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PO2. Prevention

Detailed programme, abstracts and presentations

PO2.2. Dissociative amnesia and dementia: Is there a link?

Staniloiu Angelica, Markowitsch Hans J.

Despite suggestions that chronic stress is involved in the pathogeny of dementias, no systematic studies investigated the possibility of a link between dissociative amnesic conditions and neurodegenerative dementias. In dissociative (psychogenic) amnesia, we and other researchers visualised functional imaging changes in brain areas that are agreed upon to exert crucial roles in episodic-autobiographical memory processing. Moreover, we and other authors identified a chronic course of the memory impairments in a substantial number of patients with dissociative (psychogenic) amnesic conditions. In some chronic cases of dissociative amnesia we noted a fairly stable course, while in other cases we observed a progressive global cognitive deterioration. Several factors may account for the under-investigation of a possible connection between dissociative amnesia and subsequent development of dementia, as we will outline below. Dissociative amnesic conditions continue to be under-diagnosed and even debated with respect to their pathogeny and diagnostic legitimacy. Systematic long-term longitudinal follow-up involving repeated neuropsychological testing and functional and brain imaging is missing in a substantial number of patients with these conditions. Most cases of dissociative amnesia and fugue are diagnosed in the third to fourth decade of life. Partly due to a paucity of evidence-based treatments for these conditions, a substantial number of patients with these conditions drops out from treatment and ceases contact with psychiatric or neurological or memory rehabilitation facilities. There may also be an underestimation of newly occurring or persisting dissociative amnesic conditions in elderly, due to a tendency in medical and psychiatric field to attribute cognitive symptoms in older patients to medical or more common psychiatric conditions. The search for a link between dissociative amnesic conditions and dementia is without doubt a potentially interesting topic for future research, which should take into consideration multiple variables, such as the age at the onset of trauma, gender, the recurrence, type and severity of trauma, the presence of psychiatric and medical co-morbidity (mild traumatic brain injury, obesity, cardiovascular status), pre-morbid personality characteristics (e.g. neuroticism), genetic polymorphisms, educational and occupational attainment, cognitive reserve and the progression of metabolic and microstructural brain changes.

PO2.5. Angiotensin type 1a receptor deficiency ameliorates amyloid plaque formation

Zou Kun, Liu Junjun, Liu Shuyu, Matsumoto Yukino, Tanabe Chiaki, Maeda Tomoji, Michikawa Makoto, Komano Hiroto

Alzheimer’s disease is characterised by cerebral accumulation of neurotoxic amyloid-β protein (Aβ). Midlife hypertension is a risk factor for the onset of Alzheimer’s disease; however, it is largely unknown whether blood pressure regulation is associated with Aβ production or brain amyloid plaque formation. Activation of angiotensin type Ia receptor (AT1a) plays the central role in renin-angiotensin system to elevate blood pressure in response to increased sympathetic nervous system activity, dehydration or hemorrhage. Here we show that AT1a deficiency significantly lowers amyloid plaque formation in an Alzheimer’s disease mouse model. We found that AT1a deficiency leads to decreased endocleavage of presenilin-1, which is essential for γ-secretase complex formation and Aβ production. Furthermore, we found that angiotensin II can enhance presenilin-1 endocleavage and γ-secretase complex formation and then promote Aβ production. This enhancement involved activation of PI3 kinase and phosphorylation of Akt. Our results suggest that environmental stresses or life style factors that stimulate AT1a to elevate blood pressure might enhance Aβ production and amyloid plaque accumulation, and contribute to the pathogenesis of Alzheimer’s disease.

PO2.6. Positive lysosomal modulator enhances clearance of toxic proteins in both Alzheimer’s and Parkinson’s disease mouse models

Bahr Ben A., Ikonne Uzoma S.

Lysosomes are the cellular components involved in removing misfolded/aggregating proteins, but with aging lysosomes become less effective. Age-related protein accumulation disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), and other dementias, are suspected to involve imbalances between protein production and protein clearance. Strategies targeting the lysosomal system to enhance protein clearance are prime candidates for drug discovery efforts to reduce protein accumulation pathology and prevent the onset of dementia. The positive lysosomal modulator Z-Phe-Ala-diazomethylketone (PADK) enhances the trafficking and maturation of the lysosomal enzyme cathepsin B, thus to elicit protective clearance of toxic proteins in the brain. A key pathogenic factor in AD is the amyloid β peptide (Aβ), and cathepsin B was discovered to degrade Aβ42 via C-terminal truncation and was effective at reducing higher orders of Aβ assemblies (Mueller-Steiner et al. 2006, Neuron51:703; Butler et al. 2011, PLoS One6:e20501). Treating APPSwInd and APPswe/PS1ΔE9 mouse models of AD with PADK (ip, 18 mg/kg/d for 9-14 days) led to significant reductions in Aβ42 peptide in hippocampus, cortex, and other brain regions. Similarly, in the case of the A53T α-synuclein mutant mouse model of PD, the administration of PADK led to reduced levels of α-synuclein in TX-100 extracts of spinal cord, brainstem, midbrain, as well as hippocampus. In both the AD and PD mouse models, PADK-mediated protein clearance was found to be associated with improved synaptic integrity. Synaptic pathology has long been considered the key event in age-related disorders that: 1) leads to cognitive deficits and 2) contributes to early, gradual changes that constitute risk factors for dementia. In the disease models, PADK treatment improved the levels of synaptic proteins well known for being reduced with aging and in association with protein accumulation pathology. The evidence of synaptic recovery through lysosomal enhancement indicates a link between lysosomal capacity and the maintenance of brain function, providing a unique pathway to attenuate cognitive impairment and delay the onset of dementia. The results support a plausible strategy to promote cathepsin B-mediated protein clearance for a disease-modifying treatment of early and progressive dementia that often involves multi-proteinopathy.

PO2.8. Does physical activity reduce burden in carers of people with dementia: A systematic review and meta-analysis

Orgeta Vasiliki, Miranda-Castillo Claudia

Objective: Physical exercise has been associated with a range of positive outcomes including improvements in psychological well-being. The aim of the present study was to review current evidence on the psychological benefits of physical activity interventions for carers of people with dementia.   

Method: Systematic review. We searched electronic databases and key articles of studies that have evaluated the benefits of physical activity interventions in improving psychological well-being in carers of people with dementia. Relevant papers were scored according to established criteria set by the Cochrane Group. Selection criteria for studies were a Randomised Controlled Design (RCT), and comparing physical activity with a control group receiving no specific physical activity intervention. Two reviewers worked independently to select trials, extract data, and assess risk of bias.

Results: A total of 4 RCTs met the inclusion criteria. Studies evaluated home-based supervised physical activity, of low to moderate intensity which included either aerobic exercise, or endurance training. Pooled data showed that physical activity reduced subjective caregiver burden [standardised mean difference (MD) 0.43; 95% confidence interval (CI) -0.81 to -0.04], in comparison to a control group of usual care. 

Conclusion: There is evidence from two RCTs that physical activity reduces subjective caregiver burden for carers of people with dementia. Although statistically significant, the observed benefits should be interpreted with caution as the studies conducted so far have limitations. Further high quality trials are needed for evaluating the benefits of physical activity in improving psychological well-being in carers of people with dementia.

PO2.9. Emotional and motivational aspects of coping with dementia in parents or partners

de Andrés-Jiménez Elena, Limiñana-Gras Rosa María

The aim of this study is to investigate the relationship of expression and control of anger with the motivational dimensions of personality and psychological adjustment, depending on the kinship.

Methods: 107 carers of people with dementia from different associations and day-care centers from Southern Spain participated kindly in this study. Disecting the sample according to the relationship with the person with dementia, there are 74 offspring (age: 48.11 years, SD = 9.09) and 33 partners (age: 68.76 years, SD = 6.2). These carers responded to the Millon Index of Personality Styles - MIPS, which measures personality styles organised in three fields of action: Motivating Styles, Thinking Styles and Behaviour Styles, also responded to the State-trait Anger Expression Inventory - STAXI-2 which evaluates the experience and expression of anger.

Results: The results show, in offspring carers, direct significant relationship between control of anger and motivational styles Pleasure-Enhancing and Actively Modifying of MIPS; and between the expression of anger and the Pain-Avoiding and Passively Accommodating. On the other hand, people who care for your partner with dementia, show significant direct relationships between control of anger and Pleasure-Enhancing; and between the expression of anger and the Pain-Avoiding and Passively Accommodating. Also, the results obtained in control of anger, show a significant positive relationship with increased psychological adjustment in these carers.

Conclusions: The results of this study allow us to associate particular emotional anger management with determining motivational factors regarding to the psychological adaptation to the situation of caring for a relative with dementia. The findings provide valuable information on anger management for carers of people with dementia, which can begin included in plans for both prevention and intervention to prevent carer burnout.

PO2.10. Ilion epidemic study: A new screening test for cognitive deficits

Solias Andreas, Politis Antonis, Laoutari Sophia, Degleris Nikos

Acknowlegments to Professor Constantine Lyketsos John’s Hopkins Medical School Baltimore USA for his mentorship in the present study 

The worldwide increase life expectancy makes more aged people vulnerable to some form of dementia. Many elders facing memory problems avoid seeking help in early stages. The objective of this study as to evaluate a new tool easy that can be administered by laypeople (e.g. senior center staff or caregivers) screening for cognitive decline.

Method: This is an ongoing population based study in an urban area in Greece (municipality of Ilion). A total of 331 community dwellers (55-85+years old) attending senior centers participated voluntarily in the study and were assessed with Santa Sophia Test (SST), as well as the MMSE, 3MS, and CDT tests. SST was developed so that it committed to be administered by laypeople and briefly assesses attention, concentration, memory, orientation, as well as abstract and critical thought. The test administration takes totally 6 minutes. At first we dictate the whole text (approximately 1’30”). After 5 min we demand the elder to fulfill the blank spaces (20 words in 4 min) of the story.

Results: Based on a 3MS score of less than 82, 46.3% of participants facing memory problems. The corresponding percentage of individuals with impaired scores on the SST was 45%(<median 16). The majority did not have significant difficulties in daily living activities or social interaction, suggesting that they did not have dementia.

By estimating Pearson product moment, statistically significant correlations were found between MMSE-SST (r=0.464, p=0.000) 3MS-SST (r=0.487, p=0.000) CDT-SST (r=0.372, p=0.000). Receiver operating characteristic (ROC) estimation of the SST’s screening value with other measures as gold standards, yielded sensitivity 80.8%, specificity 59.3% and AUC of 0.739 vs. the MMSE and sensitivity 70.3%, specificity 72.3% and AUC of  0.761 vs. the 3MS and sensitivity 73.6%, specificity 57.3% and AUC of 0.733 vs. the CDT.

Conclusions: SST represents a useful layperson screening tool that can assist in detecting cognitive deficits among the aged, including in individuals without dementia.

PO2.11. Α rare presentation of an a-synuclein A53T positive sibling of new Greek family with severe cortical atrophy and elevated total-tau protein

Bougea Anastasia, Paraskevas Georgios, Kapaki Elisabeth

Background: An A53T mutation of the α-synuclein gene (SNCA)is characterised by an early-onset establishment of the full-blown clinical picture of parkinsonism with rigidity, bradykinesia, L-dopa responsiveness and occasionally cognitive decline. We describe a new sibling of Greek kindred who carried an A53T mutation and predominant dementia.

Case presentation: The propositus a 31-year-old man from Patras, Greece presented with a year history of executive dysfunction, resting tremor, progressive gait instability with falls, mild short-term memory problems, and urinary urgency . For the last two months he has been treated with levodopa with moderate improvement. On examination he was alert and exhibited hypomimia, hypophonia, cogwheel rigidity, hyperactive deep tendon reflexes with flexor plantar responses and eye lid opening apraxia. His gait was shuffled with short steps and lack of recovery on pull test. Both vibration and position senses were preserved. Neuropsychological assessment revealed a mini-mental state examination (MMSE) score of 18.Brain MRI identified a pattern of global brain atrophy. DaTSCAN revealed significantly reduced uptake of dopamine transporter in the right caudate. Cerebrospinal fluid analysis showed elevated total-tau protein while CSF β-amyloid(1-42) and phospho-tau protein were in the normal reference range. An α-synuclein A53T mutation was detected in the SNCA gene.

Conclusion: Epidemiological data on A53T positive patients are limited so far to fewer than 30 multigenerational PD families worldwide. Previous studies have showed that MRI scan was generally normal and only in one report a mild cerebral atrophy was described in a patient in older age. Information regarding CSF biomarkers are lacking. To our knowledge this is the first study that reports elevated CSF total-tau protein levels in an A53T- positive affected member.

PO2.12. Meeting the needs of rural caregivers: The development and evaluation of an Alzheimer's care-giving series

Chankrachang Siwaporn, Tongsong Worawan, Tamprawate Surat,  Nadsasarn Angkana, Singhanetr Sasiwimol

Care giving for demented elderly is challenging. On a daily basis, managing the patients requires balancing illness needs with day-to-day tasks. Caregivers generally begin care giving without any information or training. To meet the needs of caregivers of demented elderly patients, we developed a first 12 week caregiver series training program for caregivers since March 2009.Twenty trainees entered the program. The evaluation of the training course was excellent except the period of training. They mentioned that 12 weeks  was too long. So we then implemented the second training course and adjusted the duration to be  5 weeks. First four week was for the class room study and one week was for the field work. From 31 January to end of February 2012 (5 weeks) 35 participants were included. After completion the training the evaluation from the participants showed that they gained more knowledge about care giving and felt more comfortable in their care giving roles. After 6 months we then re-evaluate the training again. More than 50% of the trained caregivers who had gone to work have found that 5 week duration was not enough. They need longer period of field training. The optimum time for training course  is still to be determined.

Conclusion: After two trials of training course for caregivers the optimum time for training couse is still inconclusive. So the third training course will be implemented again in June 2013 we then extend the  course duration to be 10 weeks: 4 weeks for theory and 6 weeks for field work.



Last Updated: Friday 30 August 2013


  • Acknowledgements

    The 23rd Alzheimer Europe Conference in St. Julian's, Malta received funding from the European Union, in the framework of the Health Programme. Alzheimer Europe and the Malta Dementia Society gratefully acknowledge the additional support provided by foundations and companies.
  • European Union