Association study of a functional catechol-o-methyltransferase polymorphism and cognitive function in patients with dementia.

A functional catechol-o-methyltransferase (COMT Val158/108Met) polymorphism, a valine (Val) to methionine (Met) substitution, has been associated with cognitive processing in the normal brain, older age, mild cognitive impairment and in various dementias. COMT is involved in the breakdown of dopamine and other catecholamines, especially in the frontal cortex; hence the carriers of Met allele, with the lower enzymatic activity, are expected to perform better on particular neuro-cognitive tests. The study included 46 patients with dementia and 65 healthy older subjects. The neurological status was assessed, using the Mini Mental Status Examination (MMSE), and the batery of different neurological tests. In DNA samples COMT polymorphism was genotyped. Patients with dementia exhibited significant genotype-induced differences in scores for MMSE, Visual Association Test (VAT) duration of numbers test, VAT time of response to numbers test, VAT average response to numbers test and WPLCR/PPLR unanswered. Carriers of Met/Met genotype had significantly lower scores of MMSE, significantly longer time to respond to VAT duration of numbers test, VAT time of response to numbers test and VAT average response to numbers test, and significantly greater number of unanswered questions to WPLCR/PPLR when compared to Met/Val or Val/Val genotypes. Our preliminary data showed significantly impaired performance in several neuro-cognitive tests in carriers of Met/Met genotype in patients with dementia compared to either Met/Val or Val/Val genotype carriers. Although Met/Met genotype with more dopamine available in the frontal cortex should be associated with better neuro-cognitive test results than Met/Val or Val/Val genotype, our data on patients with dementia did not confirm this hypothesis. Further study on larger sample of patients is needed to clarify the role of COMT polymorphism in cognitive functions.

Unraveling the biological mechanisms in Alzheimer's disease--lessons from genomics.

Alzheimer's disease (AD) is the most common form of dementia and the most common neurodegenerative disease, with a complex genetic background. Genome-wide association studies (GWAS) have yielded important new insights into genetic mechanisms of AD pathology. Current results unequivocally confirm apolipoprotein E (APOE) as a major genetic risk factor for development of late onset AD. Additional associations of more than twenty genes have also been identified and replicated in subsequent genetic studies. Despite the exciting new GWAS data which have emerged in the last few years, it has become clear that common variants within the genome cannot fully explain the underlying genetic risk for AD. Novel approaches such as genome-wide analysis of copy number variations (CNV) or low-frequency rare functional gene variants may provide additional insight into genetic basis of AD. In this review we summarize the findings of eighteen GWAS studies in AD performed to date, with an emphasis on potential future developments in the quest for genetic risk factors of AD.

Unusual cause of dementia in an immunocompetent host: toxoplasmic encephalitis.

A 69-year-old male was presented with a 2-month history of cognitive decline. The most profound deficit was observed in short-term verbal and visual memory and recognition. He was otherwise healthy, apart from atrial fibrillation diagnosed 5 months before. Brain MRI revealed T2 hyperintensities in the left thalamus, right pulvinar thalami, both putamina and right head of caudate nucleus without diffusion restriction on DWI sequences. CSF examination revealed elevated proteins. He was HIV negative. The course of the disease was complicated with gram negative sepsis and the patient died 14 days later. Autopsy revealed the brain lesions to have been caused by toxoplasmic encephalitis. Toxoplasmic encephalitis is an extremely rare cause of rapidly progressive dementia in immunocompetent patients. In patients with multiple lesions, hyperintense on T2 and hypointense on T1 weighted sequences, without diffusion restriction and some expansive effect, infectious causes should be considered, even in the absence of classical signs of infectious diseases and CSF pleocythosis.

Consequences of mild traumatic brain injury on information processing assessed with attention and short-term memory tasks.

In this investigation, we explored the impact of mild traumatic brain injury (mTBI) upon short term or working memory and attention. The performance of 37 individuals with mTBI was compared with that of 53 age, sex and education-matched controls. All participants were staff members or individuals seeking medical care at a University hospital serving a large metropolitan area. A battery of computerized tests measured sustained visual attention, short-term memory (STM), simple reaction time, and decision time. Individuals with mTBI showed a performance deficit at sustained visual attention, STM scanning and a trend towards slowing in choice decision making. These observed changes in the cognitive performance of mTBI individuals are hypothesized to be a consequence of impaired central information processing. Our results suggest that mTBI can elicit meaningful cognitive deficits for several months post-injury. Additionally, we believe that the tasks employed in the current investigation demonstrate their utility for understanding cognitive deficits in mTBI individuals.

Psychosis and EEG abnormalities as manifestations of Hashimoto encephalopathy.

Hashimoto encephalopathy (HE) is a distinct form of encephalopathy, which can manifest itself with purely psychiatric symptoms. A 38-year-old female with history of rheumatoid arthritis was treated with psychotropic drugs for a couple of years in psychiatric structures because of the onset of depressive symptoms, psychoticlike manifestations, and impairment of cognitive functions. The electroencephalography (EEG) was characterized by general slowing with high voltage (2 to 3 Hz) delta biphasic and triphasic waves. Once a firm diagnosis of HE was made, corticosteroid treatment resulted in resolution of her psychiatric symptoms, marked EEG improvement, and partial improvement in her cognitive functions. HE should be suspected in young females with history of autoimmune disorders and EEG abnormalities.

Bilateral thalamic astrocytoma.

We present a 68-year-old woman who presented with symptoms of frontotemporal dementia. Brain MRI revealed tumor mass in both thalami and according to WHO classification, the tumor corresponded to diffuse fibrillary astrocytoma grade II. This case points to the role of neuroimaging in patients presenting with classical symptoms of dementia.