The Value of Neuropsychological Assessment in the Differentiation Between Behavioral Variant Frontotemporal Dementia and Late-Onset Psychiatric Disorders.

OBJECTIVE: To investigate which neuropsychological tests can discriminate between behavioral variant frontotemporal dementia (bvFTD) and psychiatric disorders presenting with similar late-onset frontal behavioral changes, such as apathy, disinhibition, reduced empathy, or compulsive behavior. METHODS: Patients presenting with frontal behavioral changes in middle or late adulthood received extensive baseline examinations, including neuropsychological assessment and brain imaging. After 2 years, examinations were repeated and patients were diagnosed according to DSM-IV or international bvFTD consensus criteria. The study period was April 2011-June 2015. Two groups were selected: 32 patients with bvFTD and 53 patients with a psychiatric or psychological diagnosis. Associations between neuropsychological test scores and diagnostic group were investigated with logistic regression analyses, and diagnostic accuracy was investigated with a receiver operating characteristic curve. RESULTS: BvFTD patients scored lower on tests for confrontational naming, gestalt completion, and verbal abstraction compared to psychiatric patients (P < .01). The confrontational naming test (Boston Naming Test) showed the strongest association with diagnostic group: a lower score indicated a higher probability for a bvFTD diagnosis (P < .001). This test could discriminate between the groups with good diagnostic accuracy (area under the curve = 0.81). Tests for attention, memory, and executive functions showed no discriminative ability between the groups. CONCLUSIONS: Although one of the criteria of bvFTD is low performance on executive tests, these tests are not useful in differentiating bvFTD from psychiatric disorders. We recommend administering language tests, especially an extensive confrontational naming test, to aid differentiation between bvFTD and a psychiatric disorder in patients presenting with late-onset frontal behavioral changes.

Subjective Cognitive Impairment Cohort (SCIENCe): study design and first results.

BACKGROUND: We aimed to describe the Subjective Cognitive Impairment Cohort (SCIENCe) study design, to cross-sectionally describe participant characteristics, and to evaluate the SCD-plus criteria. METHODS: The SCIENCe is a prospective cohort study of subjective cognitive decline (SCD) patients. Participants undergo extensive assessment, including cerebrospinal fluid collection and optional amyloid positron emission tomography scan, with annual follow-up. The primary outcome measure is clinical progression. RESULTS: Cross-sectional evaluation of the first 151 participants (age 64 ± 8, 44% female, Mini-Mental State Examination 29 ± 2) showed that 28 (25%) had preclinical Alzheimer's disease (AD) (amyloid status available n = 114 (75%)), 58 (38%) had subthreshold psychiatry, and 65 (43%) had neither. More severe subjective complaints were associated with worse objective performance. The SCD-plus criteria age ≥ 60 (OR 7.7 (95% CI 1.7-38.9)) and apolipoprotein E (genotype) e4 (OR 4.8 (95% CI 1.6-15.0)) were associated with preclinical AD. CONCLUSIONS: The SCIENCe study confirms that SCD is a heterogeneous group, with preclinical AD and subthreshold psychiatric features. We found a number of SCD-plus criteria to be associated with preclinical AD. Further inclusion and follow-up will address important questions related to SCD.

A more randomly organized grey matter network is associated with deteriorating language and global cognition in individuals with subjective cognitive decline.

OBJECTIVES: Grey matter network disruptions in Alzheimer's disease (AD) are associated with worse cognitive impairment cross-sectionally. Our aim was to investigate whether indications of a more random network organization are associated with longitudinal decline in specific cognitive functions in individuals with subjective cognitive decline (SCD). EXPERIMENTAL DESIGN: We included 231 individuals with SCD who had annually repeated neuropsychological assessment (3 ± 1 years; n = 646 neuropsychological investigations) available from the Amsterdam Dementia Cohort (54% male, age: 63 ± 9, MMSE: 28 ± 2). Single-subject grey matter networks were extracted from baseline 3D-T1 MRI scans and we computed basic network (size, degree, connectivity density) and higher-order (path length, clustering, betweenness centrality, normalized path length [lambda] and normalized clustering [gamma]) parameters at whole brain and/or regional levels. We tested associations of network parameters with baseline and annual cognition (memory, attention, executive functioning, language composite scores, and global cognition [all domains with MMSE]) using linear mixed models, adjusted for age, sex, education, scanner and total gray matter volume. PRINCIPAL OBSERVATIONS: Lower network size was associated with steeper decline in language (ß ± SE = 0.12 ± 0.05, p < 0.05FDR). Higher-order network parameters showed no cross-sectional associations. Lower gamma and lambda values were associated with steeper decline in global cognition (gamma: ß ± SE = 0.06 ± 0.02); lambda: ß ± SE = 0.06 ± 0.02), language (gamma: ß ± SE = 0.11 ± 0.04; lambda: ß ± SE = 0.12 ± 0.05; all p < 0.05FDR). Lower path length values in precuneus and fronto-temporo-occipital cortices were associated with a steeper decline in global cognition. CONCLUSIONS: A more randomly organized grey matter network was associated with a steeper decline of cognitive functioning, possibly indicating the start of cognitive impairment.

Thinner cortex in patients with subjective cognitive decline is associated with steeper decline of memory.

We aimed to investigate associations between regional cortical thickness and rate of decline over time in 4 cognitive domains in patients with subjective cognitive decline (SCD). We included 233 SCD patients with the total number of 654 neuropsychological assessments (median = 3, range = 2-8) and available baseline magnetic resonance imaging from the Amsterdam Dementia Cohort (125 males, age: 63 ± 9, Mini-Mental State Examination score: 28 ± 2). We assessed longitudinal cognitive functioning at baseline and follow-up in 4 cognitive domains (composite Z-scores): memory, attention, executive function, and language. Thickness (millimeter) was estimated using FreeSurfer for frontal, temporal, parietal, cingulate, and occipital cortices. We used linear mixed models to estimate effects of cortical thickness on cognitive performance (dependent variables). There were no associations between cortical thickness and baseline cognition, but a faster subsequent rate of memory loss was associated with thinner cortex of the frontal [ß (SE) = 0.20 (0.07)], temporal [ß (SE) = 0.18 (0.07)], and occipital [ß (SE) = 0.22 (0.09)] cortices (all p < 0.05FDR). These findings illustrate that early cortical changes, particularly in the temporal cortex, herald incipient cognitive decline related to neurodegenerative diseases, most prominently Alzheimer's disease.

COMT Val(158)Met genotype and cannabis use in people with an At Risk Mental State for psychosis: Exploring Gene x Environment interactions.

BACKGROUND: Epidemiological and retrospective studies suggest a cannabis x catechol-O-methyltransferase (COMT) Val(158)Met interaction effect on development of psychosis. The aim of this study was to examine this interaction and its association with severity of subclinical symptoms in people with an At Risk Mental State (ARMS) for psychosis. METHODS: Severity of symptoms, cannabis use and genotype were assessed at baseline in 147 help-seeking young adults who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial. RESULTS: Cannabis use and COMT Val-allele showed an interaction effect in ARMS subjects. Subjects who were weekly cannabis users at some point prior to entering the study showed more severe positive symptoms. This effect increased if they were carriers of the COMT Val-allele and even more so if they were homozygous for the Val-allele. CONCLUSIONS: Our results suggest that the COMT Val(158)Met polymorphism moderates the effect of regular cannabis use on severity of subclinical psychotic symptoms.

[Deep brain stimulation for psychiatric disorders]. / Diepe hersenstimulatie bij psychiatrische aandoeningen.

Deep brain stimulation (DBS) is a treatment using implanted electrodes to deliver electrical pulses to targeted areas of the brain. DBS holds great promise in psychiatry for the treatment of patients with treatment-resistant obsessive-compulsive disorder, depression and Gilles de la Tourette syndrome. Double-blind and open trials have shown that the treatment is effective in about half of these patients. Further research should focus on optimizing DBS with respect to target location for the various psychiatric disorders. More controlled double-blind trials are needed to corroborate the effectiveness of DBS in patients with psychiatric disorders.