Noora M. Scheinin

Increased fibrillar amyloid-β burden in normal individuals with a family history of late-onset Alzheimer’s

Having a parent affected with late-onset Alzheimers disease (LOAD) is a major risk factor among cognitively normal (NL) individuals. This 11C-Pittsburgh Compound B (PiB)-PET study examines whether NL individuals with LOAD parents show increased fibrillar amyloid-beta (Aβ) deposition, a hallmark of Alzheimers disease (AD) pathology and whether there are parent-of-origin effects. Forty-two 50- to 80-year-old NL persons were examined with PiB-PET. These individuals included 14 NL subjects with a maternal family history (FH) of LOAD (FHm), 14 NL subjects with a paternal FH (FHp), and 14 NL subjects with a negative family history of any dementia (FH−). Statistical parametric mapping and automated regions-of-interest were used to compare cerebral-to-cerebellar PiB standardized uptake value ratios, reflecting fibrillar Aβ burden, across groups. FH groups did not differ in age, gender, education, and apolipoprotein E (ApoE) status. NL FHm subjects showed higher PiB retention in AD-affected anterior and posterior cingulate cortex (PCC), precuneus, parietal, temporal, occipital, and frontal cortices, right basal ganglia, and thalamus, compared with FH− and FHp subjects. FHp subjects showed increased PiB retention in the PCC and frontal cortex, intermediate between FHm and FH− subjects. Results remained significant after controlling for age, gender, education, and ApoE status. Children of parents with LOAD, particularly those with affected mothers, have increased fibrillar Aβ load in AD-vulnerable regions compared with controls, perhaps accounting for the known increased risk for AD. Present findings may motivate further research on familial transmission and parent-of-origin effects in LOAD.

Amyloid and metabolic positron emission tomography imaging of cognitively normal adults with Alzheimer's parents.

This study examines the relationship between fibrillar beta-amyloid (Aβ) deposition and reduced glucose metabolism, a proxy for neuronal dysfunction, in cognitively normal (NL) individuals with a parent affected by late-onset Alzheimers disease (AD). Forty-seven 40-80-year-old NL received positron emission tomography (PET) with (11)C-Pittsburgh compound B (PiB) and 18F-fluoro-2-deoxy-d-glucose (FDG). These included 19 NL with a maternal history (MH), 12 NL with a paternal history (PH), and 16 NL with negative family history of AD (NH). Automated regions of interest, statistical parametric mapping, voxel-wise intermodality correlations, and logistic regressions were used to examine cerebral-to-cerebellar PiB and FDG standardized uptake value ratios across groups. The MH group showed higher PiB retention and lower metabolism in AD regions compared with NH and PH, which were negatively correlated in posterior cingulate, frontal, and parieto-temporal regions (Pearson r ≤ -0.57, p ≤ 0.05). No correlations were observed in NH and PH. The combination of Aβ deposition and metabolism yielded accuracy ≥ 69% for MH vs. NH and ≥ 71% for MH vs. PH, with relative risk = 1.9-5.1 (p values < 0.005). NL individuals with AD-affected mothers show co-occurring Aβ increases and hypometabolism in AD-vulnerable regions, suggesting an increased risk for AD.

Adaption of pregnancy anxiety questionnaire–revised for all pregnant women regardless of parity: PRAQ-R2

The 10-item Pregnancy-Related Anxiety Questionnaire–Revised (PRAQ-R) is a widely used instrument to assess and identify pregnancy-specific anxiety in nulliparous women. It has good psychometric values and predictive validity for birth and childhood outcomes. Nonetheless, the PRAQ-R is not designed for use in parous women, as particularly one item of the questionnaire is not relevant for women who gave birth before. We tested the factorial and scalar invariance of a modified PRAQ-R2 across nulliparous and parous women with an adapted item to fit both groups of pregnant women. A longitudinal study among 1144 pregnant women (n = 608 nulliparous and n = 536 parous) with two repeated measures of the PRAQ-R2 was used to test for measurement invariance of the instrument. Results show metric and scalar invariance, indicating that the PRAQ-R2 measures similar constructs on the same scale for all pregnant women at two different times during pregnancy. We conclude that the PRAQ-R2 can be used, compared, or combined in a sample of nulliparous and parous women.

Cytokine profile and maternal depression and anxiety symptoms in mid-pregnancy—the FinnBrain Birth Cohort Study

Maternal prenatal psychological symptoms are associated with child health outcomes, e.g., atopic diseases. Altered prenatal functioning of the immune system is a potential mechanism linking maternal symptoms with child health. Research on prenatal distress and cytokines is warranted. The study population comprised consecutive N = 139 women from a general population-based FinnBrain Birth Cohort Study. Standardized questionnaires for depressive, overall anxiety, and pregnancy-related anxiety symptoms were used. Serum concentrations of selected cytokines were analyzed using Multiplex bead arrays from samples drawn at the gestational week 24. The concentrations of T helper (Th)2-related interleukins (IL)-9 and IL-13 and Th1-related IL-12 correlated positively with prenatal depressive and overall anxiety symptom scores (p values, range 0.011–0.029). Higher interferon (IFN)-γ/IL-4 ratio (p = 0.039) and Th2-related IL-5 (p = 0.007) concentration correlated positively with depressive symptoms. Pregnancy-related anxiety score correlated positively with IL-12 (p = 0.041), IL-13 (p = 0.025), and anti-inflammatory IL-10 (p = 0.048) concentrations. IL-6 and TNF-α concentrations were unrelated to prenatal symptoms. As a novel finding, we observed positive correlations between concentrations of potentially proallergenic cytokines and maternal prenatal psychological symptoms. Different symptom measures may yield distinct cytokine responses. This provides hypotheses for studies on mechanisms bridging prenatal stress and child health.

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.

Affective and non-affective touch evoke differential brain responses in 2-month-old infants

ABSTRACT Caressing touch is an effective way to communicate emotions and to create social bonds. It is also one of the key mediators of early parental bonding. The caresses are generally thought to represent a social form of touching and indeed, slow, gentle brushing is encoded in specialized peripheral nerve fibers, the C‐tactile (CT) afferents. In adults, areas such as the posterior insula and superior temporal sulcus are activated by affective, slow stroking touch but not by fast stroking stimulation. However, whether these areas are activated in infants, after social tactile stimulation, is unknown. In this study, we compared the total hemoglobin responses measured with diffuse optical tomography (DOT) in the left hemisphere following slow and fast stroking touch stimulation in 16 2‐month‐old infants. We compared slow stroking (optimal CT afferent stimulation) to fast stroking (non‐optimal CT stimulation). Activated regions were delineated using two methods: one based on contrast between the two conditions, and the other based on voxel‐based statistical significance of the difference between the two conditions. The first method showed a single activation cluster in the temporal cortex with center of gravity in the middle temporal gyrus where the total hemoglobin increased after the slow stroking relative to the fast stroking (p = 0.04 uncorrected). The second method revealed a cluster in the insula with an increase in total hemoglobin in the insular cortex in response to slow stroking relative to fast stroking (p = 0.0005 uncorrected; p = 0.04 corrected for multiple comparisons). These activation clusters encompass areas that are involved in processing of affective, slow stroking touch in the adult brain. We conclude that the infant brain shows a pronounced and adult‐like response to slow stroking touch compared to fast stroking touch in the insular cortex but the expected response in the primary somatosensory cortex was not found at this age. The results imply that emotionally valent touch is encoded in the brain in adult‐like manner already soon after birth and this suggests a potential for involvement of touch in bonding with the caretaker.

Illuminating the clinical significance of alexithymia subtypes: A cluster analysis of alexithymic traits and psychiatric symptoms

BACKGROUND Alexithymia is a personality construct involving difficulties identifying and verbalizing feelings, and an externally oriented thinking style. There is preliminary evidence for alexithymia subtypes that may carry different risk profiles for psychiatric illness. The aim of this study was to gain support for the existence of alexithymia subtypes and further characterize their clinical relevance. METHODS To identify possible subtypes, a cluster analysis was conducted for individuals with high alexithymic traits (N=113). Current depressive and anxiety symptoms, self-reported psychiatric medical history, and self-reported early life adversity were compared between subtypes. The cluster analysis was replicated with the low (N=2471) and moderate (N=290) alexithymia groups. RESULTS We identified two alexithymia subtypes. Compared to type A, type B alexithymia was associated with higher levels of difficulties in identifying feelings, and was more strongly associated with current depressive (Cohens d=0.77, p<0.001) and anxiety symptoms (Cohens d=0.82, p<0.001), and self-reported early life adversity (Cohens d 0.42, p=0.048). Compared to type A, type B alexithymia was also associated with a higher prevalence of self-reported diagnosis of major depressive- (30.2% vs. 8.3%) and anxiety disorder (18.9% vs. 3.3%). CONCLUSIONS The results of this study support the hypothesis of alexithymia subtypes, and add support to the growing evidence showing that alexithymia is likely a heterogeneous and dimensional phenomenon. The subtype (type B) with most pronounced difficulties in identifying feelings may be associated with a higher risk for psychiatric illness compared to type A alexithymia, and may exhibit a more severe history of early life adversity.

Neural correlates of gentle skin stroking in early infancy

Highlights • The infant brain is sensitive to gentle skin stroking within the first weeks of age.• The postcentral gyrus and posterior insular cortex are responsive to stroking.• Social touch activates both somatosensory and socio-affective brain areas in infancy.

Long-Term Interrelationship between Brain Metabolism and Amyloid Deposition in Mild Cognitive Impairment

The aim of this longitudinal positron emission tomography (PET) study was to evaluate the interrelationship between brain metabolism and amyloid accumulation during the disease process from mild cognitive impairment (MCI) to Alzheimers disease (AD). Nine MCI patients, who converted to AD between two and five years, and nine healthy subjects underwent [11C]PIB and [18F]FDG PET scans at baseline and at 5 years. [11C]PIB uptake was clearly higher in MCI patients at baseline compared to controls and spread extensively to the cerebral cortex during the conversion to AD. [18F]FDG uptake was reduced especially in the temporal-parietal regions in MCI compared to controls at baseline, and widely over the cortex at the 5-year follow-up. The reduction in metabolism during the follow-up was significant in the posterior brain regions. In addition, brain amyloid load was positively associated with metabolism in posterior brain regions in MCI, but not after conversion to AD. The results suggest that there are interactions between brain amyloid accumulation and metabolism during the AD process, including a possible compensatory upregulation of posterior brain metabolism in the early phase.

PET Amyloid imaging and cognition in patients with Alzheimer's disease, Mild Cognitive Impairment (MCI) and healthy controls: a European multicenter study

were further classified according to the presence or absence of an ApoE4 allele and by their subjective memory complaints (MC). All participants underwent a comprehensive neuropsychological examination, a MRI and a PiB-PET scan. Correlational analyses were performed between the different study outcomes. Results: Cortical PIB binding was markedly elevated in all AD patients except one. MCI subjects presented either an ‘‘AD-like’’ (63%) or normal pattern. Cortical PiB retention was abnormal in 34% of HC and its prevalence increased with age. HC with subjective memory complaints carrying an ApoE4 allele had significantly higher Ab burdens than non ApoE4 carriers. Conclusions: Phase I of the AIBL study has established the foundations for the longitudinal assessment of Ab burden in HC, MCI and AD. This will assist the development of techniques for early detection of AD while providing a cohort suitable for targeted early intervention studies.