Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.

We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.

The use of EEG in Alzheimer's disease, with and without scopolamine - a pilot study.

OBJECTIVE: To use multivariate statistical analysis of EEG data in order to separate EEGs of patients with Alzheimer's disease (AD) from controls. A group of individuals with mild cognitive impairment (MCI) was evaluated using the same methodology. Additionally, the effects of scopolamine on this separation are studied. METHODS: Statistical pattern recognition (SPR) is used in conjunction with information extracted from EEGs before and after administration of scopolamine. RESULTS: There was complete separation of the AD group and controls before administration of scopolamine. The separation increased after scopolamine had been given. Of the 10 MCI individuals, five seemed to belong to the AD group. Three of those progressed to AD within 1 year and one after 3 years. CONCLUSIONS: Using SPR on EEG recordings it is possible to separate AD from controls. This separation can be increased by the use of scopolamine but the medication is not a prerequisite for classification. The results indicate that SPR is useful for predicting progress of MCI to AD. SIGNIFICANCE: EEG registration is a simple and noninvasive method. If these results are confirmed in other studies, this method could be more widely applied than the highly specialized methods used today in detection of early AD.

Music therapy in moderate and severe dementia of Alzheimer's type: a case-control study.

BACKGROUND: Music therapy is a potential non-pharmacological treatment for the behavioral and psychological symptoms of dementia, but although some studies have found it to be helpful, most are small and uncontrolled. METHODS: This case-control study was carried out by qualified music therapists in two nursing homes and two psychogeriatric wards. The participants were 38 patients with moderate or severe Alzheimer's disease (AD) assigned randomly to a music therapy group and a control group. RESULTS: The study showed a significant reduction in activity disturbances in the music therapy group during a 6-week period measured with the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). There was also a significant reduction in the sum of scores of activity disturbances, aggressiveness and anxiety. Other symptoms rated by subscales of the BEHAVE-AD did not decrease significantly. Four weeks later the effects had mostly disappeared. CONCLUSIONS: Music therapy is a safe and effective method for treating agitation and anxiety in moderately severe and severe AD. This is in line with the results of some non-controlled studies on music therapy in dementia.

Copper, ceruloplasmin and superoxide dismutase (SOD1) in patients with Down's syndrome.

The aim of this study was primarily to investigate whether similar signs of copper dyshomeostasis occur in dementia with age in Down's syndrome as previously found in Alzheimer's disease. Copper was accordingly determined in plasma, ceruloplasmin concentration in serum, ceruloplasmin oxidative activity and ceruloplasmin specific oxidative activity (activity related to mass) in serum, and superoxide dismutase (SOD1) in erythrocytes in 35 (27 males, 8 females) 18-53 years old (average 37 years) patients with Down's syndrome (Down's patients) and their age- and gender-matched controls. SOD1 activity was on an average almost 50% higher in the patients than in their controls but the evidence of a causal relationship between increased SOD1 activity and Down's syndrome appears at best equivocal. Copper and ceruloplasmin levels and ceruloplasmin activities were similar in the patients and their controls. Ceruloplasmin and copper levels increased significantly with age in the patients but not in the controls. Ceruloplasmin activities or SOD1 activity did not change significantly with age, neither in the patients nor in the controls as whole groups. When SOD1 activity and ceruloplasmin activities of the oldest in the patients group (40 years or older) were compared with those of the younger patients, respectively, SOD1 activity and specific oxidative activity, but not ceruloplasmin oxidative activity were found to decrease significantly with age. The results thus suggest that development of dementia in Down's patients with age is paralleled with decrease in SOD1 activity and specific oxidative activity but not with decrease in ceruloplasmin oxidative activity itself as was also found in Alzheimer's patients.

Copper, ceruloplasmin and superoxide dismutase (SOD) in amyotrophic lateral sclerosis.

In two previous studies we found copper dyshomeostasis in patients with Alzheimer's disease and in patients with Parkinson's disease. In this study, the levels of copper in plasma, of ceruloplasmin in serum, ceruloplasmin oxidative activity, ceruloplasmin specific oxidative activity (activity related to mass) as well as superoxide dismutase (SOD) activity in erythrocytes have been determined in 14 patients with amyotrophic lateral sclerosis and their healthy age- and gender-matched controls. Three of the patients had a familial form of the disease or were suspected of having it. The mean values of all parameters were found not to differ significantly between the patients and their controls (Student's t-test; P>0.05). By testing the equality of variances (F distribution) we found that the variances of individual results for ceruloplasmin specific oxidative activity and SOD activity differed significantly between the patients group and the controls group (P= 0.021 and P=0.003), but the individual results of these two activities were not correlated (P>0.05). We conclude that disturbances in ceruloplasmin specific oxidative activity and SOD activity could contribute to motor neurone death in amyotrophic lateral sclerosis, and since the two enzyme activities are not correlated it is uncertain which one is more closely related to the pathology of the disease.

Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease.

In a previous study we found copper dyshomeostasis in patients with Alzheimer's disease. In this study, levels of copper in plasma, of ceruloplasmin in serum and ceruloplasmin oxidative activity as well as superoxide dismutase (SOD) activity in erythrocytes were determined in 40 patients with Parkinson's disease and their healthy age- and gender-matched controls. Copper concentrations did not differ significantly in the two groups, whereas both ceruloplasmin concentrations and ceruloplasmin oxidative activity were significantly lower in the patients, also relative to ceruloplasmin mass. SOD activity was not significantly different in the two groups but decreased significantly with the duration of disease. The same was found for ceruloplasmin oxidative activity. Ceruloplasmin oxidative activity and SOD activity did not decrease with age. Levels of serum iron, serum ferritin and total iron binding capacity were determined in about 30 of the patients and an equal number of controls and were not found to differ. Transferrin levels were significantly lower in the patients than in their controls but, conversely, the transferrin saturation was significantly higher in the patients. The results indicate that patients with Alzheimer's disease and Parkinson's disease have defective ceruloplasmin and SOD activities in common and that these defects are not necessarily associated with major disturbances in iron homeostasis.

Copper, ceruloplasmin and superoxide dismutase in patients with Alzheimer's disease . a case-control study.

The copper-containing enzyme superoxide dismutase (SOD) is a key enzyme in suppressing the amounts of superoxide anion radicals. Ceruloplasmin, the copper-transporting protein in plasma, also possesses an important redox capacity. In this study the levels of copper and ceruloplasmin as well as SOD-activity and ceruloplasmin oxidative activity were analyzed in order to throw some light on possible defects in copper mechanisms in patients diagnosed with Alzheimer's disease (AD). The study included 44 patients with AD and their healthy age- and gender-matched controls. No difference of significance was seen when comparing the copper or ceruloplasmin concentration in plasma of AD patients to that of their paired controls. The SOD activity in red blood cells was significantly lower in the patients than in their controls (p = 0.019). The ceruloplasmin oxidative activity in plasma of Alzheimer's patients was greatly reduced as compared to that of age- and gender-matched controls and the difference was highly significant (p = 0.0005). Ceruloplasmin activity and SOD activity were not found to be intrinsically correlated. It was postulated that reduced oxidative activity of ceruloplasmin in plasma might be either a cause or a consequence of AD and that reduced SOD activity might further add to the oxidative disturbances in AD due to defective ceruloplasmin activity.

[Survival of patients with dementia in an Icelandic daycare center.].

OBJECTIVE: This study was undertaken to estimate the survival of patients with dementia and to evaluate change in prognosis over time. MATERIAL AND METHODS: Individuals attending a day care center for dementia in a 10 year period were followed until December 1st 1996 or until death. These individuals are quite repres notentative for demented patients living in this area. RESULTS: Of 180 individuals, 167 had either been diagnosed with Alzheimer's disease or multi infarct dementia. Ninety seven had died during follow up. Crude survival as well as relative survival was calculated with regards to the onset of symptoms of dementia. Patients with Alzheimer's disease seemed to live 40% shorter than age and gender matched individuals in the society. CONCLUSION: Dementia is correlated with a definite shortening of survival. Patients in this time period seem to live longer than patients diagnosed 10-15 years earlier but any comparison is hampered by different methods of diagnosis.

[Epidemiological study on cognitive abilities in the elderly in two separate rural areas in Iceland.].

OBJECTIVES: This study was undertaken to estimate the cognitive abilities in an elderly population in rural areas in Iceland and to get an idea of the prevalence of dementia. By examining inhabitants in two different areas it was further possible to detect any possible difference in these areas. MATERIAL AND METHODS: All persons aged 70 and over, living independently in the community and in institutions in two geographically separate areas were contacted. The areas were an agricultural (area A) and a fishing (area F) one. Four simple neuropsychological tests where used, the MMSE (Mini Mental State Examination), WAIS (Wechsler Adult Intelligence Scale)-Similarities, Trail making test A and Trail making test B. Two students in psychology and a teacher were trained in applying the tests but the results were scored and interpreted by the authors. RESULTS: In area A, 280 of 353 (79.3%) participated and in area F, 190 of 238 (79.8%). Participation was thus similar in both areas. There was a highly significant difference in all the tests with p<0.01 in Trail making test B but p<0.001 in the other three tests. In all the tests the results were better among the population in area A. The prevalence of dementia as estimated by the MMSE showed a prevalence of 14.4% in area A and 35.7% in area F. CONCLUSION: A significant difference in cognitive abilities was found between the elderly inhabitants of two separate rural areas in Iceland. There is substantial evidence to suggest that this difference is real but it is however not clear if the prevalence of dementia is higher in this study than in others. It is postulated that the difference found is due to cultural differences.

Geriatric work-up in the Nordic countries. The Nordic approach to comprehensive geriatric assessment.

A group established by the Nordic professors of geriatrics has developed a position document presenting a shared and updated review of geriatric work-up as a way of comprehensive geriatric assessment in the Nordic countries. The main intention is that the document will serve as support and help for the clinician concerned with hospital based geriatric medicine. It may also be useful for quality control and teaching. Not least, it may be useful for health professionals other than geriatricians. To some extent, the position of geriatric medicine in the Nordic countries varies between the countries. However, the background for developing a Nordic version of geriatric work-up is shared attitudes and principally the same organization of the health care system, and collaboration within geriatrics for many years. Several trials on comprehensive geriatric assessment and management performed in different settings have shown favourable outcomes. Results from controlled Nordic trials are compiled and summaries of meta-analyses are presented. The concept of Nordic geriatric work-up is based on a model defining health and disease in old age as dimensions of pathology, impairments, functional limitations, and disability, all being modified by extra- and intraindividual factors. Handicap is defined as the disability gap. Different health professionals have varying responsibilities in the geriatric team-work, but all should be dedicated to establish common goals. The geriatric work-up is presented with success factors and barriers, stating important differences between multidisciplinary and interdisciplinary processes. Checklists and assessment scales may be very useful when performing a geriatric work-up, but they should be used with caution. Specific scales covering different functional areas of the geriatric patient are recommended for clinical practice. Such scales must be valid, reliable, acceptable to the patient, responsive to change, and should be in an appropriate format, as well as easy to administer. Prior to the use among geriatric teams in the Nordic countries the scales should be translated into all the Nordic languages, and the translated versions should ideally have been subjected to validity and reliability testing. However, so far no scale meets these demands regarding all the five Nordic languages.

The effects of nicotine in dermal plaster on cognitive functions in patients with Alzheimer's disease.

Eighteen patients with probable Alzheimer's disease (NINCDS/ADRDA criteria) participated in a placebo-controlled, double-blind study, with a crossover design. The patients had mild or moderate dementia (MMSE = 20.3 +/- 4.6, range 12-28). The trial consisted of two 4-week periods with a 2-week washout period in between. Nicotine was given in the form of dermal plasters. Most of the patients tolerated the highest doses of 21 mg nicotine/24 h, but some received 14 mg/24 h. The effect was monitored with tests of short-term memory, verbal fluency, attention and psychomotor speed. Nicotine was also determined in the blood. Short-term memory improved significantly after 4 weeks of treatment, both on nicotine and placebo (p < 0.05/p < 0.01). The results of our study thus do not indicate that nicotine applied in the form of dermal plasters is of any significance in the treatment of memory deficits in patient with Alzheimer's disease.

A progression in the neuropsychological decline of Icelandic patients with probable or possible dementia of the Alzheimer's type: a longitudinal study.

To investigate the nature and rate of cognitive decline in dementia of the Alzheimer's type (DAT), 44 patients with probable or possible DAT (mean age 73.9, range 59-87 years) were given a comprehensive neuropsychological assessment. Twenty-five patients were retested 6 months later, and 11 were tested for the third time another 6 months later. Some tests of mental flexibility and double conceptual tracking ability were beyond the capabilities of the patients, and were left out of the statistical analysis because of floor effect. Poor initial performance on tests of attention, concentration, response speed, general cognitive ability, verbal memory, constructional skills, and perceptual closure ability resulted in nonsignificant changes over time (paired t tests). Tests of expressive speech, visuoperceptual functions and nonverbal memory, on the other hand, showed a significant deterioration over time. These findings indicate that when patients with DAT first receive medical attention, many neuropsychological functions are so severe impaired that there is little room for further decline. To describe the longitudinal course of cognitive decline in DAT, tests should be limited to those that assess the more resistant cerebral functions, and are more sensitive to progressive changes.

Study of restriction fragment length polymorphism in the cystatin C gene of elderly patients with dementia and aged Down's syndrome patients.

Using a full length cystatin C cDNA probe and the Alu I restriction enzyme a total of 33 patients with senile dementia, Alzheimer type and 31 Down's syndrome patients have been investigated for the presence of the 630 bp Alu I restriction fragment length polymorphism in the cystatin C gene detected in Icelandic patients with hereditary cystatin C amyloid angiopathy. Results showed that all the patients had normal cystatin C fragment length of 600 bp.

Outcome of patients with a nailed hip fracture requiring rehabilitation in a hospital for chronic care.

The rehabilitation outcome of seventy-eight consecutive patients with nailed hip fractures admitted to a hospital for chronic care from an orthopaedic department during 1977 through 1980 was followed for two years. They comprised only 13% of all hip fracture patients, the others being discharged to their own homes or old people's homes. Thirty-four of the admitted patients came originally from their own homes, 23 from old people's homes and the others from hospitals for chronic care. Each had been selected for long-term care by the orthopaedic surgeon and his staff as the likelihood of rehabilitation in his/her original habitat was considered poor. Because of an active rehabilitation at the hospital for chronic care, one-third of the surviving patients were discharged to their own homes or old people's homes within one year after the fracture. Most of these patients came originally from their own homes. Once discharged, the patients did not need to return to the hospital for chronic care.

Persistent water diuresis in renal amyloidosis. A case report.

A 67-year-old male with previous history of osteomyelitis presented with persistent thirst and polyuria. His urine remained hyposmolar to plasma after overnight fasting and administration of pitressin. Biopsy and postmortem examination revealed renal amyloidosis with involvement of many glomeruli and smaller vessels. Amyloid was also found in the medulla, particularly around the collecting tubules. It is suggested that amyloid interfered directly with diffusion of water through the walls of the collecting tubules.