Frontotemporal Dementia Research Coming of Age: Alzheimer Research Forum

Long the obscure cousins of Alzheimer's, the frontotemporal dementias last month stood in the glare of a large three-day meeting devoted specifically to this particular group of diseases. FTD is an isolating and ruinous progressive illness. Sufferers exhibit a range of disturbing, aberrant behaviors and often reckless financial decisions, all coupled with a puzzling emotional flatness that makes it impossible for them to realize it's actually wrong to cheat on a spouse or spend the family savings. In the wake of some recent genetic and biochemical advances, FTD research is now quickly picking up speed, and a new sense of optimism pervaded the 7th International Conference on Frontotemporal Dementias. Madolyn Bowman Rogers captured its essence-read her series to learn what FTD is, and how new research is changing its diagnosis, biological understanding, and the search for new treatments.Frontotemporal Dementia Research Comes of AgeNeuroimaging Opens Window to Disease, Better DiagnosisDissecting the Pathways Behind Frontotemporal DementiaClinical Trials a Ripple, Scientists Hope for a WaveView PDF of the entire series.��

Frontotemporal Dementia Research Coming of Age: Alzheimer Research Forum

Long the obscure cousins of Alzheimer's, the frontotemporal dementias last month stood in the glare of a large three-day meeting devoted specifically to this particular group of diseases. FTD is an isolating and ruinous progressive illness. Sufferers exhibit a range of disturbing, aberrant behaviors and often reckless financial decisions, all coupled with a puzzling emotional flatness that makes it impossible for them to realize it's actually wrong to cheat on a spouse or spend the family savings. In the wake of some recent genetic and biochemical advances, FTD research is now quickly picking up speed, and a new sense of optimism pervaded the 7th International Conference on Frontotemporal Dementias. Madolyn Bowman Rogers captured its essence-read her series to learn what FTD is, and how new research is changing its diagnosis, biological understanding, and the search for new treatments.Frontotemporal Dementia Research Comes of AgeNeuroimaging Opens Window to Disease, Better DiagnosisDissecting the Pathways Behind Frontotemporal DementiaClinical Trials a Ripple, Scientists Hope for a WaveView PDF of the entire series.��

World Alzheimer Report

The World Alzheimer Report 2010 provides the clearest, most comprehensive global picture yet of the economic impact of Alzheimer's disease and dementia.The report includes an estimate of the worldwide cost of dementia, including direct medical costs, direct non-medical costs and costs of informal (family) care. The estimates are broken down by world region and include analysis of the differences between low and high income countries. The report also contains important policy recommendations and makes clear to key decision-makers that doing nothing is not an option.The report can be found here.

World Alzheimer Report 2011 - The benefits of early diagnosis and intervention

Alzheimer's Disease International released the World Alzheimer Report 2011 - The benefits of early diagnosis and intervention on the 13th September 2011. Key Findings:As many as three-quarters of the estimated 36 million people worldwide living with dementia have not been diagnosed and hence cannot benefit from treatment, information and care. In high-income countries, only 20-50% of dementia cases are recognized and documented in primary care. In low- and middle-income countries, this proportion could be as low as 10%.Failure to diagnose often results from the false belief that dementia is a normal part of aging, and that nothing can be done to help. On the contrary, the new report finds that interventions can make a difference, even in the early stages of the illness.Drugs and psychological interventions for people with early-stage dementia can improve cognition, independence, and quality of life. Support and counseling for caregivers can improve mood, reduce strain and delay institutionalization of people with dementia.Governments, concerned about the rising costs of long-term care linked to dementia, should “spend now to save later.” Based on a review of economic analyses, the report estimates that earlier diagnosis could yield net savings of up to US$10,000 per patient in high-income countries.��World Alzheimer Report 2011 - Executive Summary (PDF, 36 pages, 1128KB)World Alzheimer Report 2011 (PDF, 72 pages, 1710KB)����

New Alzheimer's Association report reveals 1 in 3 seniors dies with Alzheimer's or another dementia

2.3 Million Americans are “Long-Distance Caregivers” for people with Alzheimer’s; Costs for Long-Distance Caregivers are Almost Twice as High.According to the Alzheimer's Association 2013 Alzheimer's Disease Facts and Figures report released today, one in three seniors dies with Alzheimer’s or another dementia in the United States. The new report shows that while deaths from other major diseases, such as heart disease, HIV/AIDS and stroke, continue to experience significant declines, Alzheimer’s deaths continue to rise — increasing 68 percent from 2000-2010.��“Unfortunately, today there are no Alzheimer’s survivors. If you have Alzheimer's disease, you either die from it or diewith it,” said Harry Johns, president and CEO of the Alzheimer’s Association. “Now we know that 1 in 3 seniors dies with Alzheimer’s disease or another dementia. Urgent, meaningful��action is necessary, particularly as more and more people age into greater risk for developing a disease��that today has no cure and no way to slow or stop its progression.”Read more here.����������

Multifunctional ligands for application in Alzheimer’s Disease: molecular modelling and biological evaluation

Projecte de recerca elaborat a partir d’una estada a la University of British Columbia, Canadà, entre 2010 i 2012 La malaltia d'Alzheimer (MA) representa avui la forma més comuna de demència en la població envellida. Malgrat fa 100 anys que va ser descoberta, encara avui no existeix cap tractament preventiu i/o curatiu ni cap agent de diagnòstic que permeti valorar quantitativament l'evolució d'aquesta malaltia. L'objectiu en el que s'emmarca aquest treball és contribuir a aportar solucions al problema de la manca d'agents terapèutics i de diagnosi, unívocs i rigorosos, per a la MA. Des del camp de la química bioinorgànica és fàcil fixar-se en l'excessiva concentració d'ions Zn(II) i Cu(II) en els cervells de malalts de MA, plantejar-se la seva utilització com a dianes terapèutica i, en conseqüència, cercar agents quelants que evitin la formació de plaques senils o contribueixin a la seva dissolució. Si bé aquest va ser el punt de partida d’aquest projecte, els múltiples factors implicats en la patogènesi de la MA fan que el clàssic paradigma d’ ¨una molècula, una diana¨ limiti la capacitat de la molècula de combatre aquesta malaltia tan complexa. Per tant, un esforç considerable s’ha dedicat al disseny d’agentsmultifuncionals que combatin els múltiples factors que caracteritzen el desenvolupament de la MA. En el present treball s’han dissenyat agents multifuncionals inspirats en dos esquelets moleculars ben establers i coneguts en el camp de la química medicinal: la tioflavina-T (ThT) i la deferiprona (DFP). La utilització de tècniques in silico que inclouen càlculs farmacocinètics i modelatge molecular ha estat un procés cabdal per a l’avaluació dels millors candidats en base als següents requeriments: (a) compliment de determinades propietats farmacocinètiques que estableixin el seu possible ús com a fàrmac (b) hidrofobicitat adequada per travessar la BBB i (c) interacció amb el pèptid Aen solució.

Stable complexes involving acetylcholinesterase and amyloid-ß-peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer's fibrils

Brain acetylcholinesterase (AChE) forms stable complexes with amyloid-beta peptide (Abeta) during its assembly into filaments, in agreement with its colocalization with the Abeta deposits of Alzheimer's brain. The association of the enzyme with nascent Abeta aggregates occurs as early as after 30 min of incubation. Analysis of the catalytic activity of the AChE incorporated into these complexes shows an anomalous behavior reminiscent of the AChE associated with senile plaques, which includes a resistance to low pH, high substrate concentrations, and lower sensitivity to AChE inhibitors. Furthermore, the toxicity of the AChE-amyloid complexes is higher than that of the Abeta aggregates alone. Thus, in addition to its possible role as a heterogeneous nucleator during amyloid formation, AChE, by forming such stable complexes, may increase the neurotoxicity of Abeta fibrils and thus may determine the selective neuronal loss observed in Alzheimer's brain.

Social capabilities in Alzheimer's patients

Patients with stage-I (very mild and mild) Alzheimer's disease were asked to participate in a Dictator Game, a type of game in which a subject has to decide how to allocate a certain amount of money between himself and another person. The game enables the experimenter to examine the influence of social norms and social preferences on the decision-making process. When the results of treatments involving Alzheimer's disease patients were compared with those of identical treatments involving patients with mild cognitive impairment or healthy control subjects, with similar ages and social backgrounds, no statistically significant difference was found. This finding suggests that stage-I Alzheimer's disease patients may be as capable of making decisions involving social norms and preferences as other individuals of their age. Whatever brain structures are affected by the disease, they do not appear to influence, at this early stage, the neural basis for cooperation-enhancing social interactions.

Iowa's Rural Alzheimer's Demonstration Project, July 1, 2004 - June 31, 2007

The Iowa Department of Elder Affairs, in collaboration with the Iowa Department of Elder Affairs (IDEA) and the University of Iowa College of Nursing (UI CON), has been engaged in developing and evaluating community based services for persons with dementia in the state of Iowa over the past 7 years under two grants form the Administration on Aging. In the current grant period, the involved agencies have completed a collaborative effort aimed to increase the capacity of Adult Day Health and Respite (ADR) providers in serving persons with dementia. Adult day services and respite care were identified by participants in the initial grant through various processes and service providers as important components of caring for persons with dementia and that there was a gap of these services in the state. Therefore, adult day and respite services were chosen as a target for the second AoA grant. The focus, in particular, was to enhance capacity to care for persons with later stages of the disease and those in rural settings as well as to begin to develop services that are more responsive to emerging minority populations. The process of the grant provided the state with a rich amount of information about the status of Iowa’s Adult Day Service providers in general and in regard to provision of dementia specific services, as well as valuable insights into the capability of rural communities to serve persons with dementia and their caregivers at home. Final Performance Report

Microvascular burden and Alzheimer-type lesions across the age spectrum.

The occurrence of microvascular and small macrovascular lesions and Alzheimer's disease (AD)-related pathology in the aging human brain is a well-described phenomenon. Although there is a wide consensus about the relationship between macroscopic vascular lesions and incident dementia, the cognitive consequences of the progressive accumulation of these small vascular lesions in the human brain are still a matter of debate. Among the vast group of small vessel-related forms of ischemic brain injuries, the present review discusses the cognitive impact of cortical microinfarcts, subcortical gray matter and deep white matter lacunes, periventricular and diffuse white matter demyelinations, and focal or diffuse gliosis in old age. A special focus will be on the sub-types of microvascular lesions not detected by currently available neuroimaging studies in routine clinical settings. After providing a critical overview of in vivo data on white matter demyelinations and lacunes, we summarize the clinicopathological studies performed by our center in large cohorts of individuals with microvascular lesions and concomitant AD-related pathology across two age ranges (the younger old, 65-85 years old, versus the oldest old, nonagenarians and centenarians). In conjunction with other autopsy datasets, these observations fully support the idea that cortical microinfarcts are the only consistent determinant of cognitive decline across the entire spectrum from pure vascular cases to cases with combined vascular and AD lesion burden.

Hippocampal atrophy predicts conversion to dementia after STN-DBS in Parkinson's disease.

BACKGROUND: Hippocampal atrophy (HA) is a known predictor of dementia in Alzheimer's disease. HA has been found in advanced Parkinson's disease (PD), but no predicting value has been demonstrated yet. The identification of such a predictor in candidates for subthalamic deep brain stimulation (STN-DBS) would be of value. Our objective was to compare preoperative hippocampal volumes (HV) between PD patients who subsequently converted to dementia (PDD) after STN-DBS and those who did not (PDnD). METHODS: From a cohort of 70 consecutive STN-DBS treated PD patients, 14 converted to dementia over 25.6+/-20.2 months (PDD). They were compared to 14 matched controls (PDnD) who did not convert to dementia after 43.9+/-11.7 months. On the preoperative 3D MPRAGE MRI images, HV and total brain volumes (TBV) were measured by a blinded investigator using manual and automatic segmentation respectively. RESULTS: PDD had smaller preoperative HV than PDnD (1.95+/-0.29 ml; 2.28+/-0.33 ml; p<0.01). This difference reinforced after normalization for TBV (3.28+/-0.48, 3.93+/-0.60; p<0.01). Every 0.1 ml decrease of HV increased the likelihood to develop dementia by 24.6%. A large overlap was found between PD and PDnD HVs, precluding the identification of a cut-off score. CONCLUSIONS: As in Alzheimer's disease, HA may be a predictor of the conversion to dementia in PD. This preoperative predictor suggests that the development of dementia after STN-DBS is related to the disease progression, rather then the procedure. Further studies are needed to define a cut-off score for HA, in order to affine its predictive value for an individual patient.

Maladaptive exploratory behavior and neuropathology of the PS-1 P117L Alzheimer transgenic mice.

Patients with the early-onset Alzheimer's disease P117L mutation in the presenilin-1 gene (PS-1) present pathological hallmarks in the hippocampus, the frontal cortex and the basal ganglia. In the present work we determined by immunohistochemistry which brain regions were injured in the transgenic PS-1 P117L mice, in comparison to their littermates, the B6D2 mice. Furthermore, as these regions are involved in novelty detection, we investigated the behavior of these mice in tests for object and place novelty recognition. Limited numbers of senile plaques and neurofibrillary tangles were detected in aged PS-1 P117L mice in the CA1 only, indicating that the disease is restrained to an initial neuropathological stage. Western blots showed a change in PSD-95 expression (p=0.03), not in NR2A subunit, NR2B subunit and synaptophysin expressions in the frontal cortex, suggesting specific synaptic alterations. The behavioral tests repeatedly revealed, despite a non-significant preference for object or place novelty, maladaptive exploratory behavior of the PS-1 P117L mice in novel environmental conditions, not due to locomotor problems. These mice, unlike the B6D2 mice, were less inhibited to visit the center of the cages (p=0.01) and they continued to move excessively in the presence of a displaced object (p=0.021). Overall, the PS-1 P117L mice appear to be in an initial Alzheimer's disease-like neuropathological stage, and they showed a lack of reaction toward novel environmental conditions.

Un programa psicosocial: programa psicoestimulatiu integral (P.P.I.) amb persones afectades de malaltia d' Alzheimer

L'any 2011 la malaltia d'Alzheimer es situava com la quarta causa de mort més freqüent amb un augment de fins a 11.907, més del doble de morts que l'any 2000 (INE). Aquestes dades demostren l'augment del número de persones que pateixen una demència a mesura que envelleixen i una de les explicacions és l'augment de l'esperança de vida. Per aquest motiu l'estudi de la qualitat de vida ha adquirit una gran importància des de la dècada dels 90. La qualitat de vida és un concepte especialment subjectiu pel fet que cada persona la viu segons la pròpia percepció de salut i benestar i el grau d'adaptació a l'entorn que l'envolta. Per aquest motiu es planteja un programa de psicoestimulació integral (PPI) centrat en les individualitats de cada persona: valors, interessos, història ocupacional..., des de la filosofia de la Teràpia Ocupacional. El projecte està elaborat mitjançant la metodologia qualitativa utilitzant l'enquesta en profunditat semi-estructurada per a realitzar les entrevistes i obtenir la informació principal a l'inici i al final del programa juntament amb tota la informació que s'obtingui de l'observació participant del dia a dia de cada un dels professionals per tal d'estudiar fins a quin punt aquesta atenció centrada en la persona contribueix a millorar la qualitat de vida de les persones afectades de Malaltia d'Alzheimer que reben tractaments no farmacològics com el proposat en aquest projecte. Com a tot estudi es poden trobar alguns factors condicionants com pot ser l'evolució pròpia de la malaltia amb les conseqüències negatives que això comporta i/o el número de participants que formen la mostra.

Multiway Array Decomposition Analysis of EEGs in Alzheimer’s Disease

Methods for the extraction of features from physiological datasets are growing needs as clinical investigations of Alzheimer’s disease (AD) in large and heterogeneous population increase. General tools allowing diagnostic regardless of recording sites, such as different hospitals, are essential and if combined to inexpensive non-invasive methods could critically improve mass screening of subjects with AD. In this study, we applied three state of the art multiway array decomposition (MAD) methods to extract features from electroencephalograms (EEGs) of AD patients obtained from multiple sites. In comparison to MAD, spectral-spatial average filter (SSFs) of control and AD subjects were used as well as a common blind source separation method, algorithm for multiple unknown signal extraction (AMUSE). We trained a feed-forward multilayer perceptron (MLP) to validate and optimize AD classification from two independent databases. Using a third EEG dataset, we demonstrated that features extracted from MAD outperformed features obtained from SSFs AMUSE in terms of root mean squared error (RMSE) and reaching up to 100% of accuracy in test condition. We propose that MAD maybe a useful tool to extract features for AD diagnosis offering great generalization across multi-site databases and opening doors to the discovery of new characterization of the disease.

Dietary resveratrol prevents alzheimer's markers and increases life span in SAMP8

Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR. In this study, we examined the role of dietary resveratrol in SAMP8 mice, a model of age-related AD. We found that resveratrol supplements increased mean life expectancy and maximal life span in SAMP8 and in their control, the related strain SAMR1. In addition, we examined the resveratrol-mediated neuroprotective effects on several specific hallmarks of AD. We found that long-term dietary resveratrol activates AMPK pathways and pro-survival routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a neuroprotective role, decreasing the amyloid burden and reducing tau hyperphosphorylation.