Mira Karrasch

Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer's disease.

The reduced risk for Alzheimers disease (AD) in high‐educated individuals has been proposed to reflect brain cognitive reserve, which would provide more efficient compensatory mechanisms against the underlying pathology, and thus delayed clinical expression. Our aim was to find possible differences in brain amyloid ligand 11C‐labeled Pittsburgh Compound B ([11C]PIB) uptake and glucose metabolism in high‐ and low‐educated patients with mild AD.

Cognitive slowing in Parkinson's disease is related to frontostriatal dopaminergic dysfunction

BACKGROUND Frontostriatal and cognitive dysfunctions in Parkinsons disease (PD) are hypothesized to be linked predominately to dopaminergic dysfunction within neural networks linking dorsal striatum to dorsolateral prefrontal cortex. METHODS The authors evaluated the relationship between frontostriatal dopaminergic function and cognitive performance, especially cognitive processing speed by performing [(18)F]fluorodopa PET and computerized tests of automatic and controlled cognitive processing speed (CogniSpeed) in 23 newly diagnosed and unmedicated PD patients and 14 controls. RESULTS PD patients were slower than the controls in all the CogniSpeed measures studied. The Fdopa uptake in caudate nucleus correlated negatively with slowing on all the tests. Slower performance in relatively automatic processes measured by choice reaction tasks as well as in more controlled processes measured by a calculation task was related to reduced Fdopa uptake in the anterior cingulate gyrus. The reduced dopaminergic function in the thalamus was associated with the slower performance in the subtraction test. CONCLUSION Our study indicates that dopaminergic dysfunction within neural networks linking striatum to prefrontal cortex is involved in the slowing of both automatic and controlled cognitive processing in PD patients.

Childhood-onset epilepsy five decades later. A prospective population-based cohort study

To study the impact of childhood‐onset epilepsy on a variety of outcomes across the life span.

Applicability of the CANTAB-PAL Computerized Memory Test in Identifying Amnestic Mild Cognitive Impairment and Alzheimer’s Disease

Aim: To compare the diagnostic accuracy of a computerized test, the CANTAB paired associate learning (PAL) to that of an established and validated noncomputerized test, the CERAD Wordlist Learning task in differentiating between normal aging, aMCI and AD in a cross-sectional design. Methods: 58 participants were assessed (19 with mild probable AD, 17 aMCI, 22 healthy controls). Results: The variables found to best discriminate between the three groups were the CANTAB PAL total errors adjusted (p < 0.0001, 81.0% of the cases correctly classified), and CERAD Wordlist Learning Delayed Recall (p < 0.0001, 77.6% of the cases correctly classified). Using both PAL total errors adjusted and Wordlist Learning Delayed Recall, 84.5% of the cases were correctly classified. Discussion: The results suggest that the CANTAB could be used for screening of AD-typical memory impairment.

Valence and Arousal Ratings for 420 Finnish Nouns by Age and Gender

Language-and culture-specific norms are needed for research on emotion-laden stimuli. We present valence and arousal ratings for 420 Finnish nouns for a sample of 996 Finnish speakers. Ratings are provided both for the whole sample and for subgroups divided by age and gender in light of previous research suggesting age- and gender-specific reactivity to the emotional content in stimuli. Moreover, corpus-based frequency values and word length are provided as objective psycholinguistic measures of the nouns. The relationship between valence and arousal mainly showed the curvilinear relationship reported in previous studies. Age and gender effects on valence and arousal ratings were statistically significant but weak. The inherent affective properties of the words in terms of mean valence and arousal ratings explained more of the variance in the ratings. In all, the findings suggest that language- and culture-related factors influence the way affective properties of words are rated to a greater degree than demographic factors. This database will provide researchers with normative data for Finnish emotion-laden and emotionally neutral words. The normative database is available in Database S1.

The diagnostic accuracy of an incidental memory modification of the Boston Naming Test (memo-BNT) in differentiating between normal aging and mild Alzheimer's disease

Early Alzheimers disease (AD) is associated with deficits in episodic memory. Semantic memory and naming have also been found to be affected, although to a lesser degree than episodic memory. Most episodic memory tests used in clinical settings assess intentional memory. The aim of the present paper was to present an incidental memory modification of the Boston Naming Test (memo-BNT) and to study the diagnostic accuracy of the BNT and the memo-BNT in differentiating between healthy old controls and AD patients. There were three groups in the study: 22 young controls (mean age 21.7), 23 normally aged old controls (mean age 70.6), and 23 patients with mild AD (mean age 74.0). There were no differences in the memo-BNT test scores between the old and young control participants. There were, however, significant differences between the AD patients and both control groups in several of the memo-BNT measures. Incidental free recall was the best measure in discriminating between the healthy aged controls and the AD patients (AUC = .939) and it had a better diagnostic accuracy than naming (AUC = 880). The results indicate that the memo-BNT could be used in clinical settings especially to differentiate between normal aging and mild AD.

Cognitive decline and amyloid accumulation in patients with mild cognitive impairment.

Background/Aims: The relationship between baseline 11C-Pittsburgh compound B (11C-PIB) uptake and cognitive decline during a 2-year follow-up was studied in 9 patients with mild cognitive impairment (MCI) who converted to Alzheimer’s disease (AD) and 7 who remained with MCI. Methods:11C-PIB PET scan was conducted at baseline and cognitive assessment both at baseline and at follow-up. To obtain quantitative regional values of 11C-PIB uptake, automated region of interest analysis was done using spatially normalized parametric ratio (region-to-cerebellar cortex) images. Results: At baseline, there were statistically significant differences in 11C-PIB uptake, but not in cognitive test performances between the converters and nonconverters. Memory and executive function declined only in the converters during follow-up. In the converters, lower baseline frontal 11C-PIB uptake was associated with faster decline in verbal learning. Higher baseline uptake in the caudate nucleus was related to faster decline in memory consolidation, and higher temporal uptake was associated with decline in executive function. Conclusion: Higher 11C-PIB uptake in the caudate nucleus and temporal lobe was related to decline in memory and executive functions, whereas lower frontal uptake was related to decline in verbal learning. The results indicate that in prodromal AD, frontal amyloid accumulation reaches its maximum in the MCI stage, characterized by memory problems without full-blown dementia.

Brain volumetric correlates of memory in early Parkinson's disease

BACKGROUND Free recall memory deficits are common in Parkinsons disease (PD), even at early stages before mild cognitive impairment or dementia. Their association with brain structural changes has not been established. OBJECTIVE We studied local gray matter volumes in relation to different memory tasks in early stage PD. METHODS Magnetic resonance images (MRI) and neuropsychological data were obtained from 28 non-demented, medicated PD patients, and 28 healthy controls. The gray matter segments of T1-weighted MRI images were analyzed using voxel-based morphometry in relation to visual and verbal memory tasks. Measures of immediate free recall, verbal learning, delayed recall and memory consolidation were obtained. A novel measure of incidental memory was included. RESULTS Patients and controls showed no significant group differences in local gray matter volumes. Voxel-based morphometry analyses revealed that worse performance on an incidental visual memory task was associated with smaller right parietal gray matter volume (Family-wise error corrected P = 0.002). This association was present in the PD group (corrected P = 0.005), but not in controls (corrected P > 0.99). No associations between gray matter volumes and the other memory tasks were found in either group. CONCLUSIONS The results suggest that right parietal cortical gray matter volume is related to free recall memory deficits in early stage PD in conditions not involving an intention to memorize visual items. This preliminary finding needs to be established in further studies utilizing incidental memory tasks in PD.

Voxel-based analysis of cerebral glucose metabolism in mono- and dizygotic twins discordant for Alzheimer disease

Background: Sporadic Alzheimer disease (AD) is a multifactorial disease to which both genetic and environmental factors contribute. Therefore, twin pairs are useful in studying its pathogenesis and aetiology. Cerebral glucose metabolism has been found to be reduced in AD patients. Methods: Cerebral glucose metabolism was studied in seven monozygotic (MZ) and nine same-sexed dizygotic (DZ) twin pairs discordant for AD using positron emission tomography. To obtain objective and explorative results concerning differences in glucose metabolism, the analysis was performed utilising modern voxel-based analysis methodology statistical parametric mapping and automated region-of-interest analysis. Results: In the demented MZ and DZ co-twins, cerebral glucose metabolism was extensively reduced compared with controls. The non-demented MZ co-twins showed reduced metabolism in inferior frontal, lateral temporal, parietal and medial temporal cortices as well as in the thalamus, putamen and right amygdala. In contrast, no reductions were found in the non-demented DZ co-twins. The reduction found in the non-demented MZ co-twins may be an indicator of genetic susceptibility to AD.

Association between childhood-onset epilepsy and amyloid burden 5 decades later

Importance The effect of childhood epilepsy on later-life cognitive and brain health is an unclear and little-explored issue. Objective To determine whether adults with a history of childhood-onset epilepsy exhibit increased brain amyloid accumulation, possibly predisposing to accelerated cognitive impairment or even frank cognitive disorders in later life. Design, Setting, and Participants Forty-one adults from a population-based cohort of individuals with childhood-onset epilepsy in southwestern Finland, together with 46 matched population-based controls, underwent amyloid ligand carbon 11–labeled Pittsburgh Compound B (PiB) positron emission tomography after long-term prospective follow-up. The PiB uptake was quantified as a region to cerebellar cortex ratio. Tracer uptake was evaluated visually and analyzed voxel by voxel over the entire brain to investigate the spatial distribution of amyloid deposition. The study was conducted from May 2011 to October 2013; data analysis was performed from January 2014 to October 2016. Main Outcomes and Measures Brain amyloid accumulation. Results The 41 individuals with epilepsy were originally enrolled in the Turku Adult Childhood Onset Epilepsy study at the mean (SD) age of 5.1 (4.5) years (range, 0-14 years). After a mean 52.5 (4.0) years of follow-up, the participants were evaluated (26 [63%] were women; the mean [SD] age was 56.0 [4.3] years). Nine individuals with childhood-onset epilepsy (22%) and 3 control participants (7%) had a visually abnormal PiB scan showing high cortical uptake in at least 1 of the evaluated brain regions (P = .04). In semiquantitative analyses, there was a significant interaction effect indicating higher prefrontal cortex uptake in apolipoprotein E (APOE) &egr;4 allele carriers than in noncarriers in participants (mean [SD], 1.66 [0.41] vs 1.43 [0.15]) compared with controls (1.40 [0.26) vs 1.41 [0.12]) (group × APOE interaction, F = 6.8; P = .01). In addition, there was a significant group effect showing higher tracer uptake in participants compared with controls (group effect, F = 8.0; P = .006). Conclusions and Relevance Adults with childhood-onset epilepsy, particularly APOE &egr;4 carriers, have an increased brain amyloid load at late middle age. Thus, epilepsy is linked with a biomarker that might be related to accelerated brain aging and can be considered a neurobiological predisposition to later-life cognitive disorders.