Görsev Yener

Dietary Changes, Compulsions and Sexual Behavior in Frontotemporal Degeneration

The occurrence of weight gain, sweet and carbohydrate craving, hyposexuality, and compulsions in frontal lobe dementia (FLD) compared to Alzheimers disease (AD) was evaluated. FLD is a progressive dementia with a high rate of misdiagnosis and therefore better diagnostic criteria for FLD are needed. Fourteen patients meeting research criteria for AD were compared to 14 with suspected FLD. All had cerebral perfusion measured with xenon-133 and imaged with HMPAO using brain-dedicated SPECT. The FLD group showed frontotemporal and AD posterior temporoparietal hypoperfusion. The primary caregivers were queried regarding weight gain, sweet/carbohydrate preference, sexual drive, and compulsions. Differences were compared with Fishers exact test. The following was found in FLD versus AD: Weight gain in FLD patients amounted to 64% (AD 7%), carbohydrate craving was 79% (vs. 0%) and compulsive behavior 64% (vs. 14%). The differences for these symptoms were statistically significant, whereas for the symptoms increased sexual drive (8 vs. 8%) and reduced sexual drive (54 vs. 23%) no significant difference could be found. In FLD the first symptoms were often dietary changes or hyposexuality. Compulsions were more bizarre and severely disabling in FLD than in AD. Dietary changes, hyposexuality, and disabling compulsions are prominent early symptoms in FLD but not AD. The cause of these symptoms may be due to both frontal and subcortical serotonin loss and dysfunction of the anterior temporal lobes.

The effects of rasagiline on cognitive deficits in Parkinson's disease patients without dementia: A randomized, double-blind, placebo-controlled, multicenter study

Cognitive impairment can occur at all stages of Parkinsons disease. Rasagiline is a selective monoamine oxidase type‐B inhibitor that enhances central dopaminergic transmission. Dopamine is thought to be involved in certain cognitive processes such as working memory. We assessed the effects of rasagiline on cognitive deficits in cognitively impaired, nondemented patients with Parkinsons disease. This was a randomized, double‐blind, placebo‐controlled prospective study. Patients with Parkinsons disease receiving stable dopaminergic treatment were assigned to receive rasagiline 1 mg/day or placebo for 3 months. Patients were eligible if they had impairment in 2 of 4 cognitive domains (attention, executive functions, memory, visuospatial functions) in the screening neuropsychological tests, yet did not fulfill criteria for Parkinsons disease dementia. Fifty‐five patients were randomized; 48 patients completed the study. Patients in the rasagiline group showed significant improvement in digit span–backward compared with the placebo group (P = .04), with trends favoring rasagiline in digit span total and digit‐ordering tests. Verbal fluency total score showed a significant difference in favor of rasagiline (P = .038), with trends favoring rasagiline in semantic fluency test and Stroop spontaneous corrections. The composite cognitive domain Z scores revealed a significant difference in favor of rasagiline compared with placebo in the attentional Z score (P < .005). There were no significant differences between the 2 groups in the other cognitive tests or cognitive domain Z scores. The monoamine oxidase type‐B inhibitor rasagiline may exert beneficial effects on certain aspects of attention and executive functions in nondemented patients with Parkinsons disease with cognitive impairment.

Quantitative EEG in frontotemporal dementia.

Accurate diagnosis of the major degenerative dementias continues to be problematic. Although diagnostic precision for Alzheimers disease (AD) approaches 90%, for Frontotemporal dementias (FTD) it has been less than 20%. Previous work has shown that AD patients have both focal and generalized slowing, while in FTD the EEG is normal. We studied 26AD,13FTD and 27 health control subjects with Quantitative Electroencephalography (QEEG). Using only five QEEG measures with stepwise discriminant function analysis, we distinguished the AD from FTD groups each with 84.6% accuracy, and controls (100%) from FTD groups (84.6%) with high accuracy. The most informative QEEG variables for distinguishing FTD and AD were relative power from the temporal region in beta-2 band, and from the parietal region in the theta and alpha and beta-2 bands. These results suggest that QEEG may be helpful in distinguishing subjects with AD from subjects with FTD.

Event-related delta oscillatory responses of Alzheimer patients

Background and purpose:  Alzheimer type of dementia (AD) is the most common neuropsychiatric morbidity in elderly individuals. Event‐related oscillations (ERO) provide an useful tool for detecting subtle abnormalities of cognitive processes with high temporal resolution.

Sensory evoked and event related oscillations in Alzheimer’s disease: a short review

Diagnosis and treatment of Alzheimer’s disease (AD) depend on clinical evaluation and there is a strong need for an objective tool as a biomarker. Our group has investigated brain oscillatory responses in a small group of AD subjects. We found that the de novo (untreated) AD group differs from both the cholinergically-treated AD group and aged-matched healthy controls in theta and delta responses over left frontal-central areas after cognitive stimulation. On the contrary, the difference observed in AD groups upon a sensory visual stimulation includes response increase over primary or secondary visual sensorial areas compared to controls. These findings imply at least two different neural networks, depending on type of stimulation (i.e. cognitive or sensory). The default mode defined as activity in resting state in AD seems to be affected electrophysiologically. Coherences are also very valuable in observing the group differences, especially when a cognitive stimulus is applied. In healthy controls, higher coherence values are elicited after a cognitive stimulus than after a sensory task. Our findings support the notion of disconnectivity of cortico-cortical connections in AD. The differences in comparison of oscillatory responses upon sensory and cognitive stimulations and their role as a biomarker in AD await further investigation in series with a greater number of subjects.

Effects of Gender on Burden Among Caregivers of Alzheimer's Patients

PURPOSE This study was conducted to determine the effects of gender on caregiver burden among caregivers of persons with Alzheimers disease. DESIGN Comparative descriptive study. METHODS Factors affecting the burden of female and male caregivers (age, total duration of caregiving, mean duration of daily caregiving, education, income, employment status, age of the patients cared for, and Mini-Mental State Examination [MMSE] and Neuropsychiatric Inventory [NPI] scores) were similar (p > .05). The sample consisted of 120 female and 72 male caregivers of patients with Alzheimers disease. Data were collected from patients by means of the MMSE and demographic variables, and data from the Caregiver Burden Inventory [CBI] and NPI were obtained from caregivers, as well as from face-to-face interviews using a questionnaire. Descriptive statistics and t-tests were used to describe and analyze data. FINDINGS Female caregivers had significantly higher scores for caregiver burden than their male counterparts (p= .002). Subscale analysis on the CSI revealed that female caregivers had significantly higher scores for caregiver burden than male caregivers on time dependence (p= .040), developmental (p= .002), physical (p= .001), and social burdens (p= .045). No difference was found with respect to emotional burden (p= .718). CONCLUSIONS Results of this study suggest that female caregivers are subjected to a higher level of caregiver burden than male caregivers in Turkey. In subscales, female caregivers experienced more burden than male caregivers in the time dependence, developmental, physical, and social burdens. Emotional burden was similar in both genders. CLINICAL RELEVANCE Although caregiver burden has been a much debated issue for many years, it is a relatively new topic in Turkey. In order to provide appropriate care for the patients and familys cultural values and needs, more studies are needed to be conducted on family members giving care to Alzheimers patients. It is thought that the findings of the present study will facilitate cross-cultural comparisons and culture-oriented care planning.

Brain oscillations as biomarkers in neuropsychiatric disorders: following an interactive panel discussion and synopsis.

This survey covers the potential use of neurophysiological changes as a biomarker in four neuropsychiatric diseases (attention deficit hyperactivity disorder (ADHD), Alzheimers disease (AD), bipolar disorder (BD), and schizophrenia (SZ)). Great developments have been made in the search of biomarkers in these disorders, especially in AD. Nevertheless, there is a tremendous need to develop an efficient, low-cost, potentially portable, non-invasive biomarker in the diagnosis, course, or treatment of the above-mentioned disorders. Electrophysiological methods would provide a tool that would reflect functional brain dynamic changes within milliseconds and also may be used as an ensemble of biomarkers that is greatly needed in the evaluation of cognitive changes seen in these disorders. The strategies for measuring cognitive changes include spontaneous electroencephalography (EEG), sensory evoked oscillation (SEO), and event-related oscillations (ERO). Further selective connectivity deficit in sensory or cognitive networks is reflected by coherence measurements. Possible candidate biomarkers discussed in an interactive panel can be summarized as follows: for ADHD: (a) elevation of delta and theta, (b) diminished alpha and beta responses in spontaneous EEG; for SZ: (a) decrease of ERO gamma responses, (b) decreased ERO in all other frequency ranges, (c) invariant ERO gamma response in relation to working memory demand; for euthymic BD: (a) decreased event-related gamma coherence, (b) decreased alpha in ERO and in spontaneous EEG; for manic BD: (a) lower alpha and higher beta in ERO, (b) decreased event-related gamma coherence, (c) lower alpha and beta in ERO after valproate; and for AD: (a) decreased alpha and beta, and increased theta and delta in spontaneous EEG, (b) hyperexcitability of motor cortices as shown by transcortical magnetic stimulation, (c) hyperexcitability of visual sensory cortex as indicated by increased SEO theta responses, (d) lower delta ERO, (e) lower delta, theta, and alpha event-related coherence, (f) higher theta synchrony and higher alpha event-related coherence in cholinergically treated AD subjects. In further research in the search for biomarkers, multimodal methods should be introduced to electrophysiology for validation purposes. Also, providing the protocols for standardization and harmonization of user-friendly acquisition or analysis methods that would be applied in larger cohort populations should be used to incorporate these electrophysiologic methods into the clinical criteria. In an extension to conventional anatomical, biochemical and brain imaging biomarkers, the use of neurophysiologic markers may lead to new applications for functional interpretrations and also the possibility to monitor treatments tailored for individuals.

Occipital sources of resting-state alpha rhythms are related to local gray matter density in subjects with amnesic mild cognitive impairment and Alzheimer's disease

Occipital sources of resting-state electroencephalographic (EEG) alpha rhythms are abnormal, at the group level, in patients with amnesic mild cognitive impairment (MCI) and Alzheimers disease (AD). Here, we evaluated the hypothesis that amplitude of these occipital sources is related to neurodegeneration in occipital lobe as measured by magnetic resonance imaging. Resting-state eyes-closed EEG rhythms were recorded in 45 healthy elderly (Nold), 100 MCI, and 90 AD subjects. Neurodegeneration of occipital lobe was indexed by weighted averages of gray matter density, estimated from structural MRIs. EEG rhythms of interest were alpha 1 (8-10.5 Hz) and alpha 2 (10.5-13 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography. Results showed a positive correlation between occipital gray matter density and amplitude of occipital alpha 1 sources in Nold, MCI, and AD subjects as a whole group (r = 0.3, p = 0.000004, N = 235). Furthermore, there was a positive correlation between the amplitude of occipital alpha 1 sources and cognitive status as revealed by Mini Mental State Examination score across all subjects (r = 0.38, p = 0.000001, N = 235). Finally, amplitude of occipital alpha 1 sources allowed a moderate classification of individual Nold and AD subjects (sensitivity: 87.8%; specificity: 66.7%; area under the receiver operating characteristic curve: 0.81). These results suggest that the amplitude of occipital sources of resting-state alpha rhythms is related to AD neurodegeneration in occipital lobe along pathologic aging.

Beta oscillatory responses in healthy subjects and subjects with mild cognitive impairment

The aim of the present study was to investigate the role of beta oscillatory responses upon cognitive load in healthy subjects and in subjects with mild cognitive impairment (MCI). The role of beta oscillations upon cognitive stimulation is least studied in comparison to other frequency bands. The study included 17 consecutive patients with MCI (mean age = 70.8 ± 5.6 years) according to Petersens criteria, and 17 age- and education-matched normal elderly controls (mean age = 68.5 ± 5.5 years). The experiments used a visual oddball paradigm. EEG was recorded at 30 cortical locations. EEG-evoked power, inter-trial phase synchronization, and event-related beta responses filtered in 15–20 Hz were obtained in response to target and non-target stimuli for both groups of subjects. In healthy subjects, EEG-evoked beta power, inter-trial phase synchronization of beta responses and event-related filtered beta responses were significantly higher in responses to target than non-target stimuli (p < 0.05). In MCI patients, there were no differences in evoked beta power between target and non-target stimuli. Furthermore, upon presentation of visual oddball paradigm, occipital electrodes depict higher beta response in comparison to other electrode sites. The increased beta response upon presentation of target stimuli in healthy subjects implies that beta oscillations could shift the system to an attention state, and had important function in cognitive activity. This may, in future, open the way to consider beta activity as an important operator in brain cognitive processes.

Neurodegenerative disease phenotypes in carriers of MAPT p.A152T, a risk factor for frontotemporal dementia spectrum disorders and Alzheimer disease.

Recently, Coppola and colleagues demonstrated that a rare microtubule-associated protein tau (MAPT) sequence variant, c.454G>A (p.A152T) significantly increases the risk of frontotemporal dementia (FTD) spectrum disorders and Alzheimer disease (AD) in a screen of 15,369 subjects. We describe clinical features of 9 patients with neurodegenerative disease (4 women) harboring p.A152T, aged 51 to 79 years at symptom onset. Seven developed FTD spectrum clinical syndromes, including progressive supranuclear palsy syndrome (n=2), behavioral variant FTD (bvFTD, n=1), nonfluent variant primary progressive aphasia (nfvPPA, n=2), and corticobasal syndrome (n=2); 2 patients were diagnosed with clinical AD. Thus, MAPT p.A152T is associated with a variety of FTD spectrum clinical presentations, although patients with clinical AD are also identified. These data warrant larger studies with clinicopathologic correlation to elucidate the influence of this genetic variant on neurodegenerative disease.