bluuebunny/crossref_metadata_2025 huggingface dataset:
Lower levels of episodic memory associated with long‐term air pollution exposures in older women: Differences in midlife versus late‐life exposures and effect modification by hormone treatment
Authors: Wang Xinhui , Younan Diana , Petkus Andrew J , Beavers Daniel P , Espeland Mark A , Chui Helena C , Resnick Susan M , Gatz Margaret , Kaufman Joel D , Wellenius Gregory , Whitsel Eric A , Manson JoAnn E , Chen Jiu‐Chiuan
Published: December 2020

Background

Late‐life exposure to ambient air pollutants may accelerate episodic memory (EM) declines in older women, but very little is known about the midlife exposure effects. Animal data suggests that hormone therapy (HT) may protect female brain from neurotoxic insult. We examined the EM trajectories associated with air pollutants and whether the associations varied by HT, exposure time‐window or pollution sources.

Method

We studied 916 women from the Women’s Health Initiative Memory Study in Younger (WHIMS‐Y) Women. At age of 50‐54, postmenopausal women were randomly assigned to an average of 5 years of conjugated equine estrogen alone (E‐alone) if they had hysterectomy, its combination with medroxyprogesterone acetate (E+P) if without hysterectomy or matching placebos. From the WHIMS‐Y inception age of 62‐71, EM was assessed annually (2008‐16) using the telephone‐based California Verbal Learning Test. Three‐year average exposures at midlife (aged 50‐59) and late‐life (at inception) were derived from yearly exposures estimated by regionalized universal kriging models for PM2.5 (particulate matter <2.5μm) and NO2 (a proxy of traffic‐related air pollutants). We used linear mixed‐effect models to estimate the associations, adjusting for social‐demographic variables, lifestyles, HT, hysterectomy, cardiovascular risk factors and other clinical covariates.

Result

EM performance improved (0.60/year, p<0.001) over the study period. Higher PM2.5 exposures in midlife, but not in late‐life, were associated with lower EM levels (β=‐0.49, per inter‐quartile‐range [IQR]=3.44 µg/m3, p=0.045). NO2 exposures in midlife or late‐life were not associated with EM levels. Compared to the women assigned to placebo group, the observed association between midlife PM2.5 and EM level differed by HT (interaction p=0.005). The putative adverse PM2.5 effect was greater (β=‐1.29 per IQR; p=0.03) in the E‐alone group, with no statistically significant difference in the E+P group (p=0.16). A similar pattern of effect modification was found for NO2 exposure (interaction p=0.09) in midlife, but not in late‐life. The slope of EM trajectory was not associated with either exposure, HT, or their interactions.

Conclusion

Higher midlife PM2.5 exposure decrease the EM levels of older women, with stronger associations in those randomly assigned to E‐alone treatment, which did not support the protection of HT against air pollution neurotoxicity.
Plasma Aβ in cerebral microbleeds‐positive subjects with cognitive impairment
Authors: Liu Shan , Ito Hitomi , Ogawa Norihiro , Akatsu Hiroyasu , Uchida Kazuhiko
Published: December 2020

Background

Cerebral amyloid angiopathy (CAA) is strongly related to Alzheimer’s disease (AD). Accumulation of amyloid affects pathophysiology of parenchyma and vessels in amyloidosis. Continuum of amyloid pathology may result in complicated clinical symptoms due to overlap of vascular and neurodegenerative factors during amyloidosis. MRI can detect hemosiderin deposits as cerebral microbleeds (CMBs) and cortical superficial siderosis. CMBs may be involved in amyloid pathology in AD and mixed dementia. Here, we analyzed relationship of these cerebrovascular changes to plasma Aβ42 and Aβ40 levels.

Method

Age‐matched subjects with cognitive impairment were classified into CMBs‐positive, ‐suspective and ‐negative groups by MRI. Plasma Aβ42, Aβ40, BACE1 levels were determined by ELISA (ADx, Euroimun).

Result

There is no significant changes of MMSE score and hippocampal atrophy among the CMBs groups. CMBs‐positive subjects showed lower Aβ42 levels and higher Aβ40/42 ratio in plasma. Plasma BACE1 levels showed no significant change in CMBs‐positive subjects.

Conclusion

CMBs, plasma Aβ42 and Aβ40/42 ratio may be potential biomarkers for amyloid pathology in cognitive impairment.
Development of the Computer and Technology Attitude Questionnaire (CaTAQ) to inform performance on computerised cognitive testing in older adults in the CogSCAN Study
Authors: Croot Karen , Allison Karen C. , Sachdev Perminder S. , Brodaty Henry , Crawford John D. , Lam Ben C.P. , Lee Teresa , Henry Julie D. , Draper Brian , Close Jacqueline , Ong Min Yee , Rossie Matilda , Kochan Nicole A.
Published: December 2020

Background

Computer‐administered neuropsychological assessment batteries (CNAs) have the potential to allow large‐scale cognitive screening and monitoring, increasing older adults’ access to cognitive assessment, and earlier diagnosis of and intervention for cognitive impairment. There is, however, little research on whether experience with and attitudes to computers and technology affect the validity, reliability and acceptability of CNAs in older adults. Here, we report the development and validation of an instrument to measure computer attitudes and computer experience in an older adult cohort from the CogSCAN study.

Method

The Computer and Technology Attitude Questionnaire (CaTAQ) is a new 27‐item self‐report questionnaire comprising five subscales (computer anxiety, comfort with computers, positive and negative attitudes to computers and computer learning self‐efficacy) that have been individually validated in diverse populations (young, predominantly Hispanic Los Angeles adults; Canadian business employees; older Pennsylvanian Caucasian adults), as well as items measuring experience with computers and related technologies. Responses from 196 community‐living older adults without dementia in Sydney, Australia (67% female, mean age 72.1 years, range 60‐91 years, mean years’ education 14.7, limited/no computer experience 9.2%) have been analysed to date.

Result

Confirmatory factor analysis supported a three‐factor model (anxiety/discomfort, positive about technology, negative about technology) with good fit to items from the first four subscales (Figure 1), and four computer learning efficacy items formed a single factor with good fit in a subsample of 79 participants who reported not knowing how to use a computer (Figure 2). Our measurement models for this older Australian sample therefore replicate previous validation of these subscales. Analyses in progress will further clarify the factor structure of the questionnaire and remove redundant items.

Conclusion

Results suggest the CaTAQ can provide nuanced information about older adults’ attitudes to computers and technology that have the potential to influence CNA performance and acceptability. The results will need to be confirmed in a less‐educated sample with less computer experience, and in people with Mild Cognitive Impairment or mild dementia. This new instrument has the potential to inform decisions about suitability of computerised cognitive testing for older adults in research and clinical settings.
MRI investigations of white matter hyperintensity and structural abnormalities of brain in urban and rural cohorts of India
Authors: Tiwari Vivek , Kallur Kumar , Rao Naren P , Sivakumar Palanimuthu T , Balakrishnan Aditi , Ravindranath Vijayalakshmi ,   SANSCOG and TLSA Investigators
Published: December 2020

Background

White‐matter degeneration appears as white‐matter‐hyperintensities (WMHs) on T2‐weighted FLAIR (T2w‐FLAIR) MRI. WMH load and alterations in hippocampal volume may serve as an imaging‐marker to identify brain‐health in aging and associated disorders. Here, we have investigated periventricular‐white‐matter‐hyperintensities (PVWMHs) and deep‐white‐matter‐hyperintensities (DWMHs) together with brain volumetric‐measurements in an urban‐cohort TATA longitudinal study on aging (TLSA) and a rural‐cohort Srinivaspura Aging, Neuro Senescence and COGnition study (SANSCOG) at the baseline visit of the longitudinal‐study. These study cohorts have distinct population characteristics: SANSCOG participants are recruited from the rural area Srinivaspura, whereas, those in TLSA are recruited from urban Bangalore. The study cohorts comprise of cognitively healthy individuals aged ≥45 years.

Method

MRI experiments were conducted on 3T whole‐body scanner. T2w‐FLAIR, 3D‐MPRAGE and DWI MR‐images were obtained. WMHs volume‐burden was measured using Fazekas grading on T2w‐FLAIR images. WMHs load and volumetric‐measures were stratified across three age‐groups, early (45‐54 years), intermediate (55‐64 years) and late (>65 years), for both cohorts.

Result

MRI analysis was performed across 117 subjects in the urban‐cohort (TLSA) and 84 from the rural‐cohort (SANSCOG) from the ongoing study. Prevalence of PVWMHs in the SANSCOG‐cohort was significantly higher (p<0.001) at the early age‐group (45‐54 years) compared to that of TLSA‐cohort. PVWMHs in SANSCOG was significantly higher across all the age‐groups, although PVWMHs in TLSA closely catched‐up at the late‐age group. This suggests that rural cohort had severe vascular abnormality at much earlier age while vascular health deteriorated with increasing age for the urban cohort. Prevalence of PVWMHs in SANSCOG‐cohort did not significantly change across age‐groups, while TLSA‐cohort showed significant increase with increasing age. Similarly, DWMH prevalence was also higher in the SANSCOG at the early age‐group but did not increase significantly with age. However, WMH‐load (Fazekas grading) with aging showed significant positive correlation, indicating that WMH volume‐burden increases with age for both cohorts. Gender based segregation showed that WMH‐prevalence was significantly higher for males (>55%) in both cohorts.

Conclusion

Increased WMHs prevalence at the early‐age in the rural‐cohort indicates occurrence of small vessel pathology of brain at much earlier age compared to the urban‐cohort. This may predispose the rural population towards aging associated disorders.
Plasma biomarkers Aβ42, Aβ40, and tau in Down syndrome dementia
Authors: Honig Lawrence S , Kang Min Suk , Lee Joseph H. , Silverman Wayne , Lott Ira T. , Lai Florence , Rosas H. Diana , Petersen Melissa , O'Bryant Sid , Andrews Howard , Pang Deborah , Krinsky‐McHale Sharon J. , Schupf Nicole
Published: December 2020

Background

Adults with Down syndrome (DS) develop Alzheimer’s disease (AD) brain changes, including excess Aβ42, Aβ40, and tau aggregates, generally by the fifth decade of life, and with time ultimately develop a dementia syndrome. Here we examine the relationship of baseline plasma biomarkers Aβ42, Aβ40, and tau, to dementia status, in adults with DS from a large DS cohort (ADDS funded by NIH grant U01AG051412).

Methods

Participants included 164 adults with DS who provided blood sample for plasma isolation at enrollment baseline, with mean age 50.9±6.9 yr (range 40 to 81), including 92 men (56%) and 72 women (44%), with ethnic distribution 87% white, 6% Hispanic, 4% Asian, 2% black, and 1% Native American. Dementia status was 18% with Dementia, 21% with Mild Cognitive Impairment (MCI), 58% without MCI or dementia, and 2% undetermined. Apolipoprotein E (APOE) status was available for N=157: 71% no e4, 29% ≥1 e4. Plasma Aβ42, Aβ40, and tau were determined using a SIMOA (Quanterix) SR‐X system with Neuroplex‐3 kits.

Results

Mean levels (pg/ml) were Aβ42 20.3±5.8 (range 9.0‐47.0) , Aβ40 468±116 (163‐896), and tau 4.78±2.85 (1.52‐20.46), with derived ratios Aβ42/Aβ40 0.044±0.010 (0.018‐0.101) and tau/Aβ42 0.236±0.124 (0.065‐1.191). Neither AB42 nor AB40 levels, nor tau/AB42 ratio correlated with age, although the AB42/AB40 ratio did show some decline with age (r = .16; p = 0.04). Dementia status, adjusted for age, did not significantly relate to baseline Aβ42, Aβ40 or Aβ42/Aβ40 ratio, but did relate to tau/Aβ42 ratio. The group of individuals with DS and MCI or Dementia had significantly greater tau/Aβ42 ratios (p= 0.001), than the group without, as did the groups just with MCI (p = 0.012), or just with dementia (p = 0.008), when adjusted for age and sex. These relationships were preserved when additionally adjusting for ethnicity and presence of APOE e4 allele, which itself was significantly related to dementia status.

Conclusions

While cerebrospinal fluid measures are the gold standard for assessing Alzheimer’ pathology, these results suggest that in persons with DS, plasma measurements of Aβ42 and tau using the SIMOA technique may allow biomarker confirmation of Alzheimer’s dementia.
Relation between CAIDE scores and cognition: Data from TATA Longitudinal Study of Ageing
Authors: M.L. Abhishek , Balakrishnan Aditi , Muralidhar Sneha Dhanvanthri , Rao Naren P. , Ravindranath Vijayalakshmi ,   TLSA Investigators
Published: December 2020

Background

The clinical and cognitive characteristics of people at increased risk of dementia may help provide insights into preclinical stage of dementia. The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study risk score is a reliable tool to estimate the individual risk of future dementia. Associations of CAIDE with performance in different cognitive domains are not fully clear in Indian population. Hence we studied the relation of CAIDE scores with cognitive performance in healthy middle aged elderly individuals from India.

Method

Data from 215 volunteers participated in TATA longitudinal study of aging was analyzed. All participants underwent cognitive tests such as Hindi mental state examination (HMSE), Digit symbol substitution test (DSST), Stroop test, Logical memory test and Addenbrooke Cognitive Examination‐III (ACE III). CAIDE scores are calculated by assigning scores to participants risk factors [age(<47 years = 0, 47–53 years=3, >53 years = 4); education (>/= 10 years = 0, 7–9 years = 2, 0–6 years = 3); sex (female = 0, male = 1); systolic blood pressure (</= 140 mmHg = 0, >140 mmHg = 2); body mass index (</= 30 kg/m2 = 0, >30 mg/m2 = 2); total cholesterol (</= 6.5 mmol/L = 0, >6.5 mmol/L = 2); physical activity (active = 0, inactive = 1)] and then totaling it. Spearman’s rank correlation analysis was conducted to examine the relation between CAIDE scores and cognitive tests.

Result

There was a significant negative correlation between CAIDE score and ACE III total score (rs = −.265, P < 0.001). DSST time and Stroop C time correlated positively with CAIDE score (rs = .241, P < 0.001 & rs = .283, P = 0.01). There was no significant correlation with HMSE.

Conclusion

Our findings indicate an inverse relation between CAIDE scores and global cognitive performance (ACE III), attention (DSST) and executive functioning (Stroop) but not with memory (Logical memory test). No relation was found with HMSE probably due to ceiling effect. If these findings are replicated then it could give insights in to clinical manifestations of preclinical stage of dementia.
Clinical utility of transcranial direct current stimulation and online language training in semantic dementia
Authors: Rangarajan Subhashini K. , Mukku Shiva Shanker Reddy , Gorthi Naga V.S.S. , Jagtap Namrata , Shetty Preetie A. , Girimaji Akhila , Sreeraj Vanteemar S. , Selvaraj Sowmya , Sivakumar Palanimuthu T. , B.K. Yamini , Shivashankar N. , Venkatasubramanian Ganesan
Published: December 2020

Background

Semantic dementia (SD) is a variant of primary progressive aphasia (PPA) which is characterised by impaired confrontation naming, single word comprehension and object recognition with preserved fluency and syntax. Similar to many other neurodegenerative dementias, there is currently no effective treatment for semantic dementia. Neuromodulatory interventions like transcranial direct current stimulation(tDCS) and repetitive transcranial magnetic stimulation(rTMS) along with language training is emerging as a potential treatment strategy for Primary progressive aphasia. Aim: Four patients with semantic dementia were administered concomitant online language training with tDCS to study the feasibility and clinical outcome.

Method

Four patients (2 males) aged between 50‐63 years, diagnosed with semantic dementia after a comprehensive clinical assessment and Addenbrooke’s cognitive examination and Clinical Dementia Rating(CDR) scale by an experienced geriatric Psychiatrist were included in the case series. Detailed assessment of neurolinguistic skills was done using Western Aphasia Battery (WAB‐Kannada/Hindi) before and after 5‐days of tDCS by qualified speech pathologist. Daily tDCS sessions were delivered using 2mA current with anode over the left dorsolateral prefrontal cortex and cathode over right supraorbital area for 30 minutes, except one female patient with moderate dementia who received 2 session daily at an interval of 3 hours. Online cognitive‐linguistic intervention was provided by the speech pathologist during tDCS sessions. Adverse effects were monitored using structured questionnaire.

Result

Three Patients had mild dementia and one had moderate dementia as per CDR. tDCS was tolerated well except for burning sensation in two sessions in one patient and all were able to attend the linguistic training. All subjects improved in the domains of Spontaneous speech, Auditory verbal comprehension, repetition and naming on the WAB.

Conclusion

tDCS can be a potential therapeutic modality in semantic dementia. Randomized Sham Controlled Clinical trials are required to establish the efficacy of tDCS and language training in the treatment of semantic dementia.
High‐resolution postmortem MRI reveals TDP‐43 association with medial temporal lobe subregional atrophy
Authors: Wisse Laura , Ravikumar Sadhana , Ittyerah Ranjit , Lim Sydney A. , Lane Jacqueline , Lavery Madigan , Xie Long , Robinson John L. , Schuck Theresa , Grossman Murray , Lee Eddie B. , Tisdall Dylan M. , Prabhakaran Karthik , Detre John A. , Das Sandhitsu R. , Mizsei Gabor , Artacho‐Perula Emilio , Martin Maria Mercedes Iniguez de Onzono , Jimenez Maria del Mar Arroyo , Munoz Monica , Romero Francisco Javier Molina , Rabal Maria del Pilar Marcos , Sanchez Sandra Cebada , Gonzalez Jose Carlos Delgado , Prieto Carlos de la Rosa , Parada Marta Corcoles , Irwin David J. , Trojanowski John Q. , Wolk David A. , Insausti Ricardo , Yushkevich Paul A.
Published: December 2020

Background

The medial temporal lobe (MTL) is a hotspot of different neurodegenerative pathologies, and recent studies have shown associations of severity of pathology with atrophy measured on antemortem MRI. However, these studies are limited by the interval between time of scan and death and the relatively low resolution of the commonly acquired in vivo MRI scans, limiting the granularity of the regions being measured. We investigate the association of different neurodegenerative pathologies, particularly TDP‐43, and the thickness of different MTL subregions measured on high‐resolution postmortem MRI. As prior work suggests an anterior‐to‐posterior gradient of atrophy for TDP‐43 in frontotemporal dementia spectrum disorders and Limbic‐predominant Age‐related TDP‐43 Encephalopathy (LATE), we also examined differences along the long axis of the MTL.

Method

Tau, TDP‐43, β‐amyloid and α‐synuclein pathology were rated (0‐absent – 3‐frequent) in the hippocampus and entorhinal cortex (ERC) of 35 individuals with and without neurodegenerative diseases (Table 1). Thickness measurements were obtained from 0.2x0.2x0.2 mm3 post‐mortem MRI scans of excised MTL specimens from the contralateral hemisphere (Figure 1) in the ERC, Brodmann Area 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare. For each region, thickness was measured at an anterior and posterior location using a semi‐automated approach (Figure 2). Spearman’s rank correlations were performed, correcting for age, sex and hemisphere, including all four proteinopathies in the model.

Result

We find strong negative associations of TDP‐43 with thickness in all cortical MTL regions (Table 2, Figure 3) and with CA1, averaged over the two locations. We repeated the analyses for the thickness measurements separately in the anterior and posterior locations, but did not find a clear difference along the longitudinal axis. This is potentially due to the severity of the TDP‐43 pathology.

Conclusion

In this unique dataset with neurodegenerative pathologies and high‐resolution scans of the MTL, preliminary results show strong associations between TDP‐43 pathology and atrophy in several MTL subregions. As this dataset continues to grow, we will be able to tease apart the effects of multiple MTL pathologies at a subregional level.
Cognitive worry in cognitively normal older adults is associated with decreased memory binding, hippocampal volume and parahippocampal thickness
Authors: Markova Hana , Mazancova Adela Fendrych , Cechova Katerina , Nikolai Tomas , Matuskova Veronika , Nedelska Zuzana , Sheardova Katerina , Laczó Jan , Hort Jakub , Vyhnalek Martin
Published: December 2020

Background

Worry associated with subjective cognitive decline (cognitive worry) in cognitively normal (CN) older adults has been established as a feature that increases the likelihood of preclinical Alzheimer´s disease (AD). Previously, it has been associated with a higher risk of progression to mild cognitive impairment and dementia. We aimed to examine whether presence of cognitive worry reflects poorer memory performance and decreased volumes or cortical thicknesses in AD‐related regions in CN older adults.

Method

In total, 85 CN older adults reporting cognitive complaints were recruited from the Czech Brain Aging Study and classified into two groups by subjective evaluation of presence/absence of cognitive worry (WORRY+/‐, n = 36 and n = 49, respectively). All participants underwent a comprehensive neuropsychological examination, including the Rey Auditory Verbal Learning Test (RAVLT), Logical Memory I (LM I) and the challenging Memory Binding Test (MBT). 1.5T MRI with T1‐weighted 3‐dimensional images and FreeSurfer 5.3. algorithm was used to measure left and right hippocampal volume (HVL, HVR), left and right entorhinal and parahippocampal thickness (ERCL, ERCR, PHCL, PHCR). Individuals with significant vascular‐related white matter hyperintensities were not included. A one‐way ANCOVA assessed the between‐groups differences, controlling for sex, age and education.

Result

The WORRY+ did not differ from the WORRY‐ group in the RAVLT or LM I scores, but performed significantly lower in the MBT scores evaluating both free and cued recall in immediate and delayed conditions (ps ≤ 0.012). Consistently, the WORRY+ group had significantly decreased adjusted HVR, decreased PHCL and PHCR (ps ≤ 0.019). No other between‐group differences were found in medial temporal lobe measures.

Conclusion

Cognitive worry in CN older adults is associated with both poorer memory performance in the challenging test of memory binding and decreased hippocampal volume and parahippocampal thickness even cross‐sectionally. Given that cortical thinning and hippocampal atrophy on MRI, together with poor cognitive performance on challenging tests, are detectable in late stages of preclinical AD, cognitive worry may be a risk factor for imminent functional impairment and disease progression.
Socioeconomic inequalities in cognitive function in midlife and early late‐life are partially attributable to modifiable health and lifestyle factors
Authors: Roehr Susanne , Pabst Alexander , Witte A Veronica , Schroeter Matthias L , Loeffler Markus , Villringer Arno , Riedel‐Heller Steffi G
Published: December 2020

Background

There are socioeconomic inequalities in dementia risk. Growing evidence highlights the prevention potential of dementia through modifiable health and lifestyle factors. We aimed to investigate whether health and lifestyle factors play a mediating role in the association of socioeconomic inequalities and cognitive function in midlife and early late life in the general population.

Method

The “LIfestyle for BRAin health” (LIBRA) score was computed for 6.203 baseline participants of the LIFE‐Adult study, a population‐based cohort to investigate civilization diseases in the German population. LIBRA is a validated score (range: ‐5.9 to +12.7) that predicts dementia in midlife and early late life, consisting of twelve modifiable health and lifestyle factors (heart disease, kidney disease, diabetes, obesity, hypertension, hypercholesterolemia, alcohol consumption, smoking, physical inactivity, diet, depression, cognitive activity). Socioeconomic status (SES; low/middle/high) was calculated based on education, net equivalence income, and occupational status. We used structural equation modelling to inspect potential mediation of the LIBRA score between SES and measures of cognitive function (Verbal Fluency Test/VFT; Trail Making Test/TMT A and B). Analyses were adjusted for age, sex, marital status, living situation, employment, and social network.

Result

Participants were M = 57.7 (SD = 12.0, range: 40‐79) years old and dementia‐free; 50.7% were female. Individuals with low SES had significantly higher LIBRA scores (indicating higher dementia risk) compared to individuals with middle SES and high SES, who had the lowest LIBRA scores (M = 1.2, SD = 2.3 vs. M = ‐0.4, SD = ‐2.6 vs. M = ‐1.2, SD = 2.5; F(2) = 271.8, p < .001). Likewise, all neuropsychological test scores showed that cognitive function was lowest in individuals with low SES and highest in individuals with high SES. Bootstrapped mediation analysis indicated that 12.4% (VFT) to 22.8% (TMT) of the differences in cognitive function between low SES and high SES were significantly mediated by differences in LIBRA scores.

Conclusion

Differences in cognitive function due to socioeconomic inequalities can be partially attributed to differences in modifiable health and lifestyle factors. Thus, promoting health and lifestyle changes in individuals with low SES could contribute to attenuate socioeconomic inequalities in cognitive function, potentially benefiting dementia prevention.
Sex differences in subcortical aging: A nomogram study of age, sex, and apoe (N = 9,414)
Authors: Ching Christopher , Abaryan Zvart , Santhalingam Vigneshwaran , Zhu Alyssa , Bright Joanna , Jahanshad Neda , Thompson Paul M
Published: December 2020

Background

Common variants in the APOE gene are associated with cognitive decline, brain atrophy and risk for developing Alzheimer’s disease (AD). APOE polymorphism effects may also vary with age, sex, body mass index (BMI), and other risk factors. Here we create percentile charts ‐ or ‘nomograms’ ‐ plotting the trajectory of subcortical volumes with age, stratified by sex and by APOE genotype, in a large population‐based sample from the UK Biobank. We hypothesized that age effects would differ in men and women and APOE e4 allele carriers would tend to show steeper age‐related decline compared to those carrying APOE e3 and e2 genotypes.

Method

T1‐weighted brain MRI UK Biobank data (N=9,414; age range: 44‐79 yrs (Table 1) were processed using FreeSurfer v5.3 to derive quality inspected volumes averaged across hemispheres: lateral ventricles, hippocampus, thalamus, putamen, pallidum, amygdala, caudate, nucleus accumbens, and intracranial volume (ICV). The R package rstandard was used to adjust subcortical volumes for effects of ICV and BMI. R package GAMLSS, specifically the centile function, was used to compute percentile curves for each ROI based on standardized residuals, with ROI volume as the dependent variable and age as the independent variable. Separate models were fitted by sex and for each APOE genotype and visualized for trends with age.

Result

Nomograms for the full cohort showed trends for increasing lateral ventricle and decreasing thalamus, putamen, hippocampus, amygdala, and nucleus accumbens volumes with increasing age (Figures 1‐2). In men, volumes decreased at a faster rate until age 60, when volumetric decline in women appeared to accelerate and catch up with males. Nomograms separated by APOE genotype (Figure 1) all followed similar patterns, though smaller samples of APOE e2/2 and e4/4 genotypes limit the interpretability of those age trends.

Conclusion

Nomograms plotted by sex show a differential age trajectory for men and women offering clues for future sex‐dependent brain related assessment and intervention. APOE genotype did not strongly influence nomograms, though a greater number of APOE e2/2 and e4/4 individuals are needed to obtain reliable normative trends.
The Aβ42/Aβ40 ratio in plasma is associated with amyloid‐PET status and rate of progression in individuals with subjective cognitive decline: The Fundació ACE Healthy Brain Initiative
Authors: de Rojas Itziar , Fandos Noelia , Romero Judith , Pesini Pedro , Marquié Marta , Tartari Juan Pablo , Sanabria Angela , Sotolongo‐Grau Oscar , Ruiz Agustin , Boada Mercè , Sarasa Manuel ,   the FACEHBI study group
Published: December 2020

Background

Cumulative data suggest that subjective cognitive decline (SCD) could be an early clinical manifestation of Alzheimer’s disease (AD). The performance of blood based AD‐related biomarkers at this early stage of the disease continuum has not been sufficiently studied yet.

Method

We explored the association between total Aβ42 to total Aβ40 ratio in plasma (TP42/40) assessed by ABtest (Araclon Biotech) and cortical β‐amyloid assessed by Florbetaben positron emission tomography (FBB‐PET, Life Molecular Imaging) scan in 162 cases of SCD from the Fundació ACE Healthy Brain Initiative (FACEHBI) with plasma and FBB‐PET data at baseline (V0) and two years follow‐up (V2) visits. All plasma samples were analyzed simultaneously at the time of V2. Cut‐off for PET‐FBB positivity was established at a global standardized uptake volume ratio (SUVR)>1.45.

Result

TP42/40 was significantly lower in FBB‐PET‐ve) than in FBB‐PET+ve group at both time points (Mann‐Whitney test P<0.0001). The AUC in the ROC analysis for the relevant demographic variables (age and APOE genotype) to discriminate FBB‐PET status at V0 and V2 was 80% and 83%, respectively. Those values increased significantly (P<0.01) up to 90% and 92%, respectively, when TP42/40 was included as a predictive variable within the model. The performance parameters of TP42/40 to discriminate FBB‐PET status in V0∼V2 were SEN 1.0∼0.94, SPE 0.49∼0.42, PPV 0.16∼0.15 and NPV 1.0∼0.98, respectively. Caution should be exerted when interpreting these values because they could be biased given the very low prevalence of FBB‐PET+ve (8.6%) in this early population, at the current SUVR cut‐off. Nevertheless, in a recruiting scenario targeting FBB‐PET+ve individuals with SCD, a pre‐screening step based on TP42/40 could save 46%∼34% of PET scans. Furthermore, those individuals with a TP42/40 ratio in the lowest quartile at V0 showed significantly (P<0.01) greater increases of FBB‐PET SUVR at V2 than those with a V0 plasma ratio in the two upper quartiles.

Conclusion

TP42/40 is consistently associated with cortical β‐amyloid burden assessed by FBB‐PET in individuals with SCD. The TP42/40 could be a useful tool helping in the recruitment of SCD individuals with preclinical Alzheimer’s.
The Barcelonabeta dementia prevention research clinic: Study design, recruitment profiles and inclusion in prevention studies — An update
Authors: Fauria Karine , Minguillón Carolina , Félez‐Sánchez Marta , Menezes‐Cabral Sofia , Sánchez‐Benavides Gonzalo , Grau‐Rivera Oriol , Gispert Juan Domingo , Molinuevo Jose Luis
Published: December 2020

Background

Up to 40% new patients in memory clinics complain of worse cognitive performance scoring within normal ranges in cognitive tests, hence presenting what is termed ‘subjective cognitive decline’ (SCD). Although usually dismissed, they present an increased progression rate to mild cognitive impairment (MCI) and dementia. There is, therefore, an emergent need for newly designed programs to provide individual risk estimates and tailored risk‐reduction plans. With the aim of assessing the emotional impact and cost‐benefit of these programs, we established the BarcelonaBeta Dementia Prevention Research Clinic (BBDPRC).

Method

A longitudinal, prospective study of 400 participants (60‐80 years) with SCD or MCI was set‐up. General population participants concerned about their cognitive performance were pre‐selected by their replies to web‐based forms capturing information about their subjective cognitive performance. Those selected undergo baseline visit for (1) diagnosis, (2) collecting data to enable the estimation of a dementia risk score and (3) produce their personalised prevention action plan. At the subsequent visit, their risk estimates are disclosed and personalised primary prevention advice presented. Individuals with MCI are readily offered to enter studies/trials they may benefit from. The emotional impact of disclosure is measured at 1 and 6 weeks and 6 and 12 months post‐disclosure. At 6‐weeks, SCD participants are offered to enter suitable prevention studies (Fig.1). A cost‐benefit analysis of this program will also be performed using standard methods.

Result

BBDPRC was presented in a press‐conference. 1,633 persons registered on the website and >50% of them were classified by an embedded algorithm as a priori eligible (Fig.2). To date, ∼300 persons (First‐Patient‐In 16/7/2018) have undergone baseline visit (screening failure 6.5%). From the ones with disclosed diagnosis, 18.5% were MCI, 55.0% SCDplus (fulfilling >3 SCDplus features) and 26.5% SCD. 52.9% of these participants comply with eligibility criteria with ongoing studies at BBRC and, remarkably, 69.9% were included in the studies proposed (Fig.3).

Conclusion

We have established a web‐based registry that is proving to be very efficient in recruiting SCDplus or MCI individuals being more than half suited for dementia prevention studies and trials. Furthermore, this infrastructure sets the basis for future personalised approaches.
Different abnormalities of electroencephalographic (EEG) markers in quiet wakefulness are related to motor visual hallucinations in patients with Parkinson’s and Lewy body diseases
Authors: Lopez Susanna , Percio Claudio Del , Pascarelli Maria Teresa , Lizio Roberta , Noce Giuseppe , Ferri Raffaele , Soricelli Andrea , Nobili Flavio Mariano , Arnaldi Dario , Famà Francesco , Bonanni Laura , Franciotti Raffaella , Onofrj Marco , Fuhr Peter , Gschwandtner Ute , Ransmayr Gerhard , Aarsland Dag , Parnetti Lucilla , Farotti Lucia , Marizzoni Moira , D'Antonio Fabrizia , de Lena Carlo , Güntekin Bahar , Hanoğlu Lutfu , Yener Görsev , Emek‐Savas Derya Durusu , Triggiani Antonio Ivano , Taylor John‐Paul , McKeith Ian , Stocchi Fabrizio , Vacca Laura , Hampel Harald , Frisoni Giovanni B , Pandis Maria Francesca , Babiloni Claudio
Published: December 2020

Background

Parkinson’s disease (PD) is the second‐most common neurodegenerative disorder that affects 2–3% of the population ≥ 65 years of age and may belong to cognitive deficits and dementia in 50% of cases. Disease with Lewy Bodies (DLB) is emerging as another important cause of dementia in pathological aging. PD and DLB are both due to intra‐neuronal Lewy bodies and are characterized not only by motor dysfunctions but also by cognitive and/or psychiatric symptoms. An open issue is the extent to which these diseases are distinct entities. In this respect, here we compared cortical sources of resting state eyes‐closed electroencephalographic (rsEEG) rhythms in PD and DLB patients having visual hallucinations.

Method

Clinical and rsEEG rhythms in demographic matched PD (N = 93), DLB (N = 46), Alzheimer’s disease dementia (AD, N= 70) and healthy elderly (Nold, N = 60) subjects were available from an international archive. Pathological groups were matched for cognitive status. Individual alpha frequency peak was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were considered. The eLORETA freeware estimated rsEEG cortical sources.

Result

As a confirmation of previous studies, compared to the Nold subjects, the AD, LBD, and PD patients showed higher widespread delta source activities and lower posterior alpha source activities. Specifically, posterior alpha source activities were more abnormal in the AD than the LBD and PD groups, while widespread delta source activities were more abnormal in the PD and DLB than the AD group. As novel results, in relation to the LBD and PD patients without visual hallucinations and the control groups (Nold, AD), those with visual hallucinations were characterized by higher parietal delta source activities (LBD, Figure 1) and parieto‐occipital alpha sources activities (PD, Figure 2).

Conclusion

These novel results suggest that in LBD and PD patients resting in the quiet wakefulness, abnormalities in cortical neural synchronization at delta and alpha frequencies in parietal cortex are differently related to visual hallucinations despite the essence of alpha‐synucleinopathy.
Association of Alzheimer's disease and amyotrophic lateral sclerosis: A series of cases and review of the literature
Authors: Vrillon Agathe , Deramecourt Vincent , Pasquier Florence , Wallon David , Lozeron Pierre , Amar Elodie Bouaziz , Paquet Claire
Published: December 2020

Background

Amyotrophic lateral sclerosis (ALS) is a sporadic or familial fatal neurodegenerative condition that affects motor neurons in primary motor cortex, brainstem and spinal cord. While predominantly a motor disorder, ALS is frequently associated with cognitive impairment, mostly of frontal type. Hippocampic syndrome is not recognized as part of the cognitive phenotype of ALS.

Method

After a national translational survey, we report a French multicentric case series of three patients that presented with an association of definite Alzheimer disease (AD) and ALS. A systematic review of the literature was carried out in January 2020 to explore already reported similar cases.

Result

Patient n°1 had a history of behavioral variant of AD followed seven years later by onset of bulbar ALS. Cerebro‐Spinal Fluid (CSF) AD biomarkers displayed AD biological profile associated with ApoE4E4 genotype. Genetic testing for C9ORF72 expansion was negative. Patient n° 2 was diagnosed with ALS, associated with dysexecutive syndrome and CSF AD biological profile (Wallon et al, 2012). Patient n°3 had clinical AD and ALS. Post‐mortem analysis was available, confirming motoneuron disease and Alzheimer type pathology. Review of the literature retrieved only few other cases of co‐occurence of AD and ALS (Nijboer et al, 2019; Farid et al, 2015; Müller et al, 1993). More frequently, association of amyloid pathology to ALS lesions at post‐mortem examination has been described in ALS patients with or without cognitive impairment. Nevertheless, the relationship between these findings and clinical manifestations is still unclear. The mechanisms that account for the underlying neurodegenerative processes that occured in our patients remain to be comprehended.

Conclusion

We report a series of cases associating AD and ALS and discuss the hypothesis of it being an under recognized phenotype.
Classification of Alzheimer’s disease dementia (ADD) by using features derived from resting‐state electroencephalography (rsEEG)
Authors: Lizio Roberta
Published: December 2020

Background

Alzheimer’s disease (AD) is the most prevalent progressive neurodegenerative disease of the brain affecting the aged people, and the most common cause of dementia (ADD). The actual diagnostic biomarkers of AD are invasive and expensive (e.g., lumbar puncture for CSF sampling; the injection of radioactive tracers in PET procedures). Resting‐state electroencephalography (rsEEG) provide topographic markers useful to assess the neurophysiological changes of the brain that correlate with the cognitive decline and dementia in AD patients.

Method

In this retrospective study, we tested whether the cortical sources of rsEEG rhythms could classify with good performance ADD patients from healthy elderly (Nold) individuals and patients with other diseases. Clinical and rsEEG data of ADD, Parkinson’s disease with dementia (PDD), dementia with Lewy body (DLB), and Nold subjects were available in an international archive. eLORETA estimated the rsEEG cortical sources. Delta, theta, low alpha, high alpha, low beta, high beta, and gamma were the frequency bands of interest. The correct blind classifications (ADD vs Nold, ADD vs PDD, ADD vs DLB individuals) of these rsEEG source activities were performed by GraphPad‐Prism software to produce the receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) provided a measure of how well the rsEEG source activities distinguished the groups (AUC>0.7 as a threshold for a moderate classification rate).

Results

The posterior delta and alpha sources allowed good classification accuracy (AUC: 0.75‐0.90) in Nold (N=40) vs ADD (N=42), ADD (N=42) vs PDD (N=42), and ADD (N=42) vs DLB (N=38) individuals (Figure.1). We also obtained a good classification accuracy (AUC > 0.80) between the Nold (N = 100) and ADD (N = 100) individuals using bipolar parieto‐occipital delta/alpha and theta/alpha rsEEG features.

Conclusion

These results suggest that cortical sources of posterior rsEEG rhythms at different frequency bands and frequency band ratios can be used to discriminate ADD individuals with good performance (AUC>0.8). A single rsEEG marker from a point of care device would provide a cost‐effective, non‐invasive, and repeatable over time biomarker for the assessment of the AD status and progression directly at home.
Psychiatric symptoms in the early detection and differential diagnosis of FTD
Authors: Ducharme Simon
Published: December 2020

Background

The early symptoms of behavioral‐variant frontotemporal dementia (bvFTD) have considerable overlap with the common primary psychiatric disorders like major depression and psychotic disorders. Consequently, about 50% are diagnosed with a psychiatric disorder before the identification of bvFTD. While this can be due to inadequate recognition of bvFTD features and lack of expertise, the diagnostic effort is also complicated by the fact that psychiatric symptoms like delusions and hallucinations are sometimes the prodrome to bvFTD—particularly in familial cases. Whereas the reliability of Alzheimer’s disease diagnoses has improved with the advent of molecular biomarkers, the diagnosis of bvFTD remains primarily based on clinical assessment and neuroimaging. The need for a systematic approach to distinguish bvFTD from psychiatric disorders is addressed in recommendations recently developed by an internal panel of experts, the Neuropsychiatric International Consortium for FTD, and are reviewed in this presentation.

Method

The Neuropsychiatric International Consortium for FTD was convened to develop recommendations for a diagnosis approach for identifying bvFTD in individuals with midlife‐onset (>45 years) behavior change. The consensus process included a systematic review of the literature to identify best practices, effective clinical measures and the utility of brain imaging.

Result

Differential diagnosis of bvFTD from psychiatric disorders is facilitated by comprehensive and chronologically‐ordered history, family history of neurodegenerative or neuromuscular disease, use of formal diagnostic criteria for bvFTD and for psychiatric disorders, use of bedside measures of general cognition and social behavior, psychiatric scales and brain imaging. These have been incorporated into an algorithm to facilitate use of the recommendations.

Conclusion

A systematic approach to the clinical examination can be facilitate the differential of bvFTD from primary psychiatric disorders. This is valuable for providing timely diagnosis, and early counseling and treatment planning to patients, for facilitating testing of novel treatments in clinical trials—and will also facilitate proper treatment for patients with primary and secondary psychiatric states.
Dorsolateral prefrontal cortex metabolites and their relationship with plasticity in Alzheimer’s disease
Authors: Kumar Sanjeev , Iwata Yusuke , Zomorrodi Reza , Blumberger Daniel M. , Fischer Corinne E. , Daskalakis Zafiris J. , Mulsant Benoit H. , Pollock Bruce G. , Graff‐Guerrero Ariel , Rajji Tarek K.
Published: December 2020

Background

Previous studies have shown that patients with Alzheimer’s disease (AD) present with deficits in neuroplasticity of their dorsolateral prefrontal cortex (DLPFC); and decreased N‐acetyl aspartate (NAA) and increased myo‐inositol (mI) concentrations in the cingulate cortex and hippocampus. In this study, we examined the relationship between these metabolites and neuroplasticity in the DLPFC of patients with AD and healthy older adults.

Method

Patients meeting the core clinical criteria for probable AD and older healthy controls (HC) were recruited. Left DLPFC plasticity was assessed using paired associative stimulation (PAS) combined with EEG. NAA and mI concentrations were assessed in the DLPFC using 3T proton Magnetic Resonance Spectroscopy (point‐resolved spectroscopy, echo time = 35 ms).

Result

48 AD participants (mean (SD) age: 75.4 (6.9) years; mean (SD) Mini Mental State Examination (MMSE) score (SD): 23.1 (3.1)) were compared with 27 HC (mean (SD) age: 72.3 (7.0) years; mean (SD) MMSE: 29.5 (0.6)): participants with AD had impaired DLPFC plasticity (t = 2.8, df = 69, p = 0.006) and decreased NAA concentration in the DLPFC (t = 2.4, df = 64, p = 0.02). In the combined group of AD and HC participants, after correcting for multiple comparisons, mI concentration in the DLPFC was negatively correlated with DLPFC plasticity (Pearson’s r = ‐ 0.4, n = 62, p corrected = 0.002).

Conclusion

Deficits in neuroplasticity in the DLPFC of patients with AD are associated with abnormalities of a metabolite indicative of neuronal injury. These findings advance our understanding of potential mechanisms underlying deficits in DLPFC plasticity in AD.