non-Alzheimer Dementia Research Articles

Antioxidant Status and Energy State of Erythrocytes in Alzheimer Dementia: Probing for Markers

Subject age and brain oxidative stress play pivotal roles in Alzheimer disease (AD) pathology. Erythrocytes (red blood cells: RBC) are considered as passive "reporter cells" for the oxidative status of the whole organism, not active participants in mechanisms of AD pathogenesis and are not well studied in AD. The aim of this work is to assess whether the antioxidant status and energy state of RBC from elderly people change in AD. We measured levels of key products and enzymes of oxidative metabolism in RBC from AD (n = 12) and non-Alzheimer dementia (NA, n = 13) patients, as well as in cells from age-matched controls (AC, n = 14) and younger adult controls (YC, n = 14). Parameters of the adenylate system served to evaluate the energy state of RBC. In both aging and dementia, oxidative stress in RBC increased and exhibited elevated concentrations of H₂O₂ and organic hydroperoxides, decreased the GSH/GSSG ratio and glutathione-S-transferase activity. Reductions in the ATP levels, adenine nucleotide pool size (AN) and adenylate energy charge accompanied these oxidative disturbances. The patterns of changes in these indices between groups strongly correlated with each other, Spearman rank correlation coefficients being r(s) = 1.0 or -1.0 (p < 0.01). Alterations of the RBC parameters of oxidative stress and adenylate metabolism were nonspecific and interpreted as age-related abnormalities. Decreased glutathione peroxidase activity in RBC may be considered as a new peripheral marker for AD.

Midlife vascular risk factors and their association with dementia deaths: Results from a Norwegian prospective study followed up for 35 years

There is growing evidence that midlife risk factors for vascular disease also are risk factors for dementia, but there is still need for long-term observational studies to address this. Our objective was to investigate the association of midlife vascular disease risk factors with dementia death. Participants were included in The Norwegian Counties Study (NCS) in the period 1974–78, aged 35–50years at baseline. Information from NCS was linked with the Cause of Death Registry through the year 2009 using the unique personal identification number. The study included 48,793 participants, 1.5million person years and 486 dementia deaths (187 Alzheimer's; 299 non-Alzheimer's dementia). Cox regression for cause-specific hazards was used. Dementia death was associated with increased total cholesterol levels (>7.80 vs. <5.20mmol/l: HR=2.01, 95% confidence interval 1.37–2.93); diabetes (HR=2.43, 95% CI 1.40–4.32) and low body mass index (<20kg/m2 vs. 20–25kg/m2: HR=1.76, 95% CI 1.15–2.68) in midlife. The associations remained after adjustment for other vascular risk factors and educational level. Smoking status or blood pressure in midlife was not significantly associated with risk of dementia death, although the results indicate a possible increased risk in heavy smokers. People suffering from high cholesterol levels, diabetes or underweight in midlife are at increased risk of dying from or with dementia later in life. Our findings add to previous results suggesting that intervention in midlife may be important. To better understand the mechanisms involved in the associations between midlife underweight, diabetes, and elevated cholesterol level and late-life dementia death, these links need to be further investigated.

TEST YOUR MEMORY (TYM) TESTING IN NON-ALZHEIMER DEMENTIAS

The Test Your Memory (TYM) test is a short cognitive test. It is completed by the patient and supervised by a clinic nurse and so takes minimal medical time. It...

Prescripciones inconvenientes en el tratamiento del paciente con deterioro cognitivo

IntroductionSome treatments are inappropriate for patients with cognitive decline. We analyse their use in 500 patients and present a literature review. DevelopmentBenzodiazepines produce dependence, and reduce attention, memory, and motor ability. They can cause disinhibition or aggressive behaviour, facilitate the appearance of delirium, and increase accident and mortality rates in people older than 60. In subjects over 65, low systolic blood pressure is associated with cognitive decline. Maintaining this figure between 130 and 140mm Hg (145 in patients older than 80) is recommended. Hypocholesterolaemia<160mg/dl is associated with increased morbidity and mortality, aggressiveness, and suicide; HDL-cholesterol<40mg/dl is associated with memory loss and increased vascular and mortality risks. Old age is a predisposing factor for developing cognitive disorders or delirium when taking opioids. The risks of prescribing anticholinesterases and memantine to patients with non-Alzheimer dementia that is not associated with Parkinson disease, mild cognitive impairment, or psychiatric disorders probably outweigh the benefits. Anticholinergic drugs acting preferentially on the peripheral system can also induce cognitive side effects. Practitioners should be aware of steroid-induced dementia and steroid-induced psychosis, and know that risk of delirium increases with polypharmacy. Of 500 patients with cognitive impairment, 70.4% were on multiple medications and 42% were taking benzodiazepines. Both conditions were present in 74.3% of all suspected iatrogenic cases. ConclusionsPolypharmacy should be avoided, if it is not essential, especially in elderly patients and those with cognitive impairment. Benzodiazepines, opioids and anticholinergics often elicit cognitive and behavioural disorders. Moreover, systolic blood pressure must be kept above 130mm Hg, total cholesterol levels over 160mg/dl, and HDL-cholesterol over 40mg/dl in this population.

Consumption of Pharmaceuticals in Primary Non-Alzheimer’s Degenerative Dementias

Limited information exists regarding the consumption of psychopharmaceuticals for non-Alzheimer's degenerative dementias (n-ADDs), despite the fact that the treatment of neuropsychiatric symptoms of these diseases is an important challenge for clinicians. The aim of this study was to describe sociodemographic and clinical data from 235 patients with various subtypes of n-ADD, together with the level of consumption of pharmaceuticals with central nervous system activity. A descriptive, observational, cross-sectional study was conducted using the data registered by the Registry of Dementias of Girona, northeast Catalunya, Spain. All drugs were categorized according to the Anatomical Therapeutic Chemical Classification System. The results showed a high level of psychopharmaceutical prescription: 48.9 % of the n-ADD patients used acetylcholinesterase inhibitors and 9.8 % used memantine. Antipsychotics and benzodiazepines were prescribed to 45.5 and 46.8 % of the patients, respectively. Antidepressants were consumed by 70.2 % of the registered cases. High levels of psychopharmaceutical prescribing were observed in our study and many of these prescriptions lacked specific indications for n-ADDs. It is necessary to consider the risk-benefit relationship before prescribing pharmaceuticals. Specific training programmes will be necessary to improve the use of pharmaceuticals in n-ADD patients.

Depressive Symptoms and Mild Cognitive Impairment in the Elderly: An Ominous Combination

Depressive Symptoms and Mild Cognitive Impairment in the Elderly: An Ominous Combination

Serum Vitamin D Deficiency as a Predictor of Incident Non-Alzheimer Dementias: A 7-Year Longitudinal Study

Background: Hypovitaminosis D has been cross-sectionally associated with dementia and stroke. The objective of this longitudinal study was to determine whether serum vitamin D deficiency at baseline could predict the onset of non-Alzheimer dementias (NAD) within 7 years among older women. Methods: Forty high-functioning older women (78.4 years, 76.4/82.0; median, 25th/75th percentile) from the EPIDOS Toulouse study were divided into two groups based on vitamin D deficiency (i.e., serum 25-hydroxyvitamin D <10 ng/ml) at baseline. At the end of the 7-year follow-up period, women matching the DSM-IV but not the NINCDS-ADRDA criteria were diagnosed with NAD while those matching the NINCDS-ADRDA criteria were considered to have Alzheimer’s disease (AD). Subtle cognitive impairments at baseline, cardiovascular risk factors and Parkinson’s disease were used as potential confounders. Results: NAD was reported in 6 women (82.8 years, 80.6/86.0) after 7 years of follow-up. More NAD were observed in women with vitamin D deficiency (p = 0.023). There was no between-group difference regarding the onset of AD (p = 0.332). We found an association between vitamin D deficiency at baseline and the onset of NAD (adjusted odds ratio = 19.57, p = 0.042). Conversely, vitamin D deficiency was not associated with AD (p = 0.222). Conclusion: Baseline vitamin D deficiency predicted the onset of NAD within 7 years among older women.

Dietary supplementation with decaffeinated green coffee improves diet-induced insulin resistance and brain energy metabolism in mice

ObjectivesThere is accumulating evidence that coffee consumption may reduce risk for type 2 diabetes, a known risk factor for Alzheimer's and other neurological diseases. Coffee consumption is also associated with reduced risk for Alzheimer's disease and non-Alzheimer's dementias. However, preventive and therapeutic development of coffee is complicated by the cardiovascular side effects of caffeine intake. As coffee is also a rich source of chlorogenic acids and many bioactive compounds other than caffeine, we hypothesized that decaffeinated coffee drinks may exert beneficial effects on the brain.MethodsWe have investigated whether dietary supplementation with a standardized decaffeinated green coffee preparation, Svetol®, might modulate diet-induced insulin resistance and brain energy metabolism dysfunction in a high-fat diet mouse model.ResultsAs expected, dietary supplementation with Svetol® significantly attenuated the development of high-fat diet-induced deficits in glucose-tolerance response. We have also found that Svetol® treatment improved brain mitochondrial energy metabolism as determined by oxygen consumption rate. Consistent with this evidence, follow-up gene expression profiling with Agilent whole-genome microarray revealed that the decaffeinated coffee treatment modulated a number of genes in the brain that are implicated in cellular energy metabolism.DiscussionOur evidence is the first demonstration that dietary supplementation with a decaffeinated green coffee preparation may beneficially influence the brain, in particular promoting brain energy metabolic processes.

Dementia and Diabetes Mellitus: Association with Apolipoprotein E4 Polymorphism from a Hospital in Southern India

Objective. To evaluate the association of Apolipoprotein E4 (ApoE4) in Alzheimer's dementia (AD) with comorbid diabetes mellitus (DM). Methods. The study included subjects with Alzheimer's dementia (AD) (n = 209), individuals with non-Alzheimer's dementia (nAD) (n = 122), individuals with parental history of AD (f/hAD) (n = 70), and control individuals who had normal cognitive functions and no parental history of dementia (NC) (n = 193). Dementia was diagnosed using International Classification of Diseases-10 revision (ICD-10) criteria. DM was assessed on the basis of self-report and/or use of antidiabetic medications. ApoE genotyping was done using sequence-specific primer polymerase chain reaction. Results. ApoE4 allele frequencies were highest among AD with comorbid DM (0.35) followed by AD without DM (0.25), nAD with DM (0.13), nAD without comorbid DM (0.12), and NC (0.08). Frequency of ApoE4 in persons with f/hAD was 0.13. The association of AD with co-morbid DM in ApoE4 carriers was more in comparison to NC with DM (OR = 5.68, P = 0.04). Conclusion. There is a significant association between AD with co-morbid DM and ApoE4 genotype.

The Mini-Cog versus the Mini-Mental State Examination and the Clock Drawing Test in daily clinical practice: screening value in a German Memory Clinic

The aim of this study was to compare the screening value of the Mini-Cog, Clock Drawing Test (CDT), Mini-Mental State Examination (MMSE) and the algorithm MMSE and/or CDT to separate elderly people with dementia from healthy depending on test time, type and severity of dementia, and demographic variables in a German Memory Clinic. Data from a heterogeneous patient sample and healthy participants (n = 502) were retrospectively analyzed. Of the 438 patients with dementia, 49.1% of the dementia diagnoses were Alzheimer's dementia and 50.9% were non-Alzheimer's dementia. Sixty-four participants were classified as cognitively unimpaired. The CDT and an extraction of the 3-item recall of the MMSE were used to constitute the Mini-Cog algorithm. Overall, the Mini-Cog showed significantly higher discriminatory power (86.8%) than the MMSE (72.6% at a cut-off ≤ 24 and 79.2% at ≤ 25, respectively) and CDT (78.1%) (each p < 0.01) and did not perform worse than the algorithm MMSE and/or CDT (each p > 0.05). The specificity of the Mini-Cog (100.0%) was similar to that of the MMSE (100.0% for both cut-offs) and CDT (96.9%) (p = 0.154). For all age and educational groups the Mini-Cog outmatched the CDT and MMSE, and was less affected by education than MMSE and less susceptible for the dementia stage than the CDT. The Mini-Cog proved to have superior discriminatory power than either CDT or MMSE and is demonstrated to be a valid "short" screening instrument taking 3 to 4 minutes to administer in the geriatric setting.

A new book about modelling dementia

A new book about modelling dementia . Animal Models of Dementia. Edited by Peter Paul De Deyn & Debby Van Dam . Published by Humana Press, Springer , New York , 2011 . 732 pp, ISBN: 978-1-60761-897-3 Dementia is a devastating condition that poses a major socio-economic burden to society. There is still no adequate treatment for dementia and the number of demented patients is rising as life expectancy is continuously increasing. There is an urgent need to investigate mechanisms underlying dementia to understand what goes wrong and what can be done for treatment. Such mechanistic studies cannot be done in patients as sophisticated experimental manipulations are not permissible. Therefore, studies with animal models are of the utmost importance to tackle dementia. Consequently, hundreds of animal model studies have been carried out. Highlights of these studies are summarized in the new book Animal Models of Dementia edited by Peter De Dyn & Debby Van Dam. In the book leading experts have written comprehensive overviews of relevant animal work and they have included useful reference lists to direct further reading. The book assumes some background knowledge and therefore it is a great add-on to more basic textbooks on mechanisms of dementia. The book not only nicely summarizes ongoing efforts to model dementia but also describes how to investigate underlying mechanisms at various levels of complexity. As Alzheimer's disease is the predominant form of dementia, the book is mostly (but not only!) dedicated to models of Alzheimer's disease. Importantly, leading mouse models are discussed, which is very useful for newcomers to the field, as there are a lot of different models. Furthermore, spontaneous mutants, lesion models, acute models (based on the injection of amyloid peptides), and models of Drosophila and C. elegans are also introduced. Whilst the book provides a very impressive description of various models of Alzheimer's disease, it does not offer an opinion about advantages and disadvantages of the different models. Unfortunately, this is a missed opportunity to help newcomers in the field. Additionally, the book does not explain how to design a great model of Alzheimer's disease. For example, that for transgene expression developmentally active promoters should be avoided. Or, that mimicry of identified expression changes in Alzheimer's disease can provide insights about the function of such changes. Nonetheless, the book provides an excellent compendium of models of Alzheimer's disease and it has also information about modelling non-Alzheimer's dementia. Importantly, the book not only describes various animal models of dementia, it makes it also clear that these models need to be investigated at various levels, which include behavioural studies, imaging experiments, neuropathological investigations, pharmacology and neurochemistry. Additionally, the book provides information about ethics on animal experimentation and information on intellectual property, issues that can be rarely found in textbooks. There are no competing interests to declare.

Anosognosia in neurodegenerative disease

Patients with neurological disorders are often partially or completely unaware of the deficits caused by their disease. This impairment is referred to as anosognosia, and it is very common in neurodegenerative disease, particularly in frontotemporal dementia. Anosognosia has significant impacts on function and quality of life for patients with neurodegenerative disease and their caregivers, but the phenomenon has received little formal study, especially in non-Alzheimer's (non-AD) dementias. Furthermore, few studies have attempted to systematically verify the potential role of specific cognitive impairments in producing anosognosia. As a result, the mechanisms underlying this phenomenon are poorly understood. Episodic memory likely plays an important role. In addition, the frontal lobe systems are important for intact self-awareness, but the most relevant frontal functions have not been identified. Motivation required to engage in self-monitoring and emotional activation marking errors as significant are often-overlooked aspects of performance monitoring that may underlie anosognosia in some patients. The present review offers a working model that incorporates these functions and stipulates specific processes that may be important for awareness of changes in one's abilities. Specification of the specific processes whose potential failure results in anosognosia can establish a roadmap for future studies.

Variably Protease-Sensitive Prionopathy: a Novel Disease of the Prion Protein

Variably protease-sensitive prionopathy (VPSPr) is a novel disease involving the prion protein (PrP) that has clinical similarities with non-Alzheimer's dementias especially frontotemporal dementia, diffuse Lewis body disease, and normal pressure hydrocephalus. VPSPr can be distinguished from sporadic Creutzfeldt-Jakob disease (sCJD) especially for the characteristics of the abnormal PrP. Furthermore, although VPSPr like sCJD affects patients with the three PrP genotypes as determined by the common methionine/valine polymorphism, the allelic prevalence is very different in the two diseases. These findings suggest that VPSPr is basically different from classical prion diseases such as sCJD being perhaps more akin to other neurodegenerative dementias.

EFNS guidelines for the diagnosis and management of Alzheimer’s disease

In 2008 a task force was set up to develop a revision of the European Federation of the Neurological Societies (EFNS) guideline for the diagnosis and management of Alzheimer's disease (AD) and other disorders associated with dementia, published in early 2007. The aim of this revised international guideline was to present a peer-reviewed evidence-based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists, and other specialist physicians responsible for the care of patients with AD. Mild cognitive impairment and non-Alzheimer dementias are not included in this guideline. The task force working group reviewed evidence from original research articles, meta-analysis, and systematic reviews, published before May 2009. The evidence was classified and consensus recommendations graded (A, B, or C) according to the EFNS guidance. Where there was a lack of evidence, but clear consensus, good practice points were provided. The recommendations for clinical diagnosis, blood tests, neuropsychology, neuroimaging, electroencephalography, cerebrospinal fluid (CSF) analysis, genetic testing, disclosure of diagnosis, treatment of AD, behavioural and psychological symptoms in dementia, legal issues, counselling and support for caregivers were all revised as compared with the previous EFNS guideline. A number of new recommendations and good practice points are made, namely in CSF, neuropsychology, neuroimaging and reviewing non-evidence based therapies. The assessment, interpretation, and treatment of symptoms, disability, needs, and caregiver stress during the course of AD require the contribution of many different professionals. These professionals should adhere to these guideline to improve the diagnosis and management of AD.

From FUS to Fibs: What's New in Frontotemporal Dementia?

Frontotemporal dementia (FTD) is an important cause of non-Alzheimer's dementia and is the second most common cause of young onset dementia. FTD presents with progressive changes in behavior and personality (behavioral variant FTD) or language deficits (also known as primary progressive aphasia), although both commonly coexist. Patients with progressive aphasia are subclassified according to the pattern of language deficits into those with progressive non-fluent aphasia (PNFA) and semantic dementia (SD). FTD is pathologically heterogeneous, both macroscopically and on a molecular level, with tau positive, TDP-43 positive, and FUS positive intraneuronal inclusions recognized on immunohistochemical analysis. TDP-43 positive inclusions are also a feature of amyotrophic lateral sclerosis pathology, corroborating the observation of overlapping clinical features between the two conditions and reaffirming the FTD-ALS disease spectrum. Most FTD cases are sporadic, but an important minority is inherited in an autosomal dominant fashion, most commonly due to MAPT or progranulin gene mutations. Familial clusters of FTD and amyotrophic lateral sclerosis are also recognized but poorly understood. This paper reviews the clinical phenotypes, assessment and treatment of FTD in light of recent pathological and genetic discoveries.

Management of Neuropsychiatric Symptoms in People with Dementia

Neuropsychiatric symptoms are frequent and troublesome in people with dementia and present a major treatment challenge for clinicians. Most good practice guidelines suggest non-pharmacological treatments as the first-line therapy and there is emerging evidence, including randomized controlled trials, that a variety of psychological and training interventions, including social interaction and person-centred care training, are effective. There is evidence from meta-analyses that some atypical antipsychotic drugs, specifically risperidone and aripiprazole, confer benefit in the treatment of aggression in people with Alzheimer's disease over a period of up to 12 weeks. However, these benefits have to be considered in the context of significant adverse events, including extrapyramidal symptoms, accelerated cognitive decline, stroke and death. In addition, the limited evidence available does not indicate ongoing treatment benefits over longer periods of therapy. The evidence is limited for other pharmacological treatment approaches, but the best evidence is probably for carbamazepine, memantine and citalopram. There is very limited evidence for any therapies in non-Alzheimer dementias. In conclusion, it is important in most situations to limit the use of antipsychotic medication to short-term treatment (up to 12 weeks) of severe neuropsychiatric symptoms to limit harm. Non-pharmacological therapies offer a viable and effective alternative in many situations. Adequately powered randomized controlled trials for the treatment of clinically significant agitation are urgently needed to explore alternative pharmacological therapies.

Plasma Amyloid-β Forms in Alzheimer's Disease and Non-Alzheimer's Disease Patients

The objective of this study was to evaluate the diagnostic performance of full-length and N-truncated plasma amyloid-beta (Abeta) forms in patients with Alzheimer's disease (AD) and non-Alzheimer's disease dementia (non-AD) as compared to healthy control subjects. Plasma samples from 50 AD, 50 non-AD, and 47 control subjects were included and analyzed using a multiparameter fluorimetric bead-based immunoassay for the simultaneous quantification of different Abeta forms. No significant differences in Abeta isoforms were detected between dementia and controls; or AD, non-AD, and controls. Compared to control subjects, pooled dementia patients (AD and non-AD) and AD patients alone had significantly lower plasma Abeta1-42/AbetaN-42 ratios. In each diagnostic group, all plasma Abeta concentrations were significantly correlated. No significant correlations between plasma Abeta forms and age were found. The low diagnostic performance of cross-sectional plasma Abeta measurements hampers future application as diagnostic markers or screening tools for dementia. CSF biomarker analysis remains superior, although the possible application of longitudinal plasma Abeta measurements as screening tools for dementia remains to be elucidated.

Pilot Trial of Memantine in Primary Progressive Aphasia

Johnson, Nancy A. PhD*; Rademaker, Alfred PhD†; Weintraub, Sandra PhD*; Gitelman, Darren MD‡; Wienecke, Christina BS§; Mesulam, Marsel MD‡ Author Information

Cognition, language, and clinical pathological features of non-Alzheimer's dementias: An overview

There are many distinct forms of dementia whose pharmacological and behavioral management differ. Differential diagnosis among the dementia variants currently relies upon a weighted combination of genetic and protein biomarkers, neuroanatomical integrity, and behavior. Diagnostic specificity is complicated by a high degree of overlap in the initial presenting symptoms across dementia subtypes. For this reason, reliable markers are of considerable diagnostic value. Communication disorders have proven to be among the strongest predictors for discriminating among dementia subtypes. As such, speech-language pathologists may be poised to make an increasingly visible contribution to dementia diagnosis and its ongoing management. The value and durability of this potential contribution, however, demands an improved discipline-wide knowledge base about the unique features associated with different dementia variants. To this end we provide an overview of cognition, language, and clinical pathological features of four of the most common non-Alzheimer's dementias: frontotemporal dementia, vascular dementia, Lewy body disease dementia, and Parkinson's disease dementia. Learning outcomes: Readers will learn characteristics and distinguishing features of several non-Alzheimer's dementias, including Parkinson's disease dementia, frontotemporal dementia, vascular dementia, and Lewy body dementia. Readers will also learn to distinguish between several variants of frontotemporal dementia. Finally, readers will gain knowledge of the term primary progressive aphasia as it relates to the aforementioned dementia etiologies.

The Cerebrospinal Fluid Amyloid β42/40 Ratio in the Differentiation of Alzheimer'sDisease from Non-Alzheimer's Dementia

The Cerebrospinal Fluid Amyloid β42/40 Ratio in the Differentiation of Alzheimer'sDisease from Non-Alzheimer's Dementia