bluuebunny/crossref_metadata_2025 huggingface dataset:
WW‐FINGERS‐SARS‐CoV2 in Finland: Changes in lifestyle and risk factors for cognitive impairment during the pandemic in the FINGER study
Authors: Ngandu Tiia , Lehtisalo Jenni , Mangialasche Francesca , Hemiö Katri , Solomon Alina , Kivipelto Miia
Published: December 2021

Background

Restrictions enforced in many counties during the COVID‐19 pandemic may have both short‐ and long‐term effects on the risk factors relevant for cognitive impairment and dementia. The COVID‐19 pandemic occurred during the post‐intervention follow‐up phase of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) postponing the planned follow‐up visits of the participants. We investigated how the first phase of the COVID‐19 pandemic affected lifestyles and other risk factors among the FINGER participants using a postal survey.

Method

A survey was sent in June 2020 to 859 eligible FINGER participants. The survey was developed to assess the effects of the COVID‐19 pandemic and related infection‐control measures on lifestyles, daily life, commitment to distancing measures, access to healthcare and social services, and changes in cognitive and social activities, as well as emotional health and wellbeing.

Result

A total of 735 participants responded to the survey (85% of the eligible participants). They were on average 78 years old at the time of the survey. Majority of the participants adopted some distancing practices during the first months of the pandemic. Older participants were more likely to practice total isolation than younger ones. Pandemic‐related changes were reported in social engagement, including less contact with friends and family, and less frequent participation in cultural events or associations, but on the other hand the frequency of remote contacts with others was increased. About a third of the participants reported that their physical activity was reduced, and this was more common among those who had been less active earlier. Pandemic‐related changes in lifestyle and activities were more evident among those living alone.

Conclusion

Finnish older persons were mainly reporting that they coped in the pandemic situation quite well. Older participants seemed to be more susceptible to negative changes. Also persons with less physical activity previously were likely to reduce their activities even more. This may have long‐term consequences on the cognitive health of older adults, and it may also impact the longer‐term effects of the FINGER intervention.
Oxidative stress mediates the effect of apathy on executive function in those at risk of vascular cognitive impairment
Authors: Lanctôt Krista L.
Published: December 2021

Background

People with coronary artery disease (CAD) are at a high risk of developing mild vascular cognitive impairment and those with cognitive decline have been shown to have higher ratios of late to early lipid peroxidation markers indicating oxidative stress. Neuropsychiatric symptoms can precede biomarker abnormalities e.g., depressive symptoms. Apathy has previously been linked to cognitive impairment, particularly executive dysfunction, but the physiological pathways underlying this relationship have not been investigated. This study investigated whether oxidative stress mediates a relationship between apathy and executive function in CAD.

Method

Participants with CAD were identified from a Cardiac Rehabilitation Program at the time of intake. The Apathy Evaluation Scale (AES) was used to measure apathy and executive function (EF) was measured via FAS test for phonemic fluency, animal naming test for semantic fluency and trails making test B. Markers of late (8‐isoprostane, 8‐ISO) and early (lipid hydroperoxides, LPH) lipid peroxidation/oxidative stress were measured in the serum. Mediation effects were tested using the PROCESS macro (version 3.4) for SPSS. A bias corrected inferential bootstrapping method with 10,000 permutations was used to obtain a 95% confidence interval (CI) for the indirect effect.

Result

Among patients with CAD (n=214, 20% women, mean±SD age= 63.2±7.5 years, years of education [YOE]= 15.8±3.4, AES score= 28.2±8.7, composite z score for EF= ‐0.18±0.71), the ratio of 8‐ISO to LPH mediated the relationship between apathy and EF in a model controlling for age, sex and YOE. The standardized regression coefficients between apathy and ratio of 8‐ISO to LPH (0.4961, p=0.02) and that between the ratio of 8‐ISO to LPH and EF (‐0.0053, p=0.005) were both statistically significant. Bootstrapping produced a statistically significant unstandardized indirect effect (‐0.0027 95% CI: ‐0.0087, ‐0.0007).

Conclusion

The results suggest that oxidative stress, specifically late markers of lipid peroxidation, plays a role in facilitating the relationship between apathy and executive dysfunction in those with CAD. As apathy is a strong predictor of conversion from cognitively normal to mild cognitive impairment, understanding mediators may suggest treatment targets.
Is it a new phenotype? Right temporal variant frontotemporal dementia
Authors: Erkoyun Hulya Ulugut , Pijnenburg Yolande A.L.
Published: December 2021

Background

Frontotemporal dementia (FTD) is heterogeneous and presents with behavioral or language symptoms with frontal and/or temporal atrophy. A variant presenting with anomia and word comprehension deficits, is termed semantic dementia (SD) and is associated with predominant left anterior temporal atrophy. Although the clinical presentation is different on the right side, no unique syndrome to identify right temporal variant FTD (rtvFTD) has been established.

Methods

We retrospectively collected 70 rtvFTD patients from our cohort based on their initial MRI and identified the clinical characteristics based on the case notes and compared them with those reported in Alzheimer’s disease (n=70), behavioral FTD (n=70), and SD (n=70). In a subset of cases we reported the genetic (n=6) and pathological (n=5) features along with a review of cases in the literature (n=49).

Results

Based on our single‐center study, rtvFTD presented a unique combination of cognitive (face recognition and memory impairments), behavioral/psychiatric (disinhibition, apathy, depression, and bizarre preoccupations), and language problems (word‐finding difficulties and anomia). It's genetic/pathological background was heterogeneous, in contrast to SD. The most common genetic mutation was MAPT, followed by GRN and TARDBP. The most common pathological diagnoses were FTLD‐TDP type C and FTLD‐tau, followed by FTLD‐TDP type A and B. Moreover, pyramidal degeneration was observed as a co‐pathology.

Conclusion

The definition of a syndrome associated with right temporal atrophy could promote its recognition as a variant of FTD, which is crucial for individual patient management. A multicenter study will shed light on the many unanswered questions about this equivocal syndrome.
Mild behavioral impairment is associated with amyloid, tau and neurodegeneration in mild cognitive impairment
Authors: Ismail Zahinoor , Chen Hung‐Yu , Gill Sascha , Naude James , Smith Eric E.
Published: December 2021

Background

Mild behavioural impairment (MBI) is a dementia at‐risk syndrome using later‐life neuropsychiatric symptoms (NPS) to determine risk. For some, MBI may be a non‐cognitive marker of neurodegeneration. A hallmark criterion of MBI is symptom persistence. We examined associations between NPS and Alzheimer’s disease (AD) proteins for amyloid, tau, and neurodegeneration in participants with mild cognitive impairment (MCI), comparing groups with persistent, transient, and no NPS.

Method

ADNI participant data was used for this study including Neuropsychiatric Inventory (NPI) scores for baseline and one‐year visits and CSF measures for β‐amyloid (Aβ42), phospho‐tau (p‐tau), and total tau (t‐tau). MBI status was derived from the NPI using a published algorithm. For each visit MBI+ was defined as an MBI score >0 and MBI‐ as MBI=0. Participants with MBI+ at both baseline and 1‐year visits were classified as having persistent NPS (i.e., MBI). An MBI+ score at only one visit was considered as transient NPS not consistent with MBI, and two consecutive MBI‐ visits were classified as no NPS. CSF protein values were log transformed due to skewness. Linear regressions were fitted to assess the association between NPS status and CSF biomarkers (Aβ42, p‐tau, t‐tau, and the derived measures p‐tau/Aβ42 and t‐tau/Aβ42), controlling for age, sex, education, and mini‐mental state examination.

Result

The sample of 480 participants had a mean age of 72.6 (SD 7.6); 195 (40.6%) were female. Compared to participants with no NPS, persistent NPS (i.e., MBI) was associated with lower CSF Aβ42 levels (p=0.02), higher CSF p‐tau (p=0.01) and t‐tau levels (p=0.026), and higher p‐tau/Aβ42 (p=0.002) and t‐tau/Aβ42 ratios (p=0.003) in adjusted models. Transient symptoms had CSF measures that did not differ from the no NPS group (Table 1).

Conclusion

In older adults with MCI, MBI was associated with abnormal CSF biomarkers of amyloid, tau and neurodegeneration. In this sample, MBI served as a marker to capture a group with greater AD neuropathological burden, extending the literature linking MBI with higher risk for AD. The findings emphasize the importance of appropriately ascertained NPS, in this case with respect to symptom persistence, in dementia detection and prognostication.
Comparing the clinical utility and diagnostic performance of cerebrospinal fluid P‐tau181, P‐tau217 and P‐tau231 assays
Authors: Leuzy Antoine , Janelidze Shorena , Mattsson‐Carlgren Niklas , Palmqvist Sebastian , Jacobs Dirk , Cicognola Claudia , Stomrud Erik , Vanmechelen Eugeen , Dage Jeffrey L , Hansson Oskar
Published: December 2021

Background

Several studies indicate that increases in cerebrospinal fluid (CSF) phosphorylated tau (P‐tau) in Alzheimer’s disease (AD) occur in response to very early amyloid‐β (Aβ) pathology and precede widespread tau aggregation. Thus far, however, there are no studies comparing different P‐tau isoforms—i.e., tau phosphorylated at threonine‐181 (P‐tau181), 217 (P‐tau217) and 213 (P‐tau231) levels—in relation to Aβ and Tau PET across the symptomatic stages of AD, nor data directly comparing their diagnostic performance for separating AD dementia from non‐AD neurodegenerative disorders and for identifying abnormal Aβ and Tau PET status. We herein aimed to address these questions using cross‐sectional data from the Swedish BioFINDER‐2 study.

Method

We included cross‐sectional data for 629 participants (cognitively unimpaired, amyloid‐β (Aβ)‐positive mild cognitive impairment, Alzheimer’s disease (AD) dementia and non‐AD disorders). In addition to comparing P‐tau181 and P‐tau217 measured using assays with the same capture antibodies from Eli Lilly (P‐tau181Lilly and P‐tau217Lilly; Meso Scale Discovery platform) with P‐tau231 from ADx NeuroSciences (P‐tau231ADx; sandwich ELISA), we also compared P‐tau181Lilly with P‐tau181 measurements from two commonly used assays (Innotest [P‐tau181Innotest; sandwich ELISA] and Elecsys [P‐tau181Elecsys; fully automated electrochemiluminescence immunoassay]). Aβ and Tau PET were performed using [18F]flutemetamol and [18F]RO948.The discriminative performance of CSF P‐tau measures was assessed using the area under the receiver operating characteristic curve (AUC).

Result

Though all P‐tau variants increased across the AD continuum, P‐tau217Lilly showed the greatest dynamic range (13‐fold‐increase vs 1.9‐5.4‐fold‐increase for other P‐tau variants for AD dementia vs non‐AD) (Figure 1). P‐tau217Lillyshowed stronger correlations with Aβ‐ and tau‐PET (P<0.0001) (Figure 2). P‐tau217Lilly exhibited higher accuracy than other P‐tau variants for separating AD dementia from non‐AD (AUC, 0.991vs 0.906‐0.982, P<0.0001) and for identifying Aβ‐PET positivity (AUC, 0.951 vs 0.816‐0.924, P<0.0001) and tau‐PET positivity (AUC, 0.957 vs 0.836‐0.938, P<0.0001) (Figure 3). Finally, P‐tau181Lilly generally performed better than the other P‐tau181 assays, (e.g., AD dementia vs non‐AD, AUC, 0.976 vs 0.923, P<0.0001).

Conclusion

CSF P‐tau217Lilly seem to be more useful than other included P‐tau assays in the diagnostic work‐up of AD and for tracking disease progression. Varied results across P‐tau181 assays also highlights the importance of anti‐tau antibodies for biomarker performance.
Memory concerns and cognitive decline in a multi‐ethnic cohort of oldest‐old individuals: The LifeAfter90 study
Authors: Corrada Maria M. , Gilsanz Paola , Kawas Claudia H. , DeCarli Charles S. , Vieira Katharine E. , Hayes‐Larson Eleanor , Farias Sarah Tomaszewski , Mayeda Elizabeth Rose , Mungas Dan M. , Glymour M. Maria , Whitmer Rachel A.
Published: December 2021

Background

Subjective memory concerns are relatively easy to assess and are useful if they can identify people with cognitive deficits or can predict cognitive decline. In a multiethnic cohort of oldest‐old individuals, we studied whether baseline cognitive performance and cognitive decline differ between individuals who report memory concerns and those who do not.

Method

LifeAfter90 participants are long‐time members of the Kaiser Permanente Northern California Health Care System without a dementia diagnosis in their medical record at recruitment. Evaluations are every six months and include the Spanish and English Neuropsychological Assessment Scales (SENAS), which assesses episodic memory, semantic memory, and executive function domains. At baseline, participants answered the question ‘Are you concerned that you have a memory or other thinking problem?’ Using linear mixed models with random intercepts, we estimated the baseline and longitudinal association of memory concerns with each SENAS domain. The models used years since baseline as the time variable, and adjusted for baseline age, sex, race/ethnicity, education, and practice effects. Potential differences in cognitive decline by presence or absence of memory concerns were assessed with an interaction term (memory concerns*time).

Result

At baseline, the 665 participants were on average 92.8 years of age, 62% were women, 34% were college graduates, 69% were racial/ethnic minorities, and 40% reported memory concerns (Table 1). The average follow‐up was 0.9 years (range: 0‐1.9). Memory concerns were associated with worse baseline performance in episodic memory (ß=‐0.21) and executive function (ß=‐0.12) but not semantic memory (ß=‐0.01) (Figure & Table 2). Although cognitive scores decreased over time for semantic memory (ß=‐0.31) and executive function (ß=‐0.10), the decline did not differ between people with and without memory concerns (Figure & Table 2).

Conclusion

In this multi‐ethnic oldest‐old cohort, individuals with memory concerns have worse baseline cognitive performance in executive function and episodic memory, but their rate of decline is similar to individuals without memory concerns. Although memory concerns appear to identify individuals with objective cognitive impairment, it does not identify those who may decline faster. With additional follow‐up, we will continue to explore the utility of memory concerns in predicting future cognitive performance.
Relationships between locus coeruleus structural integrity and nocturnal awakenings in the context of AD biomarkers: A 7T MRI study
Authors: Van Egroo Maxime , van Hooren Roy W.E. , Jacobs Heidi I.L.
Published: December 2021

Background

The brainstem locus coeruleus (LC) may constitute the intersection of the initial pathophysiological and clinical phenotypes of Alzheimer’s disease (AD). Tau protein accumulation starts early in the LC and sleep‐wake disruption occurs in early stages of AD, potentially reflecting arousal dysregulation in wake‐promoting neurons of the LC. Here, we sought to investigate whether LC structural integrity could be related to subjective sleep‐wake measures in the context of AD biomarkers.

Method

We used an in‐house developed LC‐specific MRI sequence at 7T in 72 cognitively normal older participants (mean age = 65.2 ± 8.2y; 37 women), and we identified sub‐portions of the LC using intensity‐based cluster analyses. Participants’ reports on habitual sleep quality and nocturnal awakenings were collected. In addition, blood‐based biomarker of total tau was measured, and APOE genotype was determined.

Result

Two distinct LC segments were identified, with one covering the middle‐to‐caudal LC and displaying lower intensity compared to the middle‐to‐rostral cluster (t(70) = ‐4.40, p < .0001). Generalized linear mixed models adjusted for age, sex, depression, and APOE status showed that subjective sleep quality was not related to any LC integrity measures. However, we found that lower MRI signal intensity within the middle‐to‐caudal LC, but not in the middle‐to‐rostral LC, was associated with a higher number of self‐reported nocturnal awakenings (F1,63 = 4.89, p = 0.03). Furthermore, this association was mostly evident in individuals with elevated levels of total tau (F1,61 = 4.23, p = 0.04).

Conclusion

Our findings provide in vivo evidence that worse LC structural integrity is associated with more frequent nocturnal awakenings in the context of neurodegeneration, in cognitively normal older individuals. In addition, they further emphasize the role of the LC in the arousal‐ascending system as an important neurobiological correlate of sleep‐wake regulation, and hold promise for the identification of at‐risk populations for preventive interventions.
Personality factors as cognitive resilience against early‐life disadvantage: Results from the Mexican Health and Aging Study
Authors: Saenz Joseph , Milani Sadaf Arefi , Arango Silvia Mejia
Published: December 2021

Background

Early‐life disadvantage, including low socioeconomic position (SEP), few resources, and limited education, has downstream effects on cognitive ability. However, personality‐related factors such as having an internal locus of control or a more conscientious personality have been related with greater resilience and ability to cope with adversity. Our objective is to determine if personality‐related factors position individuals to overcome the negative effects of early‐life adversity on late‐life cognitive ability.

Method

Data comes from the 2015 Mexican Health and Aging Study. First, we estimate each respondents’ expected cognitive ability (ŷ) given their markers of early‐life disadvantage by regressing observed, age‐normed, late‐life cognitive ability (y) on markers of early‐life disadvantage (own and parental education, parental occupation, and markers of early‐life SEP) to identify a subsample expected to be in the lowest quartile of cognitive ability given their early‐life. Second, we use this subsample (n=2,214) to investigate how personality‐related factors (locus of control and conscientiousness) relate with one’s odds of ultimately having above median observed cognitive ability (y) using logistic regression.

Result

Respondents in the lowest quartile of expected cognitive ability based on early‐life disadvantage had an average of less than a year of education, had parents with little education, and endorsed more markers of low early‐life SEP. However, 21% ultimately ended up above median cognitive ability. Among those in the lowest quartile of expected cognitive ability, having a more internal locus of control (OR: 1.09, 95% CI: 1.06‐1.13) or more conscientious personality (OR: 1.09, 95% CI: 1.05‐1.12) were independently related with having above median cognitive ability. Living in an urban area, and greater wealth were also associated with having above median cognitive ability.

Conclusion

Our findings suggest that individuals with an internal locus of control and a conscientious personality are better able to “break the link” between early‐life disadvantage and poor cognitive function later in life.
Association of adverse childhood experiences and late‐life cognition in Black Americans from the Study of Healthy Aging in African Americans (STAR)
Authors: Lor Yi , Gilsanz Paola , George Kristen M , Hayes‐Larson Eleanor , Peterson Rachel L , Meyer Oanh L , Barnes Lisa L , Whitmer Rachel A
Published: December 2021

Background

Though Black Americans are more likely to experience adverse childhood experiences (ACEs) not much is known how these experiences are associated with late‐life cognitive outcomes in Black Americans. We examined the association between ACEs and late life cognition in the Study of Healthy Aging in African Americans (STAR).

Methods

Launched in 2018, STAR is a cohort study of cognitive aging and brain health in 764 Black Americans ages ≥50 years. ACEs were self‐reported via a nine‐item questionnaire. Executive function, semantic memory, and verbal episodic memory were measured using the Spanish and English Neuropsychological Assessment Scales (SENAS) and scores were z‐standardized. Linear regression models were used to associate ACEs exposure with cognitive domains adjusting for age, gender, participant education, and parental education (proxy for childhood socioeconomic status).

Results

The majority of participants were female (69%) and the mean age was 69 years (SD=8.7) Table 1. Most of the respondents (73%) reported having one or more ACEs with parental separation (39%), serious family illness (36%), and witnessing domestic violence (31%) being most common. Other ACEs included parent remarried (26%), substance abuse by a family member (25%), parental job loss (15%), parental incarceration (8%), maternal death (6.5%), and paternal death (10.4%). Most ACEs were not significantly associated with domain specific cognitive scores, except experiencing the death of a father, which was associated with lower semantic memory (β=‐0.36; 95% CI: ‐0.56, ‐0.15; Table 2). Gender‐stratified models showed that the association between death of a father and lower semantic memory was significant for female (β=‐0.45; 95% CI: ‐0.69, ‐0.21) but not males (β=‐0.17; 95% CI: ‐0.54, 0.20). There was no evidence that the relationship between other ACEs and domain‐specific cognitive scores varied by gender.

Conclusions

ACEs were common among Black Americans in this cohort, but only death of a father in early life was associated with lower late life semantic memory, especially among women. Mechanisms of this association are unclear. Future studies with longitudinal data are needed to understand whether ACEs are related to cognitive decline over time in this population.
Active deep learning to detect cognitive concerns in electronic health records
Authors: Magdamo Colin G. , Hong Zhuoqiao Mia , Noori Ayush , Sheu Yi‐Han , Deodhar Mayuresh , Ye Elissa M , Ge Wendong , Sun Haoqi , Brenner Laura , Robbins Gregory K. , Mukerji Shibani , Zafar Sahar F. , Benson Nicole , Moura Lidia Maria V. , Hsu John , Arnold Steven E. , Hyman Bradley T. , Serrano‐Pozo Alberto , Westover M Brandon , Blacker Deborah , Das Sudeshna
Published: December 2021

Background

Timely diagnosis of dementia is important to patients and their caregivers for advanced planning, yet dementia is under‐diagnosed by healthcare professionals and under‐coded in claims data. Sensitive and specific tools to detect cognitive concerns in diverse clinical settings could prompt referral for cognitive evaluation and specialist care.

Method

We developed a deep learning natural language processing (NLP) method to detect cognitive concerns in unstructured clinician notes from electronic health records (EHR). We leveraged a gold‐standard set of ∼1000 patients sampled randomly from three strata: patients with diagnosis codes, patients with specialist visits but no code, or patients with neither. The physician performed a detailed chart review and adjudication of cognitive status, noting "cognitive concern" (i.e., any evidence of cognitive difficulties) and rating patients on a 5‐point scale: normal, normal vs. MCI, MCI, MCI vs. dementia, and dementia. We used 10% of the labeled data as a test set and the remaining 90% for training and validation of the model to classify patients with any cognitive concerns (normal vs. other). We also built a web‐based chart review annotation tool that facilitates labeling and enables an active learning loop to scale up labeling to thousands of charts.

Result

In a random sample from the gold‐standard dataset, 30 out of 80 patients with cognitive concerns had no diagnosis code or medication related to dementia; we hypothesized that our deep learning tool could leverage clinical text to improve detection of cognitive concerns. Indeed, a model with codes and medications had an area under the receiver operating characteristic (AUROC) curve of 0.79, sensitivity of 0.59, and specificity of 1.00 for the binary classification task. The deep learning model improved the AUROC to 0.90, increased sensitivity to 0.79, and maintained specificity of 0.98. Notes from primary care, specialties such as neurology and psychiatry, and social workers had the highest likelihood of containing information.

Conclusion

The deep learning model was successful in detecting cases without a dementia‐related diagnosis code or medication. Automatic processing of electronic medical records with a deep learning tool can be used for early detection of cognitive concern to optimize patient care and predict hospital readmission.
Risk for hospitalization surrounding dementia diagnosis: A national registry‐based study
Authors: Shahar Rotem , Lutski Miri , Zucker Inbar , Weinstein Galit
Published: December 2021

Background

Studies show that incident dementia is associated with an increased risk of hospitalization. Recent evidence also suggests that hospitalization may be a risk factor for dementia. We aimed to capture the changes in hospitalization rates, annual number of admissions and length of stay (LOS) during 4 years surrounding dementia diagnosis in a national population‐based sample. In addition, we examined the association of sociodemographic and clinical factors with hospitalization measures in the immediate years before and after dementia diagnosis.

Method

The sample for this retrospective cohort study included 11,625 individuals aged 65 years and older, who were identified as incident cases of dementia in the Israel dementia national registry during 2016 (mean age= 81.21±7.19y; 61% women). Hospitalization data were obtained from National Hospital Discharge Database (NHDD) of the Israeli Ministry of Health, and clinical and sociodemographic data were extracted from the national registry database. Mixed regression models were used to assess within‐subject changes in the likelihood of hospitalization, the number of hospitalizations and LOS among survivors of the entire follow‐up period (N=8,000). We also tested for possible interactions of time respective to diagnosis with age, sex, ethnicity, socioeconomic status, BMI and comorbidity with regard to hospitalization indices.

Result

The risk for hospitalization as well as the number of visits and LOS were highest during the year preceding dementia diagnosis (OR =3.19, 95%CI 2.51‐4.06; OR= 3.69, 95%CI 2.86‐4.76; OR=3.53, 95%CI 2.75‐4.54, respectively, compared to the reference period of 2 years prior dementia diagnosis). These hospitalization measures slightly decreased with time after dementia diagnosis, but remained high, compared to the reference period (figure 1). The associations between age, sex, comorbidity and BMI with odds of hospitalization differed significantly depending on the time respective to dementia diagnosis (figure 2‐5). Similar associations were found for annual number of hospitalizations and LOS.

Conclusion

This study points to an increased burden due to hospitalizations during the year prior to dementia diagnosis and the years proceeding it. Our findings also highlight the need to consider the time surrounding dementia diagnosis in the prediction of hospital burden based on factors such as age and comorbidities.
Smoking and the risk of dementia in the oldest‐old: The Monzino 80‐plus study
Authors: Lucca Ugo , Tettamanti Mauro , Riva Emma , Mandelli Sara , Forloni Gianluigi , Galbussera Alessia A
Published: December 2021

Background

Nicotine is a cholinergic agonist that can enhance short‐term cognitive performance. After initial findings suggesting a possible protective effect of smoking against dementia, subsequent research has pointed out smoking as a risk factor for dementia and Alzheimer’s disease. However, very few data are available on this relationship in the oldest‐old. Objectives: To explore the association of smoking with the development of dementia in advanced age in a prospective population‐based study of 80‐years or older residents in Varese province, Italy (Monzino 80‐plus Study).

Method

Information on smoking habit was obtained from the subject and/or a primary informant, mostly a family member, using a standardized questionnaire. Diagnosis of dementia fulfilled DSM‐IV criteria. Logistic regression and Cox proportional hazard models were used to investigate cross sectional and longitudinal associations between smoking and dementia risk.

Result

The initial population consisted of 2,193 individuals (mean age: 90.2 years; women: 72.7%). At first visit oldest‐old who had never smoked represented the large majority of the population (1778, 81.1%), while current smokers were very few (n=49, 2.2%). On average, they currently smoked 9.7±7.9 cigarettes daily, started smoking at 22.8±11.7 years of age, and had been smoking for 67.1±10.3 years. Former smokers (n=366; 16.7%) had quit smoking on average 29.6±18.0 years before initial interview. Prevalence of dementia was lower among current smokers (18.4%) compared to never smokers (40.0%; p=0.0036), but this difference was no longer significant after adjustment for age, sex, and education (adjusted p=0.2435). There were 1,138 individuals without dementia at first visit with at least one follow‐up available (mean age: 88.4 years; women: 69.2%). In the following 15.5 years, current smokers (n=28) had a higher occurrence of dementia (60.7%) than never smokers (50.1%; age, sex, and education adjusted HR: 1.30, 95% CI: 0.80‐2.12, p=0.2913) or non‐smokers (never and former) (46.9%; age, sex, and education adjusted HR: 1.34, 95% CI: 0.83‐2.18, p=0.2349). The low proportion of current smokers limited the possibility to investigate the effect of smoking on dementia incidence.

Conclusion

Smoking habit is very uncommon among oldest‐old and it was not significantly associated with the risk of dementia either in cross sectional or longitudinal analysis.
Subjective cognitive decline is associated with higher anxiety and depression during the COVID‐19‒related confinement
Authors: Sánchez‐Benavides Gonzalo , Akinci Muge , Minguillón Carolina , Deulofeu Carme , Salvadó Gemma , González‐de‐Echávarri José María , Brugulat‐Serrat Anna , Suarez‐Calvet Marc , Sala‐Vila Aleix , Grau‐Rivera Oriol , Fauria Karine , Molinuevo Jose , Gispert Juan Domingo , Arenaza‐Urquijo Eider M ,   ALFA study
Published: December 2021

Background

Subjective cognitive decline (SCD) is often related to affective symptoms and both predict cognitive decline. We investigated whether SCD status predicted higher anxiety/depression during the Covid19‐related confinement, along with amyloid positivity in cognitively unimpaired older adults.

Method

We included 205 participants from the ALFA+ study (Table 1). During the confinement, anxiety and depression (Hospital Depression and Anxiety scale, HADS), perceived stress (Perceived Stress Scale) and stress resilience (Brief Resilience Scale) were measured. Participants completed HADS, SCD‐Questionnaire, and underwent a [18F]flutemetamol‐PET scan on average 2.4 years before confinement (baseline). We ran linear analyses with (i) cross‐sectional HADS scores during the confinement as well as (ii) change from baseline to confinement (delta scores) as dependent variables. SCD and amyloid status (+/‐, defined with a Centiloid threshold of 12) and their interaction were considered as predictors, and demographics, APOE‐ε4 status, and baseline HADS (for longitudinal analyses) as covariates. In a second step, perceived stress and stress resilience were considered in the models among covariates.

Result

Twenty‐seven percent (n=56) of the participants were classified as SCD and 12.7% as amyloid positive. When main effects were tested, both SCD (p=0.03) and amyloid positivity (p=0.003) were associated with higher HADS scores during confinement (Table 2a). Further, a significant SCD*amyloid interaction was observed (p=0.001) such that only SCD participants with an amyloid positive scan showed higher HADS scores (p=0.001). SCD participants showed higher perceived stress than non‐SCD participants (p=.044), but no differences were found in stress resilience (p=0.6). The inclusion of perceived stress and stress resilience as covariates reduced the SCD effect to a trend (p=0.06) but not the effect of amyloid (p=0.003). Longitudinal analyses with delta scores showed similar results for amyloid but not for SCD main effects (Table 2b). The amyloid*SCD interaction was also significant in longitudinal analyses (p=0.002) with amyloid status predicting an increase in HADS scores only in participants with SCD (p=0.003) (Fig. 1).

Conclusion

Having SCD and being amyloid positive is synergistically related to increased anxiety/depression during the Covid19‐related confinement. Longitudinal studies are warranted to investigate the impact of higher confinement related anxiety/depression in the clinical prognosis of the SCD population.
Atrophy and partial volume related bias in cortical region of interest NODDI metrics
Authors: Veale Thomas , Parker Christopher S , Bocchetta Martina , Malone Ian B , Slattery Catherine F , Schott Jonathan M , Fox Nick C , Zhang Hui , Cash David M
Published: December 2021

Background

Neurite Orientation Dispersion and Density Imaging (NODDI) provides in‐vivo indices of neurite density (NDI) and orientation dispersion (ODI) within the tissue compartment of each voxel. However, NDI and ODI are treated equally when calculating region of interest (ROI) means, despite tissue fraction (TF) varying within regions undergoing neurodegeneration. Covariation between TF and cortical NODDI measures bias these conventional means and we recommend using tissue‐weighted averages to address this.

Method

In this study, we included 22 healthy controls and 33 individuals affected by Young‐Onset Alzheimer’s disease (YOAD, see Table 1 for demographics) with suitable diffusion‐weighted and T1‐weighted 3T MR images. Diffusion data were corrected for eddy currents, motion and susceptibility artefacts before fitting the NODDI model to produce NDI, ODI, isotropic volume fraction (ISO) and TF maps (TF=1‐ISO). T1w images were parcellated into cortical ROIs using Geodesic Information Flow (Cardoso et al., IEEE Trans.Med.Im.; 34:1976‐1988, 2015). Five bilateral ROIs expected to undergo neurodegeneration were analysed (Precuneus, Fusiform Gyrus, Superior Parietal, Middle and Inferior Temporal cortex). ROIs were resampled into native diffusion space and two regional measures calculated: 1) conventional, unweighted NDI and ODI averages and 2) tissue‐weighted averages using voxel TF as weights. Within‐participant differences between conventional and tissue‐weighted measures were calculated. Spearman’s rank tested correlations and Wilcoxon tests evaluated within‐ and between‐participant differences (Bonferroni adjusted for multiple comparisons).

Result

TF positively correlated with GM volume (rs range=0.33‐0.68,p<0.05) in all ROIs except the left fusiform gyrus (rs=0.31,p=0.06) (Figure 1). YOAD individuals had lower TF than healthy controls in all ROIs (Figure 2a), and lower volumes in all ROIs except the right fusiform gyrus (W=475,p=0.27) (Figure 2b). NDI showed small positive/negative biases in six of the ten ROIs (Figure 3a), while ODI showed significant positive biases across all ROIs (Figure 3b). Biases decreased as TF increased towards its maximum of one (Figure 4a‐4b).

Conclusion

Lower cortical volumes in YOAD were associated with lower TF and higher bias, suggesting a greater risk for misestimation of cortical region NODDI metrics in studies involving neurodegenerative disease. We recommend tissue‐weighted averages to account for varying intra‐regional TF in NODDI measures.
Alcohol consumption and the risk of dementia in the oldest old: The Monzino 80‐plus study
Authors: Lucca Ugo , Tettamanti Mauro , Riva Emma , Mandelli Sara , Forloni Gianluigi , Galbussera Alessia A
Published: December 2021

Background

Wine, beer, spirits or liqueurs are widely popular beverages worldwide. Several studies have investigated the association between alcohol consumption and dementia with inconsistent results, however very few data are available on this relationship in the oldest‐old. Objectives: To investigate the association of alcohol consumption with the development of dementia in advanced age in a prospective population‐based study of 80‐years or older residents in Varese province, Italy (Monzino 80‐plus Study).

Method

Information on alcohol consumption (wine, beer, spirits or liqueurs) was obtained from the subject and/or a primary informant, mostly a family member, using a standardized questionnaire. Diagnosis of dementia fulfilled DSM‐IV criteria. Covariates entered in the fully adjusted logistic and Cox regression models: age, sex, education, diabetes, hypertension, heart failure, myocardial infarction, COPD, ictus, TIA, parkinsonism. Since former drinkers stopped drinking on average 12.4±13.7 (cross‐sectional study) and 16.0±17.0 (longitudinal study) years before interview, they were categorized, together with the never drinkers, in the group of non‐drinkers.

Result

Among the 2,195 participants (mean age: 90.2 years; women: 72.7%) interviewed at first visit, 1,107 (50.4%) were current drinkers (wine, only or together with other alcoholic beverages: 99.8% in cross‐sectional and 100% in longitudinal studies), 318 (14.5%) former drinkers, and 770 (35.1%) never drinkers. Consumers on average currently drank 18.2±15.5 g/day of ethanol, started drinking at 21.4±16.2 years of age, and have been drinking for 68.1±11.2 years. Prevalence of dementia was lower among current drinkers (27.8%) compared to non‐drinkers (47.2%; fully adjusted p<0.0001). There were 1,139 individuals without dementia at first visit with at least one follow‐up available (mean age: 88.4 years; women: 69.3%). In the following 15.5 years, current drinkers (n=675) had a lower occurrence of dementia (43.3%) than non‐drinkers (53.0%; fully adjusted HR: 0.8372, 95% CI: 0.7008‐1.0002, p=0.0503). When current drinkers were divided according to daily intake into two groups (>0‐24 and >24 g/day of ethanol), results of both cross‐sectional and longitudinal analyses gave analogous results.

Conclusion

Alcohol consumption, mostly of moderate amounts, is common among oldest‐old and is associated with a marginally non‐significant lower risk of incident dementia.
Everyday cognition in MCI patients and risk of conversion to Alzheimer’s disease: Evidence from a longitudinal study
Authors: Guinea Sara Fernández , Sánchez Rebeca , Otero Andrea , Marqués Javier González
Published: December 2021

Background

The Everyday Cognition scale (ECog) is an informant‐rated questionnaire of cognitive and functional abilities. In recent years, it has been shown to be sensitive for the differentiation of older adults with mild cognitive impairment (MCI) (Farias et al, 2008; Russo et al, 2014), and to the diagnosis of neurodegenerative disease such as Alzheimer’s disease (Farias et al, 2020). However, little is known about its possible utility to predict MCI‐dementia progression in Alzheimer’s clinical syndrome (ACS).

Method

130 participants (63.8% females), with an average age of 75.27 (SD=5.91), and diagnosed with MCI, were assessed with a comprehensive battery of neuropsychological tests and functional scales, including ECog. In the 2 years follow‐up assessment, 20 participants were diagnosed with ACS. Binary logistic regression and ROC curve statistical analyses were performed.

Result

Significant correlations (p<.05) were found between ECog and neuropsychological tests such as Addenbrooke's Cognitive Examination‐Revised (ACE‐R), Mini‐Mental State Examination (MMSE), a Spanish version of the California Verbal Learning Test (CVLT), the Rey–Osterrieth complex figure test (ROCF) recall, the semantic verbal fluency and the Zoo map. Binary logistic regression results showed that ECog significantly explained the conversion to AD (p<.05). Baseline scores for ECog were significantly higher in participants who developed ACS after two years (p<.05). ROC curve showed a sensitivity of 80% and a specificity of 51% on the optimal cut‐off point (48.5) (AUC=0.69).

Conclusion

Functional ability is highly related to cognitive domains. The ECog scale is an useful instrument for the early detection of MCI patients with high risk to develop ACS.
The impact of cerebrovascular disease on blood‐based biomarkers of Alzheimer’s disease
Authors: Laing Krystal K. , Lao Patrick J. , Gutierrez Jose , Sanchez Danurys , Reyes‐Dumeyer Dolly , Lantigua Rafael A. , Honig Lawrence S. , Airey David C. , Manly Jennifer J. , Dage Jeffrey L. , Mayeux Richard , Brickman Adam M.
Published: December 2021

Background

The development of ultrasensitive assays for blood‐based biomarkers may allow for detection of Alzheimer’s disease (AD)‐related pathology in large‐scale community‐based cohorts. We previously showed in the Washington Heights Inwood Columbia Aging Project (WHICAP) an association of plasma biomarker concentrations with clinical and pathological AD diagnosis, and that MRI markers of cerebrovascular disease, particularly parietal lobe white matter hyperintensities (WMH), increase the risk and progression of clinical AD. Here, we test the hypothesis that cerebrovascular disease has a direct impact on AD‐related pathology by examining the association of MRI markers of cerebrovascular disease and plasma biomarker concentrations in WHICAP.

Method

Among 300 WHICAP participants with available structural MRI (mean age 81.87+6.45 years, 67% women, 33.3% non‐Hispanic white, 33.3% African American, 33.3% Hispanic, 42% with cognitive impairment) we used SIMOA and MSD technology to measure plasma concentrations of Aβ42, Aβ40, ptau181, ptau217, total tau, and NfL from banked plasma samples. MRI scans were analyzed for regional WMH, presence of infarct, and presence of microbleeds. We first examined bivariate correlations between MRI cerebrovascular measures and plasma biomarker concentrations. For markers that were associated, we conducted demographically adjusted analyses and examined interactions with cognitive diagnostic status.

Result

Increased parietal lobe WMH, specifically, was associated with higher ptau181 (r=0.21, p=0.008) and ptau217 (r=0.13, p=0.05) concentrations. Increased WMH in frontal, temporal, and parietal regions was associated with increased NfL concentrations (rs=0.21‐0.25, ps<0.001‐0.002). Presence of one or more microbleed was associated with increased NfL (r=0.19, p=0.02). In adjusted models the associations of regional WMH with ptau181 and NfL concentrations were independent of and did not interact with diagnosis.

Conclusion

Markers of small vessel cerebrovascular disease, particularly parietal lobe WMH, are associated with AD blood‐based biomarkers of phosphorylated tau pathology and neurodegeneration.
Decrease of event related theta power is more profound in patients with Parkinson's disease dementia in comparison to Alzheimer's disease dementia
Authors: Yıldırım Ebru , Gündüz Duygu Hünerli , Hanoğlu Lutfu , Yener Gorsev , Güntekin Bahar
Published: December 2021

Background

Alzheimer's disease dementia (ADD) and Parkinson's disease dementia (PDD) are the most common types of dementia. ADD and PDD have different pathophysiology and clinical profile. It is important to understand mechanisms underlying pathophysiology, clinical symptoms, and the electrophysiological differences between these two types of dementia. Event‐related theta responses during cognitive paradimgs are one of the essential biomarkers that could succfesully show cognitive decline in dementia patients (Yener et al.,2007;Güntekin et al.,2020). The aim of the present study was to investigate the Event‐related theta responses during the visual cognitive task in patients with PDD and ADD in order to find the differentiation between these two types of dementia.

Method

EEG recordings of 15 patients with ADD, 15 patients with PDD, and matched 15 healthy elderly controls (HC) were performed during the visual oddball paradigm. Event‐related phase‐locking and power analysis were performed for theta frequency band (4‐7 Hz). Repeated measures of ANOVA was used for statistical analysis (p<0.05).

Result

There were significant differences among groups for both event‐related theta phase‐locking (p=0.004) and theta power (p<0.0001). ADD (p<0.005) and PDD (p<0.005) groups had reduced theta phase‐locking in comparison to the HC group (Figure 1). Especially, this reduction was more pronounced in the PDD group. In addition, the PDD group had decreased theta power as compared to the HC (p<0.0001) and ADD (p<0.005) group (Figure 1). Figure 1 shows the grand average of event‐related theta power (upper part) and phase‐locking (lower part) and in HC, ADD and PDD groups.

Conclusion

The present study showed decreased event‐related theta responses during the visual oddball paradigm in patients with dementia. Especially, PDD patients had the worst event‐related theta responses. These findings could be interpreted as the visual cognitive processes are more impaired in PDD patients compared to ADD patients. References: 1) Yener, G.G., Güntekin, B., Öniz, A., & Başar, E. (2007). Increased frontal phase‐locking of event‐related theta oscillations in Alzheimer patients treated with cholinesterase inhibitors. International Journal of Psychophysiology, 64(1), 46‐52. 2) Güntekin, B., Aktürk, T., Yıldırım, E., Yılmaz, N.H., Hanoğlu, L., & Yener, G. (2020). Abnormalities in auditory and visual cognitive processes are differentiated with theta responses in patients with Parkinson's disease with and without dementia. International Journal of Psychophysiology, 153, 65‐79.