Jaana Suhonen

Neuropsychiatric symptoms and Quality of Life in patients with very mild and mild Alzheimer's disease

Neuropsychiatric symptoms (NPS) are common manifestations of Alzheimers disease (AD).

Normal CSF neuron-specific enolase and S-100 protein levels in patients with recent non-complicated tonic–clonic seizures

PURPOSE Increased concentrations of the nervous-system-specific proteins neuron-specific enolase (NSE) and S-100 protein (S-100) have been measured with lesions in the CNS. Elevated levels of serum NSE (s-NSE) have been found in status epilepticus, but also after single epileptic seizures. Because larger studies addressing cerebrospinal fluid (CSF) levels of NSE or S-100 have not been performed, we measured CSF NSE and S-100 after tonic-clonic seizures to search for evidence of neuronal and glial damage. METHODS 22 consecutive patients with single, previously undiagnosed and untreated tonic-clonic seizures were studied. Serum and CSF samples were collected within 24 h after seizure. 18 serum and CSF samples were measured from a control group. RESULTS The mean CSF NSE was 8.9 ng/ml (range 0-28 ng/ml) and s-NSE 8.2 ng/ml (range 5-15 ng/ml) in the patient group. The mean concentrations in the control group were 13.1 ng/ml (range 3-24 ng/ml) and 8.0 ng/ml (range 5-12 ng/ml) respectively. The mean CSF S-100 was 3.17 microg/l (range 1.45-7.02 microg/l) and serum S-100 0.05 microg/l (range 0-0.32 microg/l), and in controls 3.19 microg/l (range 1.52-5.13 microg/l) and 0.08 microg/l (range 0-0.28 microg/l). CONCLUSION There were no significant differences between the mean concentrations of NSE or S-100 in CSF and serum between the epileptic group and controls. These results do not confirm the previous observation of elevated NSE-levels after tonic-clonic seizures, which argues against neuronal or glial damage after uncomplicated tonic-clonic seizures in unmedicated patients.

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.

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.

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.

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 Alzheimers 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.

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

To examine the association between neuropsychiatric symptoms (NPS) with self‐ and caregiver‐rated Quality of Life (QoL) for patients with Alzheimers disease (AD) during a 5‐year follow‐up.

Common and Rare Genetic Variants Associated With Alzheimer's Disease

Alzheimers 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. J. Cell. Physiol. 231: 1432–1437, 2016.

Common and Rare Variants Associated with Alzheimer's Disease

Alzheimers 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. J. Cell. Physiol. 231: 1432–1437, 2016.

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.