Turning principles into practice in Alzheimer's disease.

The prevalence of dementia is reaching epidemic proportions globally, but there remain a number of issues that prevent people with dementia, their families and caregivers, from taking control of their condition. In 2008, Alzheimer's Disease International (ADI) launched a Global Alzheimer's Disease Charter, which comprises six principles that underscore the urgency for a more ambitious approach to diagnosis, treatment and care. This review highlights some of the most important aspects and challenges of dementia diagnosis and treatment. These issues are reviewed in light of the six principles of the recent ADI Charter: promoting dementia awareness and understanding; respecting human rights; recognizing the key role of families and caregivers; providing access to health and social care; stressing the importance of optimal diagnosis and treatment; and preventing dementia through improvements in public health. The authors continue to hope that, one day, a cure for Alzheimer's disease will be found. Meanwhile, healthcare professionals need to unite in rising to the challenge of managing all cases of dementia, using the tools available to us now to work toward improved patient care.

Two polymorphisms of presenilin-2 gene (PSEN2) 5' regulatory region are not associated with Alzheimer's disease (AD) in the Polish population.

Presenilin 2 gene (PSEN2) is one of the causative genes for familial Alzheimer's disease. A delA polymorphism located in PSEN2 promoter was proposed to be a risk factor for early-onset AD. We examined association between AD and PSEN2 polymorphisms located in two 5'UTR regions in group of 217 late-onset AD patients, 109 mild cognitive impairment patients, and 225 non-demented control subjects. No significant differences for genotype and allele distributions of a delA and a novel insAC polymorphisms in the studied groups as compared to controls were observed. Univariate and multivariate risk estimation shows that neither delA, insAC alleles nor the genotypes are risk factors for AD. No significant interaction between the APOE4 and PSEN2 polymorphisms was found. A bioinformatic analysis showed that delA polymorphism influences binding sites of transcription factors involved in the cellular processes related to AD. The rare variants identified in exon 3 of the PSEN2 could have a potential influence on PSEN2 transcript splicing.

Neurocognition of centenarians: neuropsychological study of élite centenarians.

OBJECTIVE: The aim of this study was to evaluate the cognitive state of highly selected Polish centenarians and analyze the mechanisms of their functioning. METHODS: The selected centenarian group (10 persons) and a reference group (20 persons) who started aging (65 years) were examined with a sensitive set of neuropsychological tests and tasks in clinical-experimental assessment. RESULTS: As expected, the centenarians' cognitive functions were different from those of the subjects who started aging, however, not in all aspects. For instance, the former scored significantly lower in the area of linguistic functions but the ability to plan and controlled perform complex visuospatial task with use of simultaneous and sequential strategies was preserved despite unfavorable symptoms of natural aging such as permanence attention as well as prolonged action time. CONCLUSIONS: The results suggest that the studied centenarians show a dominant right-hemispheric pattern functioning not only in relation to perception, but also to planning and executing complex activities. The study and description of preserved neurocognition of centenarians was possible due to introducing a special procedure sensitive to the preserved functions.

The rate of conversion of mild cognitive impairment to dementia: predictive role of depression.

BACKGROUND: Mild cognitive impairment (MCI) is a condition referring to the persons with cognitive deficits measurable in some form or another, but not meeting criteria for dementia, and who have an increased risk of becoming demented. OBJECTIVE: To establish the rate of progression to dementia in MCI, to investigate the risk of conversion for amnestic vs multiple-domains subtypes, and to identify the predictors of progression. METHODS: MCI (n = 105) individuals enrolled in a longitudinal study received annual clinical and psychometric examinations for up to a mean of 3 years. The diagnosis of MCI according to Mayo Clinic Petersen's Criteria was conducted by a panel of specialists. RESULTS: After 3 years of follow-up, 23 of 105 subjects with MCI were diagnosed with dementia. 40 showed cognitive decline not dementia, 34 were stable and showed no cognitive decline or improvement, while eight showed cognitive improvement. CONCLUSIONS: We conclude that conversion rate from MCI to DSM-IIIR dementia was 21.9% over a period of 3 years. The occurrence of depressive symptoms may constitute a predictor for those who are more likely to progress to dementia. The risk of conversion to dementia was higher among the subjects with an evidence of impairment extending beyond memory than with those who suffered only from memory deficits, and the subjects who converted to dementia in this subtype had significantly higher baseline plasma total homocysteine levels than non-converters.

Prevalence of major and minor depression in elderly persons with mild cognitive impairment--MADRS factor analysis.

OBJECTIVE: The aim of the study was to detect the prevalence of depressive syndromes and symptoms in the sample of elderly persons with Mild Cognitive Impairment (MCI), and to analyse Montgomery-Asberg Depression Rating (MADRS) item scores. METHOD: The subjects of the study were 102 consecutive out-patients with MCI. All subjects were assessed by an experienced psychiatrist and MADRS was applied. Major and minor depressive episodes were defined according to DSM-IV criteria. Factor analysis was used to analyse baseline MADRS item scores. RESULTS: Three patient groups emerged according to the depressive symptoms distribution and severity scores basis: those with major depression constituted 19.6% (n = 20), with minor depression 26.5% (n = 27), and with very few depressive symptoms 53.9% (n = 55). Three interpretable MADRS factors were identified, using the factor analysis with Varimax rotation: the first consisting of apparent and reported sadness, inability to feel, pessimistic thoughts, the second consisting of inner tension, reduced sleep, reduced appetite, suicidal thoughts, and the third with concentration difficulties and lassitude. CONCLUSIONS: It was concluded that both major and minor depression is common in MCI. Three MADRS factors were identified and labelled as anhedonia-pessimism, anxiety-vegetative, and cognitive-inhibition.

Homocysteine, apolipoproteine E and methylenetetrahydrofolate reductase in Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Alzheimer's disease (AD) is the most common dementia disorder in elderly people. Currently, the only known genetic factor associated with the development of sporadic AD is the apolipoprotein E (ApoE) 4 allele. There is a need to identify other environmental and genetic risk factors that could modulate the risk of developing sporadic AD. OBJECTIVE: To analyse the correlation between the ApoE and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma homocysteine levels and vitamins (B(12) and folic acid) concentrations in serum from patients with AD and mild cognitive impairment (MCI) as compared with control group. METHODS: The study was carried out in 99 AD patients, 98 subjects with MCI and 100 healthy subjects. Diagnosis of probable AD was made according to the NINCDS-ADRDA and DSM-IV criteria. The following factors were analysed: age, gender, duration of disease, concentration of plasma total homocysteine, folic acid and vitamin B(12) in the serum and the polymorphism of MTHRF and ApoE genes. The results obtained were analysed by multivariate analysis of regression. RESULTS: We found that plasma total homocysteine is increased in AD patients (p < 0.0001) and depended on the MTHFR T/T genotype in the presence of low folate levels (p < 0.05). The increased frequency of ApoE4 allele in the AD population was independent of homocysteine, folic acid and vitamin B(12) levels and MTHFR status. CONCLUSIONS: We conclude that the concentration of plasma total homocysteine is increased in AD patients. This may be associated with the T/T genotype in the MTHFR gene; however, the distribution of the MTHRF C677T polymorphism in the Polish population does not differ in AD and controls.

Behavioural pathology in Alzheimer's disease with special reference to apolipoprotein E genotype.

The aim of this study was to define the co-occurrence of behavioural symptoms and Alzheimer's disease (AD) in relation to apolipoprotein E (APOE) genotype. Probable AD patients from the Alzheimer's Day Clinic (n = 139) were assessed with the 'Behavioural Pathology in Alzheimer's Disease' rating scale, and their APOE genotype was determined. This study demonstrated no relationship between presence of the APOE epsilon4 allele and any of the behavioural symptoms assessed, including delusions, hallucinations, depression, activity disturbances, aggressiveness and anxiety. Activity disturbances, delusions, hallucinations and aggressiveness paralleled the severity of AD, increasing in frequency with the severity of the dementia. The prevalence of delusions, hallucinations, aggressiveness and depression were found to be associated with lower levels of education.

[Frequency and intensity of behavioral and psychological symptoms in the course of Alzheimer's disease]. / Czestosc oraz intensywnosc wystepowania zaburzen psychicznych i zachowania w otepieniu o róznym nasileniu w przebiegu choroby Alzheimera.

The aim of the study was: 1) to estimate the occurrence and intensity of some psychopathological symptoms in the course of Alzheimer's disease, and 2) to examine whether the occurrence of behavioral and psychological symptoms increases with the deepening of dementia process among persons with Alzheimer's disease living in their homes with outpatient treatment. The study was conducted among 94 persons (38 men and 56 women ageing from 52 to 86 years (x = 72.4 +/- 6.9), with education: from 2 to 17 years (x = 11.2 +/- 3.7). Three subgroups were selected for study with regard to the intensity of dementia process, estimated according to Clinical Dementia Rating (CDR): very mild (n = 16, x = 71.4 +/- 6.7), mild (n = 43, x = 72.6 +/- 7.9), moderate (n = 35, x = 72.5 +/- 6.9). Subjects in group II and III fulfill diagnostic criteria of dementia according to ICD-10, DSM IV and criteria of probable AD according to NINCDS-ADRDA. In the estimation of occurrence of behavioral and psychological disturbances: Alzheimer's Disease Assessment Scale--non-cognitive behavior (ADAS-non-cog) and subscale "Change in Personality, Interests, Drive" of Blessed Dementia Scale were used. The results have shown that with the progress of dementia process, the occurrence of the following psychopathological symptoms such as: hallucinations, intensive motor activity, purposeless hyperactivity, pacing, rigidity increases and there is a relinquishment of hobbies. In addition, regardless of the stage of dementia, such behaviors as: apathy, depression, tearfullness, impaired emotional control and disturbances of appetite were observed relatively frequently.

[Mild cognitive impairment]. / Lagodne zaburzenia poznawcze.

Mild Cognitive Impairment (MCI) is a clinical syndrome (with well-established diagnostic criteria) that carries a high risk of the patient developing dementia, which means that it requires early detection, diagnosis and treatment to alleviate suffering and to attempt to reduce the resulting the burden.

[Prevalence of dementia syndromes]. / Rozpowszechnienie zespolów otepiennych.

A survey is presented of epidemiological data on the prevalence of dementia syndromes. Most studies have demonstrated that the prevalence index of dementia is doubled after the age of 60 years at intervals of 5.1 years. The data on Alzheimer's disease point out that its prevalence after the age of 65 years is between 1.9% and 5.8%. In the study of the population of the Mokotów City District of Warsaw aged 65-84 years the prevalence of dementia was 5.7%.

[The prevalence of dementia in old age]. / Rozpowszechnienie zespolów otepiennych w podeszlym wieku.

The risk of manifestation of dementia increases as the population grows older. The prevalence of dementia increases from 0.7% in age group 60-64 years to 38.8% in age group 90-94 years. Over 60, the prevalence rate doubles every 5.1 years. The most common types of dementia are Alzheimer's dementia and vascular dementia.

[The prevalence of dementia in the population of the Warsaw district of Mokotów from 65 to 84 years of age]. / Rozpowszechnienie zespolów otepiennych wsród mieszkanców warszawskiej dzielnicy Mokotów w wieku 65-84 lat.

The aim of the two-phase population based study was to estimate the prevalence of dementia. Among the population aged 65-84 years of the Warsaw district Mokotów, the stratified sample consisted of 1,000 persons taken randomly. The first-screening phase (MMSE) was conducted by raters among 893 persons. 92 subjects with disturbances of cognitive functions were qualified to the second-diagnostic phase and 89 were given a diagnostic examination with the Cambridge Mental Disorders of the Elderly Examination. The following age-specific prevalences of dementia were found in the age-groups 65-69, 70-74, 75-79, 80-84: 1.9, 5.8, 8.6 and 16.5% respectively. Rates for vascular dementia (2.7) were higher than those for dementia of the Alzheimer's type (2.3), mixed dementia (0.5), and secondary dementia (0.2%). In the younger subgroups (65-74 y), vascular dementia was the most frequent and in the older subgroups (75-84 y) the most frequent was Alzheimer's type. The rates of dementia were quite similar to those found in other European studies.

[Usefulness of CAMDEX test in the analysis of clinical picture of dementia]. / Przydatnosc testu CAMDEX w analizie obrazu klinicznego zespolów otepiennych.

Mild to moderate dementia fulfilling ICD-10 criteria and with MMSE score below 24 was analyzed in a sample of 46 randomly chosen elderly people. Selected scales derived from Polish version of CAMDEX and its cognitive section (CAMCOG) were used for assessment of clinical picture. Psychopathological symptoms, e.g., depression were frequent, especially in female group. According to the results of multivariate analyses of CAMCOG subscales, the most frequent symptoms in mild dementia were: the impairment of recent memory, abstract thinking, and praxis (p < 0.001).

[Prevalence of the dementia syndrome among elderly people in an urban area. A pilot study]. / Rozpowszechnienie zespolów otepiennych w populacji wielkomiejskiej--badanie pilotazowe.

Data was collected from a group of 100 randomly selected subjects from a city population above the age of 65 years. The aim of the research was to prove the reliability and validity of the research tools: the Folstein's MMSE and the Blessed's IMC. Thirty subjects were eliminated from the sample the remaining 70 were grouped according to gender for further analysis. The intergroup correlation indicated a high reliability of both tests. The hypothesis about the normal distribution of both groups was supported. In eleven subjects the results indicated the existence of a dementia syndrome f not great severity.