Quality of Life in relation to neuropsychiatric symptoms in Alzheimer's disease: 5-year prospective ALSOVA cohort study.

OBJECTIVE: To examine the association between neuropsychiatric symptoms (NPS) with self- and caregiver-rated Quality of Life (QoL) for patients with Alzheimer's disease (AD) during a 5-year follow-up. METHODS: The ALSOVA 5-year follow-up study included, at baseline, 236 patients with either very mild (Clinical Dementia Rating Scale (CDR) 0.5), or mild (CDR 1) AD, together with their caregivers from three Finnish hospital districts. QoL was evaluated using patient self-reported, and caregiver-rated, QoL in AD (QoL-AD) scores. NPS were assessed using the Neuropsychiatric Inventory (NPI), and AD severity was evaluated using the CDR, with cognition tested by the mini-mental state examination. The performance of daily activities was assessed using the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. RESULTS: Over the 5-year follow-up period, patient self-reported QoL-AD scores did not change significantly (p = 0.245), despite increases in their NPS. However, caregiver-rated patient QoL-AD scores declined significantly (p ≤ 0.001), as total NPI scores increased during follow-up. No NPS at baseline, and only apathy at follow-up, correlated significantly (p = 0.007) with patient self-rated QoL-AD scores. Caregiver-rated patient QoL-AD scores correlated significantly with most NPS, especially (p ≤ 0.001) apathy, agitation, anxiety, irritability, depression, and delusions at baseline, and delusions, hallucinations, apathy, appetite disturbances, and anxiety during follow-up. CONCLUSIONS: Patient rated QoL-AD scores are an unreliable tool with which to evaluate the success of therapy for NPS. Instead, caregiver-rated scores for patients correlated well with NPI scores, and health care professionals in the clinic should preferentially use these. Copyright © 2017 John Wiley & Sons, Ltd.

Common and Rare Genetic Variants Associated With Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most devastating disorders. Despite the continuing increase of its incidence among aging populations, no effective cure has been developed mainly due to difficulties in early diagnosis of the disease before damaging of the brain, and the failure to explore its complex underlying molecular mechanisms. Recent technological advances in genome-wide association studies (GWAS) and high throughput next generation whole genome, and exome sequencing had deciphered many of AD-related loci, and discovered single nucleotide polymorphisms (SNPs) that are associated with altered AD molecular pathways. Highlighting altered molecular pathways linked to AD pathogenesis is crucial to identify novel diagnostic and therapeutic AD targets.

Self-Rated and Caregiver-Rated Quality of Life in Alzheimer Disease with a Focus on Evolving Patient Ability to Respond to Questionnaires: 5-Year Prospective ALSOVA Cohort Study.

OBJECTIVE: To examine and compare self-rated and caregiver-rated measures of quality of life (QoL) in relation to disease progression in patients with very mild or mild Alzheimer disease (AD) and at what disease stage patient's ability to respond to QoL questionnaires with or without assistance begins to diminish. METHODS: 236 patients with very mild or mild AD and their family caregivers from three Finnish hospital districts participated in this prospective, longitudinal study with 5 years of follow-up. Three patient-reported instruments were used to assess QoL (the generic 15D, the Quality of Life in Alzheimer Disease [QoL-AD] questionnaire, and a visual analogue scale) as well as one caregiver-rated assessment of patient QoL (QoL-AD). AD severity was evaluated with the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB). RESULTS: All self- and caregiver-rated QoL estimates correlated with AD severity. The self- and caregiver-rated QoL scores began to diverge even with very mild cognitive impairment after CDR-SOB reached 4, the value that corresponds with a Mini-Mental State Examination (MMSE) score of 25-30. Patients also began to need assistance in responding to questionnaires at very early stages of AD (CDR-SOB score: 4-6). Furthermore, their ability to respond to QoL questionnaires with or without assistance declined after CDR-SOB reached 11 points, a value that correlates with an early moderate stage of AD and MMSE score of 11-20. CONCLUSIONS: AD patients' self-rated QoL ratings are much more insensitive to disease progression than caregiver ratings.

Neuropsychiatric symptoms and quality of life in patients with very mild and mild Alzheimer's disease.

BACKGROUND: Neuropsychiatric symptoms (NPS) are common manifestations of Alzheimer' s disease (AD). OBJECTIVE: To examine the prevalence and significance of NPS in very mild and mild AD patients with emphasis on their influence on the well-being of the patients and their caregivers. METHODS: The participants were 240 patient-caregiver dyads who participated in a prospective, controlled rehabilitation study (ALSOVA). Three Quality of Life (QoL) instruments were used; generic 15D, disease-specific QoL-AD and Visual Analog Scale (VAS). The disease-specific QoL-AD was both self-rated and caregiver rated. Other scales used were Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), ADCS-ADL, Neuropsychiatric Inventory (NPI) and Beck Depression Inventory (BDI). RESULTS: NPS were present in 76.5% of patients with very mild AD (CDR 0.5) and in 84.9% of patients with mild to moderate AD (CDR 1). The most frequent symptoms were apathy, depression, irritability, and agitation. The strongest predictor of self-reported QoL-AD scores was depressive symptoms whereas functional decline and presence of NPS predicted poor caregiver ratings of patients' QoL. However, caregiver depression also influenced significantly their ratings. CONCLUSION: NPS are common even in the early stages of AD. NPS were significantly associated with caregiver assessment of the patient's QoL but not with patients' self-assessed QoL. Depression decreases QoL, but may remain unrecognized in AD patients, emphasizing the need for careful and structured assessment of NPS before deciding on the appropriate treatment.

[The treatment pathway of a memory disorder patient]. / Muistipotilaan hoitoketju.

The treatment of a memory disorder patient is multiprofessional teamwork requiring professional personnel specialized in memory disorders. The memory disorder clinic plays a central role especially at the diagnostic stage. Treatment should be carried out as local services and according to the needs of the patients. A memory coordinator is a central person in the monitoring and supporting of a memory patient and his/her close relatives within outpatient care. In long-term therapy, know-how in rehabilitation and palliative treatment are essential. Development of the treatment and service chain requires capable management, systematic planning, regular updating of guidelines and contracts as well as financial input.

Electroconvulsive therapy and biomarkers of neuronal injury and plasticity: Serum levels of neuron-specific enolase and S-100b protein.

Electroconvulsive therapy (ECT) is considered an effective and safe treatment in major depressive disorders. However, the possibility that it may induce cognitive adverse effects observed in selected patients has raised a concern that ECT may induce neuronal damage. The biomarkers of brain damage, neuron-specific enolase (NSE) and S-100b protein (S-100b), were measured in serum before and after ECT to determine whether this treatment induces neuronal injury or glial activation. ECT was administered to 10 patients with major depressive disorder. The serum samples were analyzed before (baseline) and after ECT at 1 h, 2 h, 6 h, 24 h and 48 h. The severity of depression was scored with the Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI) pre-to-post ECT. There were no statistically significant changes in the median concentrations of NSE or S-100b at various time points before or after ECT. However, there were substantial elevations in the levels of S-100b in four patients. High levels of S-100 at 2 and 6 h correlated with the response to the treatment. These results suggest that ECT does not produce neuronal injury. The transient increase in the levels of S-100b reflecting activation of glial cells may play a part in mediating the antidepressant effects of ECT.

[Update on current care guidelines. The diagnosis and medical treatment of memory disorders]. / Muistisairauksien diagnostiikka ja lääkehoito.

Any complaints from a patient about their memory should be examined. Diagnosis is based on international criteria. The basic evaluation consists of the medical history, clinical evaluation, cognitive tests and brain imaging, especially using MRI. When a diagnosis of Alzheimer's disease, AD with cerebrovascular disease or with Lewy Body disease, or Dementia associated with Parkinson's disease or LBD is made, evidence based medical therapy is indicated as part of comprehensive care. An acetylcholinesterase inhibitor or memantine can be used. These drugs are ineffective in the case of frontotemporal degenerations. For severe behavioural disorders, other psychoactive medications can be applied.

Elevated serum neuron-specific enolase in patients with temporal lobe epilepsy: a video-EEG study.

Established markers of brain damage, neuron-specific enolase (NSE) and S-100b protein (S-100), may increase after status epilepticus, but whether a single tonic-clonic or complex partial seizure induces elevation of these markers is not known. Furthermore, it is unclear whether the risk of seizure-related neuronal damage in temporal lobe epilepsy (TLE) differs from that in extratemporal lobe epilepsies (XTLE). The aim of this study was to analyze NSE and S-100 in patients with TLE and XTLE after acute seizures. The levels of NSE and S-100 were measured in serum before (0h) and at 3, 6, 12, and 24h after acute seizures in 31 patients during inpatient video-EEG monitoring. The patients were categorized into the TLE and the XTLE group based on video-EEG recordings and MRI findings. Fifteen patients had TLE and 16 XTLE. Index seizures were mainly complex partial seizures (n=21). In TLE mean+/-S.D. values for NSE levels (mug/L) were 8.36+/-2.64 (0h), 11.35+/-3.84 (3h), 13.48+/-4.49 (6h), 12.95+/-5.46 (12h) and 10.33+/-3.13 (24h) (p=0.006, ANOVA). In XTLE the changes were not significant (p=0.3). There was less increase in the levels of S-100 in TLE (p=0.05) and no significant change in XTLE (p=0.4). The levels of markers of neuronal damage were increased in patients with TLE, not only after tonic-clonic but also after complex partial seizures. These data suggest that TLE may be associated with brain damage.

The Use of MoCA and Other Cognitive Tests in Evaluation of Cognitive Impairment in Elderly Patients Undergoing Arthroplasty.

OBJECTIVE: To examine the prevalence and effect of cognitive impairment on treatment outcomes in elderly patients undergoing arthroplasty and to describe the feasibility of cognitive tests. MATERIALS AND METHODS: The participants were 52 patients with a mean age of 78 years 11 months (SD: 3.3), waiting for primary arthroplasty. We translated Montreal Cognitive Assessment (MoCA) into Finnish and compared it with Mini-Mental State Examination (MMSE), Mini-Cog, and clock-drawing tests prior to and 3 months after the surgery. The ability to perform activities of daily living, depression, quality of life, and years of education were evaluated. RESULTS: The mean MoCA score on the first visit was 20.7 (SD: 4.1). The pre- and postoperative cognitive tests implied there were no changes in cognitive functioning. Unambiguous delirium was detected in 6 patients. Delirium was not systematically assessed and consequently hypoactive delirium cases were possibly missed. Both MMSE and Mini-Cog found 3/6 of those and clock drawing and MoCA 6/6. Low preoperative MoCA, MMSE, and Mini-Cog scores predicted follow-up treatment in health-care center hospitals (P = .02, .011, and .044, respectively). During the 5-year follow-up period, 11/52 patients died. Higher education was the only variable associated with survival. The survivors had attained the median of 8 (range: 4-19) years of education compared with 6 (range: 4-8) years among the deceased. CONCLUSION: The prevalence of cognitive impairment among older patients presenting for arthroplasty is high and mostly undiagnosed. It is feasible to use the MoCA to identify cognitive impairment preoperatively in this group. The clock-drawing test was abnormal in all patients with postoperative delirium, which could be used as a screening test. Higher education predicted survival on a 5-year follow-up period.

Changes in plasma amino acids after electroconvulsive therapy of depressed patients.

There are indications that mood disorders may be related to perturbations in the amino acid transmitters. The amino acids may thus be targets of treatment of depression. The purpose of this pilot study was to measure the acute effects of a single administration of electroconvulsive therapy (ECT) on the plasma levels of amino acids in depressed patients. ECT was administered to 10 patients with major depressive disorder. Altogether 23 plasma amino acids were analyzed before and at 2, 6, 24 and 48 h after ECT. The levels of glutamate and aspartate increased at 6 h after ECT compared with the baseline. Also the levels of total tryptophan increased 2-24 h after ECT. There were also elevations in other amino acids at 6 and 24 h. The levels of gamma-aminobutyric acid (GABA) decreased at 2 h. In this study the acute effects of single ECT were associated with changes in the levels of glutamate, aspartate, GABA, tryptophan and some other amino acids. The preliminary data suggest that the therapeutic effects of ECT in depression may be due to mechanisms involving these amino acid transmitters.

Cerebrospinal fluid tau as a marker of neuronal damage after epileptic seizure.

PURPOSE: Whether repeated brief seizures can cause neuronal damage is controversial. Cerebrospinal fluid (CSF) total tau (T-tau) and phosphorylated tau (P-tau) measurements have been suggested for the diagnosis of Alzheimer's disease, and T-tau may also be a marker of axonal damage and neuronal degeneration. We studied T-tau and P-tau levels and P-tau/T-tau ratio in CSF after epileptic seizures in order to determine whether they are increased after seizures. METHODS: A total of 54 patients with tonic-clonic or partial secondarily generalized seizures due to various etiologies were studied and CSF obtained within 48h after the seizure. RESULTS: There were no statistical differences in the levels of T-tau (p=0.09, ANOVA) or P-tau (p=0.60) between different etiologic groups or controls. No patients with epilepsy of unknown origin had abnormal CSF T-tau whereas 11 patients with acute or remote symptomatic seizures had abnormal T-tau levels and the P-tau/T-tau ratio showed significant differences between the groups and controls (p=0.003). CONCLUSIONS: Epileptic seizures with unknown etiology did not increase CSF tau levels. Abnormal tau levels were associated with either acute or remote symptomatic seizures with known etiology. The presence of elevated CSF tau increases the probability of symptomatic cause in a patient with a seizure.

Ex vivo and in vivo gene delivery to the brain.

This unit describes methods for grafting genetically modified cells for ex vivo delivery of specific genes into the rat brain and direct delivery of transgenes to brain cells in vivo using recombinant viral vectors. These methods assess the function of a gene in the brain. The ex vivo approach of gene transfer to the nervous system depends on genetic manipulation of cells in vitro prior to grafting of the cells into the brain to enable production of a transgene at physiologically significant levels for a long period of time. This unit also includes procedures for transcardial perfusion to fix the tissue prior to analysis of expression and for sectioning of brains by use of a freezing sledge microtome. Thionine staining of tissue sections is also described.