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1.
Alzheimer Dis Assoc Disord ; 38(2): 160-167, 2024.
Article En | MEDLINE | ID: mdl-38748658

INTRODUCTION: Enrolling individuals from underrepresented ethnoracial groups in aging research is often a challenge. METHODS: We sought a diverse sample of older adults from a small-town area for a longitudinal aging study. We employed an intensive community engagement approach encompassing a range of recruitment strategies. RESULTS: Over 4 years a steady trickle of individuals, 66% self-identifying as Black, signed up for study information; the proportion of those who eventually enroll in the study has been rising each year, from 68% to 94%. Community events, word-of-mouth referrals, and mailed postcards brought in the most contacts. The highest percentage of contacts who ultimately enrolled were from postcards, flyers, and word-of-mouth. Significantly more word-of-mouth referrals were endorsed by Black individuals than White and by Black men than other race/sex groups. CONCLUSIONS: We have had some success in building relationships and trust with the local community, enrolling Black study participants in a proportion equal to their representation in the target community using a variety of recruitment methods. Patience, immersion in the community, and partnerships with key community members alongside traditional advertisements, and the utilization of study participants as recruiters are critical to designing optimal, targeted, recruitment strategies.


Aging , Patient Selection , Humans , Longitudinal Studies , Male , Female , Aged , Aged, 80 and over , Cohort Studies
2.
Alzheimers Dement ; 20(6): 4199-4211, 2024 Jun.
Article En | MEDLINE | ID: mdl-38753951

INTRODUCTION: Plasma biomarkers of Alzheimer's disease and related dementias predict global cognitive performance and decline over time; it remains unclear how they associate with changes in different dementia syndromes affecting distinct cognitive domains. METHODS: In a prospective study with repeated assessments of a randomly selected population-based cohort (n = 787, median age 73), we evaluated performance and decline in different cognitive domains over up to 8 years in relation to plasma concentrations of amyloid beta 42/40 (Aß42/40) ratio, phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). RESULTS: Cross-sectionally, memory showed the strongest associations with p-tau181, and attention, executive, and visuospatial functions with NfL. Longitudinally, memory decline was distinguishable with all biomarker profiles dichotomized according to data-driven cutoffs, most efficiently with Aß42/40. GFAP and Aß42/40 were the best discriminators of decline patterns in language and visuospatial functions, respectively. DISCUSSION: These relatively non-invasive tests may be beneficial for clinical screening after replication in other populations and validation through neuroimaging or cerebrospinal fluid analysis. HIGHLIGHTS: We performed a prospective study with up to 8 years of repeated domain-specific cognitive assessments and baseline plasma Alzheimer's disease and related dementias biomarker measurements in a randomly selected population-based cohort. We considered distinct growth curves of trajectories of different cognitive domains and survival bias induced by missing data by adding quadratic time and applying joint modeling technique. Cross-sectionally, memory showed the strongest associations with plasma phosphorylated tau181, while attention, executive, and visuospatial functions were most strongly associated with neurofilament light chain. Longitudinally, memory and visuospatial declines were most efficiently distinguished by dichotomized amyloid beta 42/40 profile among all plasma biomarkers, while language was by dichotomized glial fibrillary acidic protein. These relatively non-invasive tests may be beneficial for clinical screening; however, they will need replication in other populations and validation through neuroimaging and/or cerebrospinal fluid assessments.


Alzheimer Disease , Amyloid beta-Peptides , Biomarkers , Cognitive Dysfunction , Neurofilament Proteins , tau Proteins , Humans , Biomarkers/blood , Female , Male , Alzheimer Disease/blood , Aged , Amyloid beta-Peptides/blood , Amyloid beta-Peptides/cerebrospinal fluid , tau Proteins/blood , tau Proteins/cerebrospinal fluid , Cognitive Dysfunction/blood , Prospective Studies , Cross-Sectional Studies , Neurofilament Proteins/blood , Peptide Fragments/blood , Peptide Fragments/cerebrospinal fluid , Glial Fibrillary Acidic Protein/blood , Longitudinal Studies , Neuropsychological Tests/statistics & numerical data , Middle Aged , Cognition/physiology , Aged, 80 and over
3.
Alzheimer Dis Assoc Disord ; 38(2): 152-159, 2024.
Article En | MEDLINE | ID: mdl-38748688

BACKGROUND: Identifying potentially modifiable risk factors associated with MCI in different ethnoracial groups could reduce MCI burden and health inequity in the population. METHODS: Among 2845 adults aged 65+ years, we investigated potential risk exposures including education, physical and mental health, lifestyle, and sensory function, and their cross-sectional associations with MCI. We compared proportions of exposures between Black and White participants and explored relationships among race, MCI, and exposures. Logistic regression modeled MCI as a function of each exposure in the overall sample adjusting for age, sex, educational level, and race, and investigating race*exposure interactions. RESULTS: Compared with White participants, Black participants had greater odds of MCI (OR 1.53; 95% CI, 1.13 to 2.06) and were more likely to report depressive symptoms, diabetes, and stroke, to have high blood pressure and BMI, and to be APOE - 4 carriers. Exposures associated with higher odds of MCI were diabetes, stroke, lifetime smoking, sleep disturbances, social isolation, loneliness, depression and anxiety symptoms, and vision and hearing loss. There were no significant interactions between race and any exposure. CONCLUSIONS: Black participants had 53% higher odds of MCI adjusting for age, sex, and education. The same exposures were associated with MCI in Black and White participants.


Cognitive Dysfunction , White People , Humans , Male , Female , Aged , Cognitive Dysfunction/ethnology , White People/statistics & numerical data , White People/psychology , Cross-Sectional Studies , Risk Factors , Black or African American/psychology , Black or African American/statistics & numerical data , Aged, 80 and over , Depression/ethnology
4.
Alzheimers Dement ; 20(6): 3972-3986, 2024 Jun.
Article It | MEDLINE | ID: mdl-38676366

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.


Dementia , Life Style , Humans , Dementia/epidemiology , Male , Female , Risk Factors , Aged , Prospective Studies , Incidence
5.
Int J Geriatr Psychiatry ; 39(4): e6086, 2024 Apr.
Article En | MEDLINE | ID: mdl-38613138

OBJECTIVES: There is a paucity of population-level data on marijuana use and mental health and functioning in older adults. METHODS: We analyzed cross-sectional data (n = 910) from a well-characterized cohort, the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. MYHAT is an age-stratified random sample of the population age 65 years and older from a small-town in the USA. Half the sample was female and half were over 75 (Mean age = 77). Most participants were non-Hispanic White. Marijuana use was assessed by self-report and symptoms of mood disorders were screened using the modified Centers for Epidemiological Studies-Depression Scale and the Generalized Anxiety Disorder screener. Cognition was assessed by the Mini-Mental State Examination and a neuropsychological test battery; functioning using the OARS Activities of Daily Living and Instrumental Activities of Daily Living; and overall assessment using the Clinical Dementia Rating (CDR®). RESULTS: One in five MYHAT participants had a history of marijuana use and 5% reported recent use, primarily for pain (41%) and recreation/relaxation (37%). Recent use was associated with cigarette and alcohol use, symptoms of depression or anxiety, and impairments in attention. CONCLUSIONS: Twenty-percent of community-dwelling older adults living in a US state where recreational marijuana use is illegal had a history of marijuana use. Recent marijuana use was less common but, consistent with prior research, associated with other substance use and poorer mental health.


Marijuana Use , Substance-Related Disorders , Female , Humans , Aged , Marijuana Use/epidemiology , Activities of Daily Living , Cross-Sectional Studies , Independent Living , Research Design
6.
PLoS One ; 19(2): e0297220, 2024.
Article En | MEDLINE | ID: mdl-38324518

INTRODUCTION: India, with its rapidly aging population, faces an alarming burden of dementia. We implemented DSM-5 criteria in large-scale, nationally representative survey data in India to characterize the prevalence of mild and major Neurocognitive disorder. METHODS: The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) (N = 4,096) is a nationally representative cohort study in India using multistage area probability sampling methods. Using neuropsychological testing and informant reports, we defined DSM-5 mild and major neurocognitive disorder, reported its prevalence, and evaluated criterion and construct validity of the algorithm using clinician-adjudicated Clinical Dementia Ratings (CDR)®. RESULTS: The prevalence of mild and major neurocognitive disorder, weighted to the population, is 17.6% and 7.2%. Demographic gradients with respect to age and education conform to hypothesized patterns. Among N = 2,390 participants with a clinician-adjudicated CDR, CDR ratings and DSM-5 classification agreed for N = 2,139 (89.5%) participants. DISCUSSION: The prevalence of dementia in India is higher than previously recognized. These findings, coupled with a growing number of older adults in the coming decades in India, have important implications for society, public health, and families. We are aware of no previous Indian population-representative estimates of mild cognitive impairment, a group which will be increasingly important in coming years to identify for potential therapeutic treatment.


Cognitive Dysfunction , Dementia , Humans , Aged , Cohort Studies , Prevalence , Dementia/diagnosis , Dementia/epidemiology , Dementia/psychology , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/psychology , Aging , Neuropsychological Tests , India/epidemiology
7.
Int Psychogeriatr ; 36(2): 142-148, 2024 Feb.
Article En | MEDLINE | ID: mdl-37231775

OBJECTIVES: Older adults commonly take benzodiazepines (BZDs) that may have long-term adverse cognitive effects. We investigated whether BZD use was related to developing mild cognitive impairment (MCI) or dementia in cognitively normal older adults in the community. SETTING/PARTICIPANTS: A population-based cohort (n = 1959) of adults aged 65 and over, recruited from communities of low socioeconomic status. MEASUREMENTS: BZD use, Clinical Dementia Rating (CDR), anxiety symptoms, depression symptoms, sleep difficulties, and APOE genotype. DESIGN: We examined time from study entry to MCI (CDR = 0.5) and time from study entry to dementia (CDR ≥ 1) in participants who were cognitively normal at baseline (CDR = 0). We used survival analysis (Cox model), adjusted for age, sex, education, sleep, anxiety, and depression. For all the models, we included an interaction term between BZD use and APOE*4. RESULTS: Taking BZDs was significantly associated with higher risk of developing MCI, but not of developing dementia. The effect was not affected by APOE genotype. CONCLUSIONS: In a population-based sample of cognitively normal older adults, BZD use is associated with developing MCI, but not dementia. BZD use may be a potentially modifiable risk factor for MCI.


Cognitive Dysfunction , Dementia , Humans , Aged , Benzodiazepines/adverse effects , Cognitive Dysfunction/diagnosis , Proportional Hazards Models , Dementia/psychology , Apolipoproteins E , Risk Factors
8.
Alzheimers Dement ; 20(2): 1239-1249, 2024 Feb.
Article En | MEDLINE | ID: mdl-37975513

INTRODUCTION: Detection of Alzheimer's disease (AD) pathophysiology among individuals with mild cognitive changes and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma phosphorylated tau 217 (p-tau217) is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited. METHODS: We employed a novel p-tau217 immunoassay (University of Gothenburg [UGOT] p-tau217) in four independent cohorts (n = 308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired (CU) and mild cognitively impaired (MCI) participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (Barcelonaßeta Brain Research Center's Alzheimer's At-Risk Cohort [ß-AARC]). RESULTS: UGOT p-tau217 showed high accuracy (area under the curve [AUC] = 0.80-0.91) identifying amyloid beta (Aß) pathology, determined either by Aß positron emission tomography or CSF Aß42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aß42/40 ratio (AUC = 0.91). DISCUSSION: UGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.


Alzheimer Disease , Cognitive Dysfunction , Humans , Amyloid beta-Peptides/cerebrospinal fluid , tau Proteins/cerebrospinal fluid , Cognitive Dysfunction/cerebrospinal fluid , Positron-Emission Tomography , Brain , Biomarkers/cerebrospinal fluid
9.
Alzheimers Dement ; 20(3): 2223-2239, 2024 Mar.
Article En | MEDLINE | ID: mdl-38159267

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the "LIfestyle for BRAin health" (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta-analyses with a two-round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts. HIGHLIGHTS: An umbrella review was combined with opinions of 18 dementia experts. Various candidate targets for dementia risk reduction were identified. Experts prioritized hearing impairment, social contact, and sleep. Re-assessment of dementia risk scores is encouraged. Future work should evaluate the predictive validity of updated risk scores.


Cognitive Dysfunction , Dementia , Hearing Loss , Humans , Dementia/epidemiology , Dementia/prevention & control , Dementia/psychology , Cognitive Dysfunction/psychology , Delphi Technique , Systematic Reviews as Topic , Risk Factors , Risk Reduction Behavior , Hearing Loss/epidemiology
10.
medRxiv ; 2023 Oct 05.
Article En | MEDLINE | ID: mdl-37873312

INTRODUCTION: Detection of Alzheimer's disease (AD) pathophysiology among cognitively unimpaired individuals and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma p-tau217 is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited. METHODS: We employed a novel p-tau217 immunoassay (UGOT p-tau217) in four independent cohorts (n=308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (ß-AARC). RESULTS: UGOT p-tau217 showed high accuracy (AUC= 0.80-0.91) identifying Aß pathology, determined either by Aß positron emission tomography or CSF Aß42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aß42/40 ratio (AUC= 0.91). DISCUSSION: UGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.

11.
J Appl Gerontol ; 42(12): 2313-2324, 2023 Dec.
Article En | MEDLINE | ID: mdl-37518906

In this study, we examined associations of social isolation and loneliness with cognitive impairment among older adults from a Rust Belt region in Southwest Pennsylvania. We used data from the population-based Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. We found that (a) 11 items combined into two reliable composites of social isolation and loneliness; (b) unique to this study, providing unpaid help to others was an indicator of reduced social isolation; (c) social isolation and loneliness were positively associated with cognitive impairment; and (d) these associations were appreciably attenuated by general health and physical functional status and depressive symptoms, respectively. We concluded that social isolation and loneliness are differentially associated with older adults' cognitive health, and that their effects might operate through separate pathways. Approaches to address social isolation and loneliness should consider the community context and its implications for older adults' cognitive health.


Cognitive Dysfunction , Healthy Aging , Humans , Aged , Loneliness/psychology , Social Isolation/psychology , Cognitive Dysfunction/psychology , Pennsylvania/epidemiology
12.
Nat Med ; 29(7): 1775-1781, 2023 07.
Article En | MEDLINE | ID: mdl-37248300

An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-ß (Aß)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aß effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (n = 1,016), we tested whether astrocyte reactivity modulates the association of Aß with tau phosphorylation in CU individuals. We found that Aß was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast+). Cross-sectional and longitudinal tau-positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of Aß only in CU Ast+ individuals. Our findings suggest astrocyte reactivity as an important upstream event linking Aß with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials.


Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/pathology , Amyloid beta-Peptides , Astrocytes/pathology , Biomarkers , Cross-Sectional Studies , Positron-Emission Tomography , tau Proteins
13.
Alzheimers Dement ; 19(11): 5114-5128, 2023 11.
Article En | MEDLINE | ID: mdl-37102417

INTRODUCTION: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. METHODS: We used individual participant data (N = 39271, Mage  = 70.67 (40-102), 58.86% female, Meducation  = 8.43 years, Mfollow-up  = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally. HIGHLIGHTS: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.


Cognitive Dysfunction , Dementia , Humans , Female , Aged , Male , Longitudinal Studies , Dementia/epidemiology , Dementia/psychology , Cohort Studies , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/psychology , Aging/psychology
14.
Alzheimers Dement ; 19(11): 5010-5022, 2023 11.
Article En | MEDLINE | ID: mdl-37089073

INTRODUCTION: Cognitive abilities have substantial heritability throughout life, as shown by twin- and population-based studies. However, there is limited understanding of the genetic factors related to cognitive decline in aging across neurocognitive domains. METHODS: We conducted a meta-analysis on 3045 individuals aged ≥65, derived from three population-based cohorts, to identify genetic variants associated with the decline of five neurocognitive domains (attention, memory, executive function, language, visuospatial function) and global cognitive decline. We also conducted gene-based and functional bioinformatics analyses. RESULTS: Apolipoprotein E (APOE)4 was significantly associated with decline of memory (p = 5.58E-09) and global cognitive function (p = 1.84E-08). We identified a novel association with attention decline on chromosome 9, rs6559700 (p = 2.69E-08), near RASEF. Gene-based analysis also identified a novel gene, TMPRSS11D, involved in the activation of SARS-CoV-2, to be associated with the decline in global cognitive function (p = 4.28E-07). DISCUSSION: Domain-specific genetic studies can aid in the identification of novel genes and pathways associated with decline across neurocognitive domains. HIGHLIGHTS: rs6559700 was associated with decline of attention. APOE4 was associated with decline of memory and global cognitive decline. TMPRSS11D, a gene involved in the activation of SARS-CoV-2, was implicated in global cognitive decline. Cognitive domain abilities had both unique and shared molecular pathways across the domains.


COVID-19 , Cognitive Dysfunction , Humans , COVID-19/genetics , SARS-CoV-2 , Cognition/physiology , Cognitive Dysfunction/genetics , Attention , Apolipoprotein E4/genetics , Neuropsychological Tests
15.
Int J Geriatr Psychiatry ; 38(3): e5899, 2023 03.
Article En | MEDLINE | ID: mdl-36855309

OBJECTIVE: To investigate the relationship between anxiety and mild cognitive impairment (MCI), and whether it is mediated by perceived stress, at the population level. METHOD AND DESIGN: In a longitudinal study of 368 adults aged 65+ from a population-based cohort, we annually assessed anxiety symptoms (GAD-7), perceived stress (PSS-4), and ratings on the Clinical Dementia Rating (CDR®), where CDR = 0.5 was operationalized as MCI. Examining data from three consecutive assessment waves, we first determined the associations between anxiety at the first wave with MCI at the third wave, and vice versa. We then used mediation analyses to determine whether the pathways in both directions were mediated by perceived stress at the second wave, adjusting for demographics and other relevant covariates. RESULTS: We confirmed significant bidirectional longitudinal associations between anxiety and MCI. Perceived stress was detected as a significant mediator for both pathways between anxiety and MCI, explaining 37.1% of the total effect (TE) of anxiety on incident MCI while conversely explaining 27.1% of the TE of MCI on anxiety. CONCLUSIONS: A bidirectional relationship with a 2-year lag between anxiety and MCI was mediated through perceived stress. Clinicians should be sensitive both to potential consequent anxiety when patients present with cognitive impairment, and to potential incipient MCI when the presenting complaint is anxiety. Managing stress may help mitigate adverse outcomes.


Anxiety , Cognitive Dysfunction , Humans , Longitudinal Studies , Anxiety/epidemiology , Anxiety Disorders , Cognitive Dysfunction/epidemiology , Mental Status and Dementia Tests
16.
Alzheimers Dement ; 19(10): 4507-4519, 2023 10.
Article En | MEDLINE | ID: mdl-36876954

INTRODUCTION: Plasma biomarkers-cost effective, non-invasive indicators of Alzheimer's disease (AD) and related disorders (ADRD)-have largely been studied in clinical research settings. Here, we examined plasma biomarker profiles and their associated factors in a population-based cohort to determine whether they could identify an at-risk group, independently of brain and cerebrospinal fluid biomarkers. METHODS: We measured plasma phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta (Aß)42/40 ratio in 847 participants from a population-based cohort in southwestern Pennsylvania. RESULTS: K-medoids clustering identified two distinct plasma Aß42/40 modes, further categorizable into three biomarker profile groups: normal, uncertain, and abnormal. In different groups, plasma p-tau181, NfL, and GFAP were inversely correlated with Aß42/40, Clinical Dementia Rating, and memory composite score, with the strongest associations in the abnormal group. DISCUSSION: Abnormal plasma Aß42/40 ratio identified older adult groups with lower memory scores, higher dementia risks, and higher ADRD biomarker levels, with potential implications for population screening. HIGHLIGHTS: Population-based plasma biomarker studies are lacking, particularly in cohorts without cerebrospinal fluid or neuroimaging data. In the Monongahela-Youghiogheny Healthy Aging Team study (n = 847), plasma biomarkers associated with worse memory and Clinical Dementia Rating (CDR), apolipoprotein E ε4, and greater age. Plasma amyloid beta (Aß)42/40 ratio levels allowed clustering participants into abnormal, uncertain, and normal groups. Plasma Aß42/40 correlated differently with neurofilament light chain, glial fibrillary acidic protein, phosphorylated tau181, memory composite, and CDR in each group. Plasma biomarkers can enable relatively affordable and non-invasive community screening for evidence of Alzheimer's disease and related disorders pathophysiology.


Alzheimer Disease , Humans , Aged , Alzheimer Disease/diagnosis , Amyloid beta-Peptides , Glial Fibrillary Acidic Protein , Apolipoprotein E4 , Biomarkers , tau Proteins
17.
Article En | MEDLINE | ID: mdl-36990900
18.
Res Sq ; 2023 Feb 01.
Article En | MEDLINE | ID: mdl-36778243

An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid ß (Aß)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes are key to unleashing Aß effects in pathological tau phosphorylation. In a large study ( n =1,016) across three cohorts, we tested whether astrocyte reactivity modulates the association of Aß with plasma tau phosphorylation in CU people. We found that Aß pathology was associated with increased plasma phosphorylated tau levels only in individuals positive for astrocyte reactivity (Ast+). Cross-sectional and longitudinal tau-PET analysis revealed that tau tangles accumulated as a function of Aß burden only in CU Ast+ individuals with a topographic distribution compatible with early AD. Our findings suggest that increased astrocyte reactivity is an important upstream event linking Aß burden with initial tau pathology which might have implications for the biological definition of preclinical AD and for selecting individuals for early preventive clinical trials.

19.
Alzheimers Dement ; 19(8): 3365-3378, 2023 08.
Article En | MEDLINE | ID: mdl-36790027

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.


Dementia , Sex Characteristics , Humans , Male , Female , Risk Factors , Alcohol Drinking , Dementia/epidemiology , Sex Factors
20.
Alzheimers Dement ; 19(7): 2898-2912, 2023 07.
Article En | MEDLINE | ID: mdl-36637034

INTRODUCTION: Prior estimates of dementia prevalence in India were based on samples from selected communities, inadequately representing the national and state populations. METHODS: From the Longitudinal Aging Study in India (LASI) we recruited a sample of adults ages 60+ and administered a rich battery of neuropsychological tests and an informant interview in 2018 through 2020. We obtained a clinical consensus rating of dementia status for a subsample (N = 2528), fitted a logistic model for dementia status on this subsample, and then imputed dementia status for all other LASI respondents aged 60+ (N = 28,949). RESULTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%, with significant age and education gradients, sex and urban/rural differences, and cross-state variation. DISCUSSION: An estimated 8.8 million Indians older than 60 years have dementia. The burden of dementia cases is unevenly distributed across states and subpopulations and may therefore require different levels of local planning and support. HIGHLIGHTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%. About 8.8 million Indians older than 60 years live with dementia. Dementia is more prevalent among females than males and in rural than urban areas. Significant cross-state variation exists in dementia prevalence.


Dementia , Male , Female , Humans , Dementia/epidemiology , Prevalence , Aging , Neuropsychological Tests , India/epidemiology
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