specific antibodies in human samples revealed that highly aggregated pGlu-ABri and pGlu-ADan peptides are mainly present in plaque cores and central vascular deposits, leading to the assumption that these peptides have seeding properties. Furthermore, in an FDD-mouse model ADan peptides were detected in presynaptic terminals of the hippocampus where they might contribute to impaired synaptic transmission. These similarities of ABri and ADan to Aβ in Alzheimer's disease suggest that the posttranslational pGlu-modification of amyloid peptides might represent a general pathological mechanism leading to increased aggregation and toxicity in these forms of degenerative dementias. Copyright © 2013 Elsevier Inc. All rights reserved.
Non-Alzheimer's contributions to dementia and cognitive resilience in The 90+ Study.
Robinson, John L; Corrada, Maria M; Kovacs, Gabor G; Dominique, Myrna; Caswell, Carrie; Xie, Sharon X; Lee, Virginia M-Y; Kawas, Claudia H; Trojanowski, John Q
2018-06-18
The diagnosis of Alzheimer's disease (AD) in the oldest-old is complicated by the increasing prevalence of age-related neurofibrillary tangles, plaques and non-AD pathologies such as cerebrovascular disease (CVD), hippocampal sclerosis (HS), aging-related tau astrogliopathy (ARTAG), as well as TDP-43 and Lewy pathology. The contribution of these non-AD pathologies to dementia and cognitive resilience is unclear. We assessed the level of AD neuropathologic change (ADNPC) and non-AD pathology in 185 participants enrolled in The 90+ Study with available cognitive assessments and brain tissue. Logistic regression models-adjusting for age, sex and education-determined the association between each pathology and dementia or between subgroups. 53% had dementia, primarily AD or mixed AD; 23% had cognitive impairment without dementia (CIND); 23% were not impaired. Both AD and non-AD pathology was prevalent. 100% had tangles, 81% had plaques, and both tangles and plaques associated with dementia. ARTAG distributed across limbic (70%), brainstem (39%) and cortical regions (24%). 49% had possible CVD and 26% had definite CVD, while HS was noted in 15%. Cortical ARTAG, CVD and HS were each associated with dementia, but limbic and brainstem ARTAGs were not. TDP-43 and Lewy pathologies were found in 36 and 17% and both associated with dementia. No pathology distinguished CIND and the not impaired. By NIA-AA criteria and dementia status, the cohort was subdivided into four groups: those with minimal ADNPC included the not dementia (ND) and Not AD dementia groups; and those with significant ADNPC included the Resilient without dementia and AD dementia groups. Compared to the ND group, the Not AD dementia group had more HS, cortical ARTAG, TDP-43, and Lewy pathology. Compared to the AD dementia group, the Resilient group had less CVD, no HS and less cortical ARTAG, TDP-43 and Lewy pathology. Our findings imply that reductions in non-AD pathologies including CVD contribute to
Association between air pollutants and dementia risk in the elderly.
Wu, Yun-Chun; Lin, Yuan-Chien; Yu, Hwa-Lung; Chen, Jen-Hau; Chen, Ta-Fu; Sun, Yu; Wen, Li-Li; Yip, Ping-Keung; Chu, Yi-Min; Chen, Yen-Ching
2015-06-01
The aging rate in Taiwan is the second highest in the world. As the population ages quickly, the prevalence of dementia increases rapidly. There are some studies that have explored the association between air pollution and cognitive decline, but the association between air pollution and dementia has not been directly evaluated. This was a case-control study comprising 249 Alzheimer's disease (AD) patients, 125 vascular dementia (VaD) patients, and 497 controls from three teaching hospitals in northern Taiwan from 2007 to 2010. Data of particulate matter <10 μm in diameter (PM10) and ozone were obtained from the Taiwan Environmental Protection Administration for 12 and 14 years, respectively. Blood samples were collected to determine the apolipoprotein E (APOE) ɛ4 haplotype. Bayesian maximum entropy was used to estimate the individual exposure level of air pollutants, which was then tertiled for analysis. Conditional logistic regression models were used to estimate adjusted odds ratios (AORs) and 95% confidence intervals between the association of PM10 and ozone exposure with AD and VaD risk. The highest tertile of PM10 (≥49.23 μg/m(3)) or ozone (≥21.56 ppb) exposure was associated with increased AD risk (highest vs. lowest tertile of PM10: AOR = 4.17; highest vs. lowest tertile of ozone: AOR = 2.00). Similar finding was observed for VaD. The association with AD and VaD risk remained for the highest tertile PM10 exposure after stratification by APOE ɛ4 status and gender. Long-term exposure to the highest tertile of PM10 or ozone was significantly associated with an increased risk of AD and VaD.
Bonanni, L; Bontempo, G; Borrelli, I; Bifolchetti, S; Buongarzone, M P; Carlesi, N; Carolei, A; Ciccocioppo, F; Colangelo, U; Colonna, G; Desiderio, M; Ferretti, S; Fiorelli, L; D'Alessio, O; D'Amico, A; D'Amico, M C; De Lucia, R; Del Re, L; Di Blasio, F; Di Giacomo, R; Di Iorio, A; Di Santo, E; Di Giuseppe, M; Felice, N; Litterio, P; Gabriele, A; Mancino, E; Manzoli, L; Maruotti, V; Mearelli, S; Molino, G; Monaco, D; Nuccetelli, F; Onofrj, M; Perfetti, B; Sacchet, C; Sensi, F; Sensi, S; Sucapane, P; Taylor, J P; Thomas, A; Viola, P; Viola, S; Zito, M; Zhuzhuni, H
2013-06-01
Ascertainment bias (AB) indicates a bias of an evaluation centre in estimating the prevalence/incidence of a disease due to the specific expertise of the centre. The aim of our study was to evaluate classification of different types of dementia in new cases appearing in secondary and tertiary centres, in order to evidence possible occurrence of AB in the various (secondary to tertiary) dementia centres. To assess the mechanism of AB, the rates of new cases of the different forms of dementia reported by different centres were compared. The centres involved in the study were 11 hospital-based centres including a tertiary centre, located in the University Department of Clinical Neurology. The tertiary centre is endowed with state-of-the-art diagnostic facilities and its scientific production is prominently focused on dementia with Lewy bodies (DLB) thus suggesting the possible occurrence of a bias. Four main categories of dementia were identified: Alzheimer's disease (AD), DLB, fronto-temporal dementia (FTD), vascular dementia (VaD), with other forms in a category apart. The classification rate of new cases of dementia in the tertiary centre was compared with rates reported by secondary centres and rates of recoding were calculated during a follow-up of 2 years. The study classified 2,042 newly diagnosed cases of dementia in a population of 1,370,000 inhabitants of which 315,000 were older than 65. AD was categorized in 48-52 % of cases, DLB in 25-28 %, FTD in 2-4 % and VaD in 17-28 %. During the 2-year follow-up the diagnosis was re-classified in 40 patients (3 %). The rate of recoding was 5 % in the tertiary centre, 2-8 % in referrals from secondary to tertiary centre, 2-10 % in recodings performed in secondary centres and addressed to tertiary centre. Recoding or percentages of new cases of AD or DLB were not different in the comparison between secondary or between secondary and tertiary centres. FTD and VaD were instead significantly recoded. The results
Serum homocysteine levels in patients with probable vascular dementia.
Alajbegović, Salem; Lepara, Orhan; Hadžović-Džuvo, Almira; Mutevelić-Turković, Alma; Alajbegović, Lejla; Zaćiragić, Asija; Avdagić, Nesina; Valjevac, Amina; Babić, Nermina; Dervišević, Amela
2017-08-01
Aim To investigate total homocysteine (tHcy) serum concentration in patients with probable vascular dementia (VD) and in agematched controls, as well as to determine an association between tHcy serum concentration and cognitive impairment in patients with probable VD. Methods Serum concentration of tHcy was determined by the Fluorescence Polarization Immunoassay on the AxSYM System. Cognitive impairment was tested by the Mini Mental Status Examination (MMSE) score. Body mass index (BMI) was calculated for each subject included in the study. Results Age, systolic, diastolic blood pressure and BMI did not differ significantly between the two groups. Mean serum tHcy concentration in the control group of subjects was 13.35 µmol/L, while in patients with probable VD it was significantly higher, 19.45 µmol/L (p=0.002). A negative but insignificant association between serum tHcy concentration and cognitive impairment in patients with probable VD was found. Conclusion Increased tHcy concentration in patients with probable VD suggests the possible independent role of Hcy in the pathogenesis of VD. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sharma, Bhupesh, E-mail: drbhupeshresearch@gmail.com; Sharma, P.M.
Arsenic toxicity has been reported to damage all the major organs including the brain and vasculature. Dementia including Alzheimer's disease (AD) and vascular dementia (VaD) are posing greater risk to the world population as it is now increasing at a faster rate. We have investigated the role of sodium butyrate, a selective histone deacetylase (HDAC) inhibitor and aminoguanidine, a selective inducible nitric oxide synthase (iNOS) inhibitor in pharmacological interdiction of arsenic toxicity induced vascular endothelial dysfunction and dementia in rats. Arsenic toxicity was done by administering arsenic drinking water to rats. Morris water-maze (MWM) test was used for assessment ofmore » learning and memory. Endothelial function was assessed using student physiograph. Oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and nitric oxide levels (serum nitrite/nitrate) were also measured. Arsenic treated rats have shown impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate and brain GSH levels along with increase in serum and brain TBARS. Sodium butyrate as well as aminoguanidine significantly convalesce arsenic induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that arsenic induces endothelial dysfunction and dementia, whereas, sodium butyrate, a HDAC inhibitor as well as aminoguanidine, a selective iNOS inhibitor may be considered as potential agents for the management of arsenic induced endothelial dysfunction and dementia. - Highlights: • As has induced endothelial dysfunction (Edf) and vascular dementia (VaD). • As has increased oxidative stress, AChE activity and decreased serum NO. • Inhibitors of HDAC and iNOS have attenuated As induced Edf and VaD. • Both the inhibitors have attenuated As induced biochemical changes. • Inhibitor of HDAC and iNOS has shown good
Öztürk, Candan; Özge, Aynur; Yalın, Osman Özgür; Yılmaz, İ. Arda; Delialioglu, Nuran; Yıldız, Çilem; Tesdelen, Bahar; Kudiaki, Cigdem
2007-01-01
In the past years, the possible involvement of inflammation in the pathogenesis of dementia has been the subject of several investigations. However there are restricted data about the profile of the inflammatory and soluble proteins in well evaluated Alzheimer’s disease (AD), vascular dementia (VD), mild cognitive impairment (MCI) and healthy controls. There are also no reliable data regarding the relationship between the overlapping protein levels and cognitive or functional decline. We measured levels of IL-1β, IL-2, IL-6, IL-18, TNF-α, β-Amlyloid 1–40 and α1-antichymotrypsin levels in plasma in groups of total 82 subjects with AD, MCI, VD and controls using enzyme-linked immunosorbent assay (ELISA) method. Our study samples showed high levels of proinflammatory cytokine levels (especially IL-18) in all patient groups but only high levels of α1-antichymotrypsine in VD patients compared to controls. There is no significant correlation between the laboratory and clinical variables except for a link between IL-1β and NPI scores of AD. In conclusion, this study yielded evidence of some shared mechanisms underlying AD and VD and thus motivates further studies of inflammatory markers in various types of dementia and MCI. PMID:18430978
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.
Depressive symptoms and risk of dementia
Saczynski, J.S.; Beiser, A.; Seshadri, S.; Auerbach, S.; Wolf, P.A.; Au, R.
2010-01-01
Objectives: Depression may be associated with an increased risk for dementia, although results from population-based samples have been inconsistent. We examined the association between depressive symptoms and incident dementia over a 17-year follow-up period. Methods: In 949 Framingham original cohort participants (63.6% women, mean age = 79), depressive symptoms were assessed at baseline (1990-1994) using the 60-point Center for Epidemiologic Studies Depression Scale (CES-D). A cutpoint of ≥16 was used to define depression, which was present in 13.2% of the sample. Cox proportional hazards models adjusting for age, sex, education, homocysteine, and APOE ε4 examined the association between baseline depressive symptoms and the risk of dementia and Alzheimer disease (AD). Results: During the 17-year follow-up period, 164 participants developed dementia; 136 of these cases were AD. A total of 21.6% of participants who were depressed at baseline developed dementia compared with 16.6% of those who were not depressed. Depressed participants (CES-D ≥16) had more than a 50% increased risk for dementia (hazard ratio [HR] 1.72, 95% confidence interval [CI] 1.04-2.84, p = 0.035) and AD (HR 1.76, 95% CI 1.03-3.01, p = 0.039). Results were similar when we included subjects taking antidepressant medications as depressed. For each 10-point increase on the CES-D, there was significant increase in the risk of dementia (HR 1.46, 95% CI 1.18-1.79, p < 0.001) and AD (HR 1.39, 95% CI 1.11-1.75, p = 0.005). Results were similar when we excluded persons with possible mild cognitive impairment. Conclusions: Depression is associated with an increased risk of dementia and AD in older men and women over 17 years of follow-up. GLOSSARY AD = Alzheimer disease; CDR = Clinical Dementia Rating; CES-D = Center for Epidemiologic Studies Depression Scale; CI = confidence interval; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; HR = hazard ratio; MCI = mild
Randomized, Placebo-Controlled, Clinical Trial of Donepezil in Vascular Dementia
Román, Gustavo C.; Salloway, Stephen; Black, Sandra E.; Royall, Donald R.; DeCarli, Charles; Weiner, Michael W.; Moline, Margaret; Kumar, Dinesh; Schindler, Rachel; Posner, Holly
2010-01-01
Background and Purpose We sought to assess the efficacy and safety of donepezil in patients with vascular dementia (VaD) fulfilling National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria. Methods This international, multicenter, 24-week trial was conducted from March 2003 to August 2005. Patients (N=974; mean age, 73.0 years) with probable or possible VaD were randomized 2:1 to receive donepezil 5 mg/d or placebo. Coprimary outcome measures were scores on the Vascular-Alzheimer Disease Assessment Scale–Cognitive Subscale and Clinician’s Interview–Based Impression of Change, plus carer interview. Analyses were performed for the intent-to-treat population with the last-observation-carried-forward method. Results Compared with placebo, donepezil-treated patients showed significant improvement from baseline to end point on the Vascular-Alzheimer Disease Assessment Scale–Cognitive Subscale (least-squares mean difference, −1.156; 95% CI, −1.98 to −0.33; P<0.01) but not on the Clinician’s Interview–Based Impression of Change, plus carer interview. Patients with hippocampal atrophy who were treated with donepezil demonstrated stable cognition versus a decline in the placebo-treated group; in those without atrophy, cognition improved with donepezil versus relative stability with placebo. Results on secondary efficacy measures were inconsistent. The incidence of adverse events was similar across groups. Eleven deaths occurred in the donepezil group (1.7%), similar to rates previously reported for donepezil trials in VaD, whereas no deaths occurred in the placebo group. Conclusions Patients treated with donepezil 5 mg/d demonstrated significant improvement in cognitive, but not global, function. Donepezil was relatively well tolerated; adverse events were consistent with current labeling. Mortality in the placebo group was unexpectedly low. The differential
León-Salas, B; Logsdon, R G; Olazarán, J; Martínez-Martín, P; The Msu-Adru
2011-08-01
To evaluate the psychometric attributes of the Spanish version of the Quality of Life-Alzheimer's Disease Scale (QoL-AD) in institutionalized patients and family caregivers in Spain. 101 patients (88.1% women; mean age, 83.2 ± 6.3) with Alzheimer's disease (AD) (n = 82) and mixed dementia (n = 19) and their closest family caregivers. Patient-related variables included severity of dementia, cognitive status, perceived general health, quality of life, behavior, apathy, depression, and functional status. QoL-AD acceptability, reliability, and construct validity were analyzed. The mean Mini-Mental State Examination (MMSE) score was 7.2 ± 6.1 and Global Deterioration Scale was: stage four (4%); five (21.2%); six (34.3%); and seven (40.4%). Both, QoL-AD patient version (QoL-ADp) (n = 40; MMSE = 12.0 ± 4.5) and QoL-AD caregiver version (QoL-ADc) (n = 101) lacked significant floor and ceiling effects and the Cronbach α index was 0.90 and 0.86, respectively. The corrected item-total correlation was 0.11-0.68 (QoL-ADc) and 0.28-0.84 (QoL-ADp). Stability was satisfactory for QoL-ADp (intraclass correlation coefficient [ICC]=0.83) but low for QoL-ADc (ICC = 0.51); the standard error of measurement was 2.72 and 4.69. Construct validity was moderate/high for QoL-ADc (QUALID=-0.43; EQ-5D = 0.65), but lower for QoL-ADp. No significant correlations were observed between QoL-ADp and patient variables or QoL-ADc. A low to high association (r = 0.18-0.55) was obtained between QoL-ADc and patient-related measures of neuropsychiatric, function, and cognitive status. Differences in their psychometric attributes, and discrepancy between them, were found for QoL-ADp and QoL-ADc. In patients with AD and advanced dementia, the QoL perceived by the patient could be based on a construct that is different from the traditional QoL construct.
Areosa, Sastre A; Sherriff, F
2003-01-01
Alzheimer's disease, vascular and mixed dementia are the three commonest forms of dementia affecting older people. There is evidence that the excitatory activity of L-glutamate plays a role in the pathogenesis of Alzheimer's disease and in the damage from an ischaemic stroke. A low affinity antagonist to N-Methyl-D-aspartate (NMDA) type receptors, such as memantine, may prevent excitatory amino acid neurotoxicity without interfering with the physiological actions of glutamate required for memory and learning. To determine the clinical efficacy and safety of memantine for people with Alzheimer's disease, or vascular or mixed dementia. Trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 15 April 2003 using the terms: memantin*, D-145, DMAA, DRG-0267. All major health care databases and trial databases within the scope of the group are searched regularly to keep this Register up to date. Double-blind, parallel group, placebo-controlled, randomized and unconfounded trials in which memantine was administered to people with dementia. Data were extracted, pooled where possible, and weighted mean differences, standardized mean differences or odds ratios were estimated. Intention-to-treat (ITT) and observed cases (OC) analyses are reported, where data were available. Effect of memantine in patients with moderate to severe Alzheimer's disease: analysis of the change from baseline at 28 weeks gave statistically significant results in favour of memantine for 20 mg/day on cognition (MD: 6.1. 95% CI 2.99 to 9.21, P=0.0001) activities of daily living (MD 2.10, 95% CI 0.46 to 3.74, p=0.01) and in the global clinical impression of change measured by the CIBIC-Plus at 28 weeks (MD -0.30, 95% CI -0.58 to -0.02, p=0.04), in all cases the analysis was the ITT-LOCF population (Reisberg 2000). There were no significant differences between memantine and placebo for the number of drop-outs and total number of adverse
Thyroid function and the risk of dementia: The Rotterdam Study.
Chaker, Layal; Wolters, Frank J; Bos, Daniel; Korevaar, Tim I M; Hofman, Albert; van der Lugt, Aad; Koudstaal, Peter J; Franco, Oscar H; Dehghan, Abbas; Vernooij, Meike W; Peeters, Robin P; Ikram, M Arfan
2016-10-18
To study the role of thyroid function in dementia, cognitive function, and subclinical vascular brain disease with MRI. Analyses were performed within the Rotterdam Study (baseline 1997), a prospective, population-based cohort. We evaluated the association of thyroid-stimulating hormone (TSH) and free thyroxine with incident dementia using Cox models adjusted for age, sex, cardiovascular risk factors, and education. Absolute risks were calculated accounting for death as a competing risk factor. Associations of thyroid function with cognitive test scores and subclinical vascular brain disease (white matter lesions, lacunes, and microbleeds) were assessed with linear or logistic regression. Additionally, we stratified by sex and restricted analyses to normal thyroid function. We included 9,446 participants with a mean age of 65 years. During follow-up (mean 8.0 years), 601 participants had developed dementia. Higher TSH was associated with lower dementia risk in both the full and normal ranges of thyroid function (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.83-0.98; and HR 0.76, 95% CI 0.64-0.91, respectively). This association was independent of cardiovascular risk factors. Dementia risk was higher in individuals with higher free thyroxine (HR 1.04, 95% CI 1.01-1.07). Absolute 10-year dementia risk decreased from 15% to 10% with higher TSH in older women. Higher TSH was associated with better global cognitive scores (p = 0.021). Thyroid function was not related to subclinical vascular brain disease as indicated by MRI. High and high-normal thyroid function is associated with increased dementia risk. Thyroid function is not related to vascular brain disease as assessed by MRI, suggesting a role for thyroid hormone in nonvascular pathways leading to dementia. © 2016 American Academy of Neurology.
Fang, Yanan; Sui, Rubo
2016-01-01
Vascular dementia (VD) is the most frequent psychiatric complication of stroke, and is often difficult to treat. Incidence rate of vascular cognition impairment is still 70% after stroke in one year (Sui R et al.2011). Stroke patients with VD suffer from a higher mortality rate and have worse functional outcomes and quality of life. However, despite the extensive literatures on this topic, there is no agreement on the causal mechanisms and effective therapy for VD. The objective of this study is to examine if electroacupuncture at the Wangu acupoint (GB 12), whose position is similar to the cerebellar fastigial nucleus, could reduce inflammatory cytokines in the hippocampus of rats with vascular dementia (VD). The 54 healthy, male, Sprague-Dawley (SD) rats, 9 months old, and of clean grade (300-450) g, were randomly divided into three groups: sham surgery group, VD group and electro-acupuncture group. The ethology scores of VD rats were evaluated and the mRNA expressions of inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the hippocampus were assessed and the hippocampal tissues were observed by hematoxylin-eosin staining. Compared with the VD group, in the electroacupuncture group, the rats' learning ability improved significantly and the mRNA expression of TNF-α, IL-6 and IL-1β decreased. Simultaneously, the damage extent of nerve cells in the hippocampal tissues decreased, with their morphology recovered to nearly normal. Electro-acupuncture at the Wangu acupoint can decrease the levels of inflammatory cytokines in the hippocampus, reduce the damage extent of nerve cells in the hippocampus, and thus provide a new neuroprotective method in VD.
Clinical utility of FDG-PET for the differential diagnosis among the main forms of dementia.
Nestor, Peter J; Altomare, Daniele; Festari, Cristina; Drzezga, Alexander; Rivolta, Jasmine; Walker, Zuzana; Bouwman, Femke; Orini, Stefania; Law, Ian; Agosta, Federica; Arbizu, Javier; Boccardi, Marina; Nobili, Flavio; Frisoni, Giovanni Battista
2018-05-07
To assess the clinical utility of FDG-PET as a diagnostic aid for differentiating Alzheimer's disease (AD; both typical and atypical forms), dementia with Lewy bodies (DLB), frontotemporal lobar degeneration (FTLD), vascular dementia (VaD) and non-degenerative pseudodementia. A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted on six different diagnostic scenarios using the Delphi method. The level of empirical study evidence for the use of FDG-PET was considered good for the discrimination of DLB and AD; fair for discriminating FTLD from AD; poor for atypical AD; and lacking for discriminating DLB from FTLD, AD from VaD, and for pseudodementia. Delphi voting led to consensus in all scenarios within two iterations. Panellists supported the use of FDG-PET for all PICOs-including those where study evidence was poor or lacking-based on its negative predictive value and on the assistance it provides when typical patterns of hypometabolism for a given diagnosis are observed. Although there is an overall lack of evidence on which to base strong recommendations, it was generally concluded that FDG-PET has a diagnostic role in all scenarios. Prospective studies targeting diagnostically uncertain patients for assessing the added value of FDG-PET would be highly desirable.
Bednarska-Makaruk, Małgorzata Ewa; Krzywkowski, Tomasz; Graban, Alla; Lipczyńska-Łojkowska, Wanda; Bochyńska, Anna; Rodo, Maria; Wehr, Hanna; Ryglewicz, Danuta Krystyna
2013-01-01
Paraoxonase 1 (PON1) activity was determined using phenylacetate as substrate (arylesterase activity) in 304 individuals with dementia--136 recognised as probable Alzheimer's disease (AD), 64 as dementia of vascular origin (VaD) and 104 as mixed dementia (MD) and in 129 persons without symptoms of dementia and in a good general health. -108C>T polymorphism in the PON1 gene promoter and p.Q192R polymorphism in the coding region were identified. PON1 activity was significantly lower in demented patients as compared with controls particularly in dementia of a neurodegenerative character (AD and MD). The prevalence of PON1-108T allele carriers was significantly higher in the AD group than in controls. The frequencies of the p.Q192R genotypes did not differ significantly between the investigated groups. An association of the rare T-R haplotype with dementia, particularly with dementia of the neurodegenerative type, was found. Multivariate regression analysis showed a significant association of PON1 activity with PON1 -108C>T and p.Q192R polymorphisms. The influence not only of promoter -108C>T, but also of p.Q192R polymorphism on PON1 arylesterase activity was observed. One has to admit that this kind of polymorphism does not preclude interference with the enzyme activity. It could be concluded that the PON1 gene promoter polymorphism plays an additional role in Alzheimer's disease development. It seems however that PON1 activity has a dominating influence on the dementia risk.
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.
Free and Cued Selective Reminding Identifies Very Mild Dementia in Primary Care
Grober, Ellen; Sanders, Amy E.; Hall, Charles; Lipton, Richard B.
2010-01-01
The Free and Cued Selective Reminding Test (FCSRT) is used widely to identify very mild dementia; three alternative scoring procedures have been proposed based on free recall, total recall, and cue efficiency. We compared the predictive validity of these scoring procedures for the identification of very mild prevalent dementia (CDR=0.5), of incident dementia and for distinguishing AD and nonAD dementias. We tested 244 elderly African American and Caucasian primary care patients at 18 month intervals using a screening neuropsychological battery that included the FCSRT and a comprehensive diagnostic neuropsychological battery. Median follow-up was 2.6 years. Dementia diagnoses were assigned using standard criteria without access to the results of the screening battery. There were 50 prevalent and 28 incident dementia cases. At scores selected to provide specificities of 90%, free recall was more sensitive to incident and prevalent dementia than the other two measures. Patients with impaired free recall were 15 times more likely to have a prevalent dementia and their risk of future dementia was four times higher than patients with intact free recall. Neither race nor education affected prediction though older patients were at increased risk of future dementia. Total recall was more impaired in AD dementia than in nonAD dementias. The results indicate that using the FCSRT, free recall is best measure for detecting prevalent dementia and predicting future dementia. Total recall impairment supports the diagnosis of AD rather than nonAD dementia. PMID:20683186
Spouse with schizophrenia and risk of dementia.
Rohde, Christopher; Agerbo, Esben; Nielsen, Philip Rising
2016-12-01
Increased prevalence of lifestyle risk factors or shared etiology may underlie the association between schizophrenia and the subsequent risk of dementia. We explored the association between having a spouse with schizophrenia and the risk of dementia. We found a positive relationship between having a spouse with schizophrenia and vascular dementia in individuals without a mental disorder themselves but no association between having a spouse with schizophrenia and Alzheimer's dementia. As spouses share environmental risk factors and lifestyle, this might suggest that the excess risk of dementia in probands with schizophrenia could be ascribed to the unhealthy living environment among individuals with schizophrenia.
Li, Tian; Wu, Huangan; Soto-Aguliar, Franscisca; Huang, Li; Li, Wentao; Lao, Lixing; Xu, Shifen
2018-01-19
Vascular cognitive impairment with no dementia (VCIND), manifested mainly as mild impairment of concentration and executive function, is the early phase of vascular dementia (VD). Currently, there is no specific treatment for VCIND. We hypothesize that electrical acupuncture can improve the mental and motor functions of patients with VCIND. Thus, we designed this randomized controlled trial to test this hypothesis by comparing the therapeutic effect of electrical acupuncture versus sham acupuncture in patients with VCIND. In this single-center 3-year study, 120 eligible patients will be recruited and randomly assigned to receive electrical acupuncture treatment (n = 60) or sham acupuncture (n = 60) for 8 consecutive weeks (24 sessions in total), with the same acupoint prescription (DU20, EX-HN3, DU24, DU17, DU26, EX-HN1, HT7, PC6, GB20, SP6). The primary assessment is the Montreal Cognitive Assessment. The secondary assessments are the Modified Barthel Index and Event-Related Potential. All outcomes will be assessed at baseline, endpoint, and follow-up at 8 and 24 weeks after the end of treatment. If the outcome confirms the effectiveness and safety of electrical acupuncture in treating VCIND, this treatment is expected to be promoted in clinical practice to treat such patients. Chinese Clinical Trial Registry identifier: ChiCTR-IIR-17011513 ; Registered on 27 May 2017.
De Reuck, Jacques; Auger, Florent; Durieux, Nicolas; Deramecourt, Vincent; Maurage, Claude-Alain; Cordonnier, Charlotte; Pasquier, Florence; Leys, Didier; Bordet, Regis
2017-01-01
Introduction: Mixed dementia (MixD) refers to a combination of definite Alzheimer's disease (AD) and vascular encephalopathy. The existence of a "pure" type of vascular dementia (VaD) is controversial. There is a need to find magnetic resonance imaging (MRI) characteristics allowing the distinction between VaD and MixD. The present post-mortem 7.0-tesla MRI compares the frequency or severity and the topography of the small cerebrovascular lesions in brains of patients with VaD and with MixD. Material and methods: Based on neuropathological criteria, 14 brains were classified as VaD, 24 as MixD and 11 as controls. Three coronal sections of a cerebral hemisphere and a horizontal section of a cerebellar hemisphere underwent T2 and T2* 7.0-tesla MRI examination. The mean values and topographic distribution of white matter changes (WMCs), lacunar infarcts (LIs), cortical microbleeds (CoMBs) and cortical microinfarcts (CoMIs) were determined and compared between the different groups. Results: Compared to the controls, both VaD and MixD brains had significantly more severe WMCs and increased numbers of CoMBs and CoMIs. Lacunar infarcts predominated only in the VaD cases. On mutual comparison of VaD and MixD brains, CoMBs and CoMIs predominated in the frontal lobe and the cerebellum of VaD, while were mainly present in the occipital lobe of MixD. White matter changes predominated in the temporal lobe of MixD cases. Lacunar infarcts were significantly increased in the corona radiata and putamen of VaD patients. Conclusions: The present post-mortem MRI study shows clear differences in the distribution and the types of cerebrovascular lesions on high-field MRI, confirming that VaD and MixD are different diseases. .
Dementia in MS complicated by coexistent Alzheimer disease
Flanagan, Eoin P.; Knopman, David S.
2014-01-01
Summary Distinguishing dementia due to multiple sclerosis (MS) from that of an accompanying neurodegenerative dementia coexisting with MS has been difficult. The recent introduction of Alzheimer disease (AD) biomarkers of amyloid-β and neuronal degeneration has improved diagnosis of AD premortem. We describe 3 patients with MS with coexisting AD, 1 diagnosed at autopsy before AD biomarkers were available and 2 diagnosed premortem by decreased CSF amyloid-β1-42/tau index, MRI, and 18F-flourodeoxyglucose-PET patterns. AD biomarkers may be of diagnostic value in selected patients with severe dementia and MS. PMID:25110620
Course of neuropsychiatric symptoms in residents with dementia in nursing homes over 2-year period.
Wetzels, Roland B; Zuidema, Sytse U; de Jonghe, Jos F M; Verhey, Frans R J; Koopmans, Raymond T C M
2010-12-01
To determine the course of neuropsychiatric symptoms (NPSs) in nursing home residents with dementia and to determine their variability across diagnosis. Prospective cohort study over 2 years. Fourteen dementia special care units in nine nursing homes in The Netherlands. One hundred seventeen residents with dementia. NPSs were measured using the Neuropsychiatric Inventory-Nursing Home version (NPI-NH). The majority of residents had moderately severe to severe dementia. All but a few residents (97%) showed any NPS, and co-occurrence of NPSs was high. Agitation, irritability, and aberrant motor behavior were the most prevalent over the 2 years. Depression and anxiety as well as NPI total score decreased over time, whereas apathy tended to increase. Agitation and aberrant motor behavior were the most persistent symptoms. In asymptomatic residents, highest incidence rates were found for apathy, aggression/ agitation, irritability, and aberrant motor behavior. Anxiety and apathy were more prevalent in Alzheimer disease (AD) compared with vascular disease (VaD); vice versa, aggression and depression were more prevalent in VaD. Differences in change over time between AD and VaD were found for irritability and disinhibition. This is the first study examining the 2-year course of NPSs in a large group of nursing home residents with dementia. Virtually all residents demonstrated and/or developed NPSs. Although affective symptoms decreased, apathy tended to increase. Agitated behaviors were particularly persistent. Our data may contribute to improve mental healthcare for demented nursing home residents.
Cognition and dementia in older patients with epilepsy
Sen, Arjune; Capelli, Valentina
2018-01-01
Abstract With advances in healthcare and an ageing population, the number of older adults with epilepsy is set to rise substantially across the world. In developed countries the highest incidence of epilepsy is already in people over 65 and, as life expectancy increases, individuals who developed epilepsy at a young age are also living longer. Recent findings show that older persons with epilepsy are more likely to suffer from cognitive dysfunction and that there might be an important bidirectional relationship between epilepsy and dementia. Thus some people with epilepsy may be at a higher risk of developing dementia, while individuals with some forms of dementia, particularly Alzheimer’s disease and vascular dementia, are at significantly higher risk of developing epilepsy. Consistent with this emerging view, epidemiological findings reveal that people with epilepsy and individuals with Alzheimer’s disease share common risk factors. Recent studies in Alzheimer’s disease and late-onset epilepsy also suggest common pathological links mediated by underlying vascular changes and/or tau pathology. Meanwhile electrophysiological and neuroimaging investigations in epilepsy, Alzheimer’s disease, and vascular dementia have focused interest on network level dysfunction, which might be important in mediating cognitive dysfunction across all three of these conditions. In this review we consider whether seizures promote dementia, whether dementia causes seizures, or if common underlying pathophysiological mechanisms cause both. We examine the evidence that cognitive impairment is associated with epilepsy in older people (aged over 65) and the prognosis for patients with epilepsy developing dementia, with a specific emphasis on common mechanisms that might underlie the cognitive deficits observed in epilepsy and Alzheimer’s disease. Our analyses suggest that there is considerable intersection between epilepsy, Alzheimer’s disease and cerebrovascular disease raising
Dementia friendly, dementia capable, and dementia positive: concepts to prepare for the future.
Lin, Shih-Yin; Lewis, Frances Marcus
2015-04-01
With an aging global population, the number of dementia cases is growing exponentially. To address the upcoming dementia crisis, the World Health Organization and Alzheimer's Disease International (2012) collaborated on an extensive report, Dementia: A Public Health Priority. In the United Kingdom, Prime Minster David Cameron initiated a national challenge on dementia, forming 3 dementia challenge champion groups aimed at improving health and care, creating dementia-friendly communities, and promoting dementia research. In the U.S., President Obama signed the National Alzheimer's Project Act, which led to the formation of the Advisory Council on Alzheimer's Research, Care, and Services and the launch of the first National Plan to Address Alzheimer's Disease. The term "dementia capable" was introduced in the 2012 Recommendations of the Public Members of the Advisory Council and has since been adopted in both the recommendations and annual updates of the national plan. This paper will first compare and contrast government usage of the concepts dementia friendly and dementia capable, along with another valuable concept, dementia positive, that was added after reviewing the literature. Finally, a new vision statement for the U.S.' national plan will be proposed and recommendations incorporating these 3 concepts in policy, research, and practice will be made. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
An endothelial link between the benefits of physical exercise in dementia.
Trigiani, Lianne J; Hamel, Edith
2017-08-01
The current absence of a disease-modifying treatment for Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID) highlights the necessity for investigating the benefits of non-pharmacological approaches such as physical exercise (PE). Although evidence exists to support an association between regular PE and higher scores on cognitive function tests, and a slower rate of cognitive decline, there is no clear consensus on the underlying molecular mechanisms of the advantages of PE. This review seeks to summarize the positive effects of PE in human and animal studies while highlighting the vascular link between these benefits. Lifestyle factors such as cardiovascular diseases, metabolic syndrome, and sleep apnea will be addressed in relation to the risk they pose in developing AD and VCID, as will molecular factors known to have an impact on either the initiation or the progression of AD and/or VCID. This will include amyloid-beta clearance, oxidative stress, inflammatory responses, neurogenesis, angiogenesis, glucose metabolism, and white matter integrity. Particularly, this review will address how engaging in PE can counter factors that contribute to disease pathogenesis, and how these alterations are linked to endothelial cell function.
Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans.
Hendrie, Hugh C; Hake, Ann; Lane, Kathleen; Purnell, Christianna; Unverzagt, Frederick; Smith-Gamble, Valerie; Murrell, Jill; Ogunniyi, Adesola; Baiyewu, Olusegun; Callahan, Chris; Saykin, Andrew; Taylor, Stanley; Hall, Kathleen; Gao, Su
2015-08-07
To investigate the association between statin use, incident dementia, and Alzheimer disease (AD) in a prospective elderly African American cohort. Two stage design with a screening interview followed by a comprehensive in-home assessment conducted over an eight-year period. Diagnoses of incident AD and dementia were made by consensus. Statin use was collected at each evaluation. Measurements of low-density lipoprotein cholesterol (LDL), C-reactive protein (CRP) and APOE genotype were obtained from baseline blood samples. Logistic regression models were used to test the association of statin use on incident dementia and AD and its possible association with lipid and CRP levels. Indianapolis, Indiana. From an original cohort of 2629 participants, a subsample of 974 African Americans aged >70 years with normal cognition, at least one follow up evaluation, complete statin information, and biomarker availability were included. Incident dementia and incident AD. After controlling for age at diagnosis, sex, education level, presence of the APOE ε4 allele and history of stroke for the incident dementia model, baseline use of statins was associated with a significantly decreased risk of incident dementia (OR=.44, P=.029) and incident AD (OR=.40, P=.029). The significant effect of statin use on reduced AD risk and trend for dementia risk was found only for those participants who reported consistent use over the observational period (incident AD: P=.034; incident dementia: P=.061). Additional models found no significant interaction between baseline statin use, baseline LDL, or CRP level and incident dementia/AD. Consistent use of statin medications during eight years of follow-up resulted in significantly reduced risk for incident AD and a trend toward reduced risk for incident dementia.
Diagnostic criteria for vascular cognitive disorders: a VASCOG statement.
Sachdev, Perminder; Kalaria, Raj; O'Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan G; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip
2014-01-01
Several sets of diagnostic criteria have been published for vascular dementia since the 1960s. The continuing ambiguity in vascular dementia definition warrants a critical reexamination. Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the fifth revision of Diagnostic and Statistical Manual (DSM-5) Task Force. Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent cooccurrence of Alzheimer disease pathology emphasized. The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathologic validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved.
Alzheimer's Disease-Related Dementias Summit 2016: National research priorities.
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.
Financial and Health Literacy Predict Incident Alzheimer's Disease Dementia and Pathology.
Yu, Lei; Wilson, Robert S; Schneider, Julie A; Bennett, David A; Boyle, Patricia A
2017-01-01
Domain specific literacy is a multidimensional construct that requires multiple resources including cognitive and non-cognitive factors. We test the hypothesis that domain specific literacy is associated with Alzheimer's disease (AD) dementia and AD pathology after controlling for cognition. Participants were community-based older persons who completed a baseline literacy assessment, underwent annual clinical evaluations for up to 8 years, and agreed to organ donation after death. Financial and health literacy was measured using 32 questions and cognition was measured using 19 tests. Annual diagnosis of AD dementia followed standard criteria. AD pathology was examined postmortem by quantifying plaques and tangles. Cox models examined the association of literacy with incident AD dementia. Performance of model prediction for incident AD dementia was assessed using indices for integrated discrimination improvement and continuous net reclassification improvement. Linear regression models examined the independent association of literacy with AD pathology in autopsied participants. All 805 participants were free of dementia at baseline and 102 (12.7%) developed AD dementia during the follow-up. Lower literacy was associated with higher risk for incident AD dementia (p < 0.001), and the association persisted after controlling for cognition (hazard ratio = 1.50, p = 0.004). The model including the literacy measure had better predictive performance than the one with demographics and cognition only. Lower literacy also was associated with higher burden of AD pathology after controlling for cognition (β= 0.07, p = 0.035). Literacy predicts incident AD dementia and AD pathology in community-dwelling older persons, and the association is independent of traditional measures of cognition.
Mixed dementia: A review of the evidence.
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.
Social relationships and risk of dementia: a population-based study.
Sörman, Daniel Eriksson; Rönnlund, Michael; Sundström, Anna; Adolfsson, Rolf; Nilsson, Lars-Göran
2015-08-01
The objective was to examine whether aspects of social relationships in old age are associated with all-cause dementia and Alzheimer's disease (AD). We studied 1,715 older adults (≥ 65 years) who were dementia-free at baseline over a period of up to 16 years. Data on living status, contact/visit frequency, satisfaction with contact frequency, and having/not having a close friend were analyzed using Cox proportional hazards regressions with all-cause dementia or AD as the dependent variable. To control for reverse causality and to identify potential long-term effects, we additionally performed analyses with delayed entry. We identified 373 incident cases of dementia (207 with AD) during follow-up. The variable visiting/visits from friends was associated with reduced risk of all-cause dementia. Further, a higher value on the relationships index (sum of all variables) was associated with reduced risk of all-cause dementia and AD. However, in analyses with delayed entry, restricted to participants with a survival time of three years or more, none of the social relationship variables was associated with all-cause dementia or AD. The results indicate that certain aspects of social relationships are associated with incident dementia or AD, but also that these associations may reflect reverse causality. Future studies aimed at identifying other factors of a person's social life that may have the potential to postpone dementia should consider the effects of reverse causality.
Bauer, J; Stadtmüller, G; Qualmann, J; Bauer, H
1995-01-01
We analyzed the premorbid biographies of 21 patients with Alzheimer's disease for possible common features. Eleven age-matched patients suffering from vascular dementia served as a control group. The observations from our qualitative study indicate that persons with a conflict-avoiding, submissive, premorbid personality predominate among Alzheimer patients. Persons who later became Alzheimer patients tended to leave important daily-life decisions to their partners (or other persons of reference). Prior to the onset of the very first neuropsychological deficits, persons who later became Alzheimer patients were found to stay in a lasting situation in which they were subject to a treatment that could be designated as "caring tutelage." Subsequently, most patients became subject to an increasingly patronizing and restricting treatment. Further elements that were frequently found as part of the premorbid development were physical or psychological burden, loss of social contacts, and loss of motivation. In contrast, assertive and dominant premorbid traits predominated in the group of vascular patients. The premorbid biographical situation of persons who later became vascular patients was characterized by a loss of the control which these persons had hitherto exerted over partners, their families, or the situation at their working place. We advance the hypothesis that in Alzheimer's disease the described psychological phenomena are part of a preclinical process, during which biological, psychological, and social factors interact, finally joining into the clinical stage of the disease. Possibilities for psychotherapeutic interventions are discussed.
Appetite and Weight Loss Symptoms in Late-Life Depression Predict Dementia Outcomes.
Saha, Sayoni; Hatch, Daniel J; Hayden, Kathleen M; Steffens, David C; Potter, Guy G
2016-10-01
Identify depression symptoms during active late-life depression (LLD) that predict conversion to dementia. The authors followed a cohort of 290 participants from the Neurocognitive Outcomes of Depression in the Elderly study. All participants were actively depressed and cognitively normal at enrollment. Depression symptom factors were derived from prior factor analysis: anhedonia and sadness, suicidality and guilt, appetite and weight loss, sleep disturbance, and anxiety and tension. Cox regression analysis modeled time to Alzheimer disease (AD) and non-AD dementia onset on depression symptom factors, along with age, education, sex, and race. Significant dementia predictors were tested for interaction with age at depression onset. Higher scores on the appetite and weight loss symptom factor were associated with an increased hazard of both AD and non-AD dementia. This factor was moderated by age at first depression onset, such that higher scores were associated with higher risk of non-AD dementia when depression first occurred earlier in life. Other depression symptom factors and overall depression severity were not related to risk of AD or non-AD dementia. Results suggest greater appetite/weight loss symptoms in active episodes of LLD are associated with increased likelihood of AD and non-AD dementia, but possibly via different pathways moderated by age at first depression onset. Results may help clinicians identify individuals with LLD at higher risk of developing AD and non-AD dementia and design interventions that reduce this risk. Copyright © 2016. Published by Elsevier Inc.
Li, Fang; Yan, Chao-Qun; Lin, Li-Ting; Li, Hui; Zeng, Xiang-Hong; Liu, Yi; Du, Si-Qi; Zhu, Wen; Liu, Cun-Zhi
2015-04-28
Decreased cognition is recognized as one of the most severe and consistent behavioral impairments in dementia. Experimental studies have reported that acupuncture may improve cognitive deficits, relieve vascular dementia (VD) symptoms, and increase cerebral perfusion and electrical activity. Multi-infarction dementia was modeled in rats with 3% microemboli saline suspension. Two weeks after acupuncture at Zusanli (ST36), all rats were subjected to a hidden platform trial to test their 3-day spatial memory using the Morris water maze test. To estimate the numbers of pyramidal neuron, astrocytes, and synaptic boutons in hippocampal CA1 area, we adopted an unbiased stereology method to accurately sample and measure the size of cells. We found that acupuncture at ST36 significantly decreased the escape latency of VD rats. In addition, acupuncture significantly increased the pyramidal neuron number in hippocampal CA1 area (P < 0.05) and tended to decrease the number of astrocytes (P = 0.063). However, there was no significant change in the synaptic bouton number of hippocampal CA1 area in any of the groups (P > 0.05). These findings suggest that acupuncture may improve cognitive deficits and increase pyramidal neuron number of hippocampal CA1 area in VD rats.
Clinical Phenotype of Dementia after Traumatic Brain Injury
Sayed, Nasreen; Culver, Carlee; Dams-O'Connor, Kristen; Hammond, Flora
2013-01-01
Abstract Traumatic brain injury (TBI) in early to mid-life is associated with an increased risk of dementia in late life. It is unclear whether TBI results in acceleration of Alzheimer's disease (AD)-like pathology or has features of another dementing condition, such as chronic traumatic encephalopathy, which is associated with more-prominent mood, behavior, and motor disturbances than AD. Data from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set was obtained over a 5-year period. Categorical data were analyzed using Fisher's exact test. Continuous parametric data were analyzed using the Student's t-test. Nonparametric data were analyzed using Mann-Whitney's test. Overall, 877 individuals with dementia who had sustained TBI were identified in the NACC database. Only TBI with chronic deficit or dysfunction was associated with increased risk of dementia. Patients with dementia after TBI (n=62) were significantly more likely to experience depression, anxiety, irritability, and motor disorders than patients with probable AD. Autopsy data were available for 20 of the 62 TBI patients. Of the patients with TBI, 62% met National Institute of Aging-Reagan Institute “high likelihood” criteria for AD. We conclude that TBI with chronic deficit or dysfunction is associated with an increased odds ratio for dementia. Clinically, patients with dementia associated with TBI were more likely to have symptoms of depression, agitation, irritability, and motor dysfunction than patients with probable AD. These findings suggest that dementia in individuals with a history of TBI may be distinct from AD. PMID:23374007
Solé, Montse; Miñano-Molina, Alfredo J; Unzeta, Mercedes
2015-02-01
An association between semicarbazide-sensitive amine oxidase (SSAO) and cerebral amyloid angiopathy (CAA) related to Alzheimer's disease (AD) has been largely postulated. Increased SSAO activity and expression have been detected in cerebrovascular tissue and plasma of AD patients, colocalizing with cerebrovascular amyloid-beta (Aβ) deposits. As an enzyme, SSAO metabolizes primary amines generating hydrogen peroxide, ammonia, and aldehydes. The ability of these products to generate oxidative stress, to enhance the advanced glycation end-product generation, to promote the Aβ aggregation in vitro, and to induce apoptosis supports its role in CAA-related vascular pathology. However, whether the SSAO increase constitutes a cause or it is a consequence of the pathologic process has not been elucidated so far. To set up the nature of this relationship, vascular cell models expressing SSAO were treated with different Aβ forms, simulating the CAA conditions in vitro. It was found that the presence of the vasculotropic Dutch-mutated Aβ1-40 increases (Aβ1-40 D) the SSAO-dependent toxicity, which is accompanied by an increase of SSAO protein availability in endothelial cell membranes. In addition, SSAO enhances Aβ1-40 D and Aβ1-42 deposition on vascular cells by both activity-dependent and -independent mechanisms. Thus, we provide evidences indicating that Aβ itself could be one of the factors inducing SSAO increase in AD, enhancing its toxic effect, and inducing the vascular dysfunction and, in turn, that SSAO stimulates Aβ deposition on the vascular walls, thereby contributing to the CAA-AD progression. Therefore, molecules inhibiting SSAO could provide an alternative treatment for preventing/delaying the progress of CAA-AD-associated vasculopathy. Copyright © 2015 Elsevier Inc. All rights reserved.
Altered Sense of Humor in Dementia
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
2014-01-01
Introduction Two methods of non-invasive brain stimulation, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have demonstrable positive effects on cognition and can ameliorate neuropsychiatric symptoms such as depression. Less is known about the efficacy of these approaches in common neurodegenerative diseases. In this review, we evaluate the effects of TMS and tDCS upon cognitive and neuropsychiatric symptoms in the major dementias, including Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson’s disease with dementia (PDD), and frontotemporal dementia (FTD), as well as the potential pre-dementia states of Mild Cognitive Impairment (MCI) and Parkinson’s disease (PD). Methods PubMed (until 7 February 2014) and PsycINFO (from 1967 to January Week 3 2014) databases were searched in a semi-systematic manner in order to identify relevant treatment studies. A total of 762 studies were identified and 32 studies (18 in the dementias and 14 in PD populations) were included. Results No studies were identified in patients with PDD, FTD or VaD. Of the dementias, 13 studies were conducted in patients with AD, one in DLB, and four in MCI. A total of 16 of the 18 studies showed improvements in at least one cognitive or neuropsychiatric outcome measure. Cognitive or neuropsychiatric improvements were observed in 12 of the 14 studies conducted in patients with PD. Conclusions Both TMS and tDCS may have potential as interventions for the treatment of symptoms associated with dementia and PD. These results are promising; however, available data were limited, particularly within VaD, PDD and FTD, and major challenges exist in order to maximise the efficacy and clinical utility of both techniques. In particular, stimulation parameters vary considerably between studies and are likely to subsequently impact upon treatment efficacy. PMID:25478032
Multi-Infarct Dementia: A Historical Perspective.
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.
International Studies in Dementia With Particular Emphasis on Populations of African Origin
Hendrie, Hugh C.; Murrell, Jill; Gao, Sujuan; Unverzagt, Fredrick W.; Ogunniyi, Adesola; Hall, Kathleen S.
2011-01-01
Epidemiologic studies on dementia generally have 2 major interacting objectives: descriptive, where rates of dementia and Alzheimer Disease (AD) are calculated for communities and selected populations, and analytic, which attempt to explain the observed phenotypic variations in communities and populations by identifying disease risk factors. The public health benefits derived from descriptive studies are exemplified by the recent published review of the global prevalence of dementia under the auspices of Alzheimer Disease International. This review emphasized the enormous and growing burden associated with dementia particularly for countries in the developing world and outlined strategies to influence policy making, planning, and healthcare allocation. One interesting feature of descriptive studies on dementia is that although the few epidemiologic studies conducted in Africa suggest that rates of dementia and AD are relatively low, rates of AD and dementia have been reported to be relatively high for African Americans. The Indianapolis-Ibadan Dementia Project has reported that the incidence rates for AD and dementia in Yoruba are less than half the incidence rates for AD and dementia in African Americans. Analytic studies are now underway to identify risk factors that may account for these rate differences. The risk factor model being applied, attempts to identify not only putative genetic and environmental factors but also their interactions. So far the major findings have included: apolipoprotein E e4, a major risk factor for AD in most populations, is also a risk factor for AD in African Americans but not for Yoruba; African Americans are at higher risk not only for AD, but also for diseases associated with increased cardiovascular risk such as hypertension, diabetes, and metabolic syndrome; African Americans have higher rates of hypercholesterolemia than Yoruba: there is an interaction between apolipoprotein E e4, cholesterol, and AD risk in both Yoruba and
International studies in dementia with particular emphasis on populations of African origin.
Hendrie, Hugh C; Murrell, Jill; Gao, Sujuan; Unverzagt, Fredrick W; Ogunniyi, Adesola; Hall, Kathleen S
2006-01-01
Epidemiologic studies on dementia generally have 2 major interacting objectives: descriptive, where rates of dementia and Alzheimer Disease (AD) are calculated for communities and selected populations, and analytic, which attempt to explain the observed phenotypic variations in communities and populations by identifying disease risk factors. The public health benefits derived from descriptive studies are exemplified by the recent published review of the global prevalence of dementia under the auspices of Alzheimer Disease International. This review emphasized the enormous and growing burden associated with dementia particularly for countries in the developing world and outlined strategies to influence policy making, planning, and healthcare allocation. One interesting feature of descriptive studies on dementia is that although the few epidemiologic studies conducted in Africa suggest that rates of dementia and AD are relatively low, rates of AD and dementia have been reported to be relatively high for African Americans. The Indianapolis-Ibadan Dementia Project has reported that the incidence rates for AD and dementia in Yoruba are less than half the incidence rates for AD and dementia in African Americans. Analytic studies are now underway to identify risk factors that may account for these rate differences. The risk factor model being applied, attempts to identify not only putative genetic and environmental factors but also their interactions. So far the major findings have included: apolipoprotein E e4, a major risk factor for AD in most populations, is also a risk factor for AD in African Americans but not for Yoruba; African Americans are at higher risk not only for AD, but also for diseases associated with increased cardiovascular risk such as hypertension, diabetes, and metabolic syndrome; African Americans have higher rates of hypercholesterolemia than Yoruba: there is an interaction between apolipoprotein E e4, cholesterol, and AD risk in both Yoruba and
Hsu, Yen-Hsuan; Huang, Ching-Feng; Lo, Chung-Ping; Wang, Tzu-Lan; Yang, Chi-Cheng; Tu, Min-Chien
2016-01-01
Prominent executive dysfunction can differentiate vascular dementia from Alzheimer disease (AD). However, it is unclear whether the Frontal Assessment Battery (FAB) screening tool can differentiate subcortical ischemic vascular disease (SIVD) from AD at the pre-dementia stage. In addition, the neural correlates of FAB performance have yet to be clarified. Patients with mild cognitive impairment (MCI) due to SIVD (MCI-V), MCI due to AD (MCI-A), and demographically matched controls completed the Mini-Mental State Examination, Taiwanese FAB (TFAB), Category Fluency, and Chinese Version of the Verbal Learning Test, and underwent magnetic resonance imaging. White matter hyperintensities were rated according to the Scheltens scale. TFAB total scale and its Orthographical Fluency subtest were the only measures that could differentiate MCI-V from MCI-A. Discriminative analysis showed that Orthographical Fluency scores successfully identified 73.2% of the cases with MCI-V, with 85.0% sensitivity. Orthographical Fluency scores were specifically associated with lesion load within frontal periventricular, frontal deep white matter, and basal ganglia regions. The TFAB, and especially its 1-min Orthographical Fluency subtest, is a useful screening procedure to differentiate MCI due to SIVD from MCI due to AD. The discriminative ability is probably due to frontosubcortical white matter pathologies disproportionately involved in the two disease entities. © 2016 S. Karger AG, Basel.
Depression is linked to dementia in older adults.
Valkanova, Vyara; Ebmeier, Klaus P; Allan, Charlotte L
2017-01-01
Depression and dementia are both common conditions in older people, and they frequently occur together. Late life depression affects about 3.0-4.5% of adults aged 65 and older. Depression occurs in up to 20% of patients with Alzheimer’s disease and up to 45% of patients with vascular dementia. Rather than a risk factor, depression with onset in later life is more likely to be either prodromal to dementia or a condition that unmasks pre-existing cognitive impairment by compromising cognitive reserve. Depression can be a psychological response to receiving a diagnosis of dementia. The distinction between depression and early dementia may be particularly difficult. Detailed histories obtained from patients and their relatives as well as longitudinal follow-up are important. Cognitive testing can be very helpful. It is preferable to use a neuropsychological test that is sensitive to subtle cognitive changes and assesses all cognitive domains, such as the Montreal Cognitive Assessment. Older people with depression are at raised risk of dementia and this risk is increased if they have had symptoms for a long time, if their symptoms are severe, where there are multiple (vascular) comorbidities, and where there are structural brain changes including hippocampal atrophy and white matter abnormalities.
de Pedro-Cuesta, Jesús; Virués-Ortega, Javier; Vega, Saturio; Seijo-Martínez, Manuel; Saz, Pedro; Rodríguez, Fernanda; Rodríguez-Laso, Angel; Reñé, Ramón; de las Heras, Susana Pérez; Mateos, Raimundo; Martínez-Martín, Pablo; Manubens, José María; Mahillo-Fernandez, Ignacio; López-Pousa, Secundino; Lobo, Antonio; Reglà, Jordi Llinàs; Gascón, Jordi; García, Francisco José; Fernández-Martínez, Manuel; Boix, Raquel; Bermejo-Pareja, Félix; Bergareche, Alberto; Benito-León, Julián; de Arce, Ana; del Barrio, José Luis
2009-01-01
Background This study describes the prevalence of dementia and major dementia subtypes in Spanish elderly. Methods We identified screening surveys, both published and unpublished, in Spanish populations, which fulfilled specific quality criteria and targeted prevalence of dementia in populations aged 70 years and above. Surveys covering 13 geographically different populations were selected (prevalence period: 1990-2008). Authors of original surveys provided methodological details of their studies through a systematic questionnaire and also raw age-specific data. Prevalence data were compared using direct adjustment and logistic regression. Results The reanalyzed study population (aged 70 year and above) was composed of Central and North-Eastern Spanish sub-populations obtained from 9 surveys and totaled 12,232 persons and 1,194 cases of dementia (707 of Alzheimer's disease, 238 of vascular dementia). Results showed high variation in age- and sex-specific prevalence across studies. The reanalyzed prevalence of dementia was significantly higher in women; increased with age, particularly for Alzheimer's disease; and displayed a significant geographical variation among men. Prevalence was lowest in surveys reporting participation below 85%, studies referred to urban-mixed populations and populations diagnosed by psychiatrists. Conclusion Prevalence of dementia and Alzheimer's disease in Central and North-Eastern Spain is higher in females, increases with age, and displays considerable geographic variation that may be method-related. People suffering from dementia and Alzheimer's disease in Spain may approach 600,000 and 400,000 respectively. However, existing studies may not be completely appropriate to infer prevalence of dementia and its subtypes in Spain until surveys in Southern Spain are conducted. PMID:19840375
Screening Dementia in the Outpatient Department: Patients at Risk for Dementia
Huang, Shu-Wan; Chou, Mei-Chuan
2014-01-01
The targeted screening for individuals at the risks of having dementia would be crucial to the further public health issues for dementia. This study aimed to conduct a screening study in an outpatient department of a regional hospital to screen people who were at risk of developing comorbid dementia. Patients who visited Kaohsiung Municipal Ta-Tung Hospital (KMTTH) clinics during the period from June 1, 2013, to May 31, 2014, were invited to participate in this screening voluntarily. The trained interviewer collected all participants' demographic characteristics and used the instrument of ascertainment of dementia 8 (AD8) to find out suspected dementia ones. The result showed a higher ratio (24.1%) of suspected dementia in the outpatient department of a hospital, 500 out of 2017 subjects, than that in the general population. The median (interquartile range) age was significantly higher in the suspected dementia participants (70, (62, 77)) compared to that in nonsuspected dementia ones (65, (60, 73)), and the probability of suspected dementia was significantly increasing with age (P < 0.001). Instead of screening dementia in general population, screening people at the risk of dementia could be the practicable and important issues in the care of dementia. PMID:25548776
Montgomery, Valencia; Harris, Katie; Stabler, Anthony; Lu, Lisa H
2017-05-01
To examine how the duration of time delay between Wechsler Memory Scale (WMS) Logical Memory I and Logical Memory II (LM) affected participants' recall performance. There are 46,146 total Logical Memory administrations to participants diagnosed with either Alzheimer's disease (AD), vascular dementia (VaD), or normal cognition in the National Alzheimer's Disease Coordinating Center's Uniform Data Set. Only 50% of the sample was administered the standard 20-35 min of delay as specified by WMS-R and WMS-III. We found a significant effect of delay time duration on proportion of information retained for the VaD group compared to its control group, which remained after adding LMI raw score as a covariate. There was poorer retention of information with longer delay for this group. This association was not as strong for the AD and cognitively normal groups. A 24.5-min delay was most optimal for differentiating AD from VaD participants (47.7% classification accuracy), an 18.5-min delay was most optimal for differentiating AD versus normal participants (51.7% classification accuracy), and a 22.5-min delay was most optimal for differentiating VaD versus normal participants (52.9% classification accuracy). Considering diagnostic implications, our findings suggest that test administration should incorporate precise tracking of delay periods. We recommend a 20-min delay with 18-25-min range. Poor classification accuracy based on LM data alone is a reminder that story memory performance is only one piece of data that contributes to complex clinical decisions. However, strict adherence to the recommended range yields optimal data for diagnostic decisions. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Mixed dementia: A review of the evidence
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
Gregory, Michael A; Gill, Dawn P; Zou, Guangyong; Liu-Ambrose, Teresa; Shigematsu, Ryosuke; Fitzgerald, Clara; Hachinski, Vladimir; Shoemaker, Kevin; Petrella, Robert J
2016-01-01
Gait abnormalities and vascular disease risk factors are associated with cognitive impairment in aging. To determine the impact of group-based exercise and dual-task training on gait and vascular health, in active community-dwelling older adults without dementia. Participants [n=44, mean (SD) age: 73.5 (7.2) years, 68% female] were randomized to either intervention (exercise+dual-task; EDT) or control (exercise only; EO). Each week, for 26 weeks, both groups accumulated 50 or 75 min of aerobic exercise from group-based classes and 45 min of beginner-level square stepping exercise (SSE). Participants accumulating only 50 min of aerobic exercise were instructed to participate in an additional 25 min each week outside of class. The EDT group also answered cognitively challenging questions while performing SSE (i.e., dual-task training). The effect of the interventions on gait and vascular health was compared between groups using linear mixed effects models. At 26 weeks, the EDT group demonstrated increased dual-task (DT) gait velocity [difference between groups in mean change from baseline (95% CI): 0.29 m/s (0.16-0.43), p<0.001], DT step length [5.72 cm (2.19-9.24), p =0.002], and carotid intima-media thickness [0.10mm (0.003-0.20), p=0.04], as well as reduced DT stride time variability [8.31 coefficient of variation percentage points (-12.92 to -3.70), p<0.001], when compared to the EO group. Group-based exercise combined with dual-task training can improve DT gait characteristics in active older adults without dementia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Age and Vascular Burden Determinants of Cortical Hemodynamics Underlying Verbal Fluency.
Heinzel, Sebastian; Metzger, Florian G; Ehlis, Ann-Christine; Korell, Robert; Alboji, Ahmed; Haeussinger, Florian B; Wurster, Isabel; Brockmann, Kathrin; Suenkel, Ulrike; Eschweiler, Gerhard W; Maetzler, Walter; Berg, Daniela; Fallgatter, Andreas J
2015-01-01
Aging processes and several vascular burden factors have been shown to increase the risk of dementia including Alzheimer's disease. While pathological alterations in dementia precede diagnosis by many years, reorganization of brain processing might temporarily delay cognitive decline. We hypothesized that in healthy elderly individuals both age-related neural and vascular factors known to be related to the development of dementia impact functional cortical hemodynamics during increased cognitive demands. Vascular burden factors and cortical functional hemodynamics during verbal fluency were assessed in 1052 non-demented elderly individuals (51 to 83 years; cross-sectional data of the longitudinal TREND study) using functional near-infrared spectroscopy (fNIRS). The prediction of functional hemodynamic responses by age in multiple regressions and the impact of single and cumulative vascular burden factors including hypertension, diabetes, obesity, smoking and atherosclerosis were investigated. Replicating and extending previous findings we could show that increasing age predicted functional hemodynamics to be increased in right prefrontal and bilateral parietal cortex, and decreased in bilateral inferior frontal junction during phonological fluency. Cumulative vascular burden factors, with hypertension in particular, decreased left inferior frontal junction hemodynamic responses during phonological fluency. However, age and vascular burden factors showed no statistical interaction on functional hemodynamics. Based on these findings, one might hypothesize that increased fronto-parietal processing may represent age-related compensatory reorganization during increased cognitive demands. Vascular burden factors, such as hypertension, may contribute to regional cerebral hypoperfusion. These neural and vascular hemodynamic determinants should be investigated longitudinally and combined with other markers to advance the prediction of future cognitive decline and dementia.
Deep brain stimulation for the treatment of Alzheimer disease and dementias.
Laxton, Adrian W; Lozano, Andres M
2013-01-01
To review the use of deep brain stimulation (DBS) for treatment of dementia. A PubMed literature search was conducted to identify all studies that have investigated the use of DBS for treatment of dementia. Three studies examined the use of DBS for dementia. One study involved fornix DBS for Alzheimer disease (AD), and two studies involved DBS of the nucleus basalis of Meynert, one to treat AD and one to treat Parkinson disease dementia. Evidence for the use of DBS to treat dementia is preliminary and limited. Fornix and nucleus basalis of Meynert DBS can influence activity in the pathologic neural circuits that underlie AD and Parkinson disease dementia. Further investigation into the potential clinical effects of DBS for dementia is warranted. Copyright © 2013 Elsevier Inc. All rights reserved.
Kida, Hirotaka; Satoh, Masayuki; Ii, Yuichiro; Fukuyama, Hidenao; Maeda, Masayuki; Tomimoto, Hidekazu
2017-01-01
The patient was an 81-year-old man who had been treated for hypertension for several decades. In 2012, he developed gait disturbance and mild amnesia. One year later, his gait disturbance worsened, and he developed urinary incontinence. Conventional brain magnetic resonance imaging using T 2 -weighted images and fluid-attenuated inversion recovery showed multiple lacunar infarctions. These findings fulfilled the diagnostic criteria for subcortical ischaemic vascular dementia. However, susceptibility weighted imaging showed multiple lobar microbleeds in the bilateral occipitoparietal lobes, and double inversion recovery and 3-D fluid-attenuated inversion recovery images on 3-T magnetic resonance imaging revealed cortical microinfarctions in the left parietal-temporo-occipito region. Pittsburgh compound B-positron emission tomography revealed diffuse uptake in the cerebral cortex. Therefore, we diagnosed the patient with subcortical ischaemic vascular dementia associated with Alzheimer's disease. The use of the double inversion recovery and susceptibility weighted imaging on 3-T magnetic resonance imaging may be a supplemental strategy for diagnosing cerebral amyloid angiopathy, which is closely associated with Alzheimer's disease. © 2016 The Authors. Psychogeriatrics © 2016 Japanese Psychogeriatric Society.
Trichotillomania in a dementia case
Caixeta, Leonardo; Lopes, Danielly Bandeira
2011-01-01
We report an 87-year-old male case of hair pulling associated with a white-matter vascular dementia (Binswanger’s disease). Trichotillomania in our case did not resolve using mirtazapine or anticholinesterasic medication. Trichotillomania seems to be related to a form of perseveration associated with dementia. The findings in this case suggest the abnormality involving white matter in the pathogenesis of trichotillomania, may constitute a defect in connectivity in the right frontal-subcortical circuit. PMID:29213722
Zhao, Mei; Lv, Xiaozhen; Tuerxun, Maimaitirexiati; He, Jincai; Luo, Benyan; Chen, Wei; Wang, Kai; Gu, Ping; Kuang, Weihong; Zhou, Yuying; Qu, Qiumin; He, Jianhua; Zhang, Nan; Feng, Yongping; Wang, Yanping; Yu, Xin; Wang, Huali
2016-02-01
The prevalence and factors associated with delays in help seeking for people with dementia in China are unknown. Within 1,010 consecutively registered participants in the Clinical Pathway for Alzheimer's Disease in China (CPAD) study (NCT01779310), 576 persons with dementia (PWDs) and their informants reported the estimated time from symptom onset to first medical visit seeking diagnosis. Univariate analysis of general linear model was used to examine the potential factors associated with the delayed diagnosis seeking. The median duration from the first noticeable symptom to the first visit seeking diagnosis or treatment was 1.77 years. Individuals with a positive family history of dementia had longer duration (p = 0.05). Compared with other types of dementia, people with vascular dementia (VaD) were referred for diagnosis earliest, and the sequence for such delays was: VaD < Alzheimer's disease (AD) < frontotemporal dementia (FTD) (p < 0.001). Subtypes of dementia (p < 0.001), family history (p = 0.01), and education level (p = 0.03) were associated with the increased delay in help seeking. In China, seeking diagnosis for PWDs is delayed for approximately 2 years, even in well-established memory clinics. Clinical features, family history, and less education may impede help seeking in dementia care.
[Dementia and small vessel diseases of the brain].
Damulin, I V
2014-01-01
Clinical and pathogenetic characteristics of dementia caused by small vessel lesions are presented. It is emphasized that this variant of vascular dementia is the most frequent in clinical practice. Clinical examination, accurate assessment of the disease history and using of modern neuroimaging techniques are important for the diagnosis. The drugs that impact on risk factors, including disaggregants, and metabolic drugs (nicergoline) are widely used in the treatment of dementia. These drugs are highly effective and safe.
Lorius, Natacha; Locascio, Joseph J; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Viswanathan, Anand; Marshall, Gad A
2015-01-01
We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control, mild cognitive impairment, and mild Alzheimer disease (AD) dementia subjects. A total of 812 participants (229 normal older control, 395 mild cognitive impairment, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed-effects, and Cox proportional hazards models were used. Greater homocysteine level and white matter hyperintensity volume were associated with processing speed impairment (homocysteine: P=0.02; white matter hyperintensity: P<0.0001); greater Vascular Index score was associated with memory impairment (P=0.007); and greater number of apolipoprotein E ε4 (APOE4) alleles was associated with global cognitive impairment (P=0.007) at baseline. Apolipoprotein E ε4 was associated with greater rate of increase in global cognitive impairment (P=0.002) and processing speed impairment (P=0.001) over time, whereas higher total cholesterol was associated with greater rate of increase in global cognitive impairment (P=0.02) and memory impairment (P=0.06) over time. These results suggest a significant association of increased vascular disease and risk factors with cognitive impairment at baseline and over time in the AD spectrum in a sample that was selected to have low vascular burden at baseline.
Lu, Z Kevin; Li, Minghui; Yuan, Jing; Wu, Jun
2016-01-01
The aim of this study is to assess whether diabetes mellitus is associated with overall dementia and its subtypes (Alzheimer's disease and vascular dementia) among the elderly and to identify the role of cerebrovascular disease in the association between diabetes and dementia. In a retrospective cross-sectional study, 5160 community-dwelling and institutionalized Medicare beneficiaries aged 65 years or over without health maintenance organization enrollment from the Medicare Current Beneficiary Survey in 2010 were included. The International Classification of Diseases-9 codes were used to identify the outcome and independent variables from the Medicare claims. The key predictor was diabetes mellitus and the outcomes were overall dementia and its subtypes. Logistic regression was employed to assess the association between dementia and diabetes after adjusting for age, gender, race, education, income, smoking status, and Charlson Comorbidity Index. After adjusting for potential confounders, diabetes mellitus was significantly associated with overall dementia (odds ratio [OR] = 1.42; 95% confidence interval [CI], 1.14-1.77), vascular dementia (OR = 1.29; 95% CI, 1.02-1.64), and Alzheimer's disease (OR = 1.51, 95% CI, 1.10-2.09). The OR decreased to 1.26 (95% CI, 1.01-1.58) for overall dementia, controlling for cerebrovascular disease. The associations between diabetes mellitus and vascular dementia (OR = 1.13, 95% CI, 0.89-1.44) and Alzheimer's disease (OR = 1.39, 95% CI, 1.00-1.92) were no longer statistically significant once cerebrovascular disease was controlled. The association between diabetes mellitus and dementia is only partially mediated through cerebrovascular disease, suggesting that diabetes mellitus is associated independently with overall dementia among the elderly, but not with vascular dementia and Alzheimer's disease. Copyright © 2015 John Wiley & Sons, Ltd.
Dementia in Urban Black Outpatients: Initial Experience at the Emory Satellite Clinics.
ERIC Educational Resources Information Center
Auchus, Alexander P.
1997-01-01
Describes the demographic features and clinical diagnoses in a sample of 58 demented urban black outpatients. Results indicate that probable Alzheimer's disease was the most common cause of dementia whereas probable vascular dementia was uncommon. A multiple etiology dementia was identified in more than one-third of the patients. (RJM)
Advance Directives among Nursing Home Residents with Mild, Moderate, and Advanced Dementia.
Tjia, Jennifer; Dharmawardene, Marisa; Givens, Jane L
2018-01-01
To describe prevalence and content of AD documentation among NH residents by dementia stage. The prevalence of advance directives (ADs) among nursing home (NH) residents with mild, moderate, and advanced dementia remains unclear. Population-based, cross-sectional study of all licensed NHs in five U.S. states. Subjects included all long-stay (>90 day) NH residents with dementia, aged ≥65 years, and a Cognitive Performance Scale (CPS) score ≥1 from the 2007 to 2008 Minimum Data Set 2.0 (n = 180,621). Dementia severity was classified as follows: mild (CPS 1-2), moderate (CPS 3-4), and advanced (CPS 5-6). ADs were defined as the presence of a living will, do-not-resuscitate order, do-not-hospitalize order, medication restriction, or feeding restriction). Overall, 59% of residents had any AD and 17% had a living will. Prevalence of any AD increased by dementia severity: mild (51.2%), moderate (58.2%), and advanced (61.5%) (p < 0.001). In adjusted analysis, resident characteristics associated with any AD documentation included older age, female gender, being white, and having more severe dementia. Having a living will was associated with higher education (≥high school graduate vs. some high school or less) and being married. While dementia severity was associated with greater likelihood of having documented any AD, almost 4 in 10 residents with dementia lacked any AD. Effective outreach may focus efforts on subgroups with lower odds of any AD or living wills, including non-white, less educated, and unmarried NH residents. A greater understanding of how such factors impact care planning will help to address barriers to patient-centered care for this population.
Self-perceived memory complaints predict progression to Alzheimer disease. The LADIS study.
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.
Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia
Wilson, Robert S.; Weuve, Jennifer; Barnes, Lisa L.; Evans, Denis A.
2015-01-01
Objective: To examine the relation of performance on brief cognitive tests to development of clinically diagnosed Alzheimer disease (AD) dementia over the following 18 years in a sample of African Americans and European Americans. Methods: A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants (55% African American and 61% female) aged 65 years and older residing in 4 Chicago neighborhoods. Time before AD dementia diagnosis was categorized into 6 groups corresponding to data collection periods: 0.1–0.9, 1.0–3.9, 4.0–6.9, 7.0–9.9, 10.0–12.9, and 13.0–17.9 years. Results: Of 2,125 participants without clinical AD dementia, 442 (21%) developed clinical AD dementia over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of AD dementia over the duration of the study. The magnitude of association between composite cognitive test score and development of AD dementia increased from an odds ratio of 3.39 (95% confidence interval 1.72, 6.67; p < 0.001) at 13.0–17.9 years to 9.84 (95% confidence interval 7.41, 13.06; p < 0.001) at 0.1–0.9 years, per SD increment. These associations were consistently larger among European Americans than among African Americans. Performance on individual cognitive tests of episodic memory, executive function, and global cognition also significantly predicted the development of AD dementia, with associations exhibiting a similar trend over 18 years. Conclusions: Our findings suggest that cognitive impairment may manifest in the preclinical phase of AD dementia substantially earlier than previously established. PMID:26109713
Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia.
Rajan, Kumar B; Wilson, Robert S; Weuve, Jennifer; Barnes, Lisa L; Evans, Denis A
2015-09-08
To examine the relation of performance on brief cognitive tests to development of clinically diagnosed Alzheimer disease (AD) dementia over the following 18 years in a sample of African Americans and European Americans. A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants (55% African American and 61% female) aged 65 years and older residing in 4 Chicago neighborhoods. Time before AD dementia diagnosis was categorized into 6 groups corresponding to data collection periods: 0.1-0.9, 1.0-3.9, 4.0-6.9, 7.0-9.9, 10.0-12.9, and 13.0-17.9 years. Of 2,125 participants without clinical AD dementia, 442 (21%) developed clinical AD dementia over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of AD dementia over the duration of the study. The magnitude of association between composite cognitive test score and development of AD dementia increased from an odds ratio of 3.39 (95% confidence interval 1.72, 6.67; p < 0.001) at 13.0-17.9 years to 9.84 (95% confidence interval 7.41, 13.06; p < 0.001) at 0.1-0.9 years, per SD increment. These associations were consistently larger among European Americans than among African Americans. Performance on individual cognitive tests of episodic memory, executive function, and global cognition also significantly predicted the development of AD dementia, with associations exhibiting a similar trend over 18 years. Our findings suggest that cognitive impairment may manifest in the preclinical phase of AD dementia substantially earlier than previously established. © 2015 American Academy of Neurology.
Approximate entropy analysis of event-related potentials in patients with early vascular dementia.
Xu, Jin; Sheng, Hengsong; Lou, Wutao; Zhao, Songzhen
2012-06-01
This study investigated differences in event-related potential (ERP) parameters among early vascular dementia (VD) patients, healthy elder controls (ECs), and young controls (YCs). A visual "oddball" color identification task was performed while individuals' electroencephalograms (EEGs) were recorded. Approximate entropy (ApEn), a nonlinear measure, along with P300 latencies and amplitudes were used to analyze ERP data and compare these three groups. The patients with VD showed more complex ERP waveforms and higher ApEn values than did ECs while performing the visual task. It was further found that patients with VD showed reduced P300 amplitudes and increased latencies. The results indicate that patients with VD have fewer attention resources to devote to processing stimuli, lower speed of stimulus classification, and lower synchrony in their cortical activity during the response period. We suggest that ApEn, as a measure of ERP complexity, is a promising marker for early diagnosis of VD.
Khoo, K F; Tan, H J; R, Rosdinom; Raymond, A A; M I, Norlinah; A, Shamsul; W Y, Nafisah
2013-04-01
Depression among patients with vascular dementia is frequently overlooked and potentially causes significant morbidity. There is limited data in Malaysia on the subject and this study was conducted to determine the prevalence of depression in vascular dementia (VaD) in UKMMC. This was a cross-sectional study involving diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria and who had a mini mental state examination (MMSE) score of less than 26. All patients were interviewed, examined clinically and their previous brain computer tomography (CT) were reviewed. The prevalence of depression was determined using the Cornell scale of depression. A total of 76 patients were recruited with a mean age of 70.5 ± 9.5 years. The median duration of illness was 2.0 (1.0-4.8) years. The prevalence of depression in the study population was 31.6%. The patients with depression had a significant older mean age (74.5±8.7 years old) compared to those without depression (68.6±9.4 years old). Patients with large artery stroke of less than 3 years had significant higher frequency of depression (53.6%) compared to patients with small artery stroke (23.8%) and patients with right sided large artery stroke had significantly higher frequency of depression compared to left (70% vs. 44.4%). Median MMSE score (17.0) for depressed patients was significantly lower compared with median MMSE score (22.5) for non depressed patients. Median Barthel Index (30.0) for depressed patients was significantly lower compared with median Barthel score for non depressed patients. Depression was prevalent among post stroke patients with VaD in UKMMC particularly for patients with older age, large artery stroke, right sided large artery stroke, low MMSE score and low Barthel Index. Early recognition of high risk patients is important in the holistic management of patients to prevent significant morbidity arising from depression.
Predicting outcome of Morris water maze test in vascular dementia mouse model with deep learning
Mogi, Masaki; Iwanami, Jun; Min, Li-Juan; Bai, Hui-Yu; Shan, Bao-Shuai; Kukida, Masayoshi; Kan-no, Harumi; Ikeda, Shuntaro; Higaki, Jitsuo; Horiuchi, Masatsugu
2018-01-01
The Morris water maze test (MWM) is one of the most popular and established behavioral tests to evaluate rodents’ spatial learning ability. The conventional training period is around 5 days, but there is no clear evidence or guidelines about the appropriate duration. In many cases, the final outcome of the MWM seems predicable from previous data and their trend. So, we assumed that if we can predict the final result with high accuracy, the experimental period could be shortened and the burden on testers reduced. An artificial neural network (ANN) is a useful modeling method for datasets that enables us to obtain an accurate mathematical model. Therefore, we constructed an ANN system to estimate the final outcome in MWM from the previously obtained 4 days of data in both normal mice and vascular dementia model mice. Ten-week-old male C57B1/6 mice (wild type, WT) were subjected to bilateral common carotid artery stenosis (WT-BCAS) or sham-operation (WT-sham). At 6 weeks after surgery, we evaluated their cognitive function with MWM. Mean escape latency was significantly longer in WT-BCAS than in WT-sham. All data were collected and used as training data and test data for the ANN system. We defined a multiple layer perceptron (MLP) as a prediction model using an open source framework for deep learning, Chainer. After a certain number of updates, we compared the predicted values and actual measured values with test data. A significant correlation coefficient was derived form the updated ANN model in both WT-sham and WT-BCAS. Next, we analyzed the predictive capability of human testers with the same datasets. There was no significant difference in the prediction accuracy between human testers and ANN models in both WT-sham and WT-BCAS. In conclusion, deep learning method with ANN could predict the final outcome in MWM from 4 days of data with high predictive accuracy in a vascular dementia model. PMID:29415035
Predicting outcome of Morris water maze test in vascular dementia mouse model with deep learning.
Higaki, Akinori; Mogi, Masaki; Iwanami, Jun; Min, Li-Juan; Bai, Hui-Yu; Shan, Bao-Shuai; Kukida, Masayoshi; Kan-No, Harumi; Ikeda, Shuntaro; Higaki, Jitsuo; Horiuchi, Masatsugu
2018-01-01
The Morris water maze test (MWM) is one of the most popular and established behavioral tests to evaluate rodents' spatial learning ability. The conventional training period is around 5 days, but there is no clear evidence or guidelines about the appropriate duration. In many cases, the final outcome of the MWM seems predicable from previous data and their trend. So, we assumed that if we can predict the final result with high accuracy, the experimental period could be shortened and the burden on testers reduced. An artificial neural network (ANN) is a useful modeling method for datasets that enables us to obtain an accurate mathematical model. Therefore, we constructed an ANN system to estimate the final outcome in MWM from the previously obtained 4 days of data in both normal mice and vascular dementia model mice. Ten-week-old male C57B1/6 mice (wild type, WT) were subjected to bilateral common carotid artery stenosis (WT-BCAS) or sham-operation (WT-sham). At 6 weeks after surgery, we evaluated their cognitive function with MWM. Mean escape latency was significantly longer in WT-BCAS than in WT-sham. All data were collected and used as training data and test data for the ANN system. We defined a multiple layer perceptron (MLP) as a prediction model using an open source framework for deep learning, Chainer. After a certain number of updates, we compared the predicted values and actual measured values with test data. A significant correlation coefficient was derived form the updated ANN model in both WT-sham and WT-BCAS. Next, we analyzed the predictive capability of human testers with the same datasets. There was no significant difference in the prediction accuracy between human testers and ANN models in both WT-sham and WT-BCAS. In conclusion, deep learning method with ANN could predict the final outcome in MWM from 4 days of data with high predictive accuracy in a vascular dementia model.
Subclinical hyperthyroidism and dementia: the Sao Paulo Ageing & Health Study (SPAH)
2010-01-01
Background Several epidemiologic studies have shown a possible association between thyroid function and cognitive decline. Our aim was to evaluate the association of subclinical hyperthyroidism and dementia in a population sample of older people Methods A cross-sectional study - São Paulo Ageing & Health Study (SPAH) - in a population sample of low-income elderly people ≥ 65 years-old to evaluate presence of subclinical thyroid disease as a risk factor for dementia. Thyroid function was assessed using thyrotropic hormone and free-thyroxine as well as routine use of thyroid hormones or antithyroid medications. Cases of dementia were assessed using a harmonized one-phase dementia diagnostic procedure by the "10/66 Dementia Research Group" including Alzheimer's disease and vascular dementia. Logistic regression models were used to test a possible association between subclinical hyperthyroidism and dementia. Results and discussion Prevalence of dementia and of subclinical hyperthyroidism were respectively of 4.4% and 3.0%. After age adjustment, we found an association of subclinical hyperthyroidism and any type of dementia and vascular dementia (Odds Ratio, 4.1, 95% Confidence Interval [95% CI] 1.3-13.1, and 5.3 95% CI, 1.1-26.4; respectively). Analyzing data by gender, we found an association of subclinical hyperthyroidism with dementia and Alzheimer's disease only for men (OR, 8.0; 95% CI, 1.5-43.4; OR, 12.4; 95% CI, 1.2-128.4; respectively). No women with subclinical hypothyroidism presented Alzheimer's disease in the sample. Conclusion The results suggest a consistent association among people with subclinical hyperthyroidism and dementia. PMID:20515500
Physiological phenotyping of dementias using emotional sounds.
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.
Toru, Shuta; Kanouchi, Tadashi; Yokota, Takanori; Yagi, Yosuke; Machida, Akira; Kobayashi, Takayoshi
2018-01-01
We studied autonomic disturbance in patients with dementia with Lewy bodies (DLB), Parkinson disease with dementia (PDD), Alzheimer disease (AD), to determine whether autonomic function tests can be used to distinguish these disorders. Autonomic function was tested in 56 patients with DLB, 37 patients with PDD, and 59 patients with AD by using the sympathetic skin response, coefficient of variation in R-R interval, the head-up tilt test, serum norepinephrine concentration, and 123I-meta-iodobenzylguanidine cardiac scintigraphy. Symptoms of autonomic dysfunction, such as constipation, urinary symptoms, and orthostatic hypotension, were also noted. The groups did not differ on baseline characteristics other than those associated with Parkinsonism and dementia. All patients with DLB and PDD had some dysautonomia, whereas rates were much lower for patients with AD (19%). Significantly more DLB and PDD patients than AD patients showed abnormalities on autonomic function tests. Autonomic function tests might be quite useful to distinguish DLB and PDD from AD. © 2017 S. Karger AG, Basel.
Del Campo, Marta; Teunissen, Charlotte E
2014-01-01
Alzheimer's disease (AD), the most common form of dementia, shares clinical and pathological similarities with familial British and Danish dementias (FBD and FDD). Whereas the etiology of sporadic AD remains unclear, familial AD is linked to mutations in amyloid-β protein precursor (AβPP), presenilin 1 (PS1), and presenilin 2 (PS2). Similarly, FBD and FDD originate from mutations in the BRI2 gene (or ITM2b), causing amyloid angiopathy and neurofibrillary tangles analogous to those observed in AD. Recent studies on the role of BRI2 in FBD and FDD have revealed that the three diseases may share pathophysiological pathways leading to dementia. Interestingly, BRI2 is a potential regulator of AβPP processing, and it can inhibit the production and fibrillation of Aβ. This suggests a role of BRI2 in the amyloid cascade, which is the prevailing hypothesis about AD pathogenesis. To understand a possible relationship of BRI2 with AD, we reviewed the relevant studies on this protein. The data included not only the protein's structure, expression pattern, function, and involvement in FBD and FDD, but also its relationship with memory deficits and the main pathological proteins involved in AD. Thus, we highlight and discuss the potential links between BRI2 and AD, leading to the formulation of a modified hypothesis about AD etiology.
Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli
2016-01-01
We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia (VaD) using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p<0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 (AQP-4) expression around blood vessels. MMI induced glymphatic dysfunction with delayed cerebrospinal fluid (CSF) penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases AQP-4 and induces glymphatic dysfunction which may play an important role in MMI induced axonal/WM damage and cognitive deficits. PMID:27940353
Cerebral Microbleeds in Patients with Dementia with Lewy Bodies and Parkinson Disease Dementia.
Kim, S W; Chung, S J; Oh, Y-S; Yoon, J H; Sunwoo, M K; Hong, J Y; Kim, J-S; Lee, P H
2015-09-01
The burden of amyloid β is greater in patients with dementia with Lewy bodies than in those with Parkinson disease dementia, and an increased amyloid β load is closely related to a higher incidence of cerebral microbleeds. Here, we investigated the prevalence and topography of cerebral microbleeds in patients with dementia with Lewy bodies and those with Parkinson disease dementia to examine whether cerebral microbleeds are more prevalent in patients with dementia with Lewy bodies than in those with Parkinson disease dementia. The study population consisted of 42 patients with dementia with Lewy bodies, 88 patients with Parkinson disease dementia, and 35 controls who underwent brain MR imaging with gradient recalled-echo. Cerebral microbleeds were classified as deep, lobar, or infratentorial. The frequency of cerebral microbleeds was significantly greater in patients with dementia with Lewy bodies (45.2%) than in those with Parkinson disease dementia (26.1%) or in healthy controls (17.1%; P = .017). Lobar cerebral microbleeds were observed more frequently in the dementia with Lewy bodies group (40.5%) than in the Parkinson disease dementia (17%; P = .004) or healthy control (8.6%; P = .001) group, whereas the frequencies of deep and infratentorial cerebral microbleeds did not differ among the 3 groups. Logistic regression analyses revealed that, compared with the healthy control group, the dementia with Lewy bodies group was significantly associated with the presence of lobar cerebral microbleeds after adjusting for age, sex, nonlobar cerebral microbleeds, white matter hyperintensities, and other vascular risk factors (odds ratio, 4.39 [95% CI, 1.27-15.25]). However, compared with the healthy control group, the Parkinson disease dementia group was not significantly associated with lobar cerebral microbleeds. This study showed that patients with dementia with Lewy bodies had a greater burden of cerebral microbleeds and exhibited a lobar predominance of cerebral
Chatterjee, Saion; Peters, Sanne A.E.; Woodward, Mark; Mejia Arango, Silvia; Batty, G. David; Beckett, Nigel; Beiser, Alexa; Borenstein, Amy R.; Crane, Paul K.; Haan, Mary; Hassing, Linda B.; Hayden, Kathleen M.; Kiyohara, Yutaka; Larson, Eric B.; Li, Chung-Yi; Ninomiya, Toshiharu; Ohara, Tomoyuki; Peters, Ruth; Russ, Tom C.; Seshadri, Sudha; Strand, Bjørn H.; Walker, Rod; Xu, Weili
2016-01-01
OBJECTIVE Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. RESULTS Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45–1.80]; men: pooled RR 1.58 [95% CI 1.38–1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86–2.94) in women and 1.73 (95% CI 1.61–1.85) in men, and for nonvascular dementia, the RRs were 1.53 (95% CI 1.35–1.73) in women and 1.49 (95% CI 1.31–1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08–1.30]; P < 0.001). CONCLUSIONS Individuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women. PMID:26681727
Incidence of dementia in elderly Latin Americans: Results of the Maracaibo Aging Study.
Maestre, Gladys E; Mena, Luis J; Melgarejo, Jesus D; Aguirre-Acevedo, Daniel C; Pino-Ramírez, Gloria; Urribarrí, Milady; Chacon, Inara J; Chávez, Carlos A; Falque-Madrid, Luis; Gaona, Ciro A; Terwilliger, Joseph D; Lee, Joseph H; Scarmeas, Nikolaos
2018-02-01
There are few longitudinal studies of dementia in developing countries. We used longitudinal data from the Maracaibo Aging Study to accurately determine the age- and sex-specific incidence of dementia in elderly Latin Americans. The Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) was used to diagnose dementia, which was classified as Alzheimer's disease, vascular dementia, or other. Age- and sex-specific incidence was estimated as the number of new cases of dementia divided by person-years (p-y) of follow-up. The incidence of all dementia diagnoses was 9.10 per 1000 p-y (95% confidence interval [CI] 7.13-11.44; 8026 total p-y), 5.18 for Alzheimer's disease (95% CI 3.72-7.03; 7916 total p-y), and 3.35 for vascular dementia (95% CI 2.19-4.91; 7757 total p-y). Among Maracaibo Aging Study participants younger than 65 years, the incidence of dementia was higher than that of US Whites. Among individuals older than 65 years, the incidence was comparable to the mean of previous incidence estimates for other populations worldwide. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Weekman, Erica M; Sudduth, Tiffany L; Caverly, Carly N; Kopper, Timothy J; Phillips, Oliver W; Powell, Dave K; Wilcock, Donna M
2016-09-21
Vascular cognitive impairment and dementia (VCID) is the second most common form of dementia behind Alzheimer's disease (AD). It is estimated that 40% of AD patients also have some form of VCID. One promising therapeutic for AD is anti-Aβ immunotherapy, which uses antibodies against Aβ to clear it from the brain. While successful in clearing Aβ and improving cognition in mice, anti-Aβ immunotherapy failed to reach primary cognitive outcomes in several different clinical trials. We hypothesized that one potential reason the anti-Aβ immunotherapy clinical trials were unsuccessful was due to this high percentage of VCID comorbidity in the AD population. We used our unique model of VCID-amyloid comorbidity to test this hypothesis. We placed 9-month-old wild-type and APP/PS1 mice on either a control diet or a diet that induces hyperhomocysteinemia (HHcy). After being placed on the diet for 3 months, the mice then received intraperotineal injections of either IgG2a control or 3D6 for another 3 months. While we found that treatment of our comorbidity model with 3D6 resulted in decreased total Aβ levels, there was no cognitive benefit of the anti-Aβ immunotherapy in our AD/VCID mice. Further, microhemorrhages were increased by 3D6 in the APP/PS1/control but further increased in an additive fashion when 3D6 was administered to the APP/PS1/HHcy mice. This suggests that the use of anti-Aβ immunotherapy in patients with both AD and VCID would be ineffective on cognitive outcomes. Despite significant mouse model data demonstrating both pathological and cognitive efficacy of anti-Aβ immunotherapy for the treatment of Alzheimer's disease, clinical trial outcomes have been underwhelming, failing to meet any primary endpoints. We show here that vascular cognitive impairment and dementia (VCID) comorbidity eliminates cognitive efficacy of anti-Aβ immunotherapy, despite amyloid clearance. Further, cerebrovascular adverse events of the anti-Aβ immunotherapy are
Cognitive and motor symptoms in dementia: focus on dementia with Lewy bodies.
Lingler, Jennifer Hagerty; Kaufer, Daniel I
2002-09-01
To describe the clinical syndrome called dementia with Lewy bodies (DLB) and highlight its common and unique characteristics with respect to diagnosis and management. Review of the scientific literature including psychiatric literature, reports of clinical trials, and clinical practice guidelines. DLB is a clinical and histopathologic disease, which is second only to Alzheimer's disease (AD) as a cause of dementia in older adults. The clinical syndrome of DLB includes cognitive and motor deterioration reminiscent of symptoms associated with AD and Parkinson's disease (PD) respectively. The late life intersection of cognitive and motor symptoms can present significant challenges in the primary care setting. Recognizing key features of common neurodegenerative disorders is essential to accurately diagnosing and appropriately treating the growing population of older adults who suffer from AD, PD, and DLB.
Traffic-Related Air Pollution and Dementia Incidence in Northern Sweden: A Longitudinal Study
Oudin, Anna; Forsberg, Bertil; Adolfsson, Annelie Nordin; Lind, Nina; Modig, Lars; Nordin, Maria; Nordin, Steven; Adolfsson, Rolf; Nilsson, Lars-Göran
2015-01-01
Background Exposure to ambient air pollution is suspected to cause cognitive effects, but a prospective cohort is needed to study exposure to air pollution at the home address and the incidence of dementia. Objectives We aimed to assess the association between long-term exposure to traffic-related air pollution and dementia incidence in a major city in northern Sweden. Methods Data on dementia incidence over a 15-year period were obtained from the longitudinal Betula study. Traffic air pollution exposure was assessed using a land-use regression model with a spatial resolution of 50 m × 50 m. Annual mean nitrogen oxide levels at the residential address of the participants at baseline (the start of follow-up) were used as markers for long-term exposure to air pollution. Results Out of 1,806 participants at baseline, 191 were diagnosed with Alzheimer’s disease during follow-up, and 111 were diagnosed with vascular dementia. Participants in the group with the highest exposure were more likely than those in the group with the lowest exposure to be diagnosed with dementia (Alzheimer’s disease or vascular dementia), with a hazard ratio (HR) of 1.43 (95% CI: 0.998, 2.05 for the highest vs. the lowest quartile). The estimates were similar for Alzheimer’s disease (HR 1.38) and vascular dementia (HR 1.47). The HR for dementia associated with the third quartile versus the lowest quartile was 1.48 (95% CI: 1.03, 2.11). A subanalysis that excluded a younger sample that had been retested after only 5 years of follow-up suggested stronger associations with exposure than were present in the full cohort (HR = 1.71; 95% CI: 1.08, 2.73 for the highest vs. the lowest quartile). Conclusions If the associations we observed are causal, then air pollution from traffic might be an important risk factor for vascular dementia and Alzheimer’s disease. Citation Oudin A, Forsberg B, Nordin Adolfsson A, Lind N, Modig L, Nordin M, Nordin S, Adolfsson R, Nilsson LG. 2016. Traffic
Levada, O A; Traïlin, A V
2012-01-01
We evaluated serum level of S100B in 11 patients with subcortical vascular dementia (SVD) and 19 patients with subcortical vascular mild cognitive impairment (SVMCI). Comparable groups were age-matched (79.18 +/- 7.76 in SVD group, 77.84 +/- 3.83 in SVMCI; P = 0.53). 22 patients were assessed after 1 month therapy. It was shown that the serum S100B level significantly increased--(0.065 +/- 0.020) micro/l (P = 0.0005) in SVD patients comparing to SVMCI ones - (0.043 +/- 0.010) microg/l. S100B level was significantly correlated with the clinical parameters: MMSE performance (r(s) = -0.61), CDR (r(s) = 0.58), attention task (r(s) = -0.46), pseudobulbar syndrome severity (r(s) = 0.37) and walking alteration (r(s)= 0.37). In patients with reduction of S100B level due to therapy (positive dynamics, n = 12) we registered significant improvement of some clinical parameters: MMSE, attention level, walking. In patients with increasing of S100B level (negative dynamics, n = 10) we didn't registered improvement of any clinical parameters. We made the conclusion that the serum level of S100B could be used as marker of progression SVMCI into SVD and therapy effectiveness.
Shah, Ajit; Ellanchenny, Nalini; Suh, Guk-Hee
2004-06-01
There is a paucity of cross-cultural studies of behavioral and psychological symptoms of dementia (BPSD). BPSD were examined in a consecutive series of referrals to a psychogeriatric service in the United Kingdom (U.K.) and in Korea, using the BEHAVE-AD, the Cornell Scale for Depression in Dementia and the Mini-mental State Examination (MMSE). The U.K. service served a well-defined geographical catchment area with a multidisciplinary team and emphasis on home assessments. The Korean service was a nationwide service with limited community resources. The correlates of individual BPSD in each country and the differences between the two countries were examined. Koreans were younger, were more likely to be married, less likely to be single, had a greater number of people in their household and were more likely to live in their own homes than the U.K. sample. Koreans were more likely to be referred by general psychiatrists or family members, and the U.K. sample was more likely to be referred by general practitioners. Koreans were more likely to have Alzheimer's disease and the U.K. sample to have vascular dementia. The Korean sample had a lower MMSE score than the U.K. sample. In both countries, the total BEHAVE-AD score and most subscale scores were negatively correlated with the MMSE score. The total BEHAVE-AD score and all subscale scores were higher in the Korean sample than in the U.K. sample. The prevalence of all BPSD measured with the BEHAVE-AD were higher in the Korean sample (except aggressivity). These differences may be explained by differing interpretation and administration of the measurement instruments, models of service delivery, availability of primary and secondary care services, health seeking behavior of patients and families, cultural influences, and knowledge, expectations and recognition of BPSD by professionals in primary and secondary care. However, despite this, there was possible evidence of genuine differences worthy of further cross
Relation of genomic variants for Alzheimer disease dementia to common neuropathologies
Yu, Lei; Buchman, Aron S.; Schneider, Julie A.; De Jager, Philip L.; Bennett, David A.
2016-01-01
Objective: To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. Methods: This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 × 10−8) for pathologic AD for all variants. Results: APOE ε4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67–5.46, p = 1.9 × 10−13), while ε2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30–0.61, p = 3.1 × 10−6). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Conclusions: Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. PMID:27371493
Relation of genomic variants for Alzheimer disease dementia to common neuropathologies.
Farfel, Jose M; Yu, Lei; Buchman, Aron S; Schneider, Julie A; De Jager, Philip L; Bennett, David A
2016-08-02
To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 × 10(-8)) for pathologic AD for all variants. APOE ε4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67-5.46, p = 1.9 × 10(-13)), while ε2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30-0.61, p = 3.1 × 10(-6)). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. © 2016 American Academy of Neurology.
Multiple pathologies are common and related to dementia in the oldest-old
Kim, Ronald C.; Sonnen, Joshua A.; Bullain, Szofia S.; Trieu, Thomas; Corrada, María M.
2015-01-01
Objective: The purpose of this study was to examine the role of multiple pathologies in the expression of dementia in the oldest-old. Methods: A total of 183 participants of The 90+ Study with longitudinal follow-up and autopsy were included in this clinical-pathologic investigation. Eight pathologic diagnoses (Alzheimer disease [AD], microinfarcts, hippocampal sclerosis, macroinfarcts, Lewy body disease, cerebral amyloid angiopathy, white matter disease, and others) were dichotomized. We estimated the odds of dementia in relation to each individual pathologic diagnosis and to the total number of diagnoses. We also examined dementia severity in relation to number of pathologic diagnoses. Results: The presence of multiple pathologic diagnoses was common and occurred more frequently in those with dementia compared with those without dementia (45% vs 14%). Higher numbers of pathologic diagnoses were also associated with greater dementia severity. Participants with intermediate/high AD pathology alone were 3 times more likely to have dementia (odds ratio = 3.5), but those with single non-AD pathologies were 12 times more likely to have dementia (odds ratio = 12.4). When a second pathology was present, the likelihood of dementia increased 4-fold in those with intermediate/high AD pathology but did not change in those with non-AD pathologies, suggesting that pathologies may interrelate in different ways. Conclusions: In the oldest-old, the presence of multiple pathologies is associated with increased likelihood and severity of dementia. The effect of the individual pathologies may be additive or perhaps synergistic and requires further research. Multiple pathologies will need to be targeted to reduce the burden of dementia in the population. PMID:26180144
Non-Native Language Use and Risk of Incident Dementia in the Elderly
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.
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.
Morris, John C
2012-06-01
To evaluate the potential impact of revised criteria for mild cognitive impairment (MCI), developed by a work group sponsored by the National Institute on Aging and the Alzheimer's Association, on the diagnosis of very mild and mild Alzheimer disease (AD)dementia. Retrospective review of ratings of functional impairment across diagnostic categories. Alzheimer's Disease Centers and the National Alzheimer's Coordinating Center. Individuals (N=17 535) with normal cognition,MCI, or AD dementia. The functional ratings of individuals with normal cognition, MCI, or AD dementia who were evaluated at Alzheimer's Disease Centers and submitted to the National Alzheimer's Coordinating Center were assessed in accordance with the definition of "functional independence" allowed by the revised criteria. Pairwise demographic differences between the 3 diagnostic groups were tested using t tests for continuous variables and 2 for categorical variables. Almost all (99.8%) individuals currently diagnosed with very mild AD dementia and the large majority(92.7%) of those diagnosed with mild AD dementia could be reclassified as having MCI with the revised criteria,based on their level of impairment in the Clinical Dementia Rating domains for performance of instrumental activities of daily living in the community and at home.Large percentages of these individuals with AD dementia also meet the revised "functional independence" criterion for MCI as measured by the Functional Assessment Questionnaire. The categorical distinction between MCI and milder stages of AD dementia has been compromised by the revised criteria. The resulting diagnostic overlap supports the premise that "MCI due to AD" represents the earliest symptomatic stage of AD.
Chan, W C; Lam, L C; Choy, C N; Leung, V P; Li, S W; Chiu, H F
2001-12-01
Behavioural and psychological symptoms (BPSD) are common during the course of dementia and present severe problems to patients and their caregivers. To assess the therapeutic efficacy and safety of haloperidol and risperidone in treating BPSD in Chinese dementia patients. A 12-week double-blind randomised comparison of haloperidol and risperidone treatments was conducted in 58 patients with DSM-IV diagnosis of dementia of Alzheimer's type or vascular dementia. They were randomly assigned to receive flexible doses (0.5 to 2 mg/day) of haloperidol or risperidone. Clinical response was evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Simpson-Angus Scale, Functional Assessment Staging and Cantonese version of the Mini-Mental State Examination. The mean doses at the last week were 0.90 mg/day of haloperidol and 0.85 mg/day of risperidone. Both haloperidol and risperidone significantly reduced the severity of BPSD (scores on CMAI and BEHAVE-AD), with no significant between-group differences. Haloperidol-treated patients showed a worsening on Simpson-Angus scale while there was no significant change in this measure in risperidone-treated patients. Low-dose haloperidol and risperidone were well tolerated and associated with reductions in the severity and frequency of behavioural symptoms in subjects with dementia. Risperidone may have a more favourable risk-benefit profile in view of its lower propensity to induce extrapyramidal symptoms. Copyright 2001 John Wiley & Sons, Ltd.
Posttraumatic stress disorder and dementia in Holocaust survivors.
Sperling, Wolfgang; Kreil, Sebastian Konstantin; Biermann, Teresa
2011-03-01
The incidence of mental and somatic sequelae has been shown to be very high in the group of people damaged by the Holocaust. Within the context of internal research, 93 Holocaust survivors suffering from posttraumatic stress disorder have been examined. Patients suffered on average from 4.5 (standard deviation ± 1.8) somatic diagnoses as well as 1.8 (standard deviation ± 0.5) psychiatric diagnoses. A diagnosis of dementia was ascertained according to ICD-10 criteria in 14%. Vascular dementia (66%) dominated over Alzheimer's dementia (23%) and other subtypes (11%).
Economou, Alexandra; Routsis, Christopher; Papageorgiou, Sokratis G
2016-01-01
Differences in episodic memory performance in patients with Alzheimer disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB)/Parkinson disease with dementia (PDD) are inconsistent and task dependent. The inconsistencies may be attributed to the different tasks drawing on different memory processes. Few studies have examined episodic memory impairment in the above groups using memory tests that facilitate encoding, to distinguish memory deficits due to impairment of specific processes. We examined the memory performance of 106 AD patients, 51 FTD patients, 26 DLB/PDD patients, and 37 controls using the Five-Words Test, a 5-item memory test that facilitates encoding. The patient groups did not differ in modified Mini Mental State Examination scores. AD patients scored lowest on the Five-Words Test overall, and showed the greatest reduction from immediate total recall to delayed free recall relative to the other 2 groups, consistent with a predominantly consolidation deficit. DLB/PDD patients showed the largest improvement from delayed free to delayed total recall relative to the other 2 groups, consistent with a predominantly retrieval deficit. Deficits in both consolidation and retrieval underlie the memory impairment of the patients, to different extents, and contribute to the theoretical understanding of the nature of the memory impairment of the patient groups.
Mez, Jesse; Cosentino, Stephanie; Brickman, Adam M; Huey, Edward D; Manly, Jennifer J; Mayeux, Richard
2013-01-01
The objective of this study was to compare the demographic and vascular characteristics and APOE genotypes of a dysexecutive subgroup of Alzheimer disease (AD) with an amnestic subgroup of AD early in the disease course. A total of 2224 participants from the National Alzheimer's Coordinating Center database who carried a diagnosis of mild cognitive impairment (n=1188) or mild AD (clinical dementia rating ≤1) (n=1036) were included in this study. A subset of the mild cognitive impairment (n=61) and mild AD (n=79) participants underwent an autopsy. A dysexecutive subgroup (n=587) was defined as having executive performance >1 SD worse than memory performance, and an amnestic subgroup (n=549) was defined conversely. Among the autopsy subset, the odds of an AD pathologic diagnosis were compared in the 2 subgroups. The demographics, APOE[Latin Small Letter Open E]4 status, and vascular risk factors were compared in the 2 subgroups. Among the autopsy subset, the odds of having an AD pathologic diagnosis did not differ between the dysexecutive and amnestic subgroups. Under an additive model, participants in the dysexecutive subgroup possessed the APOE[Latin Small Letter Open E]4 allele less frequently compared with those in the amnestic subgroup. The dysexecutive subgroup had a history of hypertension less frequently compared with the amnestic subgroup. These distinct characteristics add to accumulating evidence that a dysexecutive subgroup of AD may have a unique underlying pathophysiology.
Incidence and prediction of falls in dementia: a prospective study in older people.
Allan, Louise M; Ballard, Clive G; Rowan, Elise N; Kenny, Rose Anne
2009-01-01
Falls are a major cause of morbidity and mortality in dementia, but there have been no prospective studies of risk factors for falling specific to this patient population, and no successful falls intervention/prevention trials. This prospective study aimed to identify modifiable risk factors for falling in older people with mild to moderate dementia. 179 participants aged over 65 years were recruited from outpatient clinics in the UK (38 Alzheimer's disease (AD), 32 Vascular dementia (VAD), 30 Dementia with Lewy bodies (DLB), 40 Parkinson's disease with dementia (PDD), 39 healthy controls). A multifactorial assessment of baseline risk factors was performed and fall diaries were completed prospectively for 12 months. Dementia participants experienced nearly 8 times more incident falls (9118/1000 person-years) than controls (1023/1000 person-years; incidence density ratio: 7.58, 3.11-18.5). In dementia, significant univariate predictors of sustaining at least one fall included diagnosis of Lewy body disorder (proportional hazard ratio (HR) adjusted for age and sex: 3.33, 2.11-5.26), and history of falls in the preceding 12 months (HR: 2.52, 1.52-4.17). In multivariate analyses, significant potentially modifiable predictors were symptomatic orthostatic hypotension (HR: 2.13, 1.19-3.80), autonomic symptom score (HR per point 0-36: 1.055, 1.012-1.099), and Cornell depression score (HR per point 0-40: 1.053, 1.01-1.099). Higher levels of physical activity were protective (HR per point 0-9: 0.827, 0.716-0.956). The management of symptomatic orthostatic hypotension, autonomic symptoms and depression, and the encouragement of physical activity may provide the core elements for the most fruitful strategy to reduce falls in people with dementia. Randomised controlled trials to assess such a strategy are a priority.
McKeith, Ian
2004-01-01
Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia in older people, accounting for 10% to 15% of all cases, it occupies part of a spectrum that includes Parkinson's disease and primary autonomic failure. All these diseases share a neuritic pathology based upon abnormal aggregation of the synaptic protein α-synuciein. It is important to identify DLB patients accurately because they have specific symptoms, impairments, and functional disabilities thai differ from other common dementia syndromes such as Alzheimer's disease, vascular cognitive impairment, and frontotemporal dementia. Clinical diagnostic criteria for DLB have been validated against autopsy, but fail to detect a substantial minority of cases with atypical presentations that are often due to the presence of mixed pathology. DLB patients frequently have severe neuroleptic sensitivity reactions, which are associated with significantly increased morbidity and mortality. Cholinesterase inhibitor treatment is usually well tolerated and substantially improves cognitive and neuropsychiatrie symptoms. Although virtually unrecognized 20 years ago, DLB could within this decade become one of the most treatable neurodegenerative disorders of late life. PMID:22033743
Meta-analysis of the efficacy and safety of Ginkgo biloba extract for the treatment of dementia.
Hashiguchi, Masayuki; Ohta, Yuriko; Shimizu, Mikiko; Maruyama, Junya; Mochizuki, Mayumi
2015-01-01
The benefit of Ginkgo biloba for the treatment of dementia remains controversial. The aim of this study was to evaluate the efficacy and safety of Ginkgo biloba in patients with dementia in whom administration effects were reported using meta-analysis. We searched MEDLINE, Embase, the Cochrane databases, and Ichushi for controlled trials of Ginkgo biloba for the treatment dementia. Clinical characteristics and outcomes were extracted. Meta-analysis results were expressed as standard mean differences (SMDs) in scores of the Syndrome Kurztest (SKT), Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) for cognition efficacy, or odds ratios (ORs) for dropouts and adverse drug reactions. Thirteen studies using the extract EGb761 met our inclusion criteria, which were duration of 12 to 52 weeks and daily dose of more than 120 mg, and included a total of 2381 patients. Meta-analysis was performed by using 9 of 13 studies, 7 of which used the SKT and 2 ADAS-Cog (dose 120 mg, 26 weeks) scores as efficacy parameters. In meta-analysis of all patients, SMDs (95% confidence interval [CI]) in the change in SKT scores (7 studies) were in favor of Ginkgo biloba over placebo (SMD = -0.90 [-1.46, -0.34]), but 2 studies that used ADAS-Cog did not show a statistically significant difference from placebo for ADAS-Cog (-0.06 [-0.41, 0.30]). For Alzheimer's disease (AD) and vascular dementia (VaD) subgroups, SMDs [95% CI] in SKT in the combined AD and VaD subgroup (-1.07 [-1.66, -0.47]) and AD subgroup (-1.36 [-2.27, -0.46]) were in favor of Ginkgo biloba over placebo. In terms of daily dose of Ginkgo biloba in the combined AD and VaD subgroup, SMD in SKT score in 240-mg daily dose groups was significantly greater than with placebo (-0.71 [-1.28, -0.14]). Dropout rates for any reason did not differ between two groups, but dropout rates due to side effects were significantly lower in Ginkgo biloba groups compared with placebo groups (OR = 1.72 [1.06, 2.80]). Taking a 240-mg
Considering sex and gender in Alzheimer disease and other dementias.
Podcasy, Jessica L; Epperson, C Neill
2016-12-01
Suffering related to dementia is multifaceted because cognitive and physical functioning slowly deteriorates. Advanced age and sex, two of the most prominent risk factors for dementia, are not modifiable. Lifestyle factors such as smoking, excessive alcohol use, and poor diet modulate susceptibility to dementia in both males and females. The degree to which the resulting health conditions (eg, obesity, type 2 diabetes, and cardiovascular disease) impact dementia risk varies by sex. Depending on the subtype of dementia, the ratio of male to female prevalence differs. For example, females are at greater risk of developing Alzheimer disease dementia, whereas males are at greater risk of developing vascular dementia. This review examines sex and gender differences in the development of dementia with the goal of highlighting factors that require further investigation. Considering sex as a biological variable in dementia research promises to advance our understanding of the pathophysiology and treatment of these conditions.
López-Olóriz, Jorge; López-Cancio, Elena; Arenillas, Juan F; Hernández, María; Jiménez, Marta; Dorado, Laura; Barrios, Maite; Soriano-Raya, Juan José; Miralbell, Júlia; Cáceres, Cynthia; Forés, Rosa; Pera, Guillem; Dávalos, Antoni; Mataró, Maria
2013-10-01
Carotid atherosclerosis has emerged as a relevant contributor to cognitive impairment and dementia whereas the role of intracranial stenosis and vascular resistance in cognition remains unknown. This study aims to assess the association of asymptomatic cervicocerebral atherosclerosis and intracranial vascular resistance with cognitive performance in a large dementia-free population. The Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) Neuropsychology Study included 747 Caucasian subjects older than 50 with a moderate-high vascular risk (assessed by REGICOR score) and without history of neither symptomatic vascular disease nor dementia. Extracranial and transcranial color-coded duplex ultrasound examination was performed to assess carotid intima-media thickness (IMT), presence of carotid plaques (ECAD group), intracranial stenosis (ICAD group), and middle cerebral artery pulsatility index (MCA-PI) as a measure of intracranial vascular resistance. Neuropsychological assessment included tests in three cognitive domains: visuospatial skills and speed, verbal memory and verbal fluency. In univariate analyses, carotid IMT, ECAD and MCA-PI were associated with lower performance in almost all cognitive domains, and ICAD was associated with poor performance in some visuospatial and verbal cognitive tests. After adjustment for age, sex, vascular risk score, years of education and depressive symptoms, ECAD remained associated with poor performance in the three cognitive domains and elevated MCA-PI with worse performance in visuospatial skills and speed. Carotid plaques and increased intracranial vascular resistance are independently associated with low cognitive functioning in Caucasian stroke and dementia-free subjects. We failed to find an independent association of intracranial large vessel stenosis with cognitive performance. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Berggren, Åke; Gustafson, Lars; Höglund, Peter; Johanson, Aki
2016-08-01
In this study, the long term effects of ECT on patients with depression were investigated through repeated rCBF and EEG measures as well as clinical characteristics over several years. The aim of the investigation was to establish an association with the eventual development of dementia. A cohort of forty-nine patients (21 men and 28 women) with a mean age of 61 years underwent ECT. A subsequent evaluation from medical records and three rating-scales for diagnosis of Alzheimer´s disease (AD), fronto-temporal dementia (FTD), and for vascular dementia (VaD), revealed that 17 patients (8 men and 9 women), had developed dementia. These cases were compared to the 32 patients (13 men and 19 women), who had not developed dementia. Initially, the dementia group, compared to those without dementia, showed a lower hemispheric CBF (left side; p=.029, right side; p=.033), and a lower mean occipital EEG frequency (p=.048). After the first ECT-series, an increase in general disorientation (p=.015), personal disorientation (p=.009), and subsequently, spatial disorientation (p=.021), were seen in the dementia group. There were no differences in the clinical response or remissions after treatment in the groups. The small sample-size, which did not allow for the comparison of characteristics between different dementias. Depressed older patients who later developed dementia showed lower hemispheric mean level of CBF and EEG mean frequency before ECT and higher personal and spatial disorientation following ECT. Copyright © 2016 Elsevier B.V. All rights reserved.
Are we comparing frontotemporal dementia and Alzheimer disease patients with the right measures?
Deutsch, Mariel B; Liang, Li-Jung; Jimenez, Elvira E; Mather, Michelle J; Mendez, Mario F
2016-09-01
Clinical research studies of behavioral variant frontotemporal dementia (bvFTD) often use Alzheimer disease (AD) as a comparison group for control of dementia variables, using tests of cognitive function to match the groups. These two dementia syndromes, however, are very different in clinical manifestations, and the comparable severity of these dementias may not be reflected by commonly used cognitive scales such as the Mini-Mental State Examination (MMSE). We evaluated different measures of dementia severity and symptoms among 20 people with bvFTD compared to 24 with early-onset AD. Despite similar ages, disease-duration, education, and cognitive performance on two tests of cognitive function, the MMSE and the Montreal Cognitive Assessment (MoCA), the bvFTD participants, compared to the AD participants, were significantly more impaired on other measures of disease severity, including function (Functional Assessment Questionnaire (FAQ)), neuropsychiatric symptoms (Neuropsychiatric Inventory (NPI)), and global dementia stage (Clinical Dementia Rating Scales (CDRs)). However, when we adjusted for the frontotemporal lobar degeneration-CDR (FTLD-CDR) in the analyses, the two dementia groups were comparable across all measures despite significant differences on the cognitive scales. We found tests of cognitive functions (MMSE and MoCA) to be insufficient measures for ensuring comparability between bvFTD and AD groups. In clinical studies, the FTLD-CDR, which includes additional language and behavior items, may be a better overall way to match bvFTD and AD groups on dementia severity.
Are we comparing frontotemporal dementia and Alzheimer disease patients with the right measures?
Deutsch, Mariel B.; Liang, Li-Jung; Jimenez, Elvira E.; Mather, Michelle J.; Mendez, Mario F.
2016-01-01
Background Clinical research studies of behavioral variant frontotemporal dementia (bvFTD) often use Alzheimer disease (AD) as a comparison group for control of dementia variables, using tests of cognitive function to match the groups. These two dementia syndromes, however, are very different in clinical manifestations, and the comparable severity of these dementias may not be reflected by commonly used cognitive scales such as the Mini-Mental State Examination (MMSE). Methods We evaluated different measures of dementia severity and symptoms among 20 people with bvFTD compared to 24 with early-onset AD. Results Despite similar ages, disease-duration, education, and cognitive performance on two tests of cognitive function, the MMSE and the Montreal Cognitive Assessment (MoCA), the bvFTD participants, compared to the AD participants, were significantly more impaired on other measures of disease severity, including function (Functional Assessment Questionnaire (FAQ)), neuropsychiatric symptoms (Neuropsychiatric Inventory (NPI)), and global dementia stage (Clinical Dementia Rating Scales (CDRs)). However, when we adjusted for the frontotemporal lobar degeneration-CDR (FTLD-CDR) in the analyses, the two dementia groups were comparable across all measures despite significant differences on the cognitive scales. Conclusion We found tests of cognitive functions (MMSE and MoCA) to be insufficient measures for ensuring comparability between bvFTD and AD groups. In clinical studies, the FTLD-CDR, which includes additional language and behavior items, may be a better overall way to match bvFTD and AD groups on dementia severity. PMID:27079571
Impact of Adult Day Services on Behavioral and Psychological Symptoms of Dementia
ERIC Educational Resources Information Center
Femia, Elia E.; Zarit, Steven H.; Stephens, Mary Ann Parris; Greene, Rick
2007-01-01
Purpose: This study explored whether adult day service (ADS) use was associated with reductions in behavioral and psychological symptoms of dementia (BPSD) in individuals with dementia. Design and Methods: We used a quasi-experimental design to compare a group of 133 persons with dementia (PWDs) who initially enrolled in an ADS program to a…
The Appropriate Use of Neuroimaging in the Diagnostic Work-Up of Dementia
2014-01-01
Background Diagnosis of dementia is challenging and requires both ruling out potentially treatable underlying causes and ruling in a diagnosis of dementia subtype to manage patients and suitably plan for the future. Objectives This analysis sought to determine the appropriate use of neuroimaging during the diagnostic work-up of dementia, including indications for neuroimaging and comparative accuracy of alternative technologies. Data Sources A literature search was performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published between 2000 and 2013. Review Methods Data on diagnostic accuracy and impact on clinical decision making were abstracted from included studies. Quality of evidence was assessed using GRADE. Results The search yielded 5,374 citations and 15 studies were included. Approximately 10% of dementia cases are potentially treatable, though less than 1% reverse partially or fully. Neither prediction rules nor clinical indications reliably select the subset of patients who will likely benefit from neuroimaging. Clinical utility is highest in ambiguous cases or where dementia may be mixed, and lowest for clinically diagnosed Alzheimer disease or clinically excluded vascular dementia. There is a lack of evidence that MRI is superior to CT in detecting a vascular component to dementia. Accuracy of structural imaging is moderate to high for discriminating different types of dementia. Limitations There was significant heterogeneity in estimates of diagnostic accuracy, which often prohibited a statistical summary of findings. The quality of data reported by studies prohibited calculation of likelihood ratios in the present analysis. No studies from primary care were found; thus, generalizability beyond tertiary care settings may be limited. Conclusions A diagnosis of reversible dementia is rare. Imaging has the most
The cost of dementia in Denmark: the Odense Study.
Kronborg Andersen, C; Søgaard, J; Hansen, E; Kragh-Sørensen, A; Hastrup, L; Andersen, J; Andersen, K; Lolk, A; Nielsen, H; Kragh-Sørensen, P
1999-01-01
In a population-based study of dementia, the cost of care for 245 demented elderly and 490 controls matched by age and gender was estimated. Dementia of Alzheimer's type was diagnosed according to the NINCDS-ADRDA criteria, and vascular dementia and other types of dementia were diagnosed according to the DSM-IIIR criteria. Severity of dementia was determined by the Clinical Dementia Rating scale. The annual cost of medical care, domestic care, home help, nursing home and special equipment for nondemented patients was DKK 22,000 per person while the cost for very mildly, mildly, moderately and severely demented patients was DKK 49,000, DKK 93,000, DKK 138,000 and DKK 206,000, respectively. Except for very mild dementia the cost did not differ between elderly who suffer from Alzheimer's disease and those with other types of dementia. The net cost of dementia is the difference in cost between those with dementia and the matched controls and amounts on average to DKK 77,000 per person per year. However, priority setting cannot be based on the cost of dementia per se, but only on the cost of a specific dementia intervention compared to its health benefit.
Is complexity of work associated with risk of dementia? The Canadian Study of Health And Aging.
Kröger, Edeltraut; Andel, Ross; Lindsay, Joan; Benounissa, Zohra; Verreault, René; Laurin, Danielle
2008-04-01
The authors evaluated the association of complexity of work with data, people, and things with the incidence of dementia, Alzheimer's disease, and vascular dementia in the Canadian Study of Health and Aging, while adjusting for work-related physical activity. The Canadian Study of Health and Aging is a 10-year population study, from 1991 to 2001, of a representative sample of persons aged 65 years or older. Lifetime job history allowed application of complexity scores and classification of work-related physical activity. Analyses included 3,557 subjects, of whom 400 were incident dementia cases, including 299 with Alzheimer's disease and 93 with vascular dementia. In fully adjusted Cox regression models, high complexity of work with people or things reduced risk of dementia (hazard ratios were 0.66 (95% confidence interval: 0.44, 0.98) and 0.72 (95% confidence interval: 0.52, 0.99), respectively) but not Alzheimer's disease. For vascular dementia, hazard ratios were 0.36 (95% confidence interval: 0.15, 0.90) for high complexity of work with people and 0.50 (95% confidence interval: 0.25, 1.00) for high complexity of work with things. Subgroup analyses according to median duration (23 years) of principal occupation showed that associations with complexity varied according to duration of employment. High complexity of work appears to be associated with risk of dementia, but effects may vary according to subtype.
Potential Role of Neuroimaging Markers for Early Diagnosis of Dementia in Primary Care.
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.
Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli
2017-02-01
We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p < 0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age-matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 expression around blood vessels. MMI-induced glymphatic dysfunction with delayed cerebrospinal fluid penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases Aquaporin-4 and induces glymphatic dysfunction which may play an important role in MMI-induced axonal/WM damage and cognitive deficits. Copyright © 2016 Elsevier Inc. All rights reserved.
Tian, Jinzhou; Shi, Jing; Wei, Mingqing; Qin, Renan; Ni, Jingnian; Zhang, Xuekai; Li, Ting; Wang, Yongyan
2016-06-08
Vascular dementia (VaD) is the second most common subtype of dementia after Alzheimer's disease (AD). Currently, there are no medications approved for treating patients with VaD. Fufangdanshen (FFDS) tablets (Radix Salviae miltiorrhizae formula tablets) are a traditional Chinese medicine that has been reported to improve memory. However, the existing evidence for FFDS tablets in clinical practice derives from methodologically flawed studies. To further investigate the safety, tolerability, and efficacy of FFDS tables in the treatment of mild to moderate VaD, we designed and reported the methodology for a 24-week randomized, double-blind, parallel, multicenter study. This ongoing study is a double-blind, randomized, parallel placebo-controlled trial. A total of 240 patients with mild to moderate VaD will be enrolled. After a 2-week run-in period, the eligible patients will be randomized to receive either three FFDS or placebo tablets three times per day for 24 weeks, with a follow-up 12 weeks after the last treatment. The primary efficacy measurement will be the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician Interview-Based Impression of Change (CIBIC-plus). The secondary efficacy measurements will include the Mini Mental State Examination (MMSE) and activities of daily living (ADL). Adverse events will also be reported. This randomized trial will be the first rigorous study on the efficacy and safety of FFDS tablets for treating cognitive symptoms in patients with VaD using a rational design. ClinicalTrials.gov: NCT01761227 . Registered on 2 January 2013.
Muscoso, E G; Costanzo, E; Daniele, O; Maugeri, D; Natale, E; Caravaglios, G
2006-11-01
Few studies exist on ERPs and patients with subcortical vascular cognitive impairment (SVCI). This latter is a quite homogeneous subtype of vascular dementia whose cognitive profile is quite different from that of Alzheimer disease (AD). The present study aims at comparing the ERPs profile both in patients with SVCI and in patients with AD. ERPs and psychometric tests were collected from 39 healthy elderly controls, 51 patients with SVCI and 43 patients with AD. Subjects mentally count high pitched target tones that were randomly intermixed with low pitched frequent tones. We measured ERPs latencies (N1, P2, N2 and P3), and interpeak latencies (N1-P3, N1-P2, N1-N2). Grand averaged potentials in SVCI showed a significant increase of P3 latency. AD patients showed a prolongation of N1, P2, N2, P3 latencies. As far as interpeak latencies are concerned, SVCI patients showed a significant prolongation of N1-P3, AD patients had a significant increase of N1-N2, and N1-P3 intervals. When all patients were considered as a single group, correlation of neuropsychological tests scores showed a significant negative relationship between P300 latency and, respectively, Mini Mental Status Examination, auditive and visual span forward. In both groups, ERPs latency sensitivity, was low, whilst specificity values were quite high. Our finding suggest that these two dementing diseases have different electrophysiologic features that may be related to their specific underlying pathogenetic mechanism; in particular, we hypothesise that, differently from AD, P300 latency prolongation characterizes the early stage of SVCI. So, this ERPs approach could be helpful to detect early alterations of the attentional/working-memory functions in patients with subcortical ischaemic vascular disease.
Considering sex and gender in Alzheimer disease and other dementias
Podcasy, Jessica L.; Epperson, C. Neill
2016-01-01
Suffering related to dementia is multifaceted because cognitive and physical functioning slowly deteriorates. Advanced age and sex, two of the most prominent risk factors for dementia, are not modifiable. Lifestyle factors such as smoking, excessive alcohol use, and poor diet modulate susceptibility to dementia in both males and females. The degree to which the resulting health conditions (eg, obesity, type 2 diabetes, and cardiovascular disease) impact dementia risk varies by sex. Depending on the subtype of dementia, the ratio of male to female prevalence differs. For example, females are at greater risk of developing Alzheimer disease dementia, whereas males are at greater risk of developing vascular dementia. This review examines sex and gender differences in the development of dementia with the goal of highlighting factors that require further investigation. Considering sex as a biological variable in dementia research promises to advance our understanding of the pathophysiology and treatment of these conditions. PMID:28179815
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
Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia
Jack, Clifford R.; Wiste, Heather J.; Weigand, Stephen D.; Vemuri, Prashanthi; Lowe, Val J.; Kantarci, Kejal; Gunter, Jeffrey L.; Senjem, Matthew L.; Mielke, Michelle M.; Machulda, Mary M.; Roberts, Rosebud O.; Boeve, Bradley F.; Jones, David T.; Petersen, Ronald C.
2016-01-01
Objective: To examine neurodegenerative imaging biomarkers in Alzheimer disease (AD) dementia from middle to old age. Methods: Persons with AD dementia and elevated brain β-amyloid with Pittsburgh compound B (PiB)-PET imaging underwent [18F]-fluorodeoxyglucose (FDG)-PET and structural MRI. We evaluated 3 AD-related neurodegeneration biomarkers: hippocampal volume adjusted for total intracranial volume (HVa), FDG standardized uptake value ratio (SUVR) in regions of interest linked to AD, and cortical thickness in AD-related regions of interest. We examined associations of each biomarker with age and evaluated age effects on cutpoints defined by the 90th percentile in AD dementia. We assembled an age-, sex-, and intracranial volume-matched group of 194 similarly imaged clinically normal (CN) persons. Results: The 97 participants with AD dementia (aged 49–93 years) had PiB SUVR ≥1.8. A nonlinear (inverted-U) relationship between FDG SUVR and age was seen in the AD group but an inverse linear relationship with age was seen in the CN group. Cortical thickness had an inverse linear relationship with age in AD but a nonlinear (flat, then inverse linear) relationship in the CN group. HVa showed an inverse linear relationship with age in both AD and CN groups. Age effects on 90th percentile cutpoints were small for FDG SUVR and cortical thickness, but larger for HVa. Conclusions: In persons with AD dementia with elevated PiB SUVR, values of each neurodegeneration biomarker were associated with age. Cortical thickness had the smallest differences in 90th percentile cutpoints from middle to old age, and HVa the largest differences. PMID:27421543
Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia.
Knopman, David S; Jack, Clifford R; Wiste, Heather J; Weigand, Stephen D; Vemuri, Prashanthi; Lowe, Val J; Kantarci, Kejal; Gunter, Jeffrey L; Senjem, Matthew L; Mielke, Michelle M; Machulda, Mary M; Roberts, Rosebud O; Boeve, Bradley F; Jones, David T; Petersen, Ronald C
2016-08-16
To examine neurodegenerative imaging biomarkers in Alzheimer disease (AD) dementia from middle to old age. Persons with AD dementia and elevated brain β-amyloid with Pittsburgh compound B (PiB)-PET imaging underwent [(18)F]-fluorodeoxyglucose (FDG)-PET and structural MRI. We evaluated 3 AD-related neurodegeneration biomarkers: hippocampal volume adjusted for total intracranial volume (HVa), FDG standardized uptake value ratio (SUVR) in regions of interest linked to AD, and cortical thickness in AD-related regions of interest. We examined associations of each biomarker with age and evaluated age effects on cutpoints defined by the 90th percentile in AD dementia. We assembled an age-, sex-, and intracranial volume-matched group of 194 similarly imaged clinically normal (CN) persons. The 97 participants with AD dementia (aged 49-93 years) had PiB SUVR ≥1.8. A nonlinear (inverted-U) relationship between FDG SUVR and age was seen in the AD group but an inverse linear relationship with age was seen in the CN group. Cortical thickness had an inverse linear relationship with age in AD but a nonlinear (flat, then inverse linear) relationship in the CN group. HVa showed an inverse linear relationship with age in both AD and CN groups. Age effects on 90th percentile cutpoints were small for FDG SUVR and cortical thickness, but larger for HVa. In persons with AD dementia with elevated PiB SUVR, values of each neurodegeneration biomarker were associated with age. Cortical thickness had the smallest differences in 90th percentile cutpoints from middle to old age, and HVa the largest differences. © 2016 American Academy of Neurology.
Mixed pathology is more likely in black than white decedents with Alzheimer dementia
Leurgans, Sue; Aggarwal, Neelum T.; Shah, Raj C.; Arvanitakis, Zoe; James, Bryan D.; Buchman, Aron S.; Bennett, David A.; Schneider, Julie A.
2015-01-01
Objective: To compare the burden of neuropathology in black and white participants with clinical Alzheimer disease (AD). Methods: Participants included 122 persons enrolled in the Rush Alzheimer's Disease Clinical Core, a prospective cohort study of AD. Forty-one black decedents were matched two-to-one to 81 white decedents according to age at death, sex, years of education, and cognition proximate to death. We examined common brain pathologies related to dementia (AD, Lewy body, and macroscopic and microinfarct pathology) and arteriolar sclerosis and atherosclerosis. We calculated the frequency of each dementia pathology both alone and in combination (mixed pathologies). Racial differences in the odds of a single pathology vs mixed pathologies, and in the odds of vessel disease and its severity, were examined using logistic regression analyses. Results: AD pathology was confirmed in >93% of both black and white decedents with AD dementia. However, black decedents were less likely to have Alzheimer pathology as a single dementia pathology than white decedents (19.5% vs 42.0%), and were more likely to have AD mixed with an additional pathology (70.7% vs 50.6%), particularly Alzheimer pathology and Lewy bodies, and Alzheimer pathology, Lewy bodies, and infarcts. Black decedents also had more severe arteriolar sclerosis and atherosclerosis. Conclusion: Black decedents with AD dementia are more likely to have mixed brain pathologies compared with age-, sex-, education-, and cognition-matched white decedents with AD dementia. PMID:26180136
The neurologist facing pain in dementia.
Álvaro González, Luis Carlos
2015-01-01
Ageing, a common background in dementia, is usually associated with painful disorders. Nevertheless, the use of analgesics is limited due to poor communication. On the other hand, dementia lesions are placed in the nociceptive pathways. For this reason, the painful experience becomes different and distinctive for every lesional type. The lateral nociceptive pathway (lateral thalamic nuclei and primary parietal cortex), which is in charge of the primary pain perception, is preserved in dementia. Thereafter, the shear painful perception, including pain intensity and threshold, remains unmodified. Distinctly, the medial pain pathways are affected by dementia lesions. In this pathway are included: the intralaminar thalamic nuclei, the pons (locus ceruleus:LC), the mesencephalon (periaacueductal grey substance: PGS), the hypothalamus (paraventricular nuclei, mamilary tuberculum) and different areas of the parietal (primary, secondary, operculum), temporal (amigdala, hypoccampus) and frontal (anterior cingular: ACC). As a consequence, the features of pain executed by these areas will be compromised: the cognitive assessment, the mood and emotion inherent to pain, the pain memory or the autonomic responses are modified in dementia. Specifically, in Alzheimer's disease (AD) there is a reduction in the anticipatory and avoidance responses and also a flattening of the autonomic responses. These are essentially secondary to the degenerative changes in the medial temporal (pain memory) and ACC (cognitive and mood aspects) areas. In vascular dementias, there is a cortico-subcortical deafferentation secondary to the white matter lesions. The consequence is the presence of hyperpathy and hyperalgesia. In the frontotemporal dementias, there is a reduction in pain expressivity. It is linked to the lesions in the orbitofrontal and anterior temporal areas, which are responsible of the emotional aspects of pain. In Parkinson's disease, painful conditions are a common characteristic
Relationship between Eating Disturbance and Dementia Severity in Patients with Alzheimer’s Disease
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
Depression and dementias among military veterans.
Byers, Amy L; Yaffe, Kristine
2014-06-01
Depression is very common throughout the course of veterans' lives, and dementia is common in late life. Previous studies suggest an association between depression and dementia in military veterans. The most likely biologic mechanisms that may link depression and dementia among military veterans include vascular disease, changes in glucocorticoid steroids and hippocampal atrophy, deposition of β-amyloid plaques, inflammatory changes, and alterations of nerve growth factors. In addition, military veterans often have depression comorbid with posttraumatic stress disorder or traumatic brain injury. Therefore, in military veterans, these hypothesized biologic pathways going from depression to dementia are more than likely influenced by trauma-related processes. Treatment strategies for depression, posttraumatic stress disorder, or traumatic brain injury could alter these pathways and as a result decrease the risk for dementia. Given the projected increase of dementia, as well as the projected increase in the older segment of the veteran population, in the future, it is critically important that we understand whether treatment for depression alone or combined with other regimens improves cognition. In this review, we summarize the principal mechanisms of this relationship and discuss treatment implications in military veterans. Copyright © 2014 The Alzheimer's Association. All rights reserved.
Bilingualism, dementia, cognitive and neural reserve.
Perani, Daniela; Abutalebi, Jubin
2015-12-01
We discuss the role of bilingualism as a source of cognitive reserve and we propose the putative neural mechanisms through which lifelong bilingualism leads to a neural reserve that delays the onset of dementia. Recent findings highlight that the use of more than one language affects the human brain in terms of anatomo-structural changes. It is noteworthy that recent evidence from different places and cultures throughout the world points to a significant delay of dementia onset in bilingual/multilingual individuals. This delay has been reported not only for Alzheimer's dementia and its prodromal mild cognitive impairment phase, but also for other dementias such as vascular and fronto-temporal dementia, and was found to be independent of literacy, education and immigrant status. Lifelong bilingualism represents a powerful cognitive reserve delaying the onset of dementia by approximately 4 years. As to the causal mechanism, because speaking more than one language heavily relies upon executive control and attention, brain systems handling these functions are more developed in bilinguals resulting in increases of gray and white matter densities that may help protect from dementia onset. These neurocognitive benefits are even more prominent when second language proficiency and exposure are kept high throughout life.
Gene Therapy Models of Alzheimer’s Disease and Other Dementias
Combs, Benjamin; Kneynsberg, Andrew; Kanaan, Nicholas M.
2016-01-01
Dementias are among the most common neurological disorders, and Alzheimer’s disease (AD) is the most common cause of dementia worldwide. AD remains a looming health crisis despite great efforts to learn the mechanisms surrounding the neuron dysfunction and neurodegeneration that accompanies AD primarily in the medial temporal lobe. In addition to AD, a group of diseases known as frontotemporal dementias (FTDs) are degenerative diseases involving atrophy and degeneration in the frontal and temporal lobe regions. Importantly, AD and a number of FTDs are collectively known as tauopathies due to the abundant accumulation of pathological tau inclusions in the brain. The precise role tau plays in disease pathogenesis remains an area of strong research focus. A critical component to effectively study any human disease is the availability of models that recapitulate key features of the disease. Accordingly, a number of animal models are currently being pursued to fill the current gaps in our knowledge of the causes of dementias and to develop effective therapeutics. Recent developments in gene therapy-based approaches, particularly in recombinant adeno-associated viruses (rAAVs), have provided new tools to study AD and other related neurodegenerative disorders. Additionally, gene therapy approaches have emerged as an intriguing possibility for treating these diseases in humans. This chapter explores the current state of rAAV models of AD and other dementias, discuss recent efforts to improve these models, and describe current and future possibilities in the use of rAAVs and other viruses in treatments of disease. PMID:26611599
Depression and Risk of Developing Dementia
Byers, Amy L.; Yaffe, Kristine
2012-01-01
Depression is highly common throughout the life course and dementia is common in late life. The literature suggests an association between depression and dementia, and growing evidence implies that timing of depression may be important to defining the nature of the association. In particular, earlier-life depression or depressive symptoms consistently have been shown to be associated with a 2-fold or greater increase in risk of dementia. In contrast, studies of late-life depression have been more conflicting but the majority support an association; yet, the nature of this association is unclear (e.g., if depression is a prodrome or consequence or risk factor for dementia). The likely biological mechanisms linking depression to dementia include vascular disease, alterations in glucocorticoid steroids and hippocampal atrophy, increased deposition of β-amyloid plaques, inflammatory changes, and deficits of nerve growth factors. Treatment strategies for depression might intervene on these pathways and in turn may alter risk for dementia. Given the projected increase of dementia in the coming decades, it is critically important that we understand whether treatment for depression alone or combined with other regimens improves cognition. In this review, we summarize and analyze current evidence for late-life and earlier-life depression and their relationship to dementia, discuss the primary underlying mechanisms and implications for treatment. PMID:21537355
Whitfield, David R; Vallortigara, Julie; Alghamdi, Amani; Hortobágyi, Tibor; Ballard, Clive; Thomas, Alan J; O'Brien, John T; Aarsland, Dag; Francis, Paul T
2015-02-01
Depression is a common symptom in dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD), and Alzheimer disease (AD), yet its molecular basis remains unclear and current antidepressants do not appear to be effective. Cerebral zinc has been implicated in depression and synaptic dysfunction. We investigated the relationship between synaptic zinc regulation (for which zinc transporter 3 [ZnT3] is responsible) and depression in a large clinicopathologic study. We examined brains from people with PDD (N = 29), DLB (N = 27), and AD (N = 15) and comparison subjects without depression or dementia (N = 24). Individuals were categorized according to the presence and severity of depression (on a scale of 0-3) based on standardized assessments during life (principally Neuropsychiatric Inventory). Western blotting was used to determine ZnT3 levels in Brodmann area 9 (BA9), and regression analysis was used to determine the relationship between ZnT3 and depression. Reductions in ZnT3 in BA9 were significantly associated with elevated depression scores in the study cohort (β = -0.351, df = 93, t = -3.318 p = 0.0004). This association remained when only individuals with DLB, PDD, and no dementia or depression were examined (β = -0.347, df = 78, t = -3.271, p = 0.002) or only individuals with AD and no dementia or depression were examined (β = -0.433, df = 37, t = -2.924, p = 0.006). Although decreased zinc levels have been implicated in the genesis of depression in animal models and in major depressive disorder in humans, this study provides the first evidence of a role for zinc in depression in people with dementia and highlights zinc metabolism as a therapeutic target. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
Multicentre population-based dementia prevalence survey in Japan: a preliminary report.
Ikejima, Chiaki; Hisanaga, Akito; Meguro, Kenichi; Yamada, Tatsuo; Ouma, Shinji; Kawamuro, Yu; Hyouki, Kazushi; Nakashima, Kenji; Wada, Kenji; Yamada, Shigeto; Watanabe, Itaru; Kakuma, Tatsuyuki; Aoyama, Yoshiko; Mizukami, Katsuyoshi; Asada, Takashi
2012-06-01
Community-based surveys were performed in seven rural areas in Japan to investigate the prevalence of dementia and illnesses causing dementia. A total of 5431 elderly subjects were selected based on census data from 1 October 2009. In total, 3394 participants were examined (participation rate: 62.5%), and 768 dementia cases and 529 mild cognitive impairment cases were identified. Of the illnesses causing dementia, Alzheimer's disease was the most frequent (67.4%), followed by vascular dementia (18.9%), dementia with Lewy body disease (4.6%), mixed dementia (4.2%) and other illnesses. The prevalence of dementia according to 5-year age strata between 65 and 99 years was 5.8-77.7% among the participants. The prevalence of dementia in this study was higher than in previous reports in Japan and other countries. To verify the upward trend of dementia prevalence and its background factors, we have scheduled surveys for three other urban areas in 2011-2012. © 2012 The Authors. Psychogeriatrics © 2012 Japanese Psychogeriatric Society.
Ocular Fundus Photography as a Tool to Study Stroke and Dementia.
Cheung, Carol Y; Chen, Christopher; Wong, Tien Y
2015-10-01
Although cerebral small vessel disease has been linked to stroke and dementia, due to limitations of current neuroimaging technology, direct in vivo visualization of changes in the cerebral small vessels (e.g., cerebral arteriolar narrowing, tortuous microvessels, blood-brain barrier damage, capillary microaneurysms) is difficult to achieve. As the retina and the brain share similar embryological origin, anatomical features, and physiologic properties with the cerebral small vessels, the retinal vessels offer a unique and easily accessible "window" to study the correlates and consequences of cerebral small vessel diseases in vivo. The retinal microvasculature can be visualized, quantified and monitored noninvasively using ocular fundus photography. Recent clinic- and population-based studies have demonstrated a close link between retinal vascular changes seen on fundus photography and stroke and dementia, suggesting that ocular fundus photography may provide insights to the contribution of microvascular disease to stroke and dementia. In this review, we summarize current knowledge on retinal vascular changes, such as retinopathy and changes in retinal vascular measures with stroke and dementia as well as subclinical makers of cerebral small vessel disease, and discuss the possible clinical implications of these findings in neurology. Studying pathologic changes of retinal blood vessels may be useful for understanding the etiology of various cerebrovascular conditions; hence, ocular fundus photography can be potentially translated into clinical practice. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
FDG-PET in early AD diagnosis.
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.
Kuan, Yi-Chun; Huang, Kuang-Wei; Yen, Der-Jen; Hu, Chaur-Jong; Lin, Cheng-Li; Kao, Chia-Hung
2016-10-01
The effects of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) on dementia risk in patients with type 2 diabetes mellitus (DM) and hypertension remain unknown. We investigated the effects of ACEIs and ARBs on dementia risk in patients with type 2 DM and hypertension. We conducted a cohort study by using the Taiwan National Health Insurance Research Database. We included 2377 patients receiving ACEIs and 1780 patients receiving ARBs in the ACEI and ARB cohorts, respectively. We included a comparable number of patients not receiving ACEIs and ARBs as controls in the non-ACEI and non-ARB cohorts through propensity score matching. The effect of ACEIs and ARBs on dementia risk was estimated through multivariate Cox proportional hazard regression after adjustment for several confounding factors. During the 12-year follow-up period, compared with the non-ACEI cohort, all-cause dementia risk decreased by 26% in the ACEI cohort [hazard ratio (HR)=0.74, 95% confidence interval (CI)=0.56-0.96]. The all-cause dementia risk was nearly 40% lower in the ARB cohort than in the non-ARB cohort (HR=0.60, 95% CI=0.37-0.97). These drugs prevented the occurrence of vascular dementia (VD), however, this effect was nonsignificant for Alzheimer's dementia (AD). Treatment duration- and dosage-related protection effects on dementia occurrence were observed. ACEIs and ARBs may effectively prevent all-cause dementia, particularly VD, in patients with type 2 DM and hypertension. Moreover, compared with ACEIs, ARBs appear to be more advantageous in dementia prevention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Diagnostic criteria for vascular cognitive disorders: a VASCOG statement
Sachdev, Perminder; Kalaria, Raj; O’Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V.; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip
2014-01-01
Background Several sets of diagnostic criteria have been published for vascular dementia (VaD) since the 1960s. The continuing ambiguity in VaD definition warrants a critical re-examination. Methods Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the DSM-5 Task Force. Results Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent co-occurrence of Alzheimer’s disease pathology emphasized. Conclusions The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathological validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved. PMID:24632990
Ten-year incidence of dementia in a rural elderly US community population: the MoVIES Project.
Ganguli, M; Dodge, H H; Chen, P; Belle, S; DeKosky, S T
2000-03-14
To determine incidence rates by age, sex, and education of overall dementia and probable/ possible AD in a largely rural community. Ten-year prospective study of a randomly selected community sample aged 65+; biennial cognitive screening followed by standardized clinical evaluation. Incidence rates were estimated for overall dementia (Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised, criteria and Clinical Dementia Rating [CDR]) and for probable/possible AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria). The cohort consisted of 1,298 individuals free of dementia at study entry. Among these, 199 incident (new) cases of overall (all-cause) dementia with CDR stage > or = 0.5, including 110 with CDR > or = 1, were detected during follow-up. Among the incident cases, 153 (76.9%) had probable/ possible AD. Age-specific incidence rates are reported for all dementia and for probable/possible AD, by sex and CDR stage. Among all-cause dementias with CDR = 0.5, controlling for age and education, men had a higher incidence rate than women. In the same group, those with less than high school education had significantly higher incidence rates than those with more education. Rates did not vary significantly by sex or education for probable/possible AD or for dementia with CDR > or = 1. Incidence rates of all dementias and of AD increased with age; men and those with lesser education had higher rates of possible/incipient dementia (CDR = 0.5) in this community. Potential explanations for these sex and education effects are discussed.
Amyloid PET in neurodegenerative diseases with dementia.
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.
Severity of CIND and MCI predict incidence of dementia in an ischemic stroke cohort
Narasimhalu, K; Ang, S; De Silva, D A.; Wong, M -C.; Chang, H -M.; Chia, K -S.; Auchus, A P.; Chen, C
2009-01-01
Background: The utility of poststroke cognitive status, namely dementia, cognitive impairment no dementia (CIND), mild cognitive impairment (MCI), and no cognitive impairment (NCI), in predicting dementia has been previously examined. However, no studies to date have compared the ability of subtypes of MCI and CIND to predict dementia in a poststroke population. Methods: A cohort of ischemic stroke patients underwent neuropsychological assessment annually for up to 5 years. Dementia was defined using the DSM-IV criteria. Univariate and multivariable Cox proportional regression was performed to determine the ability of MCI subtypes, CIND severity, and individual domains of impairment to predict dementia. Results: A total of 362 patients without dementia were followed up for a mean of 3.4 years (17% drop out), with 24 developing incident dementia. Older age, previous and recurrent stroke, and CIND and MCI subtypes were significant predictors of dementia. In multivariable analysis controlling for treatment allocation, patients who were older, had previous or recurrent stroke, and had either CIND moderate or multiple domain MCI with amnestic component were at elevated risk for dementia. In multivariable domain analysis, recurrent strokes, age, and previous strokes, verbal memory, and visual memory were significant predictors of dementia. Receiver operating characteristic curve analysis showed that CIND moderate (area under the curve: 0.893) and multiple domain MCI with amnestic component (area under the curve: 0.832) were significant predictors of conversion to dementia. All other classifications of cognitive impairment had areas under the curve less than 0.7. Conclusion: Stroke patients with cognitive impairment no dementia (CIND) moderate are at higher risk of developing dementia, while CIND mild patients are not at increased risk of developing dementia. GLOSSARY AD = Alzheimer disease; AUC = area under the curve; CI = confidence interval; CIND = cognitive impairment
Recognition of dementia in ancient China.
Liu, Jia; Wang, Lu-Ning; Tian, Jin-Zhou
2012-12-01
A search of previous records in the literatures was done to summarize the opinions for dementia in ancient China. The earliest description of dementia was traced in the Yellow emperor's internal classic, a book written 2000 years ago. Hua Tuo (AD 140-208) in Han Dynasty first denominated "dementia" in the book, Hua Tuo Shen Yi Mi Zhuan. The pathogenesis of dementia could be generalized as the insufficiency of Qi, a flowing energy; the stagnation of phlegm, a harmful liquid substance in the body; and the blood stasis, which were also regarded as therapeutic targets. Therefore, we can conclude that dementia has been recognized and investigated in traditional Chinese medicine, which is definitely before the industrial civilization era. Copyright © 2012 Elsevier Inc. All rights reserved.
Katz, Mindy J; Lipton, Richard B; Hall, Charles B; Zimmerman, Molly E; Sanders, Amy E; Verghese, Joe; Dickson, Dennis W; Derby, Carol A
2012-01-01
As the population ages, the need to characterize rates of cognitive impairment and dementia within demographic groups defined by age, sex, and race becomes increasingly important. There are limited data available on the prevalence and incidence of amnestic mild cognitive impairment (aMCI) and nonamnestic mild cognitive impairment (naMCI) from population-based studies. The Einstein Aging Study, a systematically recruited community-based cohort of 1944 adults aged 70 or older (1168 dementia free at baseline; mean age, 78.8 y; average follow-up, 3.9 y), provides the opportunity to examine the prevalence and incidence rates for dementia, Alzheimer dementia (AD), aMCI, and naMCI by demographic characteristics. Dementia prevalence was 6.5% (4.9% AD). Overall dementia incidence was 2.9/100 person-years (2.3/100 person-years for AD). Dementia and AD rates increased with age but did not differ by sex. Prevalence of aMCI was 11.6%, and naMCI prevalence was 9.9%. aMCI incidence was 3.8 and naMCI incidence was 3.9/100 person-years. Rates of aMCI increased significantly with age in men and in blacks; sex, education, and race were not significant risk factors. In contrast, naMCI incidence did not increase with age; however, blacks were at higher risk compared with whites, even when controlling for sex and education. Results highlight the public health significance of preclinical cognitive disease.
Appelhof, Britt; Bakker, Christian; Van Duinen-van den Ijssel, Jeannette C L; Zwijsen, Sandra A; Smalbrugge, Martin; Verhey, Frans R J; de Vugt, Marjolein E; Zuidema, Sytse U; Koopmans, Raymond T C M
2017-01-01
The aims of this study are to (1) explore the determinants of quality of life (QoL) in nursing home residents with young-onset dementia (YOD), (2) investigate whether there are differences between dementia subtypes (Alzheimer dementia, vascular/mixed dementia, frontotemporal dementia, other) regarding these determinants, and (3) compare QoL profiles of YOD nursing home residents across dementia subtypes. This cross-sectional study included 207 nursing home residents. Multilevel modeling was used to determine the relationships between QoL and neuropsychiatric symptoms (NPS), dementia severity, psychotropic drug use (PDU), dementia subtype, age, and gender. Additional multilevel models were used to compare aspects of QoL between dementia subtypes. Residents' QoL was negatively associated with advanced dementia, PDU, and NPS. In general, the relationships between the determinants and QoL were similar across the dementia subtypes. Aspects of QoL differed by dementia subtype. Residents with frontotemporal dementia showed less negative emotions, accepted more help and experienced better quality of relationships with professional caregivers, had a more positive self-image, felt more comfortable in the nursing home environment, and experienced lower quality of social relationships. Considering the high rates of NPS and PDU in YOD residents and their negative associations with QoL, we recommend emphasizing services to manage and reduce NPS and PDU in nursing home residents with YOD. Furthermore, our findings suggest accounting for differences in aspects of QoL by dementia subtype to address specific needs and thereby improve QoL. © 2017 The Author(s) Published by S. Karger AG, Basel.
Gallaway, Patrick J.; Miyake, Hiroji; Buchowski, Maciej S.; Shimada, Mieko; Yoshitake, Yutaka; Kim, Angela S.; Hongu, Nobuko
2017-01-01
A recent alarming rise of neurodegenerative diseases in the developed world is one of the major medical issues affecting older adults. In this review, we provide information about the associations of physical activity (PA) with major age-related neurodegenerative diseases and syndromes, including Alzheimer’s disease, vascular dementia, and mild cognitive impairment. We also provide evidence of PA’s role in reducing the risks of these diseases and helping to improve cognitive outcomes in older adults. Finally, we describe some potential mechanisms by which this protective effect occurs, providing guidelines for future research. PMID:28230730
Stereotypic behaviors in degenerative dementias.
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.
Depression in dementia with Lewy bodies: A comparison with Alzheimer's disease
Chiu, Pai-Yi; Wang, Chein-Wei; Tsai, Chun-Tang; Li, Shin-Hua; Lin, Chih-Li; Lai, Te-Jen
2017-01-01
Background Depression is highly associated with dementia, and this study will compare the frequencies, severity, and symptoms of depression between dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). Methods Frequency of depression was determined according to the DSM-IV criteria for major depression or the National Institute of Mental Health criteria for depression in AD (NIMH-dAD). Severity of depression were assessed using the Hamilton Depression Rating Scale, the Cornell Scale for Depression in Dementia, and the depression subscale in Neuropsychiatric Inventory. The rates of depressive symptoms were compared between AD and DLB. Results A total of 312 patients were investigated (AD/DLB = 241/71). The frequency of major depression was significantly higher (p = 0.017) in DLB (19.7%) than in AD (8.7%). The higher frequency of depression in DLB was not reproduced by using the NIMH-dAD criteria (DLB: AD = 43.7%: 33.2%; p = 0.105). The severity of depression was higher in DLB than in AD according to the Hamilton Depression Rating Scale (p < 0.001) and the Cornell Scale for Depression in Dementia (p < 0.001). Among depressive symptoms, pervasive anhedonia had the highest odds ratio in DLB compared with AD. Conclusion This is the first study using the NIMH-dAD criteria to investigate the frequency of depression in DLB. Our study shows that co-morbid major depression is more frequent in DLB than in AD. Pervasive anhedonia had the greatest value for the differential diagnosis of depression between DLB and AD. PMID:28617831
Omega-3 fatty acids: benefits for cardio-cerebro-vascular diseases.
Siegel, G; Ermilov, E
2012-12-01
Intracranial artery stenosis (ICAS) is a narrowing of an intracranial artery, which is a common etiology for ischemic stroke. In this commentary, we review key aspects of the discrimination between non-stroke controls and ischemic stroke patients on the background of phospholipid ω3-fatty acid (DHA, EPA) composition. The discussion is embedded in the presentation of general effects of long-chain ω3 polyunsaturated fatty acids (PUFAs) in cardio-cerebro-vascular diseases (CCVDs) and Alzheimer dementia (AD). ICAS is a common stroke subtype and has emerged as a major factor in recurrent stroke and vascular mortality. DHA and EPA are important fatty acids to distinguish between NCAS (no cerebral arteriosclerotic stenosis) and ICAS in stroke. The risk of ICAS is inversely correlated with the DHA content in phospholipids. Furthermore, a mechanistic explanation has been proposed for the beneficial effects of PUFAs in CCVDs and AD. Whereas the beneficial effects of EPA/DHA for cardiovascular diseases and stroke seem to be beyond question, preventive effects in patients with very mild cognitive dysfunction and beginning Alzheimer's disease undoubtedly need confirmation by larger clinical trials. A collaborative international basic science approach is warranted considering cautiously designed studies in order to avoid ethical problems. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Delayed-onset dementia after stroke or transient ischemic attack.
Mok, Vincent C T; Lam, Bonnie Y K; Wang, Zhaolu; Liu, Wenyan; Au, Lisa; Leung, Eric Y L; Chen, Sirong; Yang, Jie; Chu, Winnie C W; Lau, Alexander Y L; Chan, Anne Y Y; Shi, Lin; Fan, Florence; Ma, Sze H; Ip, Vincent; Soo, Yannie O Y; Leung, Thomas W H; Kwok, Timothy C Y; Ho, Chi L; Wong, Lawrence K S; Wong, Adrian
2016-11-01
Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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.
The 32-year relationship between cholesterol and dementia from midlife to late life.
Mielke, M M; Zandi, P P; Shao, H; Waern, M; Östling, S; Guo, X; Björkelund, C; Lissner, L; Skoog, I; Gustafson, D R
2010-11-23
Cellular and animal studies suggest that hypercholesterolemia contributes to Alzheimer disease (AD). However, the relationship between cholesterol and dementia at the population level is less clear and may vary over the lifespan. The Prospective Population Study of Women, consisting of 1,462 women without dementia aged 38-60 years, was initiated in 1968-1969 in Gothenburg, Sweden. Follow-ups were conducted in 1974-1975, 1980-1981, 1992-1993, and 2000-2001. All-cause dementia was diagnosed according to DSM-III-R criteria and AD according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Cox proportional hazards regression examined baseline, time-dependent, and change in cholesterol levels in relation to incident dementia and AD among all participants. Analyses were repeated among participants who survived to the age of 70 years or older and participated in the 2000-2001 examination. Higher cholesterol level in 1968 was not associated with an increased risk of AD (highest vs lowest quartile: hazard ratio [HR] 2.82, 95% confidence interval [CI] 0.94-8.43) among those who survived to and participated in the 2000-2001 examination. While there was no association between cholesterol level and dementia when considering all participants over 32 years, a time-dependent decrease in cholesterol over the follow-up was associated with an increased risk of dementia (HR 2.35, 95% CI 1.22-4.58). These data suggest that midlife cholesterol level is not associated with an increased risk of AD. However, there may be a slight risk among those surviving to an age at risk for dementia. Declining cholesterol levels from midlife to late life may better predict AD risk than levels obtained at one timepoint prior to dementia onset. Analytic strategies examining this and other risk factors across the lifespan may affect interpretation of results.
Vascular signaling abnormalities in Alzheimer disease.
Grammas, Paula; Sanchez, Alma; Tripathy, Debjani; Luo, Ester; Martinez, Joseph
2011-08-01
Our laboratory has documented that brain microvessels derived from patients with Alzheimer disease (AD) express or release a myriad of factors that have been implicated in vascular activation and angiogenesis. In addition, we have documented that signaling cascades associated with vascular activation and angiogenesis are upregulated in AD-derived brain microvessels. These results are consistent with emerging data suggesting that factors and processes characteristic of vascular activation and angiogenesis are found in the AD brain. Despite increases in proangiogenic factors and signals in the AD brain, however, evidence for increased vascularity in AD is lacking. Cerebral hypoperfusion/hypoxia, a potent stimulus for vascular activation and angiogenesis, triggers hypometabolic, cognitive, and degenerative changes in the brain. In our working model, hypoxia stimulates the angiogenic process; yet, there is no new vessel growth. Therefore, there are no feedback signals to shut off vascular activation, and endothelial cells become irreversibly activated. This activation results in release of a large number of proteases, inflammatory proteins, and other gene products with biologic activity that can injure or kill neurons. Pathologic activation of brain vasculature may contribute noxious mediators that lead to neuronal injury and disease processes in AD brains. This concept is supported by preliminary experiments in our laboratory, which show that pharmacologic blockade of vascular activation improves cognitive function in an animal model of AD. Thus, "vascular activation" could be a novel, unexplored therapeutic target in AD.
Observing the preservation and decline of abilities in dementias.
Williams, Robert B; French, Laurence A; Ferrell, Richard B
2006-12-01
The Brief Cognitive Rating Scale facilitated observation of the preservation and decline of abilities due to dementias among 73 female and 52 male residents at nursing homes in a northeastern and southwestern state. They ranged in age from 41 to 102 years (M=78, SD = 10.5). Dementia diagnoses included presenile Alzheimers, senile Alzheimers, Vascular Dementia, Dementia secondary to Huntington's Disease, Dementia due to Pick's Disease, and Korsakoff Dementia secondary to chronic alcoholism. Their ratings on tasks of the scale were submitted to an order analysis procedure to explore the order of decline and preservation of abilities. Results for these nursing home residents show an apparent order: loss singly or concurrently of the abilities of concentration and recent memory, followed by past memory and functioning and self-care that also appeared to be unpredictably lost or preserved singly or concurrently by different individuals, and, finally, by orientation that was preserved in 82% of the subjects.
Ghorani-Azam, Adel; Sepahi, Samaneh; Khodaverdi, Elham; Mohajeri, Seyed Ahmad
2018-05-22
Vascular dementia (VaD) generally refers to memory deficits and cognitive abnormalities that are resulted from vascular disease. In this study, we aimed to systematically review the literature wherein therapeutic effects of medicinal plants have been studied on VaD. A systematic literature search was performed in the PubMed, Scopus, Web of Science, Google Scholar, and other databases using VaD, and medicinal plants as key terms. No strict inclusion criteria were defined, and almost all clinical studies were included. A total of 524 articles were found, of which only 28 relevant articles with 3461 studied patients were included to this systematic review. The results showed that medicinal plants, particularly Sancaijiangtang and Ginkgo biloba could improve behavioral and psychological symptoms, working memory, Mini-Mental State Examination, and activities of daily living as well as neuropsychiatric features. It was also shown that the age, average progression of the disease, and the type of folk medicines effective in treating the disease are important factors in the management of VaD. The results of this review indicated that herbal therapy can be a potential candidate in the treatment of VaD; however, further studies are needed to confirm such efficiency. Copyright © 2018 John Wiley & Sons, Ltd.
[Depression in dementia with Lewy bodies].
Sakai, Kazuo; Yamane, Yumiko; Yamamoto, Yasuji; Maeda, Kiyoshi
2013-01-01
Depression is a risk factor for dementia in general, including Alzheimer's disease (AD), its premorbid signs are commonly observed, and the morbidity of depression is higher in dementia patients. Dementia with Lewy bodies (DLB) is considered to have an even higher depression prevalence and premorbid depression rate than other dementias such as AD. This led to depression being listed as a supportive feature in the 2005 criteria for the clinical diagnosis of DLB. However, studies investigating the difference in depression between AD and DLB failed to show consistent results. We examined the Geriatric Depression Scale score, which is designed specifically to rate depression in the elderly, for DLB and AD patients. The scores for DLB patients were twice as high as those for AD patients. There was no correlation between the GDS score and age, sex, or Mini-Mental Sate Examination scores. Depression-specific symptoms were more frequent in the DLB group than non-specific symptoms, while less than one third of DLB patients with very high GDS scores were diagnosed with depression or prescribed antidepressants for depressive symptoms. Other researchers reported that depression of DLB was associated with a higher prevalence of psychiatric symptoms other than major depression, and suggested that depression of DLB might be a part of psychiatric syndrome. There has been no systematic study on the validity or risk of pharmacological therapy, as well as the necessity of intervention, for depression or a high GDS score in DLB. Therefore, intervention must rely on the clinical decision of each doctor. In spite of the paucity of current findings, studies on depression of DLB may play a key role in the elucidation of its neuropathology and psychopathology and offer a new view point on understanding depression itself.
Prevalence of Pain in Nursing Home Residents: The Role of Dementia Stage and Dementia Subtypes.
van Kooten, Janine; Smalbrugge, Martin; van der Wouden, Johannes C; Stek, Max L; Hertogh, Cees M P M
2017-06-01
To study pain prevalence, pain type, and its pharmacological treatment in Dutch nursing home residents in relation to dementia subtype and dementia severity. Data were collected as part of the PAINdemiA study, an observational cross-sectional study conducted between May 2014 and December 2015. Ten nursing homes in the Netherlands. A total of 199 nursing home residents in various stages of dementia. We collected data on pain (by observation: MOBID-2 Pain Scale and by self-report scales), pain type, pain medication, dementia subtype, dementia severity (GDS), and demographic features. In the whole sample, the prevalence of pain was 43% (95% confidence interval 36%-50%) using the MOBID-2 Pain Scale. Regardless of regularly scheduled analgesics, approximately one-third of the residents with pain suffered from moderate to severe pain. Pain assessment with the MOBID-2 Pain Scale showed no difference in pain between dementia subtypes, but residents with more severe dementia experienced pain more often than those with less severe dementia (27% vs 15%). The prevalence of self-reported pain was significantly higher in residents with vascular dementia (VaD) (54%) compared with those with Alzheimer disease (18%) and other dementia subtypes (14%). Nociceptive pain was the predominant type of pain (72%) followed by mixed pain (25%). Acetaminophen was the most prescribed analgesic (80%). Most of the participating nursing home residents had no pain; however, pain was observed more often in residents with severe dementia, whereas residents in the early stages of VaD self-reported pain more often that those with other dementia subtypes. As one-third of the residents with clinically relevant pain had moderate to severe pain regardless of using pain medication, more focus should be on how pain management could use more tailored approaches and be regularly adjusted to individual needs. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by
A clinicopathological approach to the diagnosis of dementia
Elahi, Fanny M.; Miller, Bruce L.
2018-01-01
The most definitive classification systems for dementia are based on the underlying pathology which, in turn, is categorized largely according to the observed accumulation of abnormal protein aggregates in neurons and glia. These aggregates perturb molecular processes, cellular functions and, ultimately, cell survival, with ensuing disruption of large-scale neural networks subserving cognitive, behavioural and sensorimotor functions. The functional domains affected and the evolution of deficits in these domains over time serve as footprints that the clinician can trace back with various levels of certainty to the underlying neuropathology. The process of phenotyping and syndromic classification has substantially improved over decades of careful clinicopathological correlation, and through the discovery of in vivo biomarkers of disease. Here, we present an overview of the salient features of the most common dementia subtypes — Alzheimer disease, vascular dementia, frontotemporal dementia and related syndromes, Lewy body dementias, and prion diseases — with an emphasis on neuropathology, relevant epidemiology, risk factors, and signature signs and symptoms. PMID:28708131
Clinical features and multidisciplinary approaches to dementia care
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
Financial errors in dementia: Testing a neuroeconomic conceptual framework
Chiong, Winston; Hsu, Ming; Wudka, Danny; Miller, Bruce L.; Rosen, Howard J.
2013-01-01
Financial errors by patients with dementia can have devastating personal and family consequences. We developed and evaluated a neuroeconomic conceptual framework for understanding financial errors across different dementia syndromes, using a systematic, retrospective, blinded chart review of demographically-balanced cohorts of patients with Alzheimer’s disease (AD, n=100) and behavioral variant frontotemporal dementia (bvFTD, n=50). Reviewers recorded specific reports of financial errors according to a conceptual framework identifying patient cognitive and affective characteristics, and contextual influences, conferring susceptibility to each error. Specific financial errors were reported for 49% of AD and 70% of bvFTD patients (p = 0.012). AD patients were more likely than bvFTD patients to make amnestic errors (p< 0.001), while bvFTD patients were more likely to spend excessively (p = 0.004) and to exhibit other behaviors consistent with diminished sensitivity to losses and other negative outcomes (p< 0.001). Exploratory factor analysis identified a social/affective vulnerability factor associated with errors in bvFTD, and a cognitive vulnerability factor associated with errors in AD. Our findings highlight the frequency and functional importance of financial errors as symptoms of AD and bvFTD. A conceptual model derived from neuroeconomic literature identifies factors that influence vulnerability to different types of financial error in different dementia syndromes, with implications for early diagnosis and subsequent risk prevention. PMID:23550884
[Clinical Neuropsychology of Dementia with Lewy Bodies].
Nagahama, Yasuhiro
2016-02-01
Dementia with Lewy bodies (DLB) shows lesser memory impairment and more severe visuospatial disability than Alzheimer disease (AD). Although deficits in both consolidation and retrieval underlie the memory impairment, retrieval deficit is predominant in DLB. Visuospatial dysfunctions in DLB are related to the impairments in both ventral and dorsal streams of higher visual information processing, and lower visual processing in V1/V2 may also be impaired. Attention and executive functions are more widely disturbed in DLB than in AD. Imitation of finger gestures is impaired more frequently in DLB than in other mild dementia, and provides additional information for diagnosis of mild dementia, especially for DLB. Pareidolia, which lies between hallucination and visual misperception, is found frequently in DLB, but its mechanism is still under investigation.
Shams, S; Martola, J; Granberg, T; Li, X; Shams, M; Fereshtehnejad, S M; Cavallin, L; Aspelin, P; Kristoffersen-Wiberg, M; Wahlund, L O
2015-04-01
Cerebral microbleeds are thought to represent cerebral amyloid angiopathy when in lobar regions of the brain and hypertensive arteriopathy when in deep and infratentorial locations. By studying cerebral microbleeds, their topography, and risk factors, we aimed to gain an insight into the vascular and amyloid pathology of dementia diagnoses and increase the understanding of cerebral microbleeds in dementia. We analyzed 1504 patients (53% women; mean age, 63 ± 10 years; 10 different dementia diagnoses) in this study. All patients underwent MR imaging as part of the dementia investigation, and all their clinical parameters were recorded. Among the 1504 patients with dementia, 22% had cerebral microbleeds. Cerebral microbleed topography was predominantly lobar (P = .01) and occipital (P = .007) in Alzheimer disease. Patients with cerebral microbleeds were significantly older (P < .001), were more frequently male (P < .001), had lower cognitive scores (P = .006), and more often had hypertension (P < .001). Risk factors for cerebral microbleeds varied depending on the dementia diagnosis. Odds ratios for having cerebral microbleeds increased with the number of risk factors (hypertension, hyperlipidemia, diabetes, male sex, and age 65 and older) in the whole patient group and increased differently in the separate dementia diagnoses. Prevalence, topography, and risk factors of cerebral microbleeds vary depending on the dementia diagnosis and reflect the inherent pathology of different dementia diagnoses. Because cerebral microbleeds are seen as possible predictors of intracerebral hemorrhage, their increasing prevalence with an increasing number of risk factors, as shown in our study, may require taking the number of risk factors into account when deciding on anticoagulant therapy in dementia. © 2015 by American Journal of Neuroradiology.
Morris, John C.
2012-01-01
Objective To evaluate the potential impact of revised criteria for mild cognitive impairment (MCI), developed by a Workgroup sponsored by the National Institute on Aging and the Alzheimer’s Association, on the diagnosis of very mild and mild Alzheimer disease (AD) dementia. Design Retrospective review of ratings of functional impairment across diagnostic categories. Participants: The functional ratings of individuals (N = 17,535) with normal cognition, MCI, or AD dementia who were evaluated at Alzheimer’s Disease Centers and submitted to the National Alzheimer’s Coordinating Center were assessed in accordance with the definition of “functional independence” allowed by the revised criteria. Methods Pairwise demographic differences between the 3 diagnostic groups were tested using t-tests for continuous variables and chi-square for categorical variables. Results Almost all (99.8%) of individuals currently diagnosed with very mild AD dementia and the large majority (92.7%) of those diagnosed with mild AD dementia could be reclassified as MCI with the revised criteria, based on their level of impairment in the Clinical Dementia Rating domains for performance of instrumental activities of daily living in the community and at home. Large percentages of these AD dementia individuals also meet the revised “functional independence” criterion for MCI as measured by the Functional Assessment Questionnaire. Conclusions The categorical distinction between MCI and milder stages of Alzheimer dementia has been compromised by the revised criteria. The resulting diagnostic overlap supports the premise that “MCI due to AD” represents the earliest symptomatic stage of AD. PMID:22312163
Observing conversational laughter in frontotemporal dementia
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
The diagnosis, burden and prognosis of dementia: A record-linkage cohort study in England.
Pujades-Rodriguez, Mar; Assi, Valentina; Gonzalez-Izquierdo, Arturo; Wilkinson, Tim; Schnier, Christian; Sudlow, Cathie; Hemingway, Harry; Whiteley, William N
2018-01-01
Electronic health records (EHR) might be a useful resource to study the risk factors and clinical care of people with dementia. We sought to determine the diagnostic validity of dementia captured in linked EHR. A cohort of adults in linked primary care, hospital, disease registry and mortality records in England, [CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records)]. The proportion of individuals with dementia, Alzheimer's disease, vascular and rare dementia in each data source was determined. A comparison was made of symptoms and care between people with dementia and age-, sex- and general practice-matched controls, using conditional logistic regression. The lifetime risk and prevalence of dementia and mortality rates in people with and without dementia were estimated with random-effects Poisson models. There were 47,386 people with dementia: 12,633 with Alzheimer's disease, 9540 with vascular and 1539 with rare dementia. Seventy-four percent of cases had corroborating evidence of dementia. People with dementia were more likely to live in a deprived area (conditional OR 1.26;95%CI:1.20-1.31 most vs least deprived), have documented memory impairment (cOR = 11.97;95%CI:11.24-12.75), falls (cOR = 2.36;95%CI:2.31-2.41), depression (cOR = 2.03; 95%CI:1.98-2.09) or anxiety (cOR = 1.27; 95%CI:1.23-1.32). The lifetime risk of dementia at age 65 was 9.2% (95%CI:9.0%-9.4%), in men and 14.9% (95%CI:14.7%-15.1%) in women. The population prevalence of recorded dementia increased from 0.3% in 2000 to 0.7% in 2010. A higher mortality rate was observed in people with than without dementia (IRR = 1.56;95%CI:1.54-1.58). Most people with a record of dementia in linked UK EHR had some corroborating evidence for diagnosis. The estimated 10-year risk of dementia was higher than published population-based estimations. EHR are therefore a promising source of data for dementia research.
Cai, Mudan; Lee, Jun Hwan; Yang, Eun Jin
2017-10-01
Vascular dementia (VaD) is caused by the reduction of blood supply by vessel occlusion and is characterized by progressive cognitive decline. VaD incidence has been growing due to the aging population, placing greater strain on social and economic resources. However, the pathological mechanisms underlying VaD remain unclear. Many studies have used the bilateral common carotid artery occlusion (BCCAO) animal model to investigate potential therapeutics for VaD. In this study, we investigated whether bee venom (BV) improves cognitive function and reduces neuroinflammation in the hippocampus of BCCAO animals. Animals were randomly divided into three groups: a sham group (n = 15), BCCAO control group (n = 15), and BV-treated BCCAO group (n = 15). BCCAO animals were treated with 0.1 μg/g BV at ST36 ("Joksamli" acupoint) four times every other day. In order to investigate the effect of BV treatment on cognitive function, we performed a Y-maze test. In order to uncover any potential relationship between these results and neuroinflammation, we also performed Western blotting in the BCCAO group. Animals that had been treated with BV showed an improved cognitive function and a reduced expression of neuroinflammatory proteins in the hippocampus, including Iba-1, TLR4, CD14, and TNF-α. Furthermore, we demonstrated that BV treatment increased pERK and BDNF in the hippocampus. The present study thus underlines the neuroprotective effect of BV treatment against BCCAO-induced cognitive impairment and neuroinflammation. Our findings suggest that BV may be an effective complementary treatment for VaD, as it may improve cognitive function and attenuate neuroinflammation associated with dementia.
Omega-3 fatty acids and dementia
Cole, Greg M.; Ma, Qiu-Lan; Frautschy, Sally A.
2014-01-01
More than a dozen epidemiological studies have reported that reduced levels or intake of omega-3 fatty acids or fish consumption is associated with increased risk for age-related cognitive decline or dementia such as Alzheimer's disease (AD). Increased dietary consumption or blood levels of docosahexaenoic acid (DHA) appear protective for AD and other dementia in multiple epidemiological studies; however, three studies suggest that the ApoE4 genotype limits protection. DHA is broadly neuroprotective via multiple mechanisms that include neuroprotective DHA metabolites, reduced arachidonic acid metabolites, and increased trophic factors or downstream trophic signal transduction. DHA is also protective against several risk factors for dementia including head trauma, diabetes, and cardiovascular disease. DHA is specifically protective against AD via additional mechanisms: It limits the production and accumulation of the amyloid β peptide toxin that is widely believed to drive the disease; and it also suppresses several signal transduction pathways induced by Aβ, including two major kinases that phosphorylate the microtubule associated protein tau and promote neurofibrillary tangle pathology. Based on the epidemiological and basic research data, expert panels have recommended the need for clinical trials with omega-3 fatty acids, notably DHA, for the prevention or treatment of age-related cognitive decline—with a focus on the most prevalent cause, AD. Clinical trials are underway to prevent and treat AD. Results to-date suggest that DHA may be more effective if it is begun early or used in conjunction with antioxidants. PMID:19523795
Brookmeyer, Ron; Kawas, Claudia H.; Abdallah, Nada; Paganini-Hill, Annlia; Kim, Ronald C.; Corrada, Maria M.
2016-01-01
Introduction The number of persons aged over 90 years will grow significantly in coming decades. This group has the highest rates of dementia, most commonly Alzheimer’s disease (AD). Methods Using The 90+ Study we developed a statistical model for dementia risk based on brain pathologies. Intervention scenarios which reduce or eliminate AD pathology were considered and the numbers of dementia cases among the U.S. oldest-old that could be prevented were estimated. Results U.S. dementia prevalence among the oldest-old will increase from 1.35 million in 2015 to 4.72 million in 2050.If interventions eliminate AD pathology, dementia prevalence would be reduced by approximately 50%, averting nearly 2.4 million cases in 2050. However, large numbers of dementia cases would still remain. Discussion Reducing AD pathology would significantly decrease the public health burden of dementia. However, other interventions are needed to address the burden associated with other dementing pathologies prevalent in the oldest-old. PMID:26900132
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.
Rusanen, Minna; Kivipelto, Miia; Levälahti, Esko; Laatikainen, Tiina; Tuomilehto, Jaakko; Soininen, Hilkka; Ngandu, Tiia
2014-01-01
Many cardiovascular risk factors are shown to increase the risk of dementia and Alzheimer's disease (AD), but the impact of heart disease on later development of dementia is still unclear. The aim of the study was to investigate the long-term risk of dementia and Alzheimer's disease (AD) related to midlife and late-life atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD) in a population-based study with a follow-up of over 25 years. Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study includes 2000 participants who were randomly selected from four separate, population-based samples originally studied in midlife (1972, 1977, 1982, or 1987). Re-examinations were carried out in 1998 and 2005-2008. Altogether 1,510 (75.5%) persons participated in at least one re-examination, and 127 (8.4%) persons were diagnosed with dementia (of which 102 had AD). AF in late-life was an independent risk factor for dementia (HR 2.61, 95% CI 1.05-6.47; p = 0.039) and AD (HR 2.54, 95% CI 1.04-6.16; p = 0.040) in the fully adjusted analyses. The association was even stronger among the apolipoprotein E (APOE) ε4 non-carriers. Late-life HF, but not CAD, tended to increase the risks as well. Heart diseases diagnosed at midlife did not increase the risk of later dementia and AD. Late-life heart diseases increase the subsequent risk of dementia and AD. Prevention and effective treatment of heart diseases may be important also from the perspective of brain health and cognitive functioning.
Dementia beyond 2025: Knowledge and uncertainties.
Kenigsberg, Paul-Ariel; Aquino, Jean-Pierre; Bérard, Alain; Gzil, Fabrice; Andrieu, Sandrine; Banerjee, Sube; Brémond, François; Buée, Luc; Cohen-Mansfield, Jiska; Mangialasche, Francesca; Platel, Hervé; Salmon, Eric; Robert, Philippe
2016-01-01
Given that there may well be no significant advances in drug development before 2025, prevention of dementia-Alzheimer's disease through the management of vascular and lifestyle-related risk factors may be a more realistic goal than treatment. Level of education and cognitive reserve assessment in neuropsychological testing deserve attention, as well as cultural, social, and economic aspects of caregiving. Assistive technologies for dementia care remain complex. Serious games are emerging as virtual educational and pleasurable tools, designed for individual and cooperative skill building. Public policies are likely to pursue improving awareness and understanding of dementia; providing good quality early diagnosis and intervention for all; improving quality of care from diagnosis to the end of life, using clinical and economic end points; delivering dementia strategies quicker, with an impact on more people. Dementia should remain presented as a stand-alone concept, distinct from frailty or loss of autonomy. The basic science of sensory impairment and social engagement in people with dementia needs to be developed. E-learning and serious games programs may enhance public and professional education. Faced with funding shortage, new professional dynamics and economic models may emerge through coordinated, flexible research networks. Psychosocial research could be viewed as an investment in quality of care, rather than an academic achievement in a few centers of excellence. This would help provide a competitive advantage to the best operators. Stemming from care needs, a logical, systems approach to dementia care environment through organizational, architectural, and psychosocial interventions may be developed, to help reduce symptoms in people with dementia and enhance quality of life. Dementia-friendly environments, culture, and domesticity are key factors for such interventions. © The Author(s) 2015.
Ponce, Daniela P.; Salech, Felipe; SanMartin, Carol D.; Silva, Monica; Xiong, Chengjie; Roe, Catherine M.; Henriquez, Mauricio; Quest, Andrew F.; Behrens, Maria I.
2015-01-01
We previously reported on enhanced susceptibility to death of lymphocytes from Alzheimer’s disease (AD) patients when exposed to hydrogen peroxide (H2O2)-induced oxidative stress and an increased resistance to death in those of patients with a history of skin cancer. This is consistent with our hypothesis proposing that the cellular machinery controlling cell death is deregulated in opposite directions in Alzheimer’s disease (AD) and cancer, to explain the inverse association observed in epidemiological studies. Here we investigated whether the observed increased susceptibility correlates with the degree of dementia severity. Peripheral lymphocytes from 23 AD patients, classified using the Clinical Dementia Rating (CDR) into severe dementia (CDR 3, n=10) and mild-to-moderate dementia (CDR 1–2, n=13), and 15 healthy controls (HC) (CDR 0), were exposed to H2O2 for 20 hours. Lymphocyte death was determined by flow cytometry and propidium iodide staining. The greatest susceptibility to H2O2-induced death was observed for lymphocytes from severe dementia patients, whereas those with mild-to-moderate dementia exhibited intermediate values, compared to healthy controls. A significant increase in the apoptosis/necrosis ratio was found in AD patients. Poly (ADP-ribosyl) polymerase-1 (PARP-1) inhibition significantly protected from H2O2-induced death of lymphocytes, whereby a lower degree of protection was observed in severe AD patients. Moreover, inhibition of PARP-1 abolished the differences in apoptosis/necrosis ratios observed between the three groups of patients. These results support the notion that AD is a systemic disorder, whereby enhanced susceptibility to H2O2-induced death in peripheral lymphocytes correlates with dementia severity and enhanced death in AD patients is attributable to a PARP-dependent increase in the apoptosis/necrosis ratio. PMID:25274115
Briggs, R; Dyer, A; Nabeel, S; Collins, R; Doherty, J; Coughlan, T; O'Neill, D; Kennelly, S P
2017-01-01
Studies have demonstrated that a significant minority of older persons presenting to acute hospital services are cognitively impaired; however, the impact of dementia on long-term outcomes is less clear. To evaluate the prevalence of dementia, both formally diagnosed and hitherto unrecognised in a cohort of acutely unwell older adults, as well as its impact on both immediate outcomes (length of stay and in-hospital mortality) and 12-month outcomes including readmission, institutionalisation and death. Prospective observational study. 190 patients aged 70 years and over, presenting to acute hospital services underwent a detailed health assessment including cognitive assessment (standardised Mini Mental State Examination, AD8 and Confusion Assessment Method for the Intensive Care Unit). Patients or informants were contacted directly 12 months later to compile 1-year outcome data. Dementia was defined as a score of 2 or more on the AD8 screening test. Dementia was present in over one-third of patients (73/190). Of these patients, 36% (26/73) had a prior documented diagnosis of dementia with the remaining undiagnosed before presentation. The composite outcome of death or readmission to hospital within the following 12 months was more likely to occur in patients with dementia (73% (53/73) vs. 58% (68/117), P = 0.043). This finding persisted after controlling for age, gender, frailty status and medical comorbidities, including stroke and heart disease. A diagnosis of dementia confers an increased risk of either death or further admission within the following 12 months, highlighting the need for better cognitive screening in the acute setting, as well as targeted intervention such as comprehensive geriatric assessment. © The Author 2016. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Brookmeyer, Ron; Kawas, Claudia H; Abdallah, Nada; Paganini-Hill, Annlia; Kim, Ronald C; Corrada, María M
2016-03-01
The number of persons aged >90 years will grow significantly in coming decades. This group has the highest rates of dementia, most commonly Alzheimer's disease (AD). Using The 90+ Study, we developed a statistical model for dementia risk based on brain pathologies. Intervention scenarios which reduce or eliminate AD pathology were considered, and the numbers of dementia cases among the U.S. oldest-old that could be prevented were estimated. The U.S. dementia prevalence among the oldest-old will increase from 1.35 million in 2015 to 4.72 million in 2050. If interventions eliminate AD pathology, dementia prevalence would be reduced by approximately 50%, averting nearly 2.4 million cases in 2050. However, large numbers of dementia cases would still remain. Reducing AD pathology would significantly decrease the public health burden of dementia. However, other interventions are needed to address the burden associated with other dementing pathologies prevalent in the oldest-old. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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.
Dementia in the oldest old: a multi-factorial and growing public health issue.
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
Dementia in the oldest old: a multi-factorial and growing public health issue
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
Kurisu, Kairi; Terada, Seishi; Oshima, Etsuko; Horiuchi, Makiko; Imai, Nao; Yabe, Mayumi; Yokota, Osamu; Ishihara, Takeshi; Yamada, Norihito
2016-08-01
Quality of life (QOL) has become an important outcome measure in the care of dementia patients. However, there have been few studies focusing on the difference in QOL between different dementias. Two-hundred seventy-nine consecutive outpatients with Alzheimer's disease (AD), dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD) were recruited. The QOL was evaluated objectively using the QOL Questionnaire for Dementia (QOL-D).The QOL-D comprises six domains: positive affect, negative affect and actions, communication, restlessness, attachment to others, and spontaneity. General cognition, daily activities, and behavioral and psychological symptoms of dementia were also evaluated. The scores of positive affect of QOL-D of AD patients were significantly higher than those of patients with DLB or FTD (AD 3.1 ± 0.8, DLB 2.6 ± 0.9, FTD 2.6 ± 0.7). The scores of negative affect and action of QOL-D of FTD patients were significantly higher than those of patients with AD or DLB (FTD 2.0 ± 0.8, AD 1.4 ± 0.5, DLB 1.5 ± 0.6). The apathy scores of FTD and DLB patients were significantly higher than those of patients with AD. The disinhibition scores of FTD patients were significantly higher than those of patients with AD or DLB. The apathy of FTD and DLB patients and depression of DLB patients might affect the lower positive affect of FTD and DLB patients compared to AD patients. The disinhibition of FTD patients might affect the abundance of negative affect & actions in FTD patients compared to AD and DLB patients.
Observing conversational laughter in frontotemporal dementia.
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.
B vitamins influence vascular cognitive impairment
USDA-ARS?s Scientific Manuscript database
As the number of elderly in the USA and globally continues to increase, age-related neurological disorders, such as Alzheimer's disease and vascular dementia, are a growing concern. The loss of memory, emotional changes, and impairments in general cognitive functioning frequently result in social is...
What is the Relationship of Traumatic Brain Injury to Dementia?
Mendez, Mario F
2017-01-01
There is a long history linking traumatic brain injury (TBI) with the development of dementia. Despite significant reservations, such as recall bias or concluding causality for TBI, a summary of recent research points to several conclusions on the TBI-dementia relationship. 1) Increasing severity of a single moderate-to-severe TBI increases the risk of subsequent Alzheimer's disease (AD), the most common type of dementia. 2) Repetitive, often subconcussive, mild TBIs increases the risk for chronic traumatic encephalopathy (CTE), a degenerative neuropathology. 3) TBI may be a risk factor for other neurodegenerative disorders that can be associated with dementia. 4) TBI appears to lower the age of onset of TBI-related neurocognitive syndromes, potentially adding "TBI cognitive-behavioral features". The literature further indicates several specific risk factors for TBI-associated dementia: 5) any blast or blunt physical force to the head as long as there is violent head displacement; 6) decreased cognitive and/or neuronal reserve and the related variable of older age at TBI; and 7) the presence of apolipoprotein E ɛ4 alleles, a genetic risk factor for AD. Finally, there are neuropathological features relating TBI with neurocognitive syndromes: 8) acute TBI results in amyloid pathology and other neurodegenerative proteinopathies; 9) CTE shares features with neurodegenerative dementias; and 10) TBI results in white matter tract and neural network disruptions. Although further research is needed, these ten findings suggest that dose-dependent effects of violent head displacement in vulnerable brains predispose to dementia; among several potential mechanisms is the propagation of abnormal proteins along damaged white matter networks.
Aging without Dementia is Achievable: Current Evidence from Epidemiological Research.
Qiu, Chengxuan; Fratiglioni, Laura
2018-01-01
Both the incidence and the prevalence of dementia increase exponentially with increasing age. This raises the question of whether dementia is an inevitable consequence of aging or whether aging without dementia is achievable. In this review article, we sought to summarize the current evidence from epidemiological and neuropathological studies that investigated this topic. Epidemiological studies have shown that dementia could be avoided even at extreme old ages (e.g., centenarians or supercentenarians). Furthermore, clinico-neuropathological studies found that nearly half of centenarians with dementia did not have sufficient brain pathology to explain their cognitive symptoms, while intermediate-to-high Alzheimer pathology was present in around one-third of very old people without dementia or cognitive impairment. This suggests that certain compensatory mechanisms (e.g., cognitive reserve or resilience) may play a role in helping people in extreme old ages escape dementia syndrome. Finally, evidence has been accumulating in recent years indicating that the incidence of dementia has declined in Europe and North America, which supports the view that the risk of dementia in late life is modifiable. Evidence has emerged that intervention strategies that promote general health, maintain vascular health, and increase cognitive reserve are likely to help preserve cognitive function till late life, thus achieving the goal of aging without dementia.
Aging without Dementia is Achievable: Current Evidence from Epidemiological Research
Qiu, Chengxuan; Fratiglioni, Laura
2018-01-01
Both the incidence and the prevalence of dementia increase exponentially with increasing age. This raises the question of whether dementia is an inevitable consequence of aging or whether aging without dementia is achievable. In this review article, we sought to summarize the current evidence from epidemiological and neuropathological studies that investigated this topic. Epidemiological studies have shown that dementia could be avoided even at extreme old ages (e.g., centenarians or supercentenarians). Furthermore, clinico-neuropathological studies found that nearly half of centenarians with dementia did not have sufficient brain pathology to explain their cognitive symptoms, while intermediate-to-high Alzheimer pathology was present in around one-third of very old people without dementia or cognitive impairment. This suggests that certain compensatory mechanisms (e.g., cognitive reserve or resilience) may play a role in helping people in extreme old ages escape dementia syndrome. Finally, evidence has been accumulating in recent years indicating that the incidence of dementia has declined in Europe and North America, which supports the view that the risk of dementia in late life is modifiable. Evidence has emerged that intervention strategies that promote general health, maintain vascular health, and increase cognitive reserve are likely to help preserve cognitive function till late life, thus achieving the goal of aging without dementia. PMID:29562544
Hohman, Timothy J; Bell, Susan P; Jefferson, Angela L
2015-05-01
A subset of older adults present post mortem with Alzheimer disease (AD) pathologic features but without any significant clinical manifestation of dementia. Vascular endothelial growth factor (VEGF) has been implicated in staving off AD-related neurodegeneration. To evaluate whether VEGF levels are associated with brain aging outcomes (hippocampal volume and cognition) and to further evaluate whether VEGF modifies relations between AD biomarkers and brain aging outcomes. Biomarker analysis using neuroimaging and neuropsychological outcomes from the Alzheimer's Disease Neuroimaging Initiative. This prospective longitudinal study across North America included individuals with normal cognition (n = 90), mild cognitive impairment (n = 130), and AD (n = 59) and began in October 2004, with follow-up ongoing. Cerebrospinal fluid VEGF was cross-sectionally related to brain aging outcomes (hippocampal volume, episodic memory, and executive function) using a general linear model and longitudinally using mixed-effects regression. Alzheimer disease biomarker (cerebrospinal fluid β-amyloid 42 and total tau)-by-VEGF interactions evaluated the effect of VEGF on brain aging outcomes in the presence of enhanced AD biomarkers. Vascular endothelial growth factor was associated with baseline hippocampal volume (t277 = 2.62; P = .009), longitudinal hippocampal atrophy (t858 = 2.48; P = .01), and longitudinal decline in memory (t1629 = 4.09; P < .001) and executive function (t1616 = 3.00; P = .003). Vascular endothelial growth factor interacted with tau in predicting longitudinal hippocampal atrophy (t845 = 4.17; P < .001), memory decline (t1610 = 2.49; P = .01), and executive function decline (t1597 = 3.71; P < .001). Vascular endothelial growth factor interacted with β-amyloid 42 in predicting longitudinal memory decline (t1618 = -2.53; P = .01). Elevated cerebrospinal fluid VEGF was associated with more optimal brain aging in vivo. The neuroprotective effect appeared
Trajectories of Behavioural Disturbances Across Dementia Types.
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.
Eguchi, Kumiko; Shindo, Tomohiko; Ito, Kenta; Ogata, Tsuyoshi; Kurosawa, Ryo; Kagaya, Yuta; Monma, Yuto; Ichijo, Sadamitsu; Kasukabe, Sachie; Miyata, Satoshi; Yoshikawa, Takeo; Yanai, Kazuhiko; Taki, Hirofumi; Kanai, Hiroshi; Osumi, Noriko; Shimokawa, Hiroaki
2018-05-22
Therapeutic focused-ultrasound to the hippocampus has been reported to exert neuroprotective effects on dementia. In the present study, we examined whether the whole-brain LIPUS (low-intensity pulsed ultrasound) therapy is effective and safe in 2 mouse models of dementia (vascular dementia, VaD and Alzheimer's disease, AD), and if so, to elucidate the common underlying mechanism(s) involved. We used bilateral carotid artery stenosis (BCAS) model with micro-coils in male C57BL/6 mice as a VaD model and 5XFAD transgenic mice as an AD model. We applied the LIPUS therapy (1.875 MHz, 6.0 kHz, 32cycles) to the whole brain. In both models, the LIPUS therapy markedly ameliorated cognitive impairments (Y-maze test and/or passive avoidance test) associated with improved cerebral blood flow (CBF). Mechanistically, the LIPUS therapy significantly increased CD31-positive endothelial cells and Olig2-positive oligodendrocyte precursor cells (OPCs) in the VaD model, while it reduced Iba-1-positive microglias and amyloid-β (Aβ) plaque in the AD model. In both models, endothelium-related genes were significantly upregulated in RNA-sequencing, and expressions of endothelial nitric oxide synthase (eNOS) and neurotrophins were upregulated in Western blotting. Interestingly, the increases in glia cells and neurotrophin expressions showed significant correlations with eNOS expression. Importantly, these beneficial effects of LIPUS were absent in eNOS-knockout mice. These results indicate that the whole-brain LIPUS is an effective and non-invasive therapy for dementia by activating specific cells corresponding to each pathology, for which eNOS activation plays an important role as a common mechanism. Copyright © 2018. Published by Elsevier Inc.
Neuropathologic assessment of dementia markers in identical and fraternal twins
Iacono, Diego; Volkman, Inga; Nennesmo, Inger; Pedersen, Nancy L.; Fratiglioni, Laura; Johansson, Boo; Karlsson, David; Winblad, Bengt; Gatz, Margaret
2014-01-01
Twin studies are an incomparable source of investigation to shed light on genetic and non-genetic components of neurodegenerative diseases, as Alzheimer’s disease (AD). Detailed clinicopathologic correlations using twin longitudinal data and postmortem examinations are mostly missing. We describe clinical and pathologic findings of 7 monozygotic (MZ) and dizygotic (DZ) twin pairs. Our findings show good agreement between clinical and pathologic diagnoses in the majority of the twin pairs, with greater neuropathologic concordance in MZ than DZ twins. Greater neuropathologic concordance was found for β-amyloid than tau pathology within the pairs. ApoE4 was associated with higher β-amyloid and earlier dementia onset, and importantly, higher frequency of other co-occurring brain pathologies, regardless of the zygosity. Dementia onset, dementia duration, difference between twins in age at dementia onset and at death, did not correlate with AD pathology. These clinicopathologic correlations of older identical and fraternal twins support the relevance of genetic factors in AD, but not their sufficiency to determine the pathology, and consequently the disease, even in monozygotic twins. It is the interaction among genetic and non-genetic risks which plays a major role in influencing, or probably determining, the degeneration of those brain circuits associated with pathology and cognitive deficits in AD. PMID:24450926
Lovas, Joel; Fereshtehnejad, Seyed-Mohammad; Cermakova, Pavla; Lundberg, Catarina; Johansson, Björn; Johansson, Kurt; Winblad, Bengt; Eriksdotter, Maria; Religa, Dorota
2016-05-05
Driving constitutes a very important aspect of daily life and is dependent on cognitive functions such as attention, visuo-spatial skills and memory, which are often compromised in dementia. Therefore, the driving fitness of patients with dementia needs to be addressed by physicians and those that are deemed unfit should not be allowed to continue driving. We aimed at investigating to what extent physicians assess driving fitness in dementia patients and determinant factors for revoking of their licenses. This study includes 15113 patients with newly diagnosed dementia and driver's license registered in the Swedish Dementia Registry (SveDem). The main outcomes were reporting to the licensing authority and making an agreement about driving eligibility with the patients. Physicians had not taken any action in 16% of dementia patients, whereas 9% were reported to the authority to have their licenses revoked. Males (OR = 3.04), those with an MMSE score between 20-24 (OR = 1.35) and 10-19 (OR = 1.50), patients with frontotemporal (OR = 3.09) and vascular dementia (OR = 1.26) were more likely to be reported to the authority. For the majority of patients with dementia, driving fitness was assessed. Nevertheless, physicians did not address the issue in a sizeable proportion of dementia patients. Type of dementia, cognitive status, age, sex and burden of comorbidities are independent factors associated with the assessment of driving fitness in patients with dementia. Increased knowledge on how these factors relate to road safety may pave the way for more specific guidelines addressing the issue of driving in patients with dementia.
Do subjective memory complaints predict senile Alzheimer dementia?
Jungwirth, Susanne; Zehetmayer, Sonja; Weissgram, Silvia; Weber, Germain; Tragl, Karl Heinz; Fischer, Peter
2008-01-01
Many elderly complain about their memory and undergo dementia screening by the Mini-Mental State Examination (MMSE). While objective memory impairment always precedes Alzheimer dementia (AD) it is unclear whether subjective memory complaints are predicting AD. We tried to answer this question in a prospective cohort study. The 75-years old non-demented inhabitants of Vienna-Transdanube were investigated for conversion to AD after 30 months. The predictive value of subjective memory complaints was analysed in two groups: subjects with high MMSE-score (28-30) and subjects with low MMSE-score (23-27). Only in subjects with high MMSE univariate analyses showed an association between subjective memory complaints and incident AD. In both groups the verbal memory test was the main predictor of AD in multivariate analyses. We suggest to perform memory testing in subjects complaining about memory irrespective of their performance in a screening procedure like the MMSE.
Yu, Lei; Dawe, Robert J; Buchman, Aron S; Boyle, Patricia A; Schneider, Julie A; Arfanakis, Konstantinos; Bennett, David A
2017-03-30
Alterations of the transverse relaxation rate, R 2 , measured using MRI, are observed in older persons with Alzheimer's (AD) dementia. However, the spatial pattern of these alterations and the degree to which they reflect the accumulation of common age-related neuropathologies are unknown. In this study, we characterized the profile of R 2 alterations in post-mortem brains of persons with clinical diagnosis of AD dementia and investigated how the profile differs after accounting for neuropathologic indices of AD, cerebral infarcts, Lewy body disease, hippocampal sclerosis and transactive response DNA-binding protein 43. Data came from 567 post-mortem brains donated by participants in two cohort studies of aging and dementia. R 2 was quantified using fast spin echo imaging. Voxelwise linear regression examined R 2 alterations between subjects diagnosed with AD dementia at death and those with no cognitive impairment. Voxels showing significant R 2 alterations were clustered into regions of interest (ROIs). Three R 2 profiles were compared, which were adjusted for (1) demographics only; (2) demographics and AD pathology; (3) demographics, AD pathology and other common neuropathologies. R 2 alterations were observed throughout the hemisphere, most commonly in white matter. Of the distinct ROIs identified, the largest region encompassed large portions of white matter in all lobes. This ROI became smaller in size but remained largely intact after adjusting for AD and other neuropathologic indices. Further, R 2 alterations identify AD dementia with improved accuracy, above and beyond demographics and neuropathologic indices (p<0.0001). In conclusion, R 2 alterations in AD dementia are not solely reflective of common age-related neuropathologies, suggesting that other mechanisms are at work. Copyright © 2016 Elsevier B.V. All rights reserved.
Xu, Wei-Li; Pedersen, Nancy L.; Keller, Lina; Kalpouzos, Grégoria; Wang, Hui-Xin; Graff, Caroline; Winblad, Bengt; Bäckman, Lars; Fratiglioni, Laura
2015-01-01
Background Research has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI. Methods and Findings The first cohort, which included dementia-free adults aged ≥75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged ≥60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19–2.32) and 1.66 (95% CI 1.06–2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.40–7.18) and 4.81 (95% CI 1.88–8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63–8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45–9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04–2.99) and 1.64 (1.02–2.33) for the diabetes–AD and dementia–AD associations, respectively, and 4.06 (95% CI 1.06–7.58, p = 0.039) and 3.29 (95% CI 1.02–8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without
Bradycardia in frontotemporal dementia.
Robles Bayón, A; Gude Sampedro, F; Torregrosa Quesada, J M
2014-03-01
Numerous regions of the brain, such as the medial frontal cortex, orbitofrontal cortex, insula, and amygdala, participate in the autonomic control of cardiovascular functions such as heart rate. The degenerative process in frontotemporal dementia (FTD) involves the listed anatomical structures and may therefore produce dysautonomic cardiovascular symptoms. To observe whether or not non-cardiogenic bradycardia was more frequent in a group of patients with FTD than in subjects with mild cognitive impairment or dementia of a different aetiology. Once patients with primary cardiac arrhythmia were excluded, we registered the heart rates of 258 patients with cognitive symptoms (36 with FTD, 22 with Alzheimer disease, 23 with vascular dementia, 10 with other dementias, and 167 with non-dementia cognitive impairment). Bradycardia (<60 beats/minute) was significantly more frequent in patients with FTD. This difference remained significant after excluding subjects undergoing treatment with a potentially bradycardic effect. Bradycardia was more prevalent in behavioural FTD cases than in cases of the aphasic variant, and we detected a trend toward higher frequency among patients with more pronounced right hemisphere atrophy. Moreover, mean systolic blood pressure in FTD patients was lower than in other participants, and systolic hypotension (<120 and <100mm Hg) was more prevalent. Bradycardia was more frequent in the FTD sample than in other patients with cognitive symptoms. Further investigations will be necessary before we may consider bradycardia to be a sign supporting diagnosis of FTD or its behavioural variant. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.
Drawing Disorders in Alzheimer's Disease and Other Forms of Dementia.
Trojano, Luigi; Gainotti, Guido
2016-04-21
Drawing is a multicomponential process that can be impaired by many kinds of brain lesions. Drawing disorders are very common in Alzheimer's disease and other forms of dementia, and can provide clinical information for the distinction of the different dementing diseases. In our review we started from an overview of the neural and cognitive bases of drawing, and from a recollection of the drawing tasks more frequently used for assessing individuals with dementia. Then, we analyzed drawing disorders in dementia, paying special attention to those observed in Alzheimer's disease, from the prodromal stages of the amnesic mild cognitive impairment to the stages of full-blown dementia, both in the sporadic forms with late onset in the entorhino-hippocampal structures and in those with early onset in the posterior neocortical structures. We reviewed the drawing features that could differentiate Alzheimer's disease from vascular dementia and from the most frequent forms of degenerative dementia, namely frontotemporal dementia and Lewy body disease. Finally, we examined some peculiar aspects of drawing disorders in dementia, such as perseverations, rotations, and closing-in. We argue that a careful analysis of drawing errors helps to differentiate the different forms of dementia more than overall accuracy in drawing.
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
Validation of a polygenic risk score for dementia in black and white individuals
Marden, Jessica R; Walter, Stefan; Tchetgen Tchetgen, Eric J; Kawachi, Ichiro; Glymour, M Maria
2014-01-01
Objective To determine whether a polygenic risk score for Alzheimer's disease (AD) predicts dementia probability and memory functioning in non-Hispanic black (NHB) and non-Hispanic white (NHW) participants from a sample not used in previous genome-wide association studies. Methods Non-Hispanic white and NHB Health and Retirement Study (HRS) participants provided genetic information and either a composite memory score (n = 10,401) or a dementia probability score (n = 7690). Dementia probability score was estimated for participants' age 65+ from 2006 to 2010, while memory score was available for participants age 50+. We calculated AD genetic risk scores (AD-GRS) based on 10 polymorphisms confirmed to predict AD, weighting alleles by beta coefficients reported in AlzGene meta-analyses. We used pooled logistic regression to estimate the association of the AD-GRS with dementia probability and generalized linear models to estimate its effect on memory score. Results Each 0.10 unit change in the AD-GRS was associated with larger relative effects on dementia among NHW aged 65+ (OR = 2.22; 95% CI: 1.79, 2.74; P < 0.001) than NHB (OR=1.33; 95% CI: 1.00, 1.77; P = 0.047), although additive effect estimates were similar. Each 0.10 unit change in the AD-GRS was associated with a −0.07 (95% CI: −0.09, −0.05; P < 0.001) SD difference in memory score among NHW aged 50+, but no significant differences among NHB (β = −0.01; 95% CI: −0.04, 0.01; P = 0.546). [Correction added on 29 July 2014, after first online publication: confidence intervalshave been amended.] The estimated effect of the GRS was significantly smaller among NHB than NHW (P < 0.05) for both outcomes. Conclusion This analysis provides evidence for differential relative effects of the GRS on dementia probability and memory score among NHW and NHB in a new, national data set. PMID:25328845
Financial capacity in dementia: a systematic review.
Sudo, Felipe Kenji; Laks, Jerson
2017-07-01
Financial capacity (FC) refers to a set of cognitively mediated abilities related to one's competency to manage propriety and income. Identifying intact from impaired FC in older persons with dementia is a growing concern in geriatric practice, but the best methods to assess this function still need to be determined. This study aims to review data on FC in dementia and on instruments used to assess this domain of capacity. Database search was performed in Medline, ISI Web of Knowledge, LILACS and PsycINFO. Studies that objectively assessed FC in dementia of any etiology were included. Of a total of 125 articles, 10 were included. Mild Alzheimer's Disease (AD) was associated with impaired complex FC abilities, namely checkbook management, bank statement management and financial judgment, but simple FC skills were preserved. Moderate AD was associated with impairment in all domains of FC. The Financial Capacity Instrument (FCI) was applied in most of the selected studies and correlated with neuropsychological and neuroimaging variables. Early dementia is associated with partially preserved FC. More validation studies using objective and evidence-based FC assessment tools, such as the FCI, are still needed.
Brown, Anna; Kirichek, Oksana; Balkwill, Angela; Reeves, Gillian; Beral, Valerie; Sudlow, Cathie; Gallacher, John; Green, Jane
2016-01-01
Electronic linkage of UK cohorts to routinely collected National Health Service (NHS) records provides virtually complete follow-up for cause-specific hospital admissions and deaths. The reliability of dementia diagnoses recorded in NHS hospital data is not well documented. For a sample of Million Women Study participants in England we compared dementia recorded in routinely collected NHS hospital data (Hospital Episode Statistics: HES) with dementia recorded in two separate sources of primary care information: a primary care database [Clinical Practice Research Datalink (CPRD), n = 340] and a survey of study participants' General Practitioners (GPs, n = 244). Dementia recorded in HES fully agreed both with CPRD and with GP survey data for 85% of women; it did not agree for 1 and 4%, respectively. Agreement was uncertain for the remaining 14 and 11%, respectively; and among those classified as having uncertain agreement in CPRD, non-specific terms compatible with dementia, such as 'memory loss', were recorded in the CPRD database for 79% of the women. Agreement was significantly better (p < 0.05 for all comparisons) for women with HES diagnoses for Alzheimer's disease (95 and 94% agreement with any dementia for CPRD and GP survey, respectively) and for vascular dementia (88 and 88%, respectively) than for women with a record only of dementia not otherwise specified (70 and 72%, respectively). Dementia in the same woman was first mentioned an average 1.6 (SD 2.6) years earlier in primary care (CPRD) than in hospital (HES) data. Age-specific rates for dementia based on the hospital admission data were lower than the rates based on the primary care data, but were similar if the delay in recording in HES was taken into account. Dementia recorded in routinely collected NHS hospital admission data for women in England agrees well with primary care records of dementia assessed separately from two different sources, and is sufficiently reliable for epidemiological
Protecting against vascular disease in brain
2011-01-01
Endothelial cells exert an enormous influence on blood vessels throughout the circulation, but their impact is particularly pronounced in the brain. New concepts have emerged recently regarding the role of this cell type and mechanisms that contribute to endothelial dysfunction and vascular disease. Activation of the renin-angiotensin system plays a prominent role in producing these abnormalities. Both oxidative stress and local inflammation are key mechanisms that underlie vascular disease of diverse etiology. Endogenous mechanisms of vascular protection are also present, including antioxidants, anti-inflammatory molecules, and peroxisome proliferator-activated receptor-γ. Despite their clear importance, studies of mechanisms that underlie cerebrovascular disease continue to lag behind studies of vascular biology in general. Identification of endogenous molecules and pathways that protect the vasculature may result in targeted approaches to prevent or slow the progression of vascular disease that causes stroke and contributes to the vascular component of dementia and Alzheimer's disease. PMID:21335467
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
Prediction of Alzheimer's Disease Dementia: Data from the GuidAge Prevention Trial.
Di Stefano, Francesca; Epelbaum, Stephane; Coley, Nicola; Cantet, Christelle; Ousset, Pierre-Jean; Hampel, Harald; Bakardjian, Hovagim; Lista, Simone; Vellas, Bruno; Dubois, Bruno; Andrieu, Sandrine
2015-01-01
In therapeutic trials, it is crucial to identify Alzheimer's disease (AD) at its prodromal stage. We assessed the accuracy of the free and cued selective reminding test (FCSRT) compared to other cognitive tests to predict AD dementia in subjects with subjective cognitive decline or mild cognitive impairment. Subjects from the placebo group of the GuidAge trial over 70 years old and without clinical signs of dementia at baseline who completed the 5-year follow-up free of dementia (n = 840) or developed AD dementia (n = 73) were included in our study. Among all the tests, the sum of the 3 free recall of the FCSRT (FCSRT-FR) and the sum of free and cued recall (FCSRT-TR) yielded the best results to predict AD dementia occurrence (all p values <0.05 for comparison of FCSRT-FR ROC and MMSE, CDRsb, and CVF ROCs). FCSRT-FR had an area under the ROC curve of 0.799 (95% CI 0.738-0.85) and the optimal cut-off was 20 (se 68.06% , sp 81.43% , PPV 23.90% , NPV 96,75%). Concerning FCSRT-TR, the AUC was 0.776 and the optimal cut-off was 42 (se 62.5% , sp 82.26% , PPV 23.20% and NPV 96.24%). This study sets the framework for implementing the FCSRT in clinical and therapeutic trials for efficient subject selection.
Dementia Incidence Declined in African Americans, but not in Yoruba
Gao, Sujuan; Ogunniyi, Adesola; Hall, Kathleen S.; Baiyewu, Olesegun; Unverzagt, Frederick W.; Lane, Kathleen A.; Murrell, Jill R.; Gureje, Oye; Hake, Ann M.; Hendrie, Hugh C
2015-01-01
Background To compare dementia incidence of African American and Yoruba cohorts age 70 or older enrolled in 1992 and 2001. Methods African Americans residing in Indianapolis and Yoruba in Ibadan, Nigeria without dementia were enrolled in 1992 and 2001 and evaluated every two to three years until 2009. The cohorts consist of 1440 African Americans, 1774 Yoruba in 1992 and 1835 African Americans and 1895 Yoruba in the 2001 cohorts age 70 or older. Results In African Americans, dementia and AD incidence rates were significantly lower in 2001 than 1992 for all age groups except the oldest group. The overall standardized annual dementia incidence rates were 3.6% (95% CI: 3.2–4.1%) in the1992 cohort and 1.4% (95% CI: 1.2–1.7%) in the 2001 cohort. There was no significant difference in dementia or AD incidence between the Yoruba cohorts. Conclusions Future research is needed to explore the reasons for the differential changes in incidence rates in these two populations. PMID:26218444
Dementia incidence declined in African-Americans but not in Yoruba.
Gao, Sujuan; Ogunniyi, Adesola; Hall, Kathleen S; Baiyewu, Olusegun; Unverzagt, Frederick W; Lane, Kathleen A; Murrell, Jill R; Gureje, Oye; Hake, Ann M; Hendrie, Hugh C
2016-03-01
To compare dementia incidence of African-American and Yoruba cohorts aged ≥70 years enrolled in 1992 and 2001. African-Americans residing in Indianapolis and Yoruba in Ibadan, Nigeria without dementia were enrolled in 1992 and 2001 and evaluated every 2-3 years until 2009. The cohorts consist of 1440 African-Americans, 1774 Yoruba in 1992 and 1835 African-Americans and 1895 Yoruba in the 2001 cohorts aged ≥70 years. In African-Americans, dementia and Alzheimer's disease (AD) incidence rates were significantly lower in 2001 than 1992 for all age groups except the oldest group. The overall standardized annual dementia incidence rates were 3.6% (95% confidence interval [CI], 3.2%-4.1%) in the 1992 cohort and 1.4% (95% CI, 1.2%-1.7%) in the 2001 cohort. There was no significant difference in dementia or AD incidence between the Yoruba cohorts. Future research is needed to explore the reasons for the differential changes in incidence rates in these two populations. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Brain reserve hypothesis in dementia.
Fratiglioni, Laura; Wang, Hui-Xin
2007-08-01
The concept of brain reserve refers to the ability to tolerate the age-related changes and the disease related pathology in the brain without developing clear clinical symptoms or signs. A considerable body of biological research has documented that a number of factors including education, work complexity, social network, and leisure activities may contribute to this reserve allowing cognitive function to be maintained in old ages. Epidemiological studies have also related these factors to the development of dementia, suggesting that intellectual challenges experienced across the whole life span may increase the brain reserve and be crucial for the occurrence of dementia symptoms in late life. This paper is a systematic review of the published epidemiological studies on this topic. The availability of numerous epidemiological and biological data investigating the reserve hypothesis in dementia permits some preliminary conclusions. High education, adult-life occupational work complexity, as well as a mentally and socially integrated lifestyle in late life could postpone the onset of clinical dementia and AD. The relevance of physical activity itself remains in debate, as most physical activities include also social and mental stimulation. Leisure activities with all three components--physical, mental and social--seem to have the most beneficial effect. Delaying dementia onset by five years would halve dementia prevalence and substantially decrease the number of dementia cases in the community.
Vascular cognitive impairment, a cardiovascular complication.
Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah
2016-06-22
Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension.
Vascular cognitive impairment, a cardiovascular complication
Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah
2016-01-01
Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension. PMID:27354961
Posterior cortical atrophy variant of Alzheimer's dementia-A case report.
Mukku, Shiva Shanker Reddy; Chintala, Haripriya; Nagaraj, Chandana; Mangalore, Sandhya; Sivakumar, Palanimuthu T; Varghese, Mathew
2018-05-17
Alzheimer's dementia (AD) is the commonest type of dementia presenting with initial episodic memory decline followed by involvement of other cognitive domains. Posterior cortical atrophy (PCA) is one of the variants of Alzheimer's dementia (AD) characterized by the atypical presentation of relatively persevered memory in the initial stage. PCA is an uncommon early onset dementia affecting adults between 50 and 65 years. It presents predominantly with visuo-spatial and visuo-perceptual deficits. PCA is a phenotype with varied etiology most common being Alzheimer's disease. The complex and atypical presentation with preserved memory and insight in patients with PCA poses challenge to clinicians in diagnosing at initial stages. There is also paucity of research on prevalence, course, prognosis and management of PCA. In this article we describe a middle aged gentlemen presenting with clinical features suggestive of PCA. We also discussed relevant literature. Copyright © 2018 Elsevier B.V. All rights reserved.
Evaluation of dementia by acrolein, amyloid-β and creatinine.
Igarashi, Kazuei; Yoshida, Madoka; Waragai, Masaaki; Kashiwagi, Keiko
2015-10-23
Plasma, urine and cerebrospinal fluid (CSF) were examined for biochemical markers of dementia. Protein-conjugated acrolein (PC-Acro) and the amyloid-β (Aβ)40/42 ratio in plasma can be used to detect mild cognitive impairment (MCI) and Alzheimer's disease (AD). In plasma, PC-Acro and the Aβ40/42 ratio in MCI and AD were significantly higher relative to non-demented subjects. Furthermore, urine acrolein metabolite, 3-hydroxypropyl mercapturic acid (3-HPMA)/creatinine (Cre) and amino acid-conjugated acrolein (AC-Acro)/Cre in AD were significantly lower than MCI. It was also shown that reduced urine 3-HPMA/Cre correlated with increased plasma Aβ40/42 ratio in dementia. The Aβ40/PC-Acro ratio in CSF, together with Aβ40 and Aβ40/42 ratio, was lower in AD than MCI. Increased plasma PC-Acro and Aβ40/42 ratio and decreased urine 3-HPMA/Cre correlated with cognitive ability (MMSE). These results indicate that the measurements of acrolein derivatives together with Aβ and Cre in biologic fluids is useful to estimate severity of dementia. Copyright © 2015 Elsevier B.V. All rights reserved.
Clinical criteria for the diagnosis of Alzheimer disease: still good after all these years.
Ranginwala, Najeeb A; Hynan, Linda S; Weiner, Myron F; White, Charles L
2008-05-01
To examine the impact of newer neuropathological techniques on the power of National Institute of Neurological and Communicative Disorders and Stroke-AD and Related Disorders Association criteria for Alzheimer disease (AD) to detect AD at later postmortem study. We examined clinical and postmortem diagnoses of persons evaluated postmortem with thioflavin-S staining for plaques and tangles and immunohistochemical staining techniques for alpha synuclein, uhiquitin, and tau protein. Alzheimer Disease Center. Clinically evaluated persons for whom tissue diagnosis was available. Of 313 evaluees, 166 met criteria for probable AD. An additional 59 subjects had clinical diagnoses that included AD, e.g., possible AD, Lewy body variant of AD, AD and Parkinsonism, and mixed AD and vascular dementia. Of the 166 probable AD cases, 147 of 166 (88.6%) met pathologic criteria for AD. When all five AD groups were combined, 194 of 225 subjects (86.2%) met pathologic criteria for AD. There were five cases diagnosed pathologically as tangle-only dementia, which was considered a variant of AD. A pathologic diagnosis of Lewy body variant of AD was made in 56 (17.9%) of cases, including 44 of 313 (14.1%) cases diagnosed as probable or possible AD. Pure dementia with Lewy bodies was seen in 13 (4.2%). There were 9 (2.9%) cases of mixed AD and vascular dementia, and 37 (11.4%) cases of frontotemporal dementia. McKhann et al. criteria for probable and possible AD are valid for AD but do not exclude additional Lewy body pathology.
Biessels, Geert Jan; Strachan, Mark W J; Visseren, Frank L J; Kappelle, L Jaap; Whitmer, Rachel A
2014-03-01
Type 2 diabetes is associated with dementia, and also with more slight cognitive decrements. In this Review we discuss trajectories from normal cognition to dementia in people with type 2 diabetes, and explore opportunities for treatment. Slight diabetes-associated cognitive decrements and dementia affect different age groups and show a different evolution. These cognitive entities should therefore not be regarded as a continuum, although their effects might be additive. Vascular damage is a key underlying process in both entities. Glucose-mediated processes and other metabolic disturbances might also have a role. No treatment has been established, but management of vascular risk factors and optimisation of glycaemic control could have therapeutic benefit. We identify possible opportunities for intervention to improve cognitive outcomes in people with type 2 diabetes, and suggest how treatment can be tailored to individual risk profiles and comorbidities. Copyright © 2014 Elsevier Ltd. All rights reserved.
Heser, Kathrin; Wagner, Michael; Wiese, Birgitt; Prokein, Jana; Ernst, Annette; König, Hans-Helmut; Brettschneider, Christian; Riedel-Heller, Steffi G.; Luppa, Melanie; Weyerer, Siegfried; Eifflaender-Gorfer, Sandra; Bickel, Horst; Mösch, Edelgard; Pentzek, Michael; Fuchs, Angela; Maier, Wolfgang; Scherer, Martin; Eisele, Marion
2014-01-01
Background Social relations and depressive symptoms are intertwined. They both predict subsequent dementia, but only few studies on the association between social life aspects and subsequent dementia exist. Methods The risk of subsequent dementia was estimated over 2 follow-up assessments, each 18 months apart, depending on leisure activity, social support (general scale and the 3 factors emotional support, practical support, and social integration), and depressive symptoms, using proportional hazard models in a cohort of elderly patients (n = 2,300, with a mean age of 82.45 years) recruited for the study by their general practitioners. Results Higher depressive symptoms and lower cognitive and physical activity were associated with an increased risk of subsequent all-cause dementia and Alzheimer's dementia (AD). While neither social engagement nor the general social support scale was associated with subsequent dementia, a higher level of social integration was associated with a lower dementia risk. In combined models, the results for activity variables remained similar, but the strength of the association between depressive symptoms and the subsequent risk of dementia decreased, and the association with social integration disappeared. Conclusions Depressive symptoms increased and activity variables decreased the risk of subsequent dementia; however, activity variables, namely cognitive and physical activity, partly mediated the effect of depressive symptoms on the subsequent risk of all-cause dementia and AD. In many cases, social support was not associated with a risk of subsequent dementia. PMID:25685139
Content and Quality of Information Provided on Canadian Dementia Websites
Dillon, Whitney A.; Prorok, Jeanette C.; Seitz, Dallas P.
2013-01-01
Purpose Information about dementia is important for persons with dementia (PWD) and their caregivers and the Internet has become the key source of health information. We reviewed the content and quality of information provided on Canadian websites for Alzheimer’s disease (AD). Methods We used the terms “dementia” and “Alzheimer” in Google to identify Canadian dementia websites. The contents of websites were compared to 16 guideline recommendations provided in Canadian Consensus Conference on Diagnosis and Treatment of Dementia. The quality of information provided on websites was evaluated using the DISCERN instrument. The content and quality of information provided on selected websites were then described. Results Seven websites were identified, three of which provided relatively comprehensive and high-quality information on dementia. Websites frequently provided information about diagnosis of dementia, its natural course, and types of dementia, while other topics were less commonly addressed. The quality of information provided on the websites varied, and many websites had several areas where the quality of information provided was relatively low according to the DISCERN instrument. Conclusions There is variation in the content and quality of dementia websites, although some websites provide high-quality and relatively comprehensive information which would serve as a useful resource for PWD, caregivers, and healthcare providers. Improvements in the content and quality of information provided on AD websites would provide PWD and their caregivers with access to better information. PMID:23440180
Camsari, Gamze Balci; Murray, Melissa E; Graff-Radford, Neill R
2016-08-01
Many dementia subtypes have more shared signs and symptoms than defining ones. We review 8 cases with 4 overlapping syndromes and demonstrate how to distinguish the cases. These include focal cortical presentations of Alzheimer's disease (AD; posterior cortical atrophy and corticobasal syndrome [CBS]), fluent aphasia (semantic dementia and logopenic aphasia), late-onset slowly progressive dementia (hippocampal sclerosis and limbic predominant AD) and rapidly progressive dementia (Creutzfeldt-Jakob disease and limbic encephalitis). Recognizing the different syndromes can help the clinician to improve their diagnostic skills, leading to improved patient outcomes by early and accurate diagnosis, prompt treatment, and appropriate counseling and guidance. Copyright © 2016 Elsevier Inc. All rights reserved.
McKhann, Guy M.; Knopman, David S.; Chertkow, Howard; Hyman, Bradley T.; Jack, Clifford R.; Kawas, Claudia H.; Klunk, William E.; Koroshetz, Walter J.; Manly, Jennifer J.; Mayeux, Richard; Mohs, Richard C.; Morris, John C.; Rossor, Martin N.; Scheltens, Philip; Carrillo, Maria C.; Thies, Bill; Weintraub, Sandra; Phelps, Creighton H.
2012-01-01
The National Institute on Aging and the Alzheimer’s Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer’s disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Bio-marker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. PMID:21514250
[Neuroepigenetics: Desoxyribonucleic acid methylation in Alzheimer's disease and other dementias].
Mendioroz Iriarte, Maite; Pulido Fontes, Laura; Méndez-López, Iván
2015-05-21
DNA methylation is an epigenetic mechanism that controls gene expression. In Alzheimer's disease (AD), global DNA hypomethylation of neurons has been described in the human cerebral cortex. Moreover, several variants in the methylation pattern of candidate genes have been identified in brain tissue when comparing AD patients and controls. Specifically, DNA methylation changes have been observed in PSEN1 and APOE, both genes previously being involved in the pathophysiology of AD. In other degenerative dementias, methylation variants have also been described in key genes, such as hypomethylation of the SNCA gene in Parkinson's disease and dementia with Lewy bodies or hypermethylation of the GRN gene promoter in frontotemporal dementia. The finding of aberrant DNA methylation patterns shared by brain tissue and peripheral blood opens the door to use those variants as epigenetic biomarkers in the diagnosis of neurodegenerative diseases. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.
Miller, Laurie A; Hsieh, Sharpley; Lah, Suncica; Savage, Sharon; Hodges, John R; Piguet, Olivier
2012-01-01
Patients with frontotemporal dementia (both behavioural variant [bvFTD] and semantic dementia [SD]) as well as those with Alzheimer's disease (AD) show deficits on tests of face emotion processing, yet the mechanisms underlying these deficits have rarely been explored. We compared groups of patients with bvFTD (n = 17), SD (n = 12) or AD (n = 20) to an age- and education-matched group of healthy control subjects (n = 36) on three face emotion processing tasks (Ekman 60, Emotion Matching and Emotion Selection) and found that all three patient groups were similarly impaired. Analyses of covariance employed to partial out the influences of language and perceptual impairments, which frequently co-occur in these patients, provided evidence of different underlying cognitive mechanisms. These analyses revealed that language impairments explained the original poor scores obtained by the SD patients on the Ekman 60 and Emotion Selection tasks, which involve verbal labels. Perceptual deficits contributed to Emotion Matching performance in the bvFTD and AD patients. Importantly, all groups remained impaired on one task or more following these analyses, denoting a primary emotion processing disturbance in these dementia syndromes. These findings highlight the multifactorial nature of emotion processing deficits in patients with dementia.
Current Role for Biomarkers in Clinical Diagnosis of Alzheimer Disease and Frontotemporal Dementia.
Sheikh-Bahaei, Nasim; Sajjadi, Seyed Ahmad; Pierce, Aimee L
2017-11-14
Purpose of review Alzheimer's disease (AD) and frontotemporal dementia can often be diagnosed accurately with careful clinical history, cognitive testing, neurological examination, and structural brain MRI. However, there are certain circumstances wherein detection of specific biomarkers of neurodegeneration or underlying AD pathology will impact the clinical diagnosis or treatment plan. We will review the currently available biomarkers for AD and frontotemporal dementia (FTD) and discuss their clinical importance. Recent findings With the advent of 18 F-labeled tracers that bind amyloid plaques, amyloid PET is now clinically available for the detection of amyloid pathology and to aid in a biomarker-supported diagnosis of AD or mild cognitive impairment (MCI) due to AD. It is not yet possible to test for the specific FTD pathologies (tau or TDP-43); however, a diagnosis of FTD may be "imaging supported" based upon specific MRI or FDG-PET findings. Cerebrospinal fluid measures of amyloid-beta, total-tau, and phospho-tau are clinically available and allow detection of both of the cardinal pathologies of AD: amyloid and tau pathology. Summary It is appropriate to pursue biomarker testing in cases of MCI and dementia when there remains diagnostic uncertainty and the result will impact diagnosis or treatment. Practically speaking, due to the rising prevalence of amyloid positivity with advancing age, measurement of biomarkers in cases of MCI and dementia is most helpful in early-onset patients, patients with atypical clinical presentations, or when considering referral for AD clinical trials.
Zekry, Dina; Herrmann, François R; Graf, Christophe E; Giannelli, Sandra; Michel, Jean-Pierre; Gold, Gabriel; Krause, Karl-Heinz
2011-01-01
The relative weight of various etiologies of dementia as predictors of long-term mortality after other risk factors have been taken into account remains unclear. We investigated the 5-year mortality risk associated with dementia in elderly people after discharge from acute care, taking into account comorbid conditions and functionality. A prospective cohort study of 444 patients (mean age: 85 years; 74% female) discharged from the acute geriatric unit of Geneva University Hospitals. On admission, each subject underwent a standardized diagnostic evaluation: demographic variables, cognitive, comorbid medical conditions and functional assessment. Patients were followed yearly by the same team. Predictors of survival at 5 years were evaluated by Cox proportional hazards models. The univariate model showed that being older and male, and having vascular and severe dementia, comorbidity and functional disability, were predictive of shorter survival. However, in the full multivariate model adjusted for age and sex, the effect of dementia type or severity completely disappeared when all the variables were added. In multivariate analysis, the best predictor was higher comorbidity score, followed by functional status (R(2) = 23%). The identification of comorbidity and functional impairment effects as predictive factors for long-term mortality independent of cognitive status may increase the accuracy of long-term discharge planning. Copyright © 2011 S. Karger AG, Basel.
Tewari, Devesh; Stankiewicz, Adrian M.; Mocan, Andrei; Sah, Archana N.; Tzvetkov, Nikolay T.; Huminiecki, Lukasz; Horbańczuk, Jarosław O.; Atanasov, Atanas G.
2018-01-01
Dementia is a clinical syndrome wherein gradual decline of mental and cognitive capabilities of an afflicted person takes place. Dementia is associated with various risk factors and conditions such as insufficient cerebral blood supply, toxin exposure, mitochondrial dysfunction, oxidative damage, and often coexisting with some neurodegenerative disorders such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD). Although there are well-established (semi-)synthetic drugs currently used for the management of AD and AD-associated dementia, most of them have several adverse effects. Thus, traditional medicine provides various plant-derived lead molecules that may be useful for further medical research. Herein we review the worldwide use of ethnomedicinal plants in dementia treatment. We have explored a number of recognized databases by using keywords and phrases such as “dementia”, “Alzheimer's,” “traditional medicine,” “ethnopharmacology,” “ethnobotany,” “herbs,” “medicinal plants” or other relevant terms, and summarized 90 medicinal plants that are traditionally used to treat dementia. Moreover, we highlight five medicinal plants or plant genera of prime importance and discuss the physiological effects, as well as the mechanism of action of their major bioactive compounds. Furthermore, the link between mitochondrial dysfunction and dementia is also discussed. We conclude that several drugs of plant origin may serve as promising therapeutics for the treatment of dementia, however, pivotal evidence for their therapeutic efficacy in advanced clinical studies is still lacking. PMID:29483867
Heser, K; Tebarth, F; Wiese, B; Eisele, M; Bickel, H; Köhler, M; Mösch, E; Weyerer, S; Werle, J; König, H-H; Leicht, H; Pentzek, M; Fuchs, A; Riedel-Heller, S G; Luppa, M; Prokein, J; Scherer, M; Maier, W; Wagner, M
2013-08-01
Whether late-onset depression is a risk factor for or a prodrome of dementia remains unclear. We investigated the impact of depressive symptoms and early- v. late-onset depression on subsequent dementia in a cohort of elderly general-practitioner patients (n = 2663, mean age = 81.2 years). Risk for subsequent dementia was estimated over three follow-ups (each 18 months apart) depending on history of depression, particularly age of depression onset, and current depressive symptoms using proportional hazard models. We also examined the additive prediction of incident dementia by depression beyond cognitive impairment. An increase of dementia risk for higher age cut-offs of late-onset depression was found. In analyses controlling for age, sex, education, and apolipoprotein E4 genotype, we found that very late-onset depression (aged ≥ 70 years) and current depressive symptoms separately predicted all-cause dementia. Combined very late-onset depression with current depressive symptoms was specifically predictive for later Alzheimer's disease (AD; adjusted hazard ratio 5.48, 95% confidence interval 2.41-12.46, p < 0.001). This association was still significant after controlling for cognitive measures, but further analyses suggested that it was mediated by subjective memory impairment with worries. Depression might be a prodrome of AD but not of dementia of other aetiology as very late-onset depression in combination with current depressive symptoms, possibly emerging as a consequence of subjectively perceived worrisome cognitive deterioration, was most predictive. As depression parameters and subjective memory impairment predicted AD independently of objective cognition, clinicians should take this into account.
David, Renaud; Manera, Valeria; Fabre, Roxane; Pradier, Christian; Robert, Philippe; Tifratene, Karim
2016-07-02
Safety warnings from health authorities are currently intended to limit the use of psychotropic agents in dementia-related conditions. Evidence concerning the use of antidepressants in dementia is, however, scarce and contradictory. To evaluate antidepressant use among individuals with Alzheimer's disease (AD) and related disorders in the French population between 2010 and 2014. Antidepressant prescriptions in individuals with AD, mixed dementia (MD), and vascular dementia (VaD) in the French National Alzheimer Database between 2010 and 2014 were analyzed (N = 199,544). Multivariate analysis showed an annual significant increase (p < 0.001) in the prescription rate of antidepressants from 26% (2010) to 31% (2014), and identified female gender, younger age, higher education, living in long-term facilities, more severe cognitive decline, and presence of vascular signs (VaD and MD) as associated factors for antidepressant prescribing. The annual increase of antidepressant prescribing among individuals with AD, MD, and VaD in French specialized settings may be partially related to the lack of current valuable medications for dementia-related behavioral symptoms.
Johnson, Julene K; Chow, Maggie L
2016-01-01
Music is a complex acoustic signal that relies on a number of different brain and cognitive processes to create the sensation of hearing. Changes in hearing function are generally not a major focus of concern for persons with a majority of neurodegenerative diseases associated with dementia, such as Alzheimer disease (AD). However, changes in the processing of sounds may be an early, and possibly preclinical, feature of AD and other neurodegenerative diseases. The aim of this chapter is to review the current state of knowledge concerning hearing and music perception in persons who have a dementia as a result of a neurodegenerative disease. The review focuses on both peripheral and central auditory processing in common neurodegenerative diseases, with a particular focus on the processing of music and other non-verbal sounds. The chapter also reviews music interventions used for persons with neurodegenerative diseases. PMID:25726296
Sleep architecture and the risk of incident dementia in the community.
Pase, Matthew P; Himali, Jayandra J; Grima, Natalie A; Beiser, Alexa S; Satizabal, Claudia L; Aparicio, Hugo J; Thomas, Robert J; Gottlieb, Daniel J; Auerbach, Sandford H; Seshadri, Sudha
2017-09-19
Sleep disturbance is common in dementia, although it is unclear whether differences in sleep architecture precede dementia onset. We examined the associations between sleep architecture and the prospective risk of incident dementia in the community-based Framingham Heart Study (FHS). Our sample comprised a subset of 321 FHS Offspring participants who participated in the Sleep Heart Health Study between 1995 and 1998 and who were aged over 60 years at the time of sleep assessment (mean age 67 ± 5 years, 50% male). Stages of sleep were quantified using home-based polysomnography. Participants were followed for a maximum of 19 years for incident dementia (mean follow-up 12 ± 5 years). We observed 32 cases of incident dementia; 24 were consistent with Alzheimer disease dementia. After adjustments for age and sex, lower REM sleep percentage and longer REM sleep latency were both associated with a higher risk of incident dementia. Each percentage reduction in REM sleep was associated with approximately a 9% increase in the risk of incident dementia (hazard ratio 0.91; 95% confidence interval 0.86, 0.97). The magnitude of association between REM sleep percentage and dementia was similar following adjustments for multiple covariates including vascular risk factors, depressive symptoms, and medication use, following exclusions for persons with mild cognitive impairment at baseline and following exclusions for early converters to dementia. Stages of non-REM sleep were not associated with dementia risk. Despite contemporary interest in slow-wave sleep and dementia pathology, our findings implicate REM sleep mechanisms as predictors of clinical dementia. © 2017 American Academy of Neurology.
Cerebral microbleeds are associated with cognitive decline and dementia: the Rotterdam Study
Akoudad, Saloua; Wolters, Frank J.; Viswanathan, Anand; de Bruijn, Renée F.; van der Lugt, Aad; Hofman, Albert; Koudstaal, Peter J.; Ikram, M. Arfan; Vernooij, Meike W.
2018-01-01
Importance Cerebral microbleeds are hypothesized downstream markers of brain damage caused by both vascular and amyloid pathological mechanisms. To date, it remains unclear whether their presence if associated with cognitive deterioration in the general population. Objective To determine whether microbleeds, and more specifically microbleed count and location, associate with an increased risk of cognitive impairment and dementia in the general population. Design Prospective population-based Rotterdam Study. Setting General community. Participants In the Rotterdam Study, we assessed presence, number, and location of microbleeds at baseline (2005–2011) on brain MRI of 4,841 participants aged ≥45 years. Participants underwent neuropsychological testing at two time points on average 5.9 years (SD 0.6) apart, and were followed for incident dementia throughout the study period until 2013. The association of microbleeds with cognitive decline and dementia was studied using multiple linear regression, linear mixed effects modeling, and Cox proportional hazards. Exposure cerebral microbleed presence, location, and number. Main outcomes cognitive decline and dementia. Results Microbleed prevalence was 15.3% (median count 1 [1–88]). Presence of >4 microbleeds associated with cognitive decline. Lobar (with or without cerebellar) microbleeds were associated with decline in executive functions, information processing, and memory function, whereas microbleeds in other brain regions were associated with decline in information processing and motor speed. After mean follow-up of 4.8 years (SD 1.4), 72 people developed dementia, of whom 53 had Alzheimer’s disease. Presence of microbleeds was associated with an increased risk of dementia (age, sex, education adjusted HR 2.02, 95%CI 1.25;3.24), including Alzheimer’s dementia (HR 2.10, 95%CI 1.21;3.64). Conclusions and relevance In the general population, a high microbleed count associated with an increased risk of cognitive
Sleep duration, cognitive decline, and dementia risk in older women
Chen, Jiu-Chiuan; Espeland, Mark A.; Brunner, Robert L.; Lovato, Laura C.; Wallace, Robert B.; Leng, Xiaoyan; Phillips, Lawrence S.; Robinson, Jennifer G.; Kotchen, Jane M.; Johnson, Karen C.; Manson, JoAnn E.; Stefanick, Marcia L.; Sarto, Gloria E.; Mysiw, W. Jerry
2015-01-01
Background Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. Methods We conducted a prospective study on 7444 community-dwelling women (aged 65–80) with self-reported sleep duration, within the Women’s Health Initiative Memory Study in 1995–2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. Results We found a statistically significant (p=0.03) V-shaped association, with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs.7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. Conclusion In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors. PMID:26086180
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.
Dementia with Lewy bodies: a comprehensive review for nurses.
Ajon Gealogo, Gretchel
2013-12-01
Much of the current nursing literature on dementia focuses on Alzheimer disease (AD), the dementia subtype most commonly diagnosed in the older adults. There is a paucity of nursing literature on dementia with Lewy bodies (DLB), the second most common subtype of dementia, which is closely associated with Parkinson disease with dementia (PDD), considered the third most common dementia subtype. Both are aging-related disorders attributed to Lewy bodies, abnormal protein aggregates or "clumps" found to cause cumulative neurodegeneration over time. DLB is defined as dementia onset that is preceded by Parkinsonian symptoms for 1 year or less, whereas in PDD, 2 or more years of Parkinsonian symptoms precede dementia onset. Although basic science knowledge of DLB has increased exponentially, the lack of nursing research on DLB indicates that this knowledge excludes the nursing perspective and its implications for nursing practice. The purpose of this article is to provide nurses with a comprehensive overview of DLB as it compares with PDD and Alzheimer disease and to propose key nursing interventions for clinical practice.
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.
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.
Wolfsgruber, Steffen; Kleineidam, Luca; Wagner, Michael; Mösch, Edelgard; Bickel, Horst; Lϋhmann, Dagmar; Ernst, Annette; Wiese, Birgitt; Steinmann, Susanne; König, Hans-Helmut; Brettschneider, Christian; Luck, Tobias; Stein, Janine; Weyerer, Siegfried; Werle, Jochen; Pentzek, Michael; Fuchs, Angela; Maier, Wolfgang; Scherer, Martin; Riedel-Heller, Steffi G; Jessen, Frank
2016-10-04
It is unknown whether longitudinal stability versus instability in subjective cognitive decline (SCD) is a modifying factor of the association between SCD and risk of incident Alzheimer's disease (AD) dementia. We tested the modifying role of temporal stability of the SCD report on AD dementia risk in cognitively normal elderly individuals. We analyzed data of 1,990 cognitively normal participants from the longitudinal AgeCoDe Study. We assessed SCD with/without associated worries both at baseline and first follow-up 18 months later. Participants were then classified either as (a) Controls (CO, with no SCD at both baseline and follow-up 1, n = 613), (b) inconsistent SCD (with SCD reported only at baseline or at follow-up 1, n = 637), (c) consistent SCD but without/or with inconsistent worries (n = 610) or (d) consistent SCD with worries (n = 130). We estimated incident AD dementia risk over up to 6 years for each group with Cox-Proportional Hazard Regression analyses adjusted for age, gender, education, ApoE4 status, and depression. Compared to CO, inconsistent SCD was not associated with increased risk of incident AD dementia. In contrast, risk was doubled in the group of consistent SCD without/ with inconsistent worries, and almost 4-fold in the group of consistent SCD with worries. These results could be replicated when using follow-up 1 to follow-up 2 response patterns for group definition. These findings suggest that longitudinal stability versus instability is an important modifying factor of the association between SCD and AD dementia risk. Worrisome SCD that is also consistently reported over time is associated with greatly increased risk of AD dementia.
Alzheimer’s and Dementia in the Oldest-Old: A Century of Challenges
Kawas, Claudia H.; Corrada, Maria M.
2012-01-01
Alzheimer’s disease (AD) is the most common type of dementia in the US and much of the world with rates increasing exponentially from age 65. Increases in life expectancy in the last century have resulted in a large number of people living to old ages and will result in a quadrupling of AD cases by the middle of the century. Preventing or delaying the onset of AD could have a huge impact in the number of cases expected to develop. The oldest-old are the fastest growing segment of the population and are estimated to account for 12% of the population over 65. Establishing accurate estimates of dementia and AD rates in this group is crucial for public health planning. Prevalence and incidence estimates above age 85 are imprecise and inconsistent because of the lack of very old individuals in most studies. Moreover, risk and protective factors in our oldest citizens have been studied little, and clinical-pathological correlations appear to be poor. We introduce The 90+ Study, established to address some of the unanswered questions about AD and dementia in the oldest-old. Our preliminary results show that close to half of demented oldest-old do not have known cerebral pathology to account for their cognitive deficits. Furthermore, the APOE-e4 allele appears to be a risk factor for AD only in the women in our study. In addition to the challenge of preventing and treating AD, the oldest-old will require major investigative energy to better understand the concomitants of longevity, the causes of dementia, and the factors that promote successful aging in oldest citizens. PMID:17168640
Bowling, Ann; Rowe, Gene; Adams, Sue; Sands, Paula; Samsi, Kritika; Crane, Maureen; Joly, Louise; Manthorpe, Jill
2015-01-01
Ascertaining the quality of life (QoL) in people with dementia is important for evaluating service outcomes and cost-effectiveness. This paper identifies QoL measures for people with dementia and assesses their properties. A systematic narrative review identified articles using dementia QoL measures. Electronic databases searched were AMED, CINAHL, EMBASE, Index to Theses, IBSS, MEDLINE, PsycINFO, Sociological Abstracts, and Web of Science. All available years and languages (if with an English language abstract) were included. Searches yielded 6806 citations; 3043 were multiple duplicates (759 being true duplicates). Abstracts were read; 182 full papers were selected/obtained, of which 126 were included as relevant. Few measures were based on rigorous conceptual frameworks. Some referenced Lawton's model (Dementia Quality of Life [DQOL] and Quality of Life in Alzheimer's Disease [QOL-AD]), though these tapped part of this only; others claimed relationship to a health-related QoL concept (e.g. DEMQOL), though had less social relevance; others were based on limited domains (e.g. activity, affect) or clinical opinions (Quality of Life in Late-Stage Dementia [QUALID]). Many measures were based on proxy assessments or observations of people with dementia's QoL, rather than their own ratings. The Bath Assessment of Subjective Quality of Life in Dementia (BASQID) was developed involving people with dementia and caregivers, but excluded some of their main themes. All measures were tested on selective samples only (ranging from community to hospital clinics, or subsamples/waves of existing population surveys), in a few sites. Their general applicability remains unknown, and predictive validity remains largely untested. The lack of consensus on measuring QoL in dementia suggests a need for a broader, more rigorously tested QoL measure.
Endpoints for Pre-Dementia AD Trials: A Report from the EU/US/CTAD Task Force
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
Toth, Peter; Tarantini, Stefano; Csiszar, Anna
2017-01-01
Increasing evidence from epidemiological, clinical and experimental studies indicate that age-related cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including Alzheimer’s disease. Understanding and targeting the age-related pathophysiological mechanisms that underlie vascular contributions to cognitive impairment and dementia (VCID) are expected to have a major role in preserving brain health in older individuals. Maintenance of cerebral perfusion, protecting the microcirculation from high pressure-induced damage and moment-to-moment adjustment of regional oxygen and nutrient supply to changes in demand are prerequisites for the prevention of cerebral ischemia and neuronal dysfunction. This overview discusses age-related alterations in three main regulatory paradigms involved in the regulation of cerebral blood flow (CBF): cerebral autoregulation/myogenic constriction, endothelium-dependent vasomotor function, and neurovascular coupling responses responsible for functional hyperemia. The pathophysiological consequences of cerebral microvascular dysregulation in aging are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages, microvascular rarefaction, and ischemic neuronal dysfunction and damage. Due to the widespread attention that VCID has captured in recent years, the evidence for the causal role of cerebral microvascular dysregulation in cognitive decline is critically examined. PMID:27793855
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
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.
Neuropathology of dementia with Lewy bodies in advanced age: a comparison with Alzheimer disease.
Ubhi, Kiren; Peng, Kevin; Lessig, Stephanie; Estrella, Jennilyn; Adame, Anthony; Galasko, Douglas; Salmon, David P; Hansen, Lawrence A; Kawas, Claudia H; Masliah, Eliezer
2010-11-26
Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder of the aging population characterized by α-synuclein accumulation in cortical and subcortical regions. Although neuropathology in advanced age has been investigated in dementias such as Alzheimer Disease (AD), severity of the neuropathology in the oldest old with DLB remains uncharacterized. For this purpose we compared characteristics of DLB cases divided into three age groups 70-79, 80-89 and ≥ 90 years (oldest old). Neuropathological indicators and levels of synaptophysin were assessed and correlated with clinical measurements of cognition and dementia severity. These studies showed that frequency and severity of DLB was lower in 80-89 and ≥ 90 year cases compared to 70-79 year old group but cognitive impairment did not vary with age. The extent of AD neuropathology correlated with dementia severity only in the 70-79 year group, while synaptophysin immunoreactivity more strongly associated with dementia severity in the older age group in both DLB and AD. Taken together these results suggest that the oldest old with DLB might represent a distinct group. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
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.
Prevalence rates for dementia and Alzheimer’s disease in African Americans: 1992 vs. 2001
Hall, KS; Gao, S; Baiyewu, O; Lane, KA; Gureje, O; Shen, J; Ogunniyi, A; Murrell, JR; Unverzagt, FW; Dickens, J; Smith-Gamble, V; Hendrie, HC
2009-01-01
Background This study compares age-specific and overall prevalence rates for dementia and Alzheimer’s disease (AD) in two non overlapping population-based cohorts of elderly African Americans in Indianapolis in 2001 and 1992. Methods Two-stage design, first stage is Community Screening Interview for Dementia (CSI-D). CSI-D scores grouped into good, intermediate and poor performance for selection into clinical assessment. Diagnosis was made using standard criteria in consensus diagnosis conference; clinicians blind to performance group. In 1992, interviewers went to randomly sampled addresses enrolling self identified African Americans age ≥ 65; of 2,582 eligible, 2,212 enrolled, (9.6% refused, 4.7% too sick). In 2001, Medicare roles were used for African Americans age ≥ 70 years; of 4,260 eligible, 1,892 (44%) enrolled, 1,999 (47%) refused, the remainder had other reasons. Results The overall age adjusted prevalence rate for dementia for age ≥ 70 years in 2001 was 7.45% (95 confidence interval [CI] 4.27–10.64) and for the 1992 cohort was 6.75% (95% CI 5.77–7.74). The overall age adjusted prevalence rate for age ≥ 70 years, for AD for the 2001 cohort was 6.77% (95% CI 3.65–9.90), and for the 1992 cohort was 5.47% (95% CI 4.51–6.42). Rates for dementia and AD were not significantly different in the two cohorts (dementia, p=0.3534, AD, p=0.2649). Conclusions We find no differences in prevalence rates of dementia and AD between 1992 and 2001 in spite of significant medical history and medical treatment differences in these population-based cohorts of African American elderly. PMID:19426950
Molecular Imaging and Updated Diagnostic Criteria in Lewy Body Dementias.
Bohnen, Nicolaas I; Müller, Martijn L T M; Frey, Kirk A
2017-08-14
The aims of the study were to review recent advances in molecular imaging in the Lewy body dementias (LBD) and determine if these may support the clinical but contested temporal profile distinction between Parkinson disease (PD) with dementia (PDD) versus dementia with Lewy bodies (DLB). There do not appear to be major regional cerebral metabolic or neurotransmitter distinctions between PDD and DLB. However, recent studies highlight the relative discriminating roles of Alzheimer proteinopathies. PDD patients have lower cortical β-amyloid deposition than DLB. Preliminary tau PET studies suggest a gradient of increasing tau binding from cognitively normal PD (absent to lowest) to cognitively impaired PD (low) to DLB (intermediate) to Alzheimer disease (AD; highest). However, tau binding in DLB, including the medial temporal lobe, is substantially lower than in AD. Alzheimer-type proteinopathies appear to be more common in DLB compared to PDD with relative but no absolute differences. Given the spectrum of overlapping pathologies, future α-synuclein ligands are expected to have the best potential to distinguish the LBD from pure AD.
Head circumference, education and risk of dementia: findings from the Nun Study.
Mortimer, James A; Snowdon, David A; Markesbery, William R
2003-08-01
To examine the prevalence of dementia associated with having a smaller brain, lower education or both of these characteristics, 294 Catholic sisters were assessed annually for dementia. Sixty participants died and their brains were evaluated to determine fulfillment of neuropathological criteria for Alzheimer's disease (AD). Lower educational attainment and the interaction of smaller head circumference with lower education were associated with the presence of dementia, controlling for age and the presence of one or more apolipoprotein E-epsilon 4 alleles. By contrast, neither low educational attainment nor head circumference was significantly associated with fulfillment of neuropathological criteria for AD. Individuals having both low education and small head circumference were four times as likely to be demented as the rest of the sample. The findings suggest that higher education and larger head size, alone or in combination, may reduce the risk of expressing dementia in late life.
Association between hormone replacement therapy and dementia: is it time to forget?
Almeida, Osvaldo P; Flicker, Leon
2005-06-01
The results of in vitro and animal studies provide a strong rationale for the use of hormone replacement therapy (HRT) to prevent dementia and Alzheimer's disease (AD). In humans, the results of 16 observational studies are consistent with the hypothesis that estrogen use reduces the risk of AD by 10 to 60%. However, women who are prescribed HRT are less likely to have hypertension, diabetes and history of stroke than nonusers. As all of these factors have been associated with increased risk of dementia (including AD), this "prescription bias" may have a significant impact on the results of observational studies. Randomized trials are designed with the aim of avoiding many of the potential biases and confounding (measured or unmeasured) of observational studies. The results of the Women's Health Initiative Memory Study (WHIMS) indicate that HRT (estrogen plus progestin or estrogen alone) increases the risk of dementia (hazard ratio, HR = 1.8, 95% CI = 1.2-2.6). Taking into account the results of the WHIMS and the adverse health events associated with the use of estrogen plus progestin or estrogen alone, we conclude that HRT cannot be recommended as a safe and effective strategy to prevent dementia.
Hippocampal sclerosis dementia: an amnesic variant of frontotemporal degeneration
Onyike, Chiadi U.; Pletnikova, Olga; Sloane, Kelly L.; Sullivan, Campbell; Troncoso, Juan C.; Rabins, Peter V.
2013-01-01
OBJECTIVE To describe characteristics of hippocampal sclerosis dementia. METHODS Convenience sample of Hippocampal sclerosis dementia (HSD) recruited from the Johns Hopkins University Brain Resource Center. Twenty-four cases with post-mortem pathological diagnosis of hippocampal sclerosis dementia were reviewed for clinical characterization. RESULTS The cases showed atrophy and neuronal loss localized to the hippocampus, amygdala and entorrhinal cortex. The majority (79.2%) had amnesia at illness onset, and many (54.2%) showed abnormal conduct and psychiatric disorder. Nearly 42% presented with an amnesic state, and 37.5% presented with amnesia plus abnormal conduct and psychiatric disorder. All eventually developed a behavioral or psychiatric disorder. Disorientation, executive dysfunction, aphasia, agnosia and apraxia were uncommon at onset. Alzheimer disease (AD) was the initial clinical diagnosis in 89% and the final clinical diagnosis in 75%. Diagnosis of frontotemporal dementia (FTD) was uncommon (seen in 8%). CONCLUSION HSD shows pathological characteristics of FTD and clinical features that mimic AD and overlap with FTD. The findings, placed in the context of earlier work, support the proposition that HSD belongs to the FTD family, where it may be identified as an amnesic variant. PMID:24363834
Association of Lithium in Drinking Water With the Incidence of Dementia.
Kessing, Lars Vedel; Gerds, Thomas Alexander; Knudsen, Nikoline Nygård; Jørgensen, Lisbeth Flindt; Kristiansen, Søren Munch; Voutchkova, Denitza; Ernstsen, Vibeke; Schullehner, Jörg; Hansen, Birgitte; Andersen, Per Kragh; Ersbøll, Annette Kjær
2017-10-01
Results from animal and human studies suggest that lithium in therapeutic doses may improve learning and memory and modify the risk of developing dementia. Additional preliminary studies suggest that subtherapeutic levels, including microlevels of lithium, may influence human cognition. To investigate whether the incidence of dementia in the general population covaries with long-term exposure to microlevels of lithium in drinking water. This Danish nationwide, population-based, nested case-control study examined longitudinal, individual geographic data on municipality of residence and data from drinking water measurements combined with time-specific data from all patients aged 50 to 90 years with a hospital contact with a diagnosis of dementia from January 1, 1970, through December 31, 2013, and 10 age- and sex-matched control individuals from the Danish population. The mean lithium exposure in drinking water since 1986 was estimated for all study individuals. Data analysis was performed from January 1, 1995, through December 31, 2013. A diagnosis of dementia in a hospital inpatient or outpatient contact. Diagnoses of Alzheimer disease and vascular dementia were secondary outcome measures. In primary analyses, distribution of lithium exposure was compared between patients with dementia and controls. A total of 73 731 patients with dementia and 733 653 controls (median age, 80.3 years; interquartile range, 74.9-84.6 years; 44 760 female [60.7%] and 28 971 male [39.3%]) were included in the study. Lithium exposure was statistically significantly different between patients with a diagnosis of dementia (median, 11.5 µg/L; interquartile range, 6.5-14.9 µg/L) and controls (median, 12.2 µg/L; interquartile range, 7.3-16.0 µg/L; P < .001). A nonlinear association was observed. Compared with individuals exposed to 2.0 to 5.0 µg/L, the incidence rate ratio (IRR) of dementia was decreased in those exposed to more than 15.0 µg/L (IRR, 0.83; 95% CI, 0.81-0.85; P
Bahia, Valéria S; Cecchini, Mário A; Cassimiro, Luciana; Viana, Rene; Lima-Silva, Thais B; de Souza, Leonardo Cruz; Carvalho, Viviane Amaral; Guimarães, Henrique C; Caramelli, Paulo; Balthazar, Márcio L F; Damasceno, Benito; Brucki, Sônia M D; Nitrini, Ricardo; Yassuda, Mônica S
2018-05-04
Executive dysfunction is a common symptom in neurodegenerative disorders and is in need of easy-to-apply screening tools that might identify it. The aims of the present study were to examine some of the psychometric characteristics of the Brazilian version of the INECO frontal screening (IFS), and to investigate its accuracy to diagnose executive dysfunction in dementia and its accuracy to differentiate Alzheimer disease (AD) from the behavioral variant of frontotemporal dementia (bvFTD). Patients diagnosed with bvFTD (n=18) and AD (n=20), and 15 healthy controls completed a neuropsychological battery, the Neuropsychiatric Inventory, the Cornell Scale for Depression in Dementia, the Clinical Dementia Rating, and the IFS. The IFS had acceptable internal consistency (α=0.714) and was significantly correlated with general cognitive measures and with neuropsychological tests. The IFS had adequate accuracy to differentiate patients with dementia from healthy controls (AUC=0.768, cutoff=19.75, sensitivity=0.80, specificity=0.63), but low accuracy to differentiate bvFTD from AD (AUC=0.594, cutoff=16.75, sensitivity=0.667, specificity=0.600). The present study suggested that the IFS may be used to screen for executive dysfunction in dementia. Nonetheless, it should be used with caution in the differential diagnosis between AD and bvFTD.
The role of human cognitive neuroscience in drug discovery for the dementias.
Wesnes, Keith A; Edgar, Chris J
2014-02-01
Cognitive dysfunction characterizes all the various forms of dementia. Evidence is accumulating that all of the progressive neurodegenerative dementias, such as Alzheimer's disease (AD), are preceded by years, if not decades, of pathological cognitive decline. The limited effectiveness of the four current medications registered for AD together with the failure of dozens of programmes over the last decade has influenced the decision to evaluate treatment at earlier stages of the disease; even before any cognitive symptoms have appeared. However, it has to be acknowledged that treating mild cognitive impairment (MCI) as a prodrome for AD has also had very limited success. Nonetheless a more important problem in MCI research, and dementia in general, has to be laid at the door of the limited effectiveness of the cognitive tests employed. This problem will become even more severe for the latest research direction of treating preclinical AD because such individuals will have levels of cognitive abilities which are in the normal range; and thus many of the scales currently used in dementia research will not be sufficiently demanding to identify change over time. This paper reviews and discusses the methodology and instruments available for research and clinical practice in this major area; with a focus on the challenges involved in test selection and evaluation. Copyright © 2013 Elsevier Ltd. All rights reserved.
Acupuncture Prevents the Impairment of Hippocampal LTP Through β1-AR in Vascular Dementia Rats.
Xiao, Ling-Yong; Wang, Xue-Rui; Yang, Jing-Wen; Ye, Yang; Zhu, Wen; Cao, Yan; Ma, Si-Ming; Liu, Cun-Zhi
2018-02-13
It is widely accepted that the synaptic dysfunction and synapse loss contribute to the cognitive deficits of vascular dementia (VD) patients. We have previously reported that acupuncture improved cognitive function in rats with VD. However, the mechanisms involved in acupuncture improving cognitive ability remain to be elucidated. The present study aims to investigate the pathways and molecules involved in the neuroprotective effect of acupuncture. We assessed the effects of acupuncture on hippocampal long-term potentiation (LTP), the most prominent cellular model of memory formation. Acupuncture enhanced LTP and norepinephrine (NE) levels in the hippocampus. Inhibition of the β-adrenergic receptor (AR), but not the α-AR, was able to block the effects of acupuncture on hippocampal LTP. Furthermore, inhibition of β1-AR, not β2-AR, abolished the enhanced LTP induced by acupuncture. The expression analysis revealed a significant upregulation of β1-AR and unchanged β2-AR with acupuncture, which supported the above findings. Specifically, increased β1-ARs in the dentate gyrus were expressed on neurons exclusively. Taken together, the present data supports a beneficial role of acupuncture in synaptic plasticity challenged with VD. A likely mechanism is the increase of NE and activation of β1-AR in the hippocampus.
Tang, Weizhou; Kannaley, Kristie; Friedman, Daniela B; Edwards, Valerie J; Wilcox, Sara; Levkoff, Sue E; Hunter, Rebecca H; Irmiter, Cheryl; Belza, Basia
2017-07-01
Early diagnosis of Alzheimer's disease (AD) or dementia is important so that patients can express treatment preferences, subsequently allowing caregivers to make decisions consistent with their wishes. This study explored the relationship between people's concern about developing AD/dementia, likelihood to be screened/tested, if experiencing changes in cognitive status or functioning, and concerns about sharing the diagnostic information with others. A descriptive study was conducted using Porter Novelli's SummerStyles 2013 online survey data. Of the 6105 panelists aged 18+ who received the survey, 4033 adults responded (response rate: 66%). Chi squares were used with case-level weighting applied. Almost 13% of respondents reported being very worried or worried about getting AD/dementia, with women more worried than men (p<.001), and AD/dementia caregivers more worried than other types of caregivers (p=.04). Women were also more likely than men to agree to be screened/tested if experiencing changes in memory and/or thinking (p<.001). The greater the worry, the more likely respondents would agree to be screened/tested (p<.001). Nearly 66% of respondents were concerned that sharing a diagnosis would change the way others think/feel about them, with women reporting greater concern than men (p=.003). Findings demonstrate that level of worry about AD/dementia is associated with the reported likelihood that individuals agree to be screened/tested. This information will be useful in developing communication strategies to address public concern about AD/dementia that may increase the likelihood of screening and early detection. Copyright © 2017 Elsevier B.V. All rights reserved.
Education and Risk of Dementia: Dose-Response Meta-Analysis of Prospective Cohort Studies.
Xu, Wei; Tan, Lan; Wang, Hui-Fu; Tan, Meng-Shan; Tan, Lin; Li, Jie-Qiong; Zhao, Qing-Fei; Yu, Jin-Tai
2016-07-01
Educational level has been regarded as one of the most widely accepted risk factors in the epidemiological studies for dementia, despite with discordant qualitative results. However, the dose-response relation between education and incident dementia was still unknown. To quantitatively evaluate the association between exposure level to high and low education and risk of dementia, we searched PubMed, EMBASE, and the Cochrane Library up to November 2014 and references of retrieved literatures. Specific prospective cohort studies, in which educational attainment was categorized into at least three levels, were included. Newcastle-Ottawa scale was used to assess the quality of included studies. Fifteen prospective cohort studies with 55655 for low education and eight prospective cohort studies with 20172 for high education were included. In the qualitative analysis, both low and high education showed a dose-response trend with risk of dementia and Alzheimer's disease (AD). In the quantitative analysis, the dementia risk was reduced by 7 % for per year increase in education (RR, 0.93; 95 % CI, 0.92-0.94; p for overall trend = 0.000; p for nonlinearity = 0.0643). Nonetheless, we did not find statistically significant association between per year decrease in education and dementia (RR, 1.03; 95 % CI, 0.96-1.10; p for overall trend = 0.283; p for nonlinearity = 0.0041) or AD (RR, 1.03; 95 % CI, 0.97-1.10; p for overall trend = 0.357; p for nonlinearity = 0.0022). Both low and high education showed a trend of dose-response relation with risk of dementia and AD. The dementia risk was reduced by 7 % for per year increase in education.
Depression subtypes and 5-year risk of dementia and Alzheimer disease in patients aged 70 years.
Vilalta-Franch, Joan; López-Pousa, Secundino; Llinàs-Reglà, Jordi; Calvó-Perxas, Laia; Merino-Aguado, Javier; Garre-Olmo, Josep
2013-04-01
The objective of this study was to estimate several subtypes of depressive disorders as risk factors for dementia and Alzheimer disease (AD) specifically. This is a population-based cohort study using a sample of 451 non-demented older people. Adjusted Cox proportional hazard models were calculated to determine the association of depression with dementia or AD development after 5 years. Baseline evaluation included the Cambridge Mental Disorders of the Elderly Examination (CAMDEX). Depressive disorders (major episode [MD] and minor depressive disorders [MDDIS]) were assessed following DSM-IV criteria and further classified according to the age at onset (early versus late onset). In turn, all late-onset depressions were grouped as with or without depression-executive dysfunction syndrome (DEDS). Dementia (and dementia subtypes) diagnoses were made using the CAMDEX. When the patients were deceased, the Retrospective Collateral Dementia Interview was used. Late-onset depressions (both MD and MDDIS) were associated with increased dementia (hazard ratio [HR] = 2.635; 95% CI = 1.153-6.023; and HR = 2.517; 95% CI = 1.200-5.280, respectively), and AD (HR = 6.262; 95% CI = 2.017-19.446; and HR = 4.208; 95% CI = 1.828-9.685, respectively) after adjustment by age, gender, marital status, education, cognitive impairment, executive function and stroke history. A second model revealed that only late-onset depressions with DEDS increased the risk for both dementia (late-onset MD with DEDS: HR = 6.262; 95% CI = 2.017-19.446; late-onset MDDIS with DEDS: HR = 4.208; 95% CI = 1.828-9.685) and AD (late-onset MD with DEDS: HR = 7.807; 95% CI = 1.567-38.894; late-onset MDDIS with DEDS: HR = 6.099; 95% CI = 2.123-17.524). Late-onset depressive episodes with DEDS are risk factors for dementia and AD development, regardless of the severity of the depression. Copyright © 2012 John Wiley & Sons, Ltd.
Prevalence of dementia in Al Kharga District, New Valley Governorate, Egypt.
El Tallawy, Hamdy N; Farghly, Wafaa M A; Shehata, Ghaydaa A; Rageh, Tarek A; Hakeem, Nabil Abdel; Abo-Elfetoh, Noha; Hegazy, Ahmed M; Rayan, Ibraheem; El-Moselhy, Essam A
2012-01-01
With aging, there is a parallel increase in the prevalence of dementia worldwide. The aim of this work is to determine the prevalence of dementia among the population of Al Kharga District, New Valley, Egypt. Screening of all subjects aged ≥50 years (n = 8,173 out of 62,583 inhabitants) was done through a door-to-door survey by 3 neurologists, using a short standardized Arabic screening test and a modified Mini-Mental State Examination. Suspected cases were subjected to full clinical examination, psychometric assessment using the Cognitive Abilities Screening Instrument, Instrumental Activities of Daily Living Scale, Geriatric Depression Scale, Hachinski Ischemic Score, DSM-IV-TR diagnostic criteria, neuroimaging, and laboratory investigations, when indicated. The prevalence rate of dementia was 2.26% for the population aged ≥50 years. It increased steeply with age to a maximum of 18.48% for those aged ≥80 years. Alzheimer's disease (51.2%) was the most common subtype, followed by vascular dementia (28.7%), dementia due to general medical conditions (12.8%), and lastly dementia due to multiple etiologies (7.3%). Mild dementia was the commonest (53.7%). Dementia is prevalent in Egypt as elsewhere. Detection through a door-to-door survey is the best method in developing countries for early detection of mild cases. Copyright © 2012 S. Karger AG, Basel.
Sequence variation in SORL1 and Dementia risk in Swedes
Reynolds, Chandra A.; Hong, Mun-Gwan; Eriksson, Ulrika K.; Blennow, Kaj; Johansson, Boo; Malmberg, Bo; Berg, Stig; Gatz, Margaret; Pedersen, Nancy L.; Bennet, Anna M.; Prince, Jonathan A.
2010-01-01
The gene encoding the neuronal sortilin-related receptor SORL1 has been claimed to be associated with Alzheimer Disease by independent groups and across various human populations. We evaluated six genetic markers in SORL1 in a sample of 1558 Swedish dementia cases (including 1270 Alzheimer disease cases) and 2179 controls. For both single marker and haplotype-based analyses we found no strong support for SORL1 as a dementia- or AD-risk modifying gene in our sample in isolation, nor did we observe association with AD/dementia-related traits, including CSF β-amyloid1–42, tau levels, or age-at-onset. However, meta-analyses of markers in this study together with previously published studies on SORL1 encompassing in excess of 13,000 individuals does suggest significant association with AD (best OR 1.097; 95% CI 1.038–1.158, p = 0.001). All six markers were significant in meta-analyses and it is notable that they occur in two distinct LD blocks. These data are consistent with either allelic heterogeneity or the existence of as yet untested functional variants and these will be important considerations in further attempts to evaluate the importance of sequence variation in SORL1 with AD risk. PMID:19653016
Feigin, Valery; Ratnasabapathy, Yogini; Anderson, Craig
2005-03-15
There is increasing evidence that both hypertension and stroke play important roles in the development of cognitive decline and dementia. Despite five high-quality randomised controlled trials (RCTs) in this area to date, there remains uncertainty about the role of blood pressure lowering therapy in the prevention of cognitive decline and dementia. It appears that lack of definitive results from these trials can be explained on the basis of (a) insufficient power to detect modest treatment effects; (b) measurement error in the diagnosis of dementia; (c) variations in the treatment effects between different types of antihypertensive agents; and (d) bias due to missing data, variation in baseline factors such as levels of blood pressure, and the inclusion of patients with cognitive impairment at entry. Preliminary meta-analysis of RCTs supports the hypothesis that blood pressure lowering may prevent dementia in high-risk patients, that is those with vascular disease. However, a meta-analysis of individual patient data (IPD) from these, and other relevant trials in patients with vascular disease, would provide much more reliable data. If the hypothesis were confirmed, it would certainly be of considerable importance not only in terms of our understanding of the aetiology of dementia, but also in promoting blood pressure lowering strategies for broader public health good.
Prediction of dementia in primary care patients.
Jessen, Frank; Wiese, Birgitt; Bickel, Horst; Eiffländer-Gorfer, Sandra; Fuchs, Angela; Kaduszkiewicz, Hanna; Köhler, Mirjam; Luck, Tobias; Mösch, Edelgard; Pentzek, Michael; Riedel-Heller, Steffi G; Wagner, Michael; Weyerer, Siegfried; Maier, Wolfgang; van den Bussche, Hendrik
2011-02-18
Current approaches for AD prediction are based on biomarkers, which are however of restricted availability in primary care. AD prediction tools for primary care are therefore needed. We present a prediction score based on information that can be obtained in the primary care setting. We performed a longitudinal cohort study in 3.055 non-demented individuals above 75 years recruited via primary care chart registries (Study on Aging, Cognition and Dementia, AgeCoDe). After the baseline investigation we performed three follow-up investigations at 18 months intervals with incident dementia as the primary outcome. The best set of predictors was extracted from the baseline variables in one randomly selected half of the sample. This set included age, subjective memory impairment, performance on delayed verbal recall and verbal fluency, on the Mini-Mental-State-Examination, and on an instrumental activities of daily living scale. These variables were aggregated to a prediction score, which achieved a prediction accuracy of 0.84 for AD. The score was applied to the second half of the sample (test cohort). Here, the prediction accuracy was 0.79. With a cut-off of at least 80% sensitivity in the first cohort, 79.6% sensitivity, 66.4% specificity, 14.7% positive predictive value (PPV) and 97.8% negative predictive value of (NPV) for AD were achieved in the test cohort. At a cut-off for a high risk population (5% of individuals with the highest risk score in the first cohort) the PPV for AD was 39.1% (52% for any dementia) in the test cohort. The prediction score has useful prediction accuracy. It can define individuals (1) sensitively for low cost-low risk interventions, or (2) more specific and with increased PPV for measures of prevention with greater costs or risks. As it is independent of technical aids, it may be used within large scale prevention programs.
Adelman, Simon; Blanchard, Martin; Rait, Greta; Leavey, Gerard; Livingston, Gill
2011-08-01
Preliminary studies in the UK, all using screening instruments of unknown cultural validity, indicate that there may be an increased prevalence of dementia in African-Caribbean people, possibly related to vascular risk factors and potentially amenable to preventative measures. To determine the prevalence of dementia in older people of African-Caribbean country of birth compared with their White UK-born counterparts. A total of 218 people of African-Caribbean country of birth and 218 White UK-born people aged ≥60 years were recruited from five general practices in North London. Those who screened positive for cognitive impairment using a culturally valid instrument were offered a standardised diagnostic interview. Two independent assessors diagnosed dementia according to standard operationalised criteria. African-Caribbean participants were 2 years younger, and those with dementia nearly 8 years younger than their White counterparts. The prevalence of dementia was significantly higher in the African-Caribbean (9.6%) than the White group (6.9%) after adjustment for the confounders age and socioeconomic status (odds ratio (OR) = 3.1, 95%CI 1.3-7.3, P = 0.012). There is an increased prevalence of dementia in older people of African-Caribbean country of birth in the UK and at younger ages than in the indigenous White population. These findings have implications for service provision and preventive interventions. Further research is needed to explore the role of vascular risk factors and social adversity in the excess of dementia in this population.
Kim, Jahae; Cho, Sang-Geon; Song, Minchul; Kang, Sae-Ryung; Kwon, Seong Young; Choi, Kang-Ho; Choi, Seong-Min; Kim, Byeong-Chae; Song, Ho-Chun
2016-01-01
Abstract To compare diagnostic performance and confidence of a standard visual reading and combined 3-dimensional stereotactic surface projection (3D-SSP) results to discriminate between Alzheimer disease (AD)/mild cognitive impairment (MCI), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). [18F]fluorodeoxyglucose (FDG) PET brain images were obtained from 120 patients (64 AD/MCI, 38 DLB, and 18 FTD) who were clinically confirmed over 2 years follow-up. Three nuclear medicine physicians performed the diagnosis and rated diagnostic confidence twice; once by standard visual methods, and once by adding of 3D-SSP. Diagnostic performance and confidence were compared between the 2 methods. 3D-SSP showed higher sensitivity, specificity, accuracy, positive, and negative predictive values to discriminate different types of dementia compared with the visual method alone, except for AD/MCI specificity and FTD sensitivity. Correction of misdiagnosis after adding 3D-SSP images was greatest for AD/MCI (56%), followed by DLB (13%) and FTD (11%). Diagnostic confidence also increased in DLB (visual: 3.2; 3D-SSP: 4.1; P < 0.001), followed by AD/MCI (visual: 3.1; 3D-SSP: 3.8; P = 0.002) and FTD (visual: 3.5; 3D-SSP: 4.2; P = 0.022). Overall, 154/360 (43%) cases had a corrected misdiagnosis or improved diagnostic confidence for the correct diagnosis. The addition of 3D-SSP images to visual analysis helped to discriminate different types of dementia in FDG PET scans, by correcting misdiagnoses and enhancing diagnostic confidence in the correct diagnosis. Improvement of diagnostic accuracy and confidence by 3D-SSP images might help to determine the cause of dementia and appropriate treatment. PMID:27930593
Kim, Hee Jin; Lee, Ji Eun; Shin, Soo Jeong; Sohn, Young Ho; Lee, Phil Hyu
2011-01-01
Background and Purpose The substantia innominata (SI) contains the nucleus basalis of Meynert, which is the major source of cholinergic input to the cerebral cortex. We hypothesized that degeneration of the SI and its relationship to general cognitive performance differs in amyloidopathy and synucleinopathy. Methods We used magnetic resonance imaging (MRI)-based volumetric analysis to evaluate the SI volume in patients with amnestic mild cognitive impairment (aMCI), Alzheimer’s disease (AD), Parkinson’s disease-mild cognitive impairment (PD-MCI), PD with dementia (PDD), dementia with Lewy bodies (DLB), and healthy elderly controls. The correlation between SI volume and general cognitive performance, measured using the Korean version of the Mini-Mental State Examination (K-MMSE), was examined. Results Compared to control subjects, the mean normalized SI volume was significantly decreased in all of the other groups. The normalized SI volume did not differ between the subjects with PDD and DLB, whereas it was significantly smaller in subjects with PDD (p = 0.029) and DLB (p = 0.011) compared with AD. In subjects with PD-related cognitive impairment (PD-MCI, PDD, or DLB), there was a significant positive correlation between the SI volume and K-MMSE score (r = 0.366, p < 0.001), whereas no correlation was seen in subjects with AD-related cognitive impairment (aMCI or AD). Conclusions Our data suggest that the SI loss is greater in synucleinopathy-related dementia (PDD or DLB) than in AD and that the contribution of the SI to cognitive performance is greater in synucleinopathy than in amyloidopathy. PMID:24868398
Borba, Ericksen Mielle; Duarte, Juliana Avila; Bristot, Giovana; Scotton, Ellen; Camozzato, Ana Luiza; Chaves, Márcia Lorena Fagundes
2016-01-01
Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.
Teipel, Stefan J; Keller, Felix; Thyrian, Jochen R; Strohmaier, Urs; Altiner, Attila; Hoffmann, Wolfgang; Kilimann, Ingo
2017-01-01
Once a patient or a knowledgeable informant has noticed decline in memory or other cognitive functions, initiation of early dementia assessment is recommended. Hippocampus and cholinergic basal forebrain (BF) volumetry supports the detection of prodromal and early stages of Alzheimer's disease (AD) dementia in highly selected patient populations. To compare effect size and diagnostic accuracy of hippocampus and BF volumetry between patients recruited in highly specialized versus primary care and to assess the effect of white matter lesions as a proxy for cerebrovascular comorbidity on diagnostic accuracy. We determined hippocampus and BF volumes and white matter lesion load from MRI scans of 71 participants included in a primary care intervention trial (clinicaltrials.gov identifier: NCT01401582) and matched 71 participants stemming from a memory clinic. Samples included healthy controls and people with mild cognitive impairment (MCI), AD dementia, mixed dementia, and non-AD related dementias. Volumetric measures reached similar effect sizes and cross-validated levels of accuracy in the primary care and the memory clinic samples for the discrimination of AD and mixed dementia cases from healthy controls. In the primary care MCI cases, volumetric measures reached only random guessing levels of accuracy. White matter lesions had only a modest effect on effect size and diagnostic accuracy. Hippocampus and BF volumetry may usefully be employed for the identification of AD and mixed dementia, but the detection of MCI does not benefit from the use of these volumetric markers in a primary care setting.
van Himbergen, Thomas M; Beiser, Alexa S; Ai, Masumi; Seshadri, Sudha; Otokozawa, Seiko; Au, Rhoda; Thongtang, Nuntakorn; Wolf, Philip A; Schaefer, Ernst J
2012-05-01
To investigate the contribution of biomarkers of glucose homeostasis (adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A(2) levels) to the risk of developing Alzheimer disease (AD) and all-cause dementia. Prospective cohort study. Dementia-free Framingham Heart Study participants had sera measured for these biomarkers at the 19th biennial examination (1985-1988) and were followed up prospectively for the development of AD and all-cause dementia. Eight hundred forty (541 women, median age of 76 years) subjects participated in the study. We used sex-pooled and sex-specific multivariable Cox proportional hazards models adjusted for age, education, body mass index, recent change in weight, APOE ε4 allele status, and plasma docosahexaenoic acid levels to determine association of these biomarkers with the development of all-cause dementia and AD. Over a mean follow-up period of 13 years, 159 persons developed dementia (including 125 with AD). After adjustment for other risk factors, only adiponectin in women was associated with an increased risk of all-cause dementia (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.00-1.66; P=.054) and AD (HR, 1.33; 95% CI, 1.00-1.76; P=.050) per 1-SD increase in adiponectin level. Women with baseline adiponectin values more than the median had a higher risk of all-cause dementia (HR, 1.63; 95% CI, 1.03-2.56; P=.04) and AD (HR, 1.87; 95% CI, 1.13-3.10; P=.01) as compared with those with values less than the median. In women, increased plasma adiponectin levels are an independent risk factor for the development of both all-cause dementia and AD.
Heparin Oligosaccharides as Potential Therapeutic Agents in Senile Dementia
Ma, Qing; Cornelli, Umberto; Hanin, Israel; Jeske, Walter P.; Linhardt, Robert J.; Walenga, Jeanine M.; Fareed, Jawed; Lee, John M.
2014-01-01
Heparin is a glycosaminoglycan mixture currently used in prophylaxis and treatment of thrombosis. Heparin possesses non-anticoagulant properties, including modulation of various proteases, interactions with fibroblast growth factors, and anti-inflammatory actions. Senile dementia of Alzheimer’s type is accompanied by inflammatory responses contributing to irreversible changes in neuronal viability and brain function. Vascular factors are also involved in the pathogenesis of senile dementia. Inflammation, endogenous proteoglycans, and assembly of senile plagues and neurofibrillary tangles contribute directly and indirectly to further neuronal damage. Neuron salvage can be achieved by anti-inflammation and the competitive inhibition of proteoglycans accumulation. The complexity of the pathology of senile dementia provides numerous potential targets for therapeutic interventions designed to modulate inflammation and proteoglycan assembly. Heparin and related oligosaccharides are known to exhibit anti-inflammatory effects as well as inhibitory effects on proteoglycan assembly and may prove useful as neuroprotective agents. PMID:17504153
Characterizing Sexual Behavior in Frontotemporal Dementia.
Ahmed, Rebekah M; Kaizik, Cassandra; Irish, Muireann; Mioshi, Eneida; Dermody, Nadene; Kiernan, Matthew C; Piguet, Olivier; Hodges, John R
2015-01-01
Frontotemporal dementia (FTD) is characterized by a number of prominent behavioral changes. While FTD has been associated with the presence of aberrant or unusual sexual behaviors in a proportion of patients, few studies have formally investigated changes in sexual function in this disease. We aimed to systematically quantify changes in sexual behavior, including current symptoms and changes from prior diagnoses, in behavioral-variant (bvFTD) and semantic dementia (SD), compared to Alzheimer's disease (AD). Carers of 49 dementia patients (21 bvFTD, 11 SD, 17 AD) were interviewed using the Sexual Behavior and Intimacy Questionnaire (SIQ), a survey designed to assess changes in sexual function across multiple domains including initiating, level of affection, and aberrant or unusual sexual behavior. BvFTD patients show prominent hyposexual behavior including decreased affection, initiation, and response to advances by partners, and decreased frequency of sexual relations, compared to AD and to SD patients. The greatest changes in sexual behavior compared to pre-diagnoses were found in the bvFTD group with a 90-100% decrease in initiation, response, and frequency of sexual relations. Notably, aberrant or unusual sexual behavior was reported in a minority of bvFTD and SD patients and occurred in patients who also showed hyposexual behavior toward their partner. Overall loss of affection, reduced initiation of sexual activity, and responsiveness is an overwhelming feature of bvFTD. In contrast, aberrant or unusual sexual behavior is observed in the minority of bvFTD patients. The underlying pathophysiology of these changes likely reflects structural and functional changes in frontoinsular and limbic regions including the hypothalamus.
SPECT in Alzheimer`s disease and the dementias
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bonte, F.J.
1991-12-31
Among 90 patients with a clinical diagnosis of Alzheimer`s disease (AD), two subgroups were identified for special study, including 42 patients who had a history of dementia in one or more first-degree relatives, and 14 who had a diagnosis of early AD. Of the 42 patients with a family history of dementia, 34 out of the 35 patients whose final clinical diagnosis was possible or probable AD had positive SPECT rCBF studies. Studies in the 14 patients thought to have very early AD were positive in 11 cases. This finding suggests that altered cortical physiology, and hence, rCBF, occurs quitemore » early in the course of AD, perhaps before the onset of symptoms. It is possible that Xenon 133 rCBF studies might be used to detect the presence of subclinical AD in a population of individuals at risk to this disorder. Despite the drawbacks of a radionuclide with poor photon energy, Xenon 133, with its low cost and round-the-clock availability, deserves further study. Although the physical characteristics of Xenon 127 might make it preferable as a SPECT tracer, it is still not regularly available, and some instrument systems are not designed to handle its higher photon energies.« less
The clinical diagnosis and misdiagnosis of senile dementia of Lewy body type (SDLT).
McKeith, I G; Fairbairn, A F; Perry, R H; Thompson, P
1994-09-01
Current clinical classifications do not contain specific diagnostic categories for patients with senile dementia of the Lewy body type (SDLT), recently proposed as the second commonest neuropathological cause of dementia in the elderly. This study determines how existing clinical diagnosis systems label SDLT patients and suggests how such patients may be identified. A range of clinical diagnostic criteria for dementia were applied to case notes of autopsy-confirmed SDLT (n = 20), dementia of Alzheimer type (DAT; n = 21) and multi-infarct dementia (MID; n = 9) patients who had received psychogeriatric assessment. The predictive validity of each set of clinical criteria was calculated against the external criterion of neuropathological diagnosis. Many SDLT patients erroneously met criteria for MID (35% with Hachinski scores > or = 7) or for DAT (15% by NINCDS 'probable AD', 35% by DSM-III-R DAT and 50% by NINCDS 'possible AD'). Up to 85% of SDLT cases could be correctly identified using recently published specific criteria. SDLT usually has a discernible clinical syndrome and existing clinical classifications may need revision to diagnose correctly such patients.
Memory Concerns, Memory Performance and Risk of Dementia in Patients with Mild Cognitive Impairment
Wolfsgruber, Steffen; Wagner, Michael; Schmidtke, Klaus; Frölich, Lutz; Kurz, Alexander; Schulz, Stefanie; Hampel, Harald; Heuser, Isabella; Peters, Oliver; Reischies, Friedel M.; Jahn, Holger; Luckhaus, Christian; Hüll, Michael; Gertz, Hermann-Josef; Schröder, Johannes; Pantel, Johannes; Rienhoff, Otto; Rüther, Eckart; Henn, Fritz; Wiltfang, Jens; Maier, Wolfgang; Kornhuber, Johannes; Jessen, Frank
2014-01-01
Background Concerns about worsening memory (“memory concerns”; MC) and impairment in memory performance are both predictors of Alzheimer's dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI). Methods We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models. Results Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33–4.89), lower memory performance (HR = 0.63, 95%CI: 0.56–0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18–3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment. Conclusions Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI. PMID:25019225
First translational 'Think Tank' on cerebrovascular disease, cognitive impairment and dementia.
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
Anti-Dementia Drugs, Gait Performance and Mental Imagery of Gait: A Non-Randomized Open-Label Trial.
Beauchet, Olivier; Barden, John; Liu-Ambrose, Teresa; Chester, Victoria L; Annweiler, Cedric; Szturm, Tony; Grenier, Sébastien; Léonard, Guillaume; Bherer, Louis; Allali, Gilles
2016-09-01
Few studies have examined the effect of anti-dementia drugs (i.e., acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists) on gait performance. Past studies have focused on the stride time (i.e., gait cycle duration) but not on the mental imagery of gait. To compare mental imagery of gait and spatiotemporal gait parameters in patients with dementia [i.e., Alzheimer's disease (AD) and non-AD] before and after the use of anti-dementia drugs (i.e., acetylcholinesterase inhibitors and memantine) and in controls (i.e., patients with dementia who did not take anti-dementia drugs). A total of 112 patients (mean age 82.5 ± 4.2 years, 68.8 % female) with mild-to-moderate AD and non-AD dementia were included in this non-randomized open-label trial (n = 56 in the Intervention group, and n = 56 in the Control group matched for age, sex, and stage and type of dementia) nested in a cohort study (mean follow-up 238.5 ± 79.8 days). Mental imagery of gait was assessed with the actual and imagined Timed Up and Go tests (aTUG and iTUG) and the difference between aTUG and iTUG (i.e., delta-TUG). Spatiotemporal gait parameters were measured with the GAITRite(®) system during normal walking. Participants in the Intervention group had a longer iTUG time (p < 0.001) and a lower delta-TUG value (p = 0.001) at the follow-up compared with those in the Control group. There was a significant increase in iTUG (p = 0.001) and decrease in delta-TUG (p < 0.001) from baseline to the follow-up only in the Intervention group. Multiple linear regression showed that the use of anti-dementia drugs was associated with a longer iTUG time and a lower delta-TUG value (best performance, p < 0.002). Our findings showed an improvement in mental imagery of gait with the use of anti-dementia drugs, but no changes in actual gait performance. NCT01315704.
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
Small vessels, dementia and chronic diseases - molecular mechanisms and pathophysiology.
Horsburgh, Karen; Wardlaw, Joanna M; van Agtmael, Tom; Allan, Stuart M; Ashford, Mike L J; Bath, Philip M; Brown, Rosalind; Berwick, Jason; Cader, M Zameel; Carare, Roxana O; Davis, John B; Duncombe, Jessica; Farr, Tracy D; Fowler, Jill H; Goense, Jozien; Granata, Alessandra; Hall, Catherine N; Hainsworth, Atticus H; Harvey, Adam; Hawkes, Cheryl A; Joutel, Anne; Kalaria, Rajesh N; Kehoe, Patrick G; Lawrence, Catherine B; Lockhart, Andy; Love, Seth; Macleod, Malcolm R; Macrae, I Mhairi; Markus, Hugh S; McCabe, Chris; McColl, Barry W; Meakin, Paul J; Miller, Alyson; Nedergaard, Maiken; O'Sullivan, Michael; Quinn, Terry J; Rajani, Rikesh; Saksida, Lisa M; Smith, Colin; Smith, Kenneth J; Touyz, Rhian M; Trueman, Rebecca C; Wang, Tao; Williams, Anna; Williams, Steven C R; Work, Lorraine M
2018-04-30
Cerebral small vessel disease (SVD) is a major contributor to stroke, cognitive impairment and dementia with limited therapeutic interventions. There is a critical need to provide mechanistic insight and improve translation between pre-clinical research and the clinic. A 2-day workshop was held which brought together experts from several disciplines in cerebrovascular disease, dementia and cardiovascular biology, to highlight current advances in these fields, explore synergies and scope for development. These proceedings provide a summary of key talks at the workshop with a particular focus on animal models of cerebral vascular disease and dementia, mechanisms and approaches to improve translation. The outcomes of discussion groups on related themes to identify the gaps in knowledge and requirements to advance knowledge are summarized. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
Trajectories of depressive symptoms and their relationship to the progression of dementia.
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.
Cortical Cerebral Microinfarcts on 3 Tesla MRI in Patients with Vascular Cognitive Impairment.
Ferro, Doeschka A; van Veluw, Susanne J; Koek, Huiberdina L; Exalto, Lieza G; Biessels, Geert Jan
2017-01-01
Cerebral microinfarcts (CMIs) are small ischemic lesions that are a common neuropathological finding in patients with stroke or dementia. CMIs in the cortex can now be detected in vivo on 3 Tesla MRI. To determine the occurrence of CMIs and associated clinical features in patients with possible vascular cognitive impairment (VCI). 182 memory-clinic patients (mean age 71.4±10.6, 55% male) with vascular injury on brain MRI (i.e., possible VCI) underwent a standardized work-up including 3 Tesla MRI and cognitive assessment. A control group consisted of 70 cognitively normal subjects (mean age 70.6±4.7, 60% male). Cortical CMIs and other neuroimaging markers of vascular brain injury were rated according to established criteria. Occurrence of CMIs was higher (20%) in patients compared to controls (10%). Among patients, the presence of CMIs was associated with male sex, history of stroke, infarcts, and white matter hyperintensities. CMI presence was also associated with a diagnosis of vascular dementia and reduced performance in multiple cognitive domains. CMIs on 3 Tesla MRI are common in patients with possible VCI and co-occur with imaging markers of small and large vessel disease, likely reflecting a heterogeneous etiology. CMIs are associated with worse cognitive performance, independent of other markers of vascular brain injury.
Rhee, YongJoo; Csernansky, John G.; Emanuel, Linda L.; Chang, Chang-Gok; Shega, Joseph W.
2011-01-01
Objectives To estimate the proportion of community dwelling older adults with dementia being prescribed a psychotropic and identify patient and caregiver factors associated with antipsychotics use. Methods Retrospective cohort study of The Aging, Demographics, and Memory Study (ADAMS) from 2002 to 2004 designed to assess dementia severity and service use among community-dwelling older adults. The frequency of psychotropic medication (antipsychotics, antidepressants, anticonvulsants and benzodiazepines) use was tabulated and weighted to the US population by dementia diagnosis. Logistic regression analysis identified factors associated with antipsychotic use. Results The 307 participants of ADAMS had the following dementia diagnosis: Alzheimer’s disease (69.29%), vascular dementia (17.74%) and other dementia (12.39%). The proportion of participants prescribed a psychotropic medication broken down by therapeutic class was as 19.07% antipsychotics, 29.08% antidepressants, 9.84% benzodiazepines, and 8.85% anticonvulsants. Older adults with dementia were significantly more likely to receive an antipsychotic if they had moderate dementia (OR =7.4, p<0.05), or severe dementia (OR=5.80, p<0.05), compared to mild dementia or were diagnosed with Alzheimer (OR =6.7, p<0.05) dementia compared to vascular dementia. Older adults with dementia who lived with their caregivers in were significantly less likely to be medicated with antipsychotics (OR= 0.19, p<0.05) compared to those who lived alone. Also, persons with dementia were significantly less likely to be prescribed an antipsychotic if the caregivers were clinically depressed (OR=0.03, p<0.05) compared to those who were not depressed. Conclusion We found psychotropic medication use is common among community-dwelling older adults with dementia. Caregivers appear to have a substantial impact on whether or not an antipsychotic is prescribed, which adds additional complexity to conversations discussing the risk-benefit ratio of
Anatomical Correlates of Non-Verbal Perception in Dementia Patients.
Lin, Pin-Hsuan; Chen, Hsiu-Hui; Chen, Nai-Ching; Chang, Wen-Neng; Huang, Chi-Wei; Chang, Ya-Ting; Hsu, Shih-Wei; Hsu, Che-Wei; Chang, Chiung-Chih
2016-01-01
Patients with dementia who have dissociations in verbal and non-verbal sound processing may offer insights into the anatomic basis for highly related auditory modes. To determine the neuronal networks on non-verbal perception, 16 patients with Alzheimer's dementia (AD), 15 with behavior variant fronto-temporal dementia (bv-FTD), 14 with semantic dementia (SD) were evaluated and compared with 15 age-matched controls. Neuropsychological and auditory perceptive tasks were included to test the ability to compare pitch changes, scale-violated melody and for naming and associating with environmental sound. The brain 3D T1 images were acquired and voxel-based morphometry (VBM) was used to compare and correlated the volumetric measures with task scores. The SD group scored the lowest among 3 groups in pitch or scale-violated melody tasks. In the environmental sound test, the SD group also showed impairment in naming and also in associating sound with pictures. The AD and bv-FTD groups, compared with the controls, showed no differences in all tests. VBM with task score correlation showed that atrophy in the right supra-marginal and superior temporal gyri was strongly related to deficits in detecting violated scales, while atrophy in the bilateral anterior temporal poles and left medial temporal structures was related to deficits in environmental sound recognition. Auditory perception of pitch, scale-violated melody or environmental sound reflects anatomical degeneration in dementia patients and the processing of non-verbal sounds are mediated by distinct neural circuits.
Association of APOE polymorphisms and stressful life events with dementia in a Pakistani population.
Chaudhry, M; Hasnain, S; Snitz, B E; Wang, X; Rosenthal, S; Demirci, F Y; Kamboh, M I
2014-06-06
Dementia is a major public health problem worldwide. Alzheimer's disease (AD) is a major form of dementia and the APOE 4 allele is an established genetic risk factor for AD. Similarly, stressful life events are also associated with dementia. The objective of this study was to examine the association of APOE 4 and stressful life events with dementia in a Pakistani sample, which to our knowledge has not been reported previously. We also tested for an interaction between stressful life events and APOE 4 on dementia risk. A total of 176 subjects (61 cases and 115 controls) were recruited. All cases and healthy controls were interviewed to assess cognition, co-morbidities, history of stressful life events and demographics. Blood genotyping for the APOE polymorphism (E2/E3/E4) was performed. APOE 4 and stressful life events were each independently and significantly associated with the risk of dementia (APOE 4: P=0.00697; stressful life events: P=5.29E-09). However, we did not find a significant interaction between APOE 4 carrier status and stressful life events on risk of dementia (P=0.677). Although the sample size of this study was small, the established association of APOE 4 with dementia was confirmed the first time in a Pakistani sample. Furthermore, stressful life events were also found to be significantly associated with dementia in this population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Sabbagh, Marwan N; Chen, Kewei; Rogers, Joseph; Fleisher, Adam S; Liebsack, Carolyn; Bandy, Dan; Belden, Christine; Protas, Hillary; Thiyyagura, Pradeep; Liu, Xiaofen; Roontiva, Auttawut; Luo, Ji; Jacobson, Sandra; Malek-Ahmadi, Michael; Powell, Jessica; Reiman, Eric M
2015-08-01
Down syndrome (DS) is associated with amyloid b (Ab) deposition. We characterized imaging measurements of regional fibrillar Ab burden, cerebral metabolic rate for glucose (rCMRgl), gray matter volumes (rGMVs), and age associations in 5 DS with dementia (DS/AD1), 12 DS without dementia (DS/AD2), and 9 normal controls (NCs). There were significant group differences in mean standard uptake value ratios (SUVRs) for florbetapir with DS/AD1 having the highest, followed by DS/AD2, followed by NC. For [18F]-fluorodeoxyglucose positron emission tomography, posterior cingulate rCMRgl in DS/AD1 was significantly reduced compared with DS/AD2 and NC. For volumetric magnetic resonance imaging (vMRI), hippocampal volumes were significantly reduced for the DS/AD1 compared with DS/AD2 and NC. Age-related SUVR increases and rCMRgl reductions were greater in DS participants than in NCs. DS is associated with fibrillar Ab, rCMRgl, and rGMV alterations in the dementia stage and before the presence of clinical decline. This study provides a foundation for the studies needed to inform treatment and prevention in DS. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Auditory hedonic phenotypes in dementia: A behavioural and neuroanatomical analysis
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
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
Borba, Ericksen Mielle; Duarte, Juliana Avila; Bristot, Giovana; Scotton, Ellen; Camozzato, Ana Luiza; Chaves, Márcia Lorena Fagundes
2016-01-01
Background/Aims Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Methods Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. Results MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. Discussion The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction. PMID:28101102
Age of dementia diagnosis in community dwelling bilingual and monolingual Hispanic Americans
Lawton, Deborah M.; Gasquoine, Philip G.; Weimer, Amy A.
2015-01-01
Bilingualism has been reported to delay the age of retrospective report of first symptom in dementia. This study determined if the age of clinically diagnosed Alzheimer's disease and vascular dementia occurred later for bilingual than monolingual, immigrant and U.S. born, Hispanic Americans. It involved a secondary analysis of the subset of 81 bi/monolingual dementia cases identified at yearly follow-up (1998 through 2008) using neuropsychological test results and objective diagnostic criteria from the Sacramento Area Latino Study on Aging that involved a random sampling of community dwelling Hispanic Americans (N = 1789). Age of dementia diagnosis was analyzed in a 2 × 2 (bi/monolingualism × immigrant/U.S. born) ANOVA that space revealed both main effects and the interaction were non-significant. Mean age of dementia diagnosis was descriptively (but not significantly) higher in the monolingual (M = 81.10 years) than the bilingual (M = 79.31) group. Overall, bilingual dementia cases were significantly better educated than monolinguals, but U.S. born bilinguals and monolinguals did not differ significantly in education. Delays in dementia symptomatology pertaining to bilingualism are less likely to be found in studies: (a) that use age of clinical diagnosis vs. retrospective report of first dementia symptom as the dependent variable; and (b) involve clinical cases derived from community samples rather than referrals to specialist memory clinics. PMID:25598395
Perception of emotion in frontotemporal dementia and Alzheimer disease.
Lavenu, I; Pasquier, F; Lebert, F; Petit, H; Van der Linden, M
1999-01-01
Frontotemporal dementia (FTD) is the second cause of degenerative dementia. Behavioral changes occur before the cognitive decline and remain the major feature. A poor perception of emotion could account for some behavioral symptoms. The aim of this study was to assess the perception of emotion in patients with FTD and to compare it with that of patients with Alzheimer disease (AD). Fifty subjects performed the tests: 20 patients with probable AD, 18 patients with FTD, and 12 matched controls. The two patient groups did not differ in age, sex, severity of dementia, duration of the disease, and language tests. Subjects had to recognize 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. The three groups were equally able to distinguish a face displaying affect from one not displaying affect. Naming of emotion was worse in patients with FTD than in patients with AD (correct answers 46% vs. 62%; p = 0.0006) who did not differ significantly from controls (72%). Anger, sadness, and disgust were less recognized in FTD than in AD patients who did not differ from controls, whereas fear and contempt were poorly recognized in both groups of patients compared with controls. These findings argue for different neural substrates underlying the recognition of various basic emotions. Behavioral disorders in FTD may be partly due to an impaired interpretation of the emotional environment.
Bilingualism delays age at onset of dementia, independent of education and immigration status.
Alladi, Suvarna; Bak, Thomas H; Duggirala, Vasanta; Surampudi, Bapiraju; Shailaja, Mekala; Shukla, Anuj Kumar; Chaudhuri, Jaydip Ray; Kaul, Subhash
2013-11-26
The purpose of the study was to determine the association between bilingualism and age at onset of dementia and its subtypes, taking into account potential confounding factors. Case records of 648 patients with dementia (391 of them bilingual) diagnosed in a specialist clinic were reviewed. The age at onset of first symptoms was compared between monolingual and bilingual groups. The influence of number of languages spoken, education, occupation, and other potentially interacting variables was examined. Overall, bilingual patients developed dementia 4.5 years later than the monolingual ones. A significant difference in age at onset was found across Alzheimer disease dementia as well as frontotemporal dementia and vascular dementia, and was also observed in illiterate patients. There was no additional benefit to speaking more than 2 languages. The bilingual effect on age at dementia onset was shown independently of other potential confounding factors such as education, sex, occupation, and urban vs rural dwelling of subjects. This is the largest study so far documenting a delayed onset of dementia in bilingual patients and the first one to show it separately in different dementia subtypes. It is the first study reporting a bilingual advantage in those who are illiterate, suggesting that education is not a sufficient explanation for the observed difference. The findings are interpreted in the context of the bilingual advantages in attention and executive functions.
Xu, Xiaofeng; Zhang, Bin; Lu, Kaili; Deng, Jiangshan; Zhao, Fei; Zhao, Bing-Qiao; Zhao, Yuwu
2016-07-01
Dextromethorphan (DM) is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine. Recently, its indication has been extended experimentally to a wide range of disorders including inflammation-mediated central nervous system disorders such as Parkinson disease (PD) and multiple sclerosis (MS). In this study, we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]), an animal model of vascular dementia (VaD). Sprague-Dawley (SD) (10 weeks of age) rats were subjected to the 2VO, and DM was injected intraperitoneally once per day for 37 days. Neuron death, glial activation, and cognitive function were assessed at 37 days after 2VO (0.2 mg/kg, i.p., "DM-0.2" and 2 mg/kg, i.p., "DM-2"). DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. These results suggest that DM is effective in treating VaD and protecting against oxidative stress, which is strongly implicated in the pathogenesis of VaD. Therefore, the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD.
Luo, Huabin; Lin, Michael; Castle, Nicholas
2011-02-01
To estimate the use of different types of physical restraints and assess their associations to falls and injuries among residents with and without Alzheimer's disease (AD) or dementia in US nursing homes. Data were from the 2004 National Nursing Home Survey. AD or dementia was identified using International Classification of Diseases, Ninth Revision (ICD-9) codes. Analyses were conducted with the Surveyfreq and Surveylogistic procedures in SAS v.9.1. Residents with either AD or dementia were more likely to be physically restrained (9.99% vs 3.91%, P < .001) and less likely to have bed rails (35.06% vs 38.43%, P < .001) than those residents without the disease. The use of trunk restraints was associated with higher risk for falls (adjusted odds ratio [AOR] = 1.66, P < .001) and fractures (AOR = 2.77, P < .01) among residents with the disease. The use of full bed rails was associated with lower risk for falls among residents with and without the disease (AOR = 0.67 and AOR = 0.72, Ps < .05, respectively). The use of a trunk restraint is associated with a higher risk for falls and fractures among residents with either AD or dementia.
Taste detection and recognition thresholds in Japanese patients with Alzheimer-type dementia.
Ogawa, Takao; Irikawa, Naoya; Yanagisawa, Daijiro; Shiino, Akihiko; Tooyama, Ikuo; Shimizu, Takeshi
2017-04-01
Alzheimer-type dementia (AD) is pathologically characterized by massive neuronal loss in the brain, and the taste cortex is thought to be affected. However, there are only a few reports regarding the gustatory function of AD patients, and the conclusions of this research are inconsistent. This prospective study enrolled 22 consecutive patients with mild to moderately severe Alzheimer-type dementia (AD) with mean age of 84.0 years, and 49 elderly volunteers without dementia with mean age of 71.0 years as control subjects. The control subjects were divided into two groups according to age: a younger group (N=28, mean age: 68.5) and an older group (N=21, mean age: 83.0). The gustatory function was investigated using the filter paper disc method (FPD) and electrogustometry (EGM). The gustatory function as measured by the FPD was significantly impaired in patients with AD as compared with age-matched control subjects; no such difference was found between the younger and the older control groups. On the other hand, as for the EGM thresholds, there were no differences between the AD patient group and the age-matched controls. The FPD method demonstrated decreased gustatory function in AD patients beyond that of aging. On the other hand, EGM thresholds did not differ between the AD patient group and the age-matched controls. These results suggest that failure of taste processing in the brain, but not taste transmission in the peripheral taste system, occurs in patients with AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Mueller, Christoph; Perera, Gayan; Rajkumar, Anto P; Bhattarai, Manorama; Price, Annabel; O'Brien, John T; Ballard, Clive; Stewart, Robert; Aarsland, Dag
2018-01-01
Increased hospitalization is a major component of dementia impact on individuals and cost, but has rarely been studied in dementia with Lewy bodies (DLB). Our aim was to describe the risk and duration of hospital admissions in patients with DLB, and compare these to those in Alzheimer's disease (AD) and the general population. A large database of mental health and dementia care in South London was used to assemble a cohort of patients diagnosed with DLB. These were 1:4 matched with patients diagnosed with AD on age, gender, and cognitive status. Rates of hospital admissions in the year after dementia diagnosis were significantly higher in 194 patients with DLB than in 776 patients with AD (crude incidence rate ratio 1.50; 95% confidence interval: 1.28-1.75) or the catchment population (indirectly standardized hospitalization rate 1.22; 95% confidence interval: 1.06-1.39). Patients with DLB had on average almost four additional hospital days per person-year than patients with AD. Multivariate Poisson regression models indicated poorer physical health early in the disease course as the main driver of this increased rate of hospitalization, whereby neuropsychiatric symptoms additionally explained the higher number of hospital days. Patients with DLB are more frequently admitted to general hospitals and utilize inpatient care to a substantially higher degree than patients with AD or the general elderly population. These data highlight an opportunity to reduce hospital days by identifying DLB earlier and providing more targeted care focused on the specific triggers for hospitalization and associations of prolonged stay.
Good days and bad days in dementia: a qualitative chart review of variable symptom expression.
Rockwood, Kenneth; Fay, Sherri; Hamilton, Laura; Ross, Elyse; Moorhouse, Paige
2014-08-01
Despite its importance in the lived experience of dementia, symptom fluctuation has been little studied outside Lewy body dementia. We aimed to characterize symptom fluctuation in patients with Alzheimer's disease (AD) and mixed dementia. A qualitative analysis of health records that included notations on good days and bad days yielded 52 community-dwelling patients (women, n = 30; aged 39-91 years; mild dementia, n = 26, chiefly AD, n = 36). Good days/bad days were most often described as changes in the same core set of symptoms (e.g. less/more verbal repetition). In other cases, only good or only bad days were described (e.g., no bad days, better sense of humor on good days). Good days were typically associated with improved global cognition, function, interest, and initiation. Bad days were associated with frequent verbal repetition, poor memory, increased agitation and other disruptive behaviors. Clinically important variability in symptoms appears common in AD and mixed dementia. Even so, what makes a day "good" is not simply more (or less) of what makes a day "bad". Further investigation of the factors that facilitate or encourage good days and mitigate bad days may help improve quality of life for patients and caregivers.
The Use of Cannabinoids in Treating Dementia.
Weier, Megan; Hall, Wayne
2017-08-01
To review and summarise the current evidence on the safety and efficacy of using cannabinoids to treat behavioural and neuropsychiatric symptoms of dementia. Two randomised controlled trials testing a synthetic form of tetrahydrocannabinol have shown that while well tolerated, there was no significant therapeutic effect, based on changes to scores on the neuropsychiatric inventory (NPI). Case reports and open label trials have indicated that there may be some therapeutic benefit of adding synthetic cannabinoids as an adjunctive therapy to reduce agitation, aberrant motor behaviour and nighttime behaviour. More well-controlled clinical trials in older populations with varying severity of dementia are needed to evaluate the effectiveness of cannabinoids in treating behaviour symptoms of dementia. We provide suggestions for designing such trials and evaluating possible adverse effects of cannabinoids on cognitive and neuropsychiatric functioning.
Loss of Neuroprotective Factors in Neurodegenerative Dementias: The End or the Starting Point?
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
Association of GSK3B With Alzheimer Disease and Frontotemporal Dementia
Schaffer, Barbara A. J.; Bertram, Lars; Miller, Bruce L.; Mullin, Kristina; Weintraub, Sandra; Johnson, Nancy; Bigio, Eileen H.; Mesulam, Marsel; Wiedau-Pazos, Martina; Jackson, George R.; Cummings, Jeffrey L.; Cantor, Rita M.; Levey, Allan I.; Tanzi, Rudolph E.; Geschwind, Daniel H.
2009-01-01
Background Deposits of abnormally hyperphosphorylated tau are a hallmark of several dementias, including Alzheimer disease (AD), and about 10% of familial frontotemporal dementia (FTD) cases are caused by mutations in the tau gene. As a known tau kinase, GSK3B is a promising candidate gene in the remaining cases of FTD and in AD, for which tau mutations have not been found. Objective To examine the promoter of GSK3B and all 12 exons, including the surrounding intronic sequence, in patients with FTD, patients with AD, and aged healthy subjects to identify single-nucleotide polymorphisms associated with disease. Design, Setting, and Participants Single-nucleotide polymorphism frequency was examined in a case-control cohort of 48 patients with probable AD, 102 patients with FTD, 38 patients with primary progressive aphasia, and 85 aged healthy subjects. Results were followed up in 2 independent AD family samples consisting of 437 multiplex families with AD (National Institute of Mental Health Genetics Initiative AD Study) or 150 sibships discordant for AD (Consortium on Alzheimer’s Genetics Study). Results Several rare sequence variants in GSK3B were identified in the case-control study. An intronic polymorphism (IVS2−68G>A) occurred at more than twice the frequency among patients with FTD (10.8%) and patients with AD (14.6%) than in aged healthy subjects (4.1%). The polymorphism showed association with disease in both follow-up samples independently, although only the Consortium on Alzheimer’s Genetics sample showed the same direction of association as the case-control sample. Conclusions To our knowledge, this is the first evidence that a gene known to be involved in tau phosphorylation, GSK3B, is associated with risk for primary neurodegenerative dementias. This supports previous work in animal models suggesting that such genes are therapeutic targets. PMID:18852354
Diagnosing Dementia in the Oldest-Old
Brumback-Peltz, Carrie; Balasubramanian, Archana B.; Corrada, María M.; Kawas, Claudia H.
2011-01-01
The “oldest-old” comprise the fastest growing segment of the population in much of the world. Rates of dementia are extremely high in this age group and will present a major public health burden as the numbers of these individuals quadruple by the middle of the century. Studies in this age group are rare and frequently have small numbers of participants. In research studies and the clinic, the diagnosis of dementia and determination of the etiology of the disorder are challenging. In this review, we include some of our experiences in a population-based longitudinal investigation, The 90+ Study. Oldest-old individuals are more likely to suffer from medical comorbidities and have high rates of sensory loss, psychoactive medication usage, frailty and fatigue. Moreover, social and cultural expectations affect the reporting and interpretation of behavioral changes. These and other factors make it difficult to determine the relative contributions of cognitive losses and non-cognitive losses in the development of functional disability. Contributing further to the complexities of diagnosis, current research suggests that dementia in the oldest-old, compared to younger people, is more likely to be related to mixed disease pathologies. Frequent cerebral neuropathologies include Alzheimer’s disease neurodegeneration, small and large vessel vascular disease, and hippocampal sclerosis. More research is necessary in the oldest-old to better understand the etiologies of dementia in this age group, and factors that may affect the expression of disease as we age. PMID:21831546
Comparison of Informal Care Time and Costs in Different Age-Related Dementias: A Review
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
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
Pase, Matthew P.; Himali, Jayandra J.; Beiser, Alexa S.; Aparicio, Hugo J.; Satizabal, Claudia L.; Vasan, Ramachandran S.; Seshadri, Sudha; Jacques, Paul F.
2017-01-01
Background and purpose Sugar- and artificially-sweetened beverage intake have been linked to cardiometabolic risk factors, which increase the risk of cerebrovascular disease and dementia. We examined whether sugar- or artificially-sweetened beverage consumption were associated with the prospective risks of incident stroke or dementia in the community-based Framingham Heart Study Offspring cohort. Methods We studied 2888 participants aged over 45 for incident stroke (mean age 62 [SD, 9] years; 45% men) and 1484 participants aged over 60 for incident dementia (mean age 69 [SD, 6] years; 46% men). Beverage intake was quantified using a food frequency questionnaire at cohort examinations 5 (1991–1995), 6 (1995–1998) and 7 (1998–2001). We quantified recent consumption at examination 7 and cumulative consumption by averaging across examinations. Surveillance for incident events commenced at examination 7 and continued for 10-years. We observed 97 cases of incident stroke (82 ischemic) and 81 cases of incident dementia (63 consistent with Alzheimer’s disease [AD]). Results After adjustments for age, sex, education (for analysis of dementia), caloric intake, diet quality, physical activity and smoking, higher recent and higher cumulative intake of artificially-sweetened soft drinks were associated with an increased risk of ischemic stroke, all-cause dementia, and AD dementia. When comparing daily cumulative intake to <1 per week (reference), the hazard ratios were 2.96 (95% CI, 1.26–6.97) for ischemic stroke and 2.89 (95% CI, 1.18–7.07) for AD. Sugar-sweetened beverages were not associated with stroke or dementia. Conclusions Artificially-sweetened soft drink consumption was associated with a higher risk of stroke and dementia. PMID:28428346
Linking vascular disorders and Alzheimer’s disease: Potential involvement of BACE1
Cole, Sarah L.; Vassar, Robert
2012-01-01
The etiology of Alzheimer’s disease (AD) remains unknown. However, specific risk factors have been identified, and aging is the strongest AD risk factor. The majority of cardiovascular events occur in older people and a close relationship between vascular disorders and AD exists. Amyloid plaques, composed of the beta amyloid peptide (Aβ), are hallmark lesions in AD and evidence indicates that Aβ plays a central role in AD pathophysiology. The BACE1 enzyme is essential for Aβ generation, and BACE1 levels are elevated in AD brain. The cause(s) of this BACE1 elevation remains undetermined. Here we review the potential contribution of vascular disease to AD pathogenesis. We examine the putative vasoactive properties of Aβ and how the cellular changes associated with vascular disease may elevate BACE1 levels. Despite increasing evidence, the exact role(s) vascular disorders play in AD remains to be determined. However, given that vascular diseases can be addressed by lifestyle and pharmacologic interventions, the potential benefits of these therapies in delaying the clinical appearance and progression of AD may warrant investigation. PMID:18289733
Strong, C; Anderton, B H; Perry, R H; Perry, E K; Ince, P G; Lovestone, S
1995-01-01
The relationship between Alzheimer disease (AD) and dementia with Lewy bodies (senile dementia Lewy body type, or SDLT) and dementia in Parkinson's disease is unclear. AD pathology is characterised by both amyloid deposition and abnormal phosphorylation of tau in paired helical filaments (PHF-tau). In AD, abnormally phosphorylated PHF-tau is present in neurofibrillary tangles, in neuritic processes of senile plaques, and also in neuropil threads dispersed throughout the cerebral cortex. Cortical homogenates from 12 cases each of AD and SDLT, 13 cases of Parkinson's disease, and 11 normal controls were examined by Western blot analysis with antibodies that detect PHF-tau. No PHF-tau was found in Parkinson's disease or control cortex. No PHF-tau was found in SDLT cases without histological evidence of tangles. PHF-tau was detectable in SDLT cases with a low density of tangles, and large amounts of PHF-tau were present in AD cases. This study demonstrates that abnormally phosphorylated PHF-tau is only present where tangles are found and not in SDLT cases without tangles or with only occasional tangles. It is concluded that Lewy body dementias are distinct at a molecular level from AD.
Mediterranean Diet, Alzheimer Disease, and Vascular Mediation
Scarmeas, Nikolaos; Stern, Yaakov; Mayeux, Richard; Luchsinger, Jose A.
2011-01-01
Objectives To examine the association between the Mediterranean diet (MeDi) and Alzheimer disease (AD) in a different AD population and to investigate possible mediation by vascular pathways. Design, Setting, Patients, and Main Outcome Measures A case-control study nested within a community-based cohort in New York, NY. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD status (194 patients with AD vs 1790 nondemented subjects) in logistic regression models that were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, medical comorbidity index, and body mass index (calculated as weight in kilograms divided by height in meters squared). We investigated whether there was attenuation of the association between MeDi and AD when vascular variables (stroke, diabetes mellitus, hypertension, heart disease, lipid levels) were simultaneously introduced in the models (which would constitute evidence of mediation). Results Higher adherence to the MeDi was associated with lower risk for AD (odds ratio, 0.76; 95% confidence interval, 0.67–0.87; P<.001). Compared with subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had an odds ratio of 0.47 (95% confidence interval, 0.29–0.76) and those at the highest tertile an odds ratio of 0.32 (95% confidence interval, 0.17–0.59) for AD (P for trend <.001). Introduction of the vascular variables in the model did not change the magnitude of the association. Conclusions We note once more that higher adherence to the MeDi is associated with a reduced risk for AD. The association does not seem to be mediated by vascular comorbidity. This could be the result of either other biological mechanisms (oxidative or inflammatory) being implicated or measurement error of the vascular variables. PMID:17030648
A single center study: Aβ42/p-Tau181 CSF ratio to discriminate AD from FTD in clinical setting.
Vergallo, Andrea; Carlesi, Cecilia; Pagni, Cristina; Giorgi, Filippo Sean; Baldacci, Filippo; Petrozzi, Lucia; Ceravolo, Roberto; Tognoni, Gloria; Siciliano, Gabriele; Bonuccelli, Ubaldo
2017-10-01
Abnormal levels of beta amyloid (Aβ42) and tau protein concentrations in the cerebral spinal fluid (CSF) have been largely described in Alzheimer's disease (AD). Thus, CSF analysis of these biomarkers has been incorporated in recent AD diagnostic criteria, and it is increasingly performed for neurodegenerative dementia diagnostic workout in clinical setting. Nevertheless, the precise biomarkers CSF features in neurodegenerative dementia, either AD or Frontotemporal dementia (FTD), are still not fully clear today. This is mainly due to lack of CSF clear cutoff values due to a well-known intersite (but even intrasite) variability of CSF procedures, ranging from collection to analysis. Applying CSF biomarker ratios, rather than their single values could represent a useful tool, especially for the differential diagnosis of different forms of dementia. We explored clinical values of six CSF ratios (by combining Aβ42 and tau) in order to better discriminate between AD and FTD; we identified Aβ42/p-Tau 181 ratio as a potential good candidate for helping differentiating AD from FTD in the clinical practice.
Downward finger displacement distinguishes Parkinson disease dementia from Alzheimer disease.
Lieberman, Abraham; Deep, Aman; Shi, Jiong; Dhall, Rohit; Shafer, Saulena; Moguel-Cobos, Guillermo; Dhillon, Ravneet; Frames, Christopher W; McCauley, Margaret
2018-02-01
Purpose/Aim of the study: To study finger displacement in patients with Parkinson disease dementia (PDD) and in patients with Alzheimer disease (AD). We examined 56 patients with PDD and 35 with AD. Patients were examined during their regular outpatient clinic visit. Finger displacement was measured by observers not actively involved in the study using a creative grid ruler for all PDD and AD patients. Finger displacement was examined by asking patients to point their index fingers toward the grid ruler with the nails facing upward. Patients were asked to maintain the pointing position for 15 s. After 15 s, patients were asked to close their eyes for another 15 s while maintaining the same position. A positive result was downward index finger displacement of ≥5 cm within the 15-second time window with eyes closed. Of the 56 PDD patients, 53 had bilateral finger displacement of >5 cm. In comparison, of the 35 AD patients, only 1 patient had minimal displacement. Results of the non-invasive finger displacement test may provide insight, on an outpatient basis, of the integrity of subcortical-cortical circuits. Downward finger displacement, especially bilateral downward displacement, may signal the extensive disruption of subcortical-cortical circuits that occurs in PDD patients. AChE: acetylcholinesterase; AD: Alzheimer disease; DLB: dementia with Lewy bodies; ET: essential tremor; MDS-UPDRS: Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale; MMSE: Mini-Mental State Examination; PD: Parkinson disease; PDD: Parkinson disease dementia.
Hu, Yuan Yuan; He, Shan Shu; Wang, Xiaochuan; Duan, Qiu Hong; Grundke-Iqbal, Inge; Iqbal, Khalid; Wang, Jianzhi
2002-01-01
We have developed an ultrasensitive bienzyme-substrate-recycle enzyme-linked immunosorbent assay for the measurement of Alzheimer’s disease (AD) abnormally hyperphosphorylated tau in cerebrospinal fluid (CSF). The assay, which recognizes attomolar amounts of tau, is ∼400 and ∼1300 times more sensitive than conventional enzyme-linked immunosorbent assay in determining the hyperphosphorylated tau and total tau, respectively. With this method, we measured both total tau and tau phosphorylated at Ser-396/Ser-404 in lumbar CSFs from AD and control patients. We found that the total tau was 215 ± 77 pg/ml in cognitively normal control (n = 56), 234 ± 92 pg/ml in non-AD neurological (n = 37), 304 ± 126 pg/ml in vascular dementia (n = 46), and 486 ± 168 pg/ml (n = 52) in AD patients, respectively. However, a remarkably elevated level in phosphorylated tau was only found in AD (187 ± 84 pg/ml), as compared with normal controls (54 ± 33 pg/ml), non-AD (63 ± 34 pg/ml), and vascular dementia (72 ± 33 pg/ml) groups. If we used the ratio of hyperphosphorylated tau to total tau of ≥0.33 as cutoff for AD diagnosis, we could confirm the diagnosis in 96% of the clinically diagnosed patients with a specificity of 95%, 86%, 100%, and 94% against nonneurological, non-AD neurological, vascular dementia, and all of the three control groups combined, respectively. It is suggested that the CSF level of tau phosphorylated at Ser-396/Ser-404 is a promising diagnostic marker of AD. PMID:11943712
Anatomical Correlates of Non-Verbal Perception in Dementia Patients
Lin, Pin-Hsuan; Chen, Hsiu-Hui; Chen, Nai-Ching; Chang, Wen-Neng; Huang, Chi-Wei; Chang, Ya-Ting; Hsu, Shih-Wei; Hsu, Che-Wei; Chang, Chiung-Chih
2016-01-01
Purpose: Patients with dementia who have dissociations in verbal and non-verbal sound processing may offer insights into the anatomic basis for highly related auditory modes. Methods: To determine the neuronal networks on non-verbal perception, 16 patients with Alzheimer’s dementia (AD), 15 with behavior variant fronto-temporal dementia (bv-FTD), 14 with semantic dementia (SD) were evaluated and compared with 15 age-matched controls. Neuropsychological and auditory perceptive tasks were included to test the ability to compare pitch changes, scale-violated melody and for naming and associating with environmental sound. The brain 3D T1 images were acquired and voxel-based morphometry (VBM) was used to compare and correlated the volumetric measures with task scores. Results: The SD group scored the lowest among 3 groups in pitch or scale-violated melody tasks. In the environmental sound test, the SD group also showed impairment in naming and also in associating sound with pictures. The AD and bv-FTD groups, compared with the controls, showed no differences in all tests. VBM with task score correlation showed that atrophy in the right supra-marginal and superior temporal gyri was strongly related to deficits in detecting violated scales, while atrophy in the bilateral anterior temporal poles and left medial temporal structures was related to deficits in environmental sound recognition. Conclusions: Auditory perception of pitch, scale-violated melody or environmental sound reflects anatomical degeneration in dementia patients and the processing of non-verbal sounds are mediated by distinct neural circuits. PMID:27630558
Ras, Rouyanne T; Fuchs, Dagmar; Koppenol, Wieneke P; Garczarek, Ursula; Greyling, Arno; Keicher, Christian; Verhoeven, Carole; Bouzamondo, Hakim; Wagner, Frank; Trautwein, Elke A
2015-01-01
Background: Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage. Objectives: This study was primarily designed to investigate the effect of a low-fat spread with added PSs on brachial artery endothelial function as measured by flow-mediated dilation (FMD). Second, effects on arterial stiffness, blood pressure, serum lipids, and plasma PS concentrations were investigated. We hypothesized that PSs would not worsen FMD but would rather modestly improve FMD. Design: This study had a double-blind, randomized, placebo-controlled, parallel design. After a 4-wk run-in period, 240 hypercholesterolemic but otherwise healthy men and women consumed 20 g/d of low-fat spread without (control) or with added PSs (3 g/d) during 12 wk. Pre- and postintervention, vascular function measurements and blood sampling were performed. Results: In total, 232 participants completed the study period. For the primary endpoint FMD, 199 participants were included in the statistical analysis. PS intake did not affect FMD (+0.01 percentage points; 95% CI: −0.73, 0.75) compared with control. Measures of arterial stiffness (pulse wave velocity and augmentation index) and blood pressure were also not significantly changed compared with control. After PS intervention, LDL cholesterol significantly decreased on average by 0.26 mmol/L (95% CI: −0.40, −0.12) or 6.7% compared with control. Plasma sitosterol and campesterol concentrations significantly increased in the PS group up to on average 11.5 μmol/L and 13.9 μmol/L (expressed as geometric means), respectively. Conclusions: The intake of a low-fat spread with added PSs neither improved nor worsened FMD or other vascular function markers in hypercholesterolemic men and women. As expected, serum LDL cholesterol decreased
Prediction of Dementia in Primary Care Patients
Jessen, Frank; Wiese, Birgitt; Bickel, Horst; Eiffländer-Gorfer, Sandra; Fuchs, Angela; Kaduszkiewicz, Hanna; Köhler, Mirjam; Luck, Tobias; Mösch, Edelgard; Pentzek, Michael; Riedel-Heller, Steffi G.; Wagner, Michael; Weyerer, Siegfried; Maier, Wolfgang; van den Bussche, Hendrik
2011-01-01
Background Current approaches for AD prediction are based on biomarkers, which are however of restricted availability in primary care. AD prediction tools for primary care are therefore needed. We present a prediction score based on information that can be obtained in the primary care setting. Methodology/Principal Findings We performed a longitudinal cohort study in 3.055 non-demented individuals above 75 years recruited via primary care chart registries (Study on Aging, Cognition and Dementia, AgeCoDe). After the baseline investigation we performed three follow-up investigations at 18 months intervals with incident dementia as the primary outcome. The best set of predictors was extracted from the baseline variables in one randomly selected half of the sample. This set included age, subjective memory impairment, performance on delayed verbal recall and verbal fluency, on the Mini-Mental-State-Examination, and on an instrumental activities of daily living scale. These variables were aggregated to a prediction score, which achieved a prediction accuracy of 0.84 for AD. The score was applied to the second half of the sample (test cohort). Here, the prediction accuracy was 0.79. With a cut-off of at least 80% sensitivity in the first cohort, 79.6% sensitivity, 66.4% specificity, 14.7% positive predictive value (PPV) and 97.8% negative predictive value of (NPV) for AD were achieved in the test cohort. At a cut-off for a high risk population (5% of individuals with the highest risk score in the first cohort) the PPV for AD was 39.1% (52% for any dementia) in the test cohort. Conclusions The prediction score has useful prediction accuracy. It can define individuals (1) sensitively for low cost-low risk interventions, or (2) more specific and with increased PPV for measures of prevention with greater costs or risks. As it is independent of technical aids, it may be used within large scale prevention programs. PMID:21364746
López-Pousa, S; Vilalta-Franch, J; Garre-Olmo, J; Pons, S; Cucurella, M G
To assess the prevalence of behavioural and psychological symptoms (BPS's) in patients with dementia in Spain and their dementia-specific characteristics. A cross-sectional and retrospective study of 1025 patients from 52 specialized dementia care units using the Neuropsychiatric Inventory (NPI). Patients with a probable diagnosis of Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease and dementia (PDD) were selected for BPS's characterisation. The global prevalence of BPS's was 66.7% (684 patients; 95% CI = 63.8-69.6%). BPS's were under-diagnosed in one third of cases. A total of 668 patients with NPI of 4 or superior and a diagnosis of AD (n = 380; 56.8%), DLB (n = 156; 23.3%) and PDD (n = 132; 19.7%) had a NPI mean of 21.1 (SD = 14.7), 25.6 (SD = 13.9) and 21.8 (SD = 14.2), respectively. Apathy, depression and anxiety were the most common BPS's. Delusions and hallucinations were significantly more prevalent in DLB. Dementia severity was correlated with the global NPI value and with all the sub-items, but anxiety and euphoria. The presence of agitation, euphoria or lability was associated with a deficient therapeutic fulfillment. A high prevalence of non-diagnosed BPS's was observed in the studied population. This has serious negative consequences for the quality of life of patients and their social environment. Therefore we propose an active search and subsequent correct treatment of BPS's in all patients with dementia.
Age of dementia diagnosis in community dwelling bilingual and monolingual Hispanic Americans.
Lawton, Deborah M; Gasquoine, Philip G; Weimer, Amy A
2015-05-01
Bilingualism has been reported to delay the age of retrospective report of first symptom in dementia. This study determined if the age of clinically diagnosed Alzheimer's disease and vascular dementia occurred later for bilingual than monolingual, immigrant and U.S. born, Hispanic Americans. It involved a secondary analysis of the subset of 81 bi/monolingual dementia cases identified at yearly follow-up (1998 through 2008) using neuropsychological test results and objective diagnostic criteria from the Sacramento Area Latino Study on Aging that involved a random sampling of community dwelling Hispanic Americans (N = 1789). Age of dementia diagnosis was analyzed in a 2 × 2 (bi/monolingualism × immigrant/U.S. born) ANOVA that space revealed both main effects and the interaction were non-significant. Mean age of dementia diagnosis was descriptively (but not significantly) higher in the monolingual (M = 81.10 years) than the bilingual (M = 79.31) group. Overall, bilingual dementia cases were significantly better educated than monolinguals, but U.S. born bilinguals and monolinguals did not differ significantly in education. Delays in dementia symptomatology pertaining to bilingualism are less likely to be found in studies: (a) that use age of clinical diagnosis vs. retrospective report of first dementia symptom as the dependent variable; and (b) involve clinical cases derived from community samples rather than referrals to specialist memory clinics. Copyright © 2014 Elsevier Ltd. All rights reserved.
Savaskan, Egemen; Mueller, Heiko; Hoerr, Robert; von Gunten, Armin; Gauthier, Serge
2018-03-01
ABSTRACTBackground:In randomized controlled trials, Ginkgo biloba extract EGb 761® has been found to be effective in the treatment of behavioral and psychological symptoms of dementia (BPSD). To assess the effects of EGb 761® on specific BPSD, we analyzed data from all randomized, placebo-controlled, at least 20-week, trials of EGb 761® enrolling patients with dementia (probable Alzheimer's disease (AD), probable vascular dementia or probable AD with cerebrovascular disease) who had clinically significant BPSD (Neuropsychiatric Inventory (NPI) total score at least 6). Data were pooled and joint analyses of NPI single item composite and caregiver distress scores were performed by meta-analysis with a fixed effects model. Four trials involving 1628 patients (EGb 761®, 814; placebo, 814) were identified; treatment duration was 22 or 24 weeks; the daily dose of EGb 761® was 240 mg in all trials. Pooled analyses including data from the full analysis sets of all trials (EGb 761®, 796 patients; placebo, 802 patients) revealed significant superiority of EGb 761® over placebo in total scores and 10 single symptom scores. Regarding caregiver distress scores, EGb 761®-treated patients improved significantly more than those receiving placebo in all symptoms except delusions, hallucinations, and elation/euphoria. The benefit of EGb 761® mainly consists of improvement in symptoms present at baseline, but the incidence of some symptoms was also decreased. Twenty two- to twenty four-week treatment with Ginkgo biloba extract EGb 761® improved BPSD (except psychotic-like features) and caregiver distress caused by such symptoms.
Fritz, Nora E; Kegelmeyer, Deborah A; Kloos, Anne D; Linder, Shannon; Park, Ariane; Kataki, Maria; Adeli, Anahita; Agrawal, Punit; Scharre, Douglas W; Kostyk, Sandra K
2016-10-01
Differential diagnosis of dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Parkinson's disease (PD) and Alzheimer's disease (AD) is challenging. Comparative motor profiles of these neurodegenerative disorders may aid in earlier diagnosis but have not been extensively studied. Groups were rigorously matched by age, education, and sex. DLB/PDD participants were matched by Mini-Mental State Examination Score to individuals with AD and by Unified Parkinson's Disease Rating Scale motor scores to individuals with PD. Gait, balance, dual task walking and hand dexterity measures were compared between a combined group (n=21) of individuals with Lewy body dementia (LBD) consisting of those with DLB (n=11) and PDD (n=10) to individuals with PD (n=21) or AD (n=21). Individuals at the same disease stage with LBD walked significantly slower with shorter stride lengths (p<0.05), demonstrated poorer balance on both the Tinetti and Berg Balance Scale, and poorer performance on dual-task and figure-of-eight walking compared to PD and AD (p<0.05 for all) groups. Upper extremity coordination on the 9-hole peg test differentiated LBD from both PD and AD and was the only motor test in which individuals with AD performed worse than those with PD. Tinetti balance subscores were significantly lower in PDD compared to DLB participants (10.4±2.3 versus 12.8±2.3; p=0.027). Motor features distinguish individuals with LBD from those with AD and PD. Measures of gait, balance and finger dexterity provide an additional means of differentiating individuals with LBD from those with AD and PD. Copyright © 2016 Elsevier B.V. All rights reserved.
Music models aberrant rule decoding and reward valuation in dementia
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
Boomsma, Jooske Marije Funke; Exalto, Lieza Geertje; Barkhof, Frederik; van den Berg, Esther; de Bresser, Jeroen; Heinen, Rutger; Koek, Huiberdina Lena; Prins, Niels Daniël; Scheltens, Philip; Weinstein, Henry Chanoch; van der Flier, Wiesje Maria; Biessels, Geert Jan
2017-04-19
Vascular Cognitive Impairment (VCI) refers to cognitive dysfunction due to vascular brain injury, as a single cause or in combination with other, often neurodegenerative, etiologies. VCI is a broad construct that captures a heterogeneous patient population both in terms of cognitive and noncognitive symptoms and in terms of etiology and prognosis. This provides a challenge when applying this construct in clinical practice. This paper presents the rationale and design of the TRACE-VCI study, which investigates the clinical features and prognosis of VCI in a memory clinic setting. The TRACE-VCI project is an observational, prospective cohort study of 861 consecutive memory clinic patients with possible VCI. Between 2009 and 2013, patients were recruited through the Amsterdam Dementia Cohort of the VU University Medical Centre (VUMC) (N=665) and the outpatient memory clinic and VCI cohort of the University Medical Centre Utrecht (UMCU) (N=196). We included all patients attending the clinics with magnetic resonance imaging (MRI) evidence of vascular brain injury. Patients with a primary etiology other than vascular brain injury or neurodegeneration were excluded. Patients underwent an extensive 1-day memory clinic evaluation including an interview, physical and neurological examination, assessment of biomarkers (including those for Alzheimer-type pathologies), extensive neuropsychological testing, and an MRI scan of the brain. For prognostic analyses, the composite primary outcome measure was defined as accelerated cognitive decline (change of clinical dementia rating ≥1 or institutionalization) or (recurrent) major vascular events or death over the course of 2 years. The mean age at baseline was 67.7 (SD 8.5) years and 46.3% of patients (399/861) were female. At baseline, the median Clinical Dementia Rating was 0.5 (interquartile range [IQR] 0.5-1.0) and the median Mini-Mental State Examination score was 25 (IQR 22-28). The clinical diagnosis at baseline was
Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz
2017-01-01
Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Medline, Web of Knowledge and PsycINFO were searched, using the terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no dementia" OR "vascular mild neurocognitive disorder" AND "dysexecutive" OR "executive function". Meta-analyses were conducted for each of the selected tests, using random-effect models. Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control.
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.
FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease.
Foster, Norman L; Heidebrink, Judith L; Clark, Christopher M; Jagust, William J; Arnold, Steven E; Barbas, Nancy R; DeCarli, Charles S; Turner, R Scott; Koeppe, Robert A; Higdon, Roger; Minoshima, Satoshi
2007-10-01
Distinguishing Alzheimer's disease (AD) and frontotemporal dementia (FTD) currently relies on a clinical history and examination, but positron emission tomography with [(18)F] fluorodeoxyglucose (FDG-PET) shows different patterns of hypometabolism in these disorders that might aid differential diagnosis. Six dementia experts with variable FDG-PET experience made independent, forced choice, diagnostic decisions in 45 patients with pathologically confirmed AD (n = 31) or FTD (n = 14) using five separate methods: (1) review of clinical summaries, (2) a diagnostic checklist alone, (3) summary and checklist, (4) transaxial FDG-PET scans and (5) FDG-PET stereotactic surface projection (SSP) metabolic and statistical maps. In addition, we evaluated the effect of the sequential review of a clinical summary followed by SSP. Visual interpretation of SSP images was superior to clinical assessment and had the best inter-rater reliability (mean kappa = 0.78) and diagnostic accuracy (89.6%). It also had the highest specificity (97.6%) and sensitivity (86%), and positive likelihood ratio for FTD (36.5). The addition of FDG-PET to clinical summaries increased diagnostic accuracy and confidence for both AD and FTD. It was particularly helpful when raters were uncertain in their clinical diagnosis. Visual interpretation of FDG-PET after brief training is more reliable and accurate in distinguishing FTD from AD than clinical methods alone. FDG-PET adds important information that appropriately increases diagnostic confidence, even among experienced dementia specialists.
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
Luo, Rifang; Tang, Linlin; Xie, Lingxia; Wang, Jin; Huang, Nan; Wang, Yunbing
2016-12-01
Surface properties are considered to be important factors in addressing proper functionalities. In this paper, a multifunctional mussel-inspired coating was prepared via the direct copolymerization of epigallocatechin gallate (EGCG) and arginine. The coating formation was confirmed by X-ray photoelectron spectroscopy and Fourier transform infrared spectra. The EGCG/arginine coating contained diverse functional groups like amines, phenols and carboxyls, whose densities were also tunable. Such mussel-inspired coating could also be applied as an ad-layer for its secondary reactivity, demonstrated by quartz crystal microbalance technique. Moreover, the tunable surface density of phenols showed potential ability in modulating endothelial cell and smooth muscle cell viability. The coatings rich in phenols presented excellent free radical scavenging property. Current results strongly indicated the potential of EGCG/arginine coatings to be applied as an ad-layer for vascular materials.
Averting Dementia of the Alzheimer's Type in Women: Can Counselors Help?
ERIC Educational Resources Information Center
Douthit, Kathryn Z.
2007-01-01
Alzheimer's disease (AD) is the most common cause of dementia in late life, taking its greatest toll on women over age 80. This article provides an overview of AD, including risk factors and counseling strategies targeting risk. Counseling strategies address stress, cardiovascular health, social integration, depression, and holistic wellness.
A nonmusician with severe Alzheimer's dementia learns a new song.
Baird, Amee; Umbach, Heidi; Thompson, William Forde
2017-02-01
The hallmark symptom of Alzheimer's Dementia (AD) is impaired memory, but memory for familiar music can be preserved. We explored whether a non-musician with severe AD could learn a new song. A 91 year old woman (NC) with severe AD was taught an unfamiliar song. We assessed her delayed song recall (24 hours and 2 weeks), music cognition, two word recall (presented within a familiar song lyric, a famous proverb, or as a word stem completion task), and lyrics and proverb completion. NC's music cognition (pitch and rhythm perception, recognition of familiar music, completion of lyrics) was relatively preserved. She recalled 0/2 words presented in song lyrics or proverbs, but 2/2 word stems, suggesting intact implicit memory function. She could sing along to the newly learnt song on immediate and delayed recall (24 hours and 2 weeks later), and with intermittent prompting could sing it alone. This is the first detailed study of preserved ability to learn a new song in a non-musician with severe AD, and contributes to observations of relatively preserved musical abilities in people with dementia.
Early onset dementia in New Zealand Pacific boxers: a case series.
Payman, Vahid; Yates, Susan; Cullum, Sarah
2018-05-04
To describe the biopsychosocial characteristics of a series of Pacific men living in South Auckland with a history of boxing presenting with early onset dementia. We discuss the history of boxing in Pacific people and the possibility of increased risk of early onset dementia in New Zealand Pacific men compared to their European counterparts. We reviewed the files of Pacific men with a history of amateur or professional boxing who presented to our memory and older adult mental health services with early onset dementia over a 45-month period. We gathered relevant information to construct a biopsychosocial paradigm as possible explanation of this phenomenon. We identified a series of eight New Zealand Pacific men with early onset dementia and with a history of boxing. Alcohol was a contributing factor in seven of the eight cases, and vascular risk factors in five. Historical, cultural and socio-economic factors underpin the attraction of some Pacific men to boxing as a sport. Given that New Zealand Pacific peoples may have an earlier onset of dementia than their European counterparts, further research is required to establish whether boxing is a contributory factor. Sports physicians should advise young New Zealand Pacific boxers about the long-term risks associated with their sport.
Villarejo Galende, A; Eimil Ortiz, M; Llamas Velasco, S; Llanero Luque, M; López de Silanes de Miguel, C; Prieto Jurczynska, C
2017-12-14
Knowledge of the socioeconomic impact of dementia-related disorders is essential for appropriate management of healthcare resources and for raising social awareness. We performed a literature review of the published evidence on the epidemiology, morbidity, mortality, associated disability and dependence, and economic impact of dementia and Alzheimer disease (AD) in Spain. Most population studies of patients older than 65 report prevalence rates ranging from 4% to 9%. Prevalence of dementia and AD is higher in women for nearly every age group. AD is the most common cause of dementia (50%-70% of all cases). Dementia is associated with increased morbidity, mortality, disability, and dependence, and results in a considerable decrease in quality of life and survival. Around 80% of all patients with dementia are cared for by their families, which cover a mean of 87% of the total economic cost, resulting in considerable economic and health burden on caregivers and loss of quality of life. The economic impact of dementia is huge and difficult to evaluate due to the combination of direct and indirect costs. More comprehensive programmes should be developed and resources dedicated to research, prevention, early diagnosis, multidimensional treatment, and multidisciplinary management of these patients in order to reduce the health, social, and economic burden of dementia. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Portugal, Maria da Glória; Coutinho, Evandro Silva Freire; Almeida, Cloyra; Barca, Maria Lage; Knapskog, Anne-Brita; Engedal, Knut; Laks, Jerson
2012-08-01
There are few studies on validation of depression scales in the elderly in Latin America. This study aimed to assess the validity of Montgomery-Åsberg. Depression Rating Scale (MADRS) and Cornell Scale for Depression in Dementia (CSDD) in Brazilian elderly outpatients. A convenience sample of 95 outpatients was diagnosed for dementia and depression according to DSM-IV-TR, ICD-10, and PDC-dAD criteria. Receiver Operating Curves (ROC) were used to calculate the area under the curve (AUC) and to assess MADRS and CSDD cut-offs for each diagnostic criterion. Dementia was diagnosed in 71 of 95 patients. Depression was diagnosed in 35, 30, and 51 patients by ICD-10, DSM-IV, and PDC-dAD, respectively. MADRS cut-off score of 10 correctly diagnosed 67.4% and 66.3% patients as depressed according to DSM-IV and ICD-10. A cut-off of 9 correctly identified 74.7% by PDC-dAD criteria; a CSDD cut-off score of 13 best recognized depression according to DSM-IV and ICD-10. A score of 11 diagnosed depression according to PDC-dAD, while MADRS = 9 recognized depression in dementia. CSDD was more efficient in showing depression in mild than in moderate/severe dementia according to DSM-IV/ICD-10. PDC-dAD behaved nicely for any severity stage. MADRS and CSDD cut-offs of 10 and 13 were the optimal ones to diagnose depression in elderly, respectively. CSDD cut-offs are higher than those found in other countries. Other Latin American studies are needed to compare results with our study.
The impact of bilingualism on brain reserve and metabolic connectivity in Alzheimer's dementia
Perani, Daniela; Farsad, Mohsen; Ballarini, Tommaso; Lubian, Francesca; Malpetti, Maura; Fracchetti, Alessandro; Magnani, Giuseppe; March, Albert; Abutalebi, Jubin
2017-01-01
Cognitive reserve (CR) prevents cognitive decline and delays neurodegeneration. Recent epidemiological evidence suggests that lifelong bilingualism may act as CR delaying the onset of dementia by ∼4.5 y. Much controversy surrounds the issue of bilingualism and its putative neuroprotective effects. We studied brain metabolism, a direct index of synaptic function and density, and neural connectivity to shed light on the effects of bilingualism in vivo in Alzheimer’s dementia (AD). Eighty-five patients with probable AD and matched for disease duration (45 German-Italian bilingual speakers and 40 monolingual speakers) were included. Notably, bilingual individuals were on average 5 y older than their monolingual peers. In agreement with our predictions and with models of CR, cerebral hypometabolism was more severe in the group of bilingual individuals with AD. The metabolic connectivity analyses crucially supported the neuroprotective effect of bilingualism by showing an increased connectivity in the executive control and the default mode networks in the bilingual, compared with the monolingual, AD patients. Furthermore, the degree of lifelong bilingualism (i.e., high, moderate, or low use) was significantly correlated to functional modulations in crucial neural networks, suggesting both neural reserve and compensatory mechanisms. These findings indicate that lifelong bilingualism acts as a powerful CR proxy in dementia and exerts neuroprotective effects against neurodegeneration. Delaying the onset of dementia is a top priority of modern societies, and the present in vivo neurobiological evidence should stimulate social programs and interventions to support bilingual or multilingual education and the maintenance of the second language among senior citizens. PMID:28137833
The impact of bilingualism on brain reserve and metabolic connectivity in Alzheimer's dementia.
Perani, Daniela; Farsad, Mohsen; Ballarini, Tommaso; Lubian, Francesca; Malpetti, Maura; Fracchetti, Alessandro; Magnani, Giuseppe; March, Albert; Abutalebi, Jubin
2017-02-14
Cognitive reserve (CR) prevents cognitive decline and delays neurodegeneration. Recent epidemiological evidence suggests that lifelong bilingualism may act as CR delaying the onset of dementia by ∼4.5 y. Much controversy surrounds the issue of bilingualism and its putative neuroprotective effects. We studied brain metabolism, a direct index of synaptic function and density, and neural connectivity to shed light on the effects of bilingualism in vivo in Alzheimer's dementia (AD). Eighty-five patients with probable AD and matched for disease duration (45 German-Italian bilingual speakers and 40 monolingual speakers) were included. Notably, bilingual individuals were on average 5 y older than their monolingual peers. In agreement with our predictions and with models of CR, cerebral hypometabolism was more severe in the group of bilingual individuals with AD. The metabolic connectivity analyses crucially supported the neuroprotective effect of bilingualism by showing an increased connectivity in the executive control and the default mode networks in the bilingual, compared with the monolingual, AD patients. Furthermore, the degree of lifelong bilingualism (i.e., high, moderate, or low use) was significantly correlated to functional modulations in crucial neural networks, suggesting both neural reserve and compensatory mechanisms. These findings indicate that lifelong bilingualism acts as a powerful CR proxy in dementia and exerts neuroprotective effects against neurodegeneration. Delaying the onset of dementia is a top priority of modern societies, and the present in vivo neurobiological evidence should stimulate social programs and interventions to support bilingual or multilingual education and the maintenance of the second language among senior citizens.
Dementia Research: Populations, Progress, Problems, and Predictions.
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.
Increased Risk of Dementia in Patients With Chronic Obstructive Pulmonary Disease.
Liao, Kuang-Ming; Ho, Chung-Han; Ko, Shian-Chin; Li, Chung-Yi
2015-06-01
Neurodegenerative disease in patients with chronic obstructive pulmonary disease (COPD) was observed. We aim to clarify the risk of dementia in patients with COPD. The study used claims data from Taiwan's National Health Insurance Research Database. Subjects were those who received a discharge diagnosis of COPD between January 1, 2002 and December 31, 2011. Only the first hospitalization was enrolled, and the index date was the first day of admission. Patients younger than 40 years or those with a history of Alzheimer disease (AD) or Parkinson disease (PD) before the index date were excluded. The patients with COPD were then followed until receiving a diagnosis of AD or PD, death, or the end of the study. Control subjects were selected from hospitalized patients without a history of COPD, AD, or PD and were matched according to age (±3 years), gender, and the year of admission at a 2:1 ratio. The comorbidities were measured from 1 year before the index date based on the ICD-9-CM codes. The study included 8640 patients with COPD and a mean age of 68.76 (±10.74) years. The adjusted hazard ratio of developing dementia (AD or PD) was 1.74 (95% confidence interval = 1.55-1.96) in patients with COPD compared with patients without COPD after adjusting for age, gender, and comorbidities. This nationwide cohort study demonstrates that the risk of dementia, including AD and PD, is significantly increased in patients with COPD compared with individuals in the general population.
Increased Risk of Dementia in Patients With Chronic Obstructive Pulmonary Disease
Liao, Kuang-Ming; Ho, Chung-Han; Ko, Shian-Chin; Li, Chung-Yi
2015-01-01
Abstract Neurodegenerative disease in patients with chronic obstructive pulmonary disease (COPD) was observed. We aim to clarify the risk of dementia in patients with COPD. The study used claims data from Taiwan's National Health Insurance Research Database. Subjects were those who received a discharge diagnosis of COPD between January 1, 2002 and December 31, 2011. Only the first hospitalization was enrolled, and the index date was the first day of admission. Patients younger than 40 years or those with a history of Alzheimer disease (AD) or Parkinson disease (PD) before the index date were excluded. The patients with COPD were then followed until receiving a diagnosis of AD or PD, death, or the end of the study. Control subjects were selected from hospitalized patients without a history of COPD, AD, or PD and were matched according to age (±3 years), gender, and the year of admission at a 2:1 ratio. The comorbidities were measured from 1 year before the index date based on the ICD-9-CM codes. The study included 8640 patients with COPD and a mean age of 68.76 (±10.74) years. The adjusted hazard ratio of developing dementia (AD or PD) was 1.74 (95% confidence interval = 1.55–1.96) in patients with COPD compared with patients without COPD after adjusting for age, gender, and comorbidities. This nationwide cohort study demonstrates that the risk of dementia, including AD and PD, is significantly increased in patients with COPD compared with individuals in the general population. PMID:26061317
Sequential drug treatment algorithm for agitation and aggression in Alzheimer's and mixed dementia.
Davies, Simon Jc; Burhan, Amer M; Kim, Donna; Gerretsen, Philip; Graff-Guerrero, Ariel; Woo, Vincent L; Kumar, Sanjeev; Colman, Sarah; Pollock, Bruce G; Mulsant, Benoit H; Rajji, Tarek K
2018-05-01
Behavioural and psychological symptoms of dementia (BPSD) include agitation and aggression in people with dementia. BPSD is common on inpatient psychogeriatric units and may prevent individuals from living at home or in residential/nursing home settings. Several drugs and non-pharmacological treatments have been shown to be effective in reducing behavioural and psychological symptoms of dementia. Algorithmic treatment may address the challenge of synthesizing this evidence-based knowledge. A multidisciplinary team created evidence-based algorithms for the treatment of behavioural and psychological symptoms of dementia. We present drug treatment algorithms for agitation and aggression associated with Alzheimer's and mixed Alzheimer's/vascular dementia. Drugs were appraised by psychiatrists based on strength of evidence of efficacy, time to onset of clinical effect, tolerability, ease of use, and efficacy for indications other than behavioural and psychological symptoms of dementia. After baseline assessment and discontinuation of potentially exacerbating medications, sequential trials are recommended with risperidone, aripiprazole or quetiapine, carbamazepine, citalopram, gabapentin, and prazosin. Titration schedules are proposed, with adjustments for frailty. Additional guidance is given on use of electroconvulsive therapy, optimization of existing cholinesterase inhibitors/memantine, and use of pro re nata medications. This algorithm-based approach for drug treatment of agitation/aggression in Alzheimer's/mixed dementia has been implemented in several Canadian Hospital Inpatient Units. Impact should be assessed in future research.
Dementia in developing countries: Does education play the same role in India as in the West?
Iyer, Gowri K; Alladi, Suvarna; Bak, Thomas H; Shailaja, Mekala; Mamidipudi, Annapurna; Rajan, Amulya; Gollahalli, Divyaraj; Chaudhuri, Jaydip Ray; Kaul, Subhash
2014-01-01
Evidence suggests that education protects from dementia by enhancing cognitive reserve. However, this may be influenced by several socio-demographic factors. Rising numbers of dementia in India, high levels of illiteracy and heterogeneity in socio-demographic factors provide an opportunity to explore this relationship. To study the association between education and age at dementia onset, in relation to socio-demographic factors. Association between age at dementia onset and literacy was studied in relationship to potential confounding factors such as gender, bilingualism, place of dwelling, occupation, vascular risk factors, stroke, family history of dementia and dementia subtypes. Case records of 648 dementia patients diagnosed in a specialist clinic in a University hospital in Hyderabad, India were examined. All patients were prospectively enrolled as part of an ongoing longitudinal project that aims to evaluate dementia subjects with detailed clinical, etiological, imaging, and follow-up studies. Of the 648 patients, 98 (15.1%) were illiterate. More than half of illiterate skilled workers were engaged in crafts and skilled agriculture unlike literates who were in trade or clerical jobs. Mean age at onset in illiterates was 60.1 years and in literates 64.5 years (p=0.0002). Factors independently associated with age at dementia onset were bilingualism, rural dwelling and stroke, but not education. Our study demonstrates that in India, rural dwelling, bilingualism, stroke and occupation modify the relationship between education and dementia.
A Survey of FDG- and Amyloid-PET Imaging in Dementia and GRADE Analysis
Daniela, Perani; Orazio, Schillaci; Alessandro, Padovani; Mariano, Nobili Flavio; Leonardo, Iaccarino; Pasquale Anthony, Della Rosa; Giovanni, Frisoni; Carlo, Caltagirone
2014-01-01
PET based tools can improve the early diagnosis of Alzheimer's disease (AD) and differential diagnosis of dementia. The importance of identifying individuals at risk of developing dementia among people with subjective cognitive complaints or mild cognitive impairment has clinical, social, and therapeutic implications. Within the two major classes of AD biomarkers currently identified, that is, markers of pathology and neurodegeneration, amyloid- and FDG-PET imaging represent decisive tools for their measurement. As a consequence, the PET tools have been recognized to be of crucial value in the recent guidelines for the early diagnosis of AD and other dementia conditions. The references based recommendations, however, include large PET imaging literature based on visual methods that greatly reduces sensitivity and specificity and lacks a clear cut-off between normal and pathological findings. PET imaging can be assessed using parametric or voxel-wise analyses by comparing the subject's scan with a normative data set, significantly increasing the diagnostic accuracy. This paper is a survey of the relevant literature on FDG and amyloid-PET imaging aimed at providing the value of quantification for the early and differential diagnosis of AD. This allowed a meta-analysis and GRADE analysis revealing high values for PET imaging that might be useful in considering recommendations. PMID:24772437
When one loses empathy: its effect on carers of patients with dementia.
Hsieh, Sharpley; Irish, Muireann; Daveson, Naomi; Hodges, John R; Piguet, Olivier
2013-09-01
The effects of empathy loss in frontotemporal dementia (FTD) and Alzheimer disease (AD) on carer symptomatology were investigated. Carers of patients with 2 clinical subtypes of FTD (behavioral-variant FTD [bvFTD] = 18; semantic dementia [SD] = 14) and AD (n = 18) completed the Interpersonal Reactivity Index (IRI), a standardized questionnaire of empathy as well as a measure of perceived burden (Zarit Burden Interview) and the quality of the marital relationship (Intimate Bond Measure). Patient ratings were also obtained on the IRI. Loss of empathy was most striking in the bvFTD group with a marked discrepancy observed between carer and patient ratings for change in emotional warmth and the ability to take the perspective of others. Empathy loss in bvFTD was associated with a loss of a caring marital relationship. Empathic deficits in SD were milder by comparison to bvFTD and correlated with disease severity and increased perceived carer burden. The behavioral pattern observed in AD differed from the FTD syndromes; deficits were observed only for measures of personal distress with carers reporting that patients were less able to handle emotionally evocative situations. Results highlight that changes in aspects of empathy differ across dementia syndromes and are associated with differing carer and clinical variables. These findings might be explained by the progression of atrophy in regions that are known to be critical for empathy and social behavior and has implications for the delivery and planning of services in dementia.
Creative writing and dementia care: 'making it real'.
Bailey, Catherine; Jones, Romi; Tiplady, Sue; Quinn, Isabel; Wilcockson, Jane; Clarke, Amanda
2016-12-01
Health professionals continue to seek ways to promote positive communication and self-worth when supporting people living with dementia. The value of creative writing techniques as part of reflective practice in nursing and caring for older people with dementia needs further exploration. To introduce creative writing techniques to health professionals as part of dementia-related reflective practice. A local experienced author facilitated creative writing workshops with nine preregistration nursing students (general and mental health), one family carer and five care professionals working with people with dementia. The student nurses reported that the creative writing exercises felt more 'real' than the reflective practice models they had used in their academic and practical studies. Workshop participants also reported they had learnt some creative writing techniques to reduce work-related stress and anxiety. They also saw the impact of writing activities with people living with dementia, which can enable creativity and 'alleviate the common symptoms of depression and anxiety'. Creative writing techniques can support insightful, reflective dementia focused practice. Creative writing, as a tool in reflective practice, may enable health professionals and family carers to become confident and creative partners in older people's care. The added value, time and investment needed to introduce creative writing need to be articulated and acknowledged from within supervision and staffing teams. © 2016 John Wiley & Sons Ltd.
Prevalence of dementia among population age over 45 years in Chiang Mai, Thailand.
Wangtongkum, Suparus; Sucharitkul, Phongsakorn; Silprasert, Nutcharut; Inthrachak, Rudeethawinl
2008-11-01
To determine the prevalence of dementia in Thai people with age 45 years and above. This project used a cross sectional research design to study the prevalence of dementia in Chiang Mai. Door-to-door technique was assigned in condition with multi-stage probability random sampling to obtain subjects representing the population of Chiang Mai between Oct 2004 and Sep 2005. The researchers collected the data from the subjects aged 45 years and above. All subjects were located from every Amphurs of Chiang Mai. They were first screened with Thai Mini Mental State Examination (TMSE) and Thai Beck Depression Inventory (BDI). The subjects whose TMSE was less than 24 were assessed and diagnosed by a neurologist. Subjects who were determined as having dementia might be laboratory analyzed and classified based on DSM-IV and NINDS-AIREN criteria. The authors enrolled 2,311 people and screened them with Batteries test. One thousand four hundred ninety two people qualified with 610 males and 882 females, whose mean age was 59.7 +/- 10.4 years. The authors found that among the 35 people with dementia, the mean age was 67.9 +/- 8.9 years (45-88 years). The prevalence of dementia among the study participants was 2.35%. In the present study, Alzheimer's disease was the most common type of dementia diagnosed (75.0%) and vascular dementia was the second most commonly diagnosed (12.5%). The prevalence of dementia in Chiang Mai was 2.35%, which does not differ from the previous study Alzheimer's disease was the most common type of dementia diagnosed.
Operational criteria for senile dementia of Lewy body type (SDLT).
McKeith, I G; Perry, R H; Fairbairn, A F; Jabeen, S; Perry, E K
1992-11-01
Recent reports have suggested that brain stem and cortical Lewy body formation may identify a neurodegenerative disorder in elderly demented individuals which accounts for up to 20% of cases of senile dementia coming to autopsy. Retrospective analysis of case notes of 21 autopsy patients with neuropathologically proven senile dementia of Lewy body type (SDLT) and 37 cases with neuropathologically proven Alzheimer's disease (AD) identified a characteristic clinical syndrome in SDLT. Fluctuating cognitive impairment; psychotic features including visual and auditory hallucinations, and paranoid delusions; depressive symptoms; falling and unexplained losses of consciousness were all seen significantly more often than in AD. Over half of the SDLT patients in this series who were given neuroleptics in standard dose showed acute and often irreversible adverse reactions indicative of a neuroleptic sensitivity syndrome. The survival time of drug treated patients was reduced by 50%. Operational criteria to aid in the clinical distinction between SDLT and AD patients are proposed and hypotheses regarding possible aetiology and treatment discussed.
Use and cost of outpatient visits of AD patients: CERAD XXII.
Fillenbaum, G; Heyman, A; Peterson, B L; Pieper, C F; Weiman, A L
2001-06-26
To determine the probability, frequency, and cost of outpatient visits of patients with AD in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) as a function of stage of dementia and institutional status. Clinical information on 388 patients with AD enrolled in CERAD who had no serious comorbidities at baseline and for whom the stage of disease and institutional status were known, were linked to Health Care Financing Administration Physician/Supplier and Outpatient Standard Analytic (institutional outpatient) files for 1991 through 1995. None was registered in a health maintenance organization. Repeated measures regression models were used to examine the relationship of stage of disease to probability, frequency, and cost of outpatient visits for institutionalized and noninstitutionalized patients, with demographic characteristics and calendar time controlled. The annual proportion of patients with AD and a Medicare-reimbursed outpatient visit ranged from 81% to 95% and was not related to stage of dementia or institutional status. Among those with at least one outpatient visit, however, those living at home had fewer visits than did those in institutions, but their number of visits increased as dementia worsened. Those in institutions had a larger number of outpatient visits, but these did not vary significantly by stage of dementia. Neither location of residence nor stage affected the cost of outpatient visits. Among those with an outpatient visit, the frequency of visits and their relationship to stage of disease depends on institutional status.
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.
Delaying Onset of Dementia: Are Two Languages Enough?
Freedman, Morris; Alladi, Suvarna; Chertkow, Howard; Bialystok, Ellen; Craik, Fergus I. M.; Phillips, Natalie A.; Duggirala, Vasanta; Raju, Surampudi Bapi; Bak, Thomas H.
2014-01-01
There is an emerging literature suggesting that speaking two or more languages may significantly delay the onset of dementia. Although the mechanisms are unknown, it has been suggested that these may involve cognitive reserve, a concept that has been associated with factors such as higher levels of education, occupational status, social networks, and physical exercise. In the case of bilingualism, cognitive reserve may involve reorganization and strengthening of neural networks that enhance executive control. We review evidence for protective effects of bilingualism from a multicultural perspective involving studies in Toronto and Montreal, Canada, and Hyderabad, India. Reports from Toronto and Hyderabad showed a significant effect of speaking two or more languages in delaying onset of Alzheimer's disease by up to 5 years, whereas the Montreal study showed a significant protective effect of speaking at least four languages and a protective effect of speaking at least two languages in immigrants. Although there were differences in results across studies, a common theme was the significant effect of language use history as one of the factors in determining the onset of Alzheimer's disease. Moreover, the Hyderabad study extended the findings to frontotemporal dementia and vascular dementia. PMID:24959001
Delaying onset of dementia: are two languages enough?
Freedman, Morris; Alladi, Suvarna; Chertkow, Howard; Bialystok, Ellen; Craik, Fergus I M; Phillips, Natalie A; Duggirala, Vasanta; Raju, Surampudi Bapi; Bak, Thomas H
2014-01-01
There is an emerging literature suggesting that speaking two or more languages may significantly delay the onset of dementia. Although the mechanisms are unknown, it has been suggested that these may involve cognitive reserve, a concept that has been associated with factors such as higher levels of education, occupational status, social networks, and physical exercise. In the case of bilingualism, cognitive reserve may involve reorganization and strengthening of neural networks that enhance executive control. We review evidence for protective effects of bilingualism from a multicultural perspective involving studies in Toronto and Montreal, Canada, and Hyderabad, India. Reports from Toronto and Hyderabad showed a significant effect of speaking two or more languages in delaying onset of Alzheimer's disease by up to 5 years, whereas the Montreal study showed a significant protective effect of speaking at least four languages and a protective effect of speaking at least two languages in immigrants. Although there were differences in results across studies, a common theme was the significant effect of language use history as one of the factors in determining the onset of Alzheimer's disease. Moreover, the Hyderabad study extended the findings to frontotemporal dementia and vascular dementia.
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
Oudman, Erik
2012-03-01
Depression is one of the most frequently diagnosed psychiatric disorders in patients with dementia with a prevalence of up to 50%. The detrimental effects of depression in dementia include disability in daily living, worse quality of life, and faster cognitive decline. Although electroconvulsive therapy (ECT) is a well-established and effective treatment for depression in the elderly, it is currently an overlooked treatment option in the elderly with dementia and depression. The aim of this review was to provide a critical analysis of the efficacy and safety of ECT in depression superimposed on dementia by reviewing the current literature on this topic. Current evidence suggests that ECT is an effective treatment for depression in dementia, although the relatively small number of controlled studies hampers the comparison of effectiveness between healthy nongeriatric patients and those with dementia. Moreover, the systematic reports on cognitive side effects are very limited in number and currently only apply to moderately mild or mild dementia of nonvascular origin. Some studies do suggest that cognitive side effects are likely in later stages of dementia and in patients with vascular dementia. It is therefore of crucial relevance to prospectively study effects of ECT in different types and phases of dementia in controlled trials. From a clinical perspective, it is essential to inform and educate patients and family about the possible risks and benefits of ECT treatment for depression in dementia.
Galetta, Kristin M; Chapman, Kimberly R; Essis, Maritza D; Alosco, Michael L; Gillard, Danielle; Steinberg, Eric; Dixon, Diane; Martin, Brett; Chaisson, Christine E; Kowall, Neil W; Tripodis, Yorghos; Balcer, Laura J; Stern, Robert A
2017-01-01
The King-Devick (K-D) test is a 1 to 2 minute, rapid number naming test, often used to assist with detection of concussion, but also has clinical utility in other neurological conditions (eg, Parkinson disease). The K-D involves saccadic eye and other eye movements, and abnormalities thereof may be an early indicator of Alzheimer disease (AD)-associated cognitive impairment. No study has tested the utility of the K-D in AD and we sought to do so. The sample included 206 [135 controls, 39 mild cognitive impairment (MCI), and 32 AD dementia] consecutive subjects from the Boston University Alzheimer's Disease Center registry undergoing their initial annual evaluation between March 2013 and July 2015. The K-D was administered during this period. Areas under the receiver operating characteristic curves generated from logistic regression models revealed the K-D test distinguished controls from subjects with cognitive impairment (MCI and AD dementia) [area under the curve (AUC)=0.72], MCI (AUC=0.71) and AD dementia (AUC=0.74). K-D time scores between 48 and 52 seconds were associated with high sensitivity (>90.0%) and negative predictive values (>85.0%) for each diagnostic group. The K-D correlated strongly with validated attention, processing speed, and visual scanning tests. The K-D test may be a rapid and simple effective screening tool to detect cognitive impairment associated with AD.
Peng, Mingkai; Chen, Guanmin; Tang, Karen L; Quan, Hude; Smith, Eric E; Faris, Peter; Hachinski, Vladimir; Campbell, Norm R C
2017-10-27
Vascular dementia (VaD) is the second most common form of dementia. However, there were mixed evidences about the association between blood pressure (BP) and risk of VaD in midlife and late life and limited evidence on the association between pulse pressure and VaD. This is a population-based observational study. 265,897 individuals with at least one BP measurement between the ages of 60 to 65 years and 211,116 individuals with at least one BP measurement between the ages of 70 to 75 years were extracted from The Health Improvement Network in United Kingdom. Blood pressures were categorized into four groups: normal, prehypertension, stage 1 hypertension, and stage 2 hypertension. Cases of VaD were identified from the recorded clinical diagnoses. Multivariable survival analysis was used to adjust other confounders and competing risk of death. All the analysis were stratified based on antihypertensive drug use status. Multiple imputation was used to fill in missing values. After accounting for the competing risk of death and adjustment for potential confounders, there was an association between higher BP levels in the age 60-65 cohort with the risk of developing VaD (hazard ratio [HR] 1.53 (95% confidence interval: 1.04, 2.25) for prehypertension, 1.90 (1.30, 2.78) for stage 1 hypertension, and 2.19 (1.48, 3.26) for stage 2 hypertension) in the untreated group. There was no statistically significant association between BP levels and VaD in the treated group in the age 60-65 cohort and age 70-75 cohort. Analysis on Pulse Pressure (PP) stratified by blood pressure level showed that PP was not independently associated with VaD. High BP between the ages of 60 to 65 years is a significant risk for VaD in late midlife. Greater efforts should be placed on early diagnosis of hypertension and tight control of BP for hypertensive patients for the prevention of VaD.
Service learning at dementia care programs: an orientation and training program.
Lambert-Shute, Jennifer J; Jarrott, Shannon E; Fruhauf, Christine A
2004-01-01
The present paper describes a project that addresses the unique challenge service-learners face at dementia care programs. The project was conducted in conjunction with two courses on aging that offer students a service-learning (S-L) option at a university adult day service (ADS) program that accepts service-learners from these courses. The intervention consisted of two elements: (a) an orientation and follow- up sessions in which students learned about the causes of dementia, the behavioral characteristics exhibited by persons with dementia, and the best methods of interacting effectively with cognitively impaired persons; and (b) a structured scrapbook project for service-learners to exercise their new knowledge and skills. The authors designed the project to increase students' comfort in the dementia care setting and to facilitate students' knowledge of the elderly. The following sections describe the project and its procedures, benefits, and challenges. Recommendations for continuing the project and for adapting the project to other dementia sites are provided.
Vermeiren, Yannick; Le Bastard, Nathalie; Van Hemelrijck, An; Drinkenburg, Wilhelmus H; Engelborghs, Sebastiaan; De Deyn, Peter P
2013-09-01
Behavioral and psychological signs and symptoms of dementia (BPSD) are a heterogeneous group of behavioral and psychiatric disturbances occurring in dementia patients of any etiology. Research suggests that altered activities of dopaminergic, serotonergic, (nor)adrenergic, as well as amino acid neurotransmitter systems play a role in the etiopathogenesis of BPSD. In this study we attempted to identify cerebrospinal fluid (CSF) neurochemical correlates of BPSD to provide further insight into its underlying neurochemical pathophysiological mechanisms. Patients with probable Alzheimer's disease (AD; n = 202), probable AD with cerebrovascular disease (n = 37), probable frontotemporal dementia (FTD; n = 32), and probable dementia with Lewy bodies (DLB; n = 26) underwent behavioral assessment and lumbar puncture. CSF levels of six amino acids and several biogenic amines and metabolites were analyzed using ultraperformance liquid chromatography with fluorescence detection and reversed-phase high-performance liquid chromatography with fluorescence detection. In the AD patients, CSF homovanillic acid/5-hydroxyindoleacetic acid (HVA/5HIAA) ratios correlated positively with anxieties/phobias, whereas CSF levels of taurine correlated negatively with depression and behavioral disturbances in general. In FTD patients, CSF levels of glutamate correlated negatively with verbally agitated behavior. In DLB patients, CSF levels of HVA correlated negatively with hallucinations. Several neurotransmitter systems can be linked to one specific behavioral syndrome depending on the dementia subtype. In addition to biogenic amines and metabolites, amino acids seem to play a major role in the neurochemical etiology of BPSD as well. Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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.
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.