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BackgroundThe Clock Drawing Test (CDT) has been widely used in clinic for cognitive assessment. Recently, a digital Clock Drawing Text (dCDT) that is able to capture the entire sequence of clock drawing behaviors was introduced. While a variety of domain-specific features can be derived from the dCDT, it has not yet been evaluated in a large community-based population whether the features derived from the dCDT correlate with cognitive function. ObjectiveWe aimed to investigate the association between dCDT features and cognitive performance across multiple domains. MethodsParticipants from the Framingham Heart Study, a large community-based cohort with longitudinal cognitive surveillance, who did not have dementia were included. Participants were administered both the dCDT and a standard protocol of neuropsychological tests that measured a wide range of cognitive functions. A total of 105 features were derived from the dCDT, and their associations with 18 neuropsychological tests were assessed with linear regression models adjusted for age and sex. Associations between a composite score from dCDT features were also assessed for associations with each neuropsychological test and cognitive status (clinically diagnosed mild cognitive impairment compared to normal cognition). ResultsThe study included 2062 participants (age: mean 62, SD 13 years, 51.6% women), among whom 36 were diagnosed with mild cognitive impairment. Each neuropsychological test was associated with an average of 50 dCDT features. The composite scores derived from dCDT features were significantly associated with both neuropsychological tests and mild cognitive impairment. ConclusionsThe dCDT can potentially be used as a tool for cognitive assessment in large community-based populations.

BackgroundAlthough some neuropsychological (NP) tests are considered more central for the diagnosis of Alzheimer disease (AD), there is a lack of understanding about the interaction between different cognitive tests. ObjectiveThis study aimed to demonstrate a global view of hierarchical probabilistic dependencies between NP tests and the likelihood of cognitive impairment to assist physicians in recognizing AD precursors. MethodsOur study included 2091 participants from the Framingham Heart Study. These participants had undergone a variety of NP tests, including Wechsler Memory Scale, Wechsler Adult Intelligence Scale, and Boston Naming Test. Heterogeneous cognitive Bayesian networks were developed to understand the relationship between NP tests and the cognitive status. The performance of probabilistic inference was evaluated by the 10-fold cross validation. ResultsA total of 4512 NP tests were used to build the Bayesian network for the dementia diagnosis. The network demonstrated conditional dependency between different cognitive functions that precede the development of dementia. The prediction model reached an accuracy of 82.24%, with sensitivity of 63.98% and specificity of 92.74%. This probabilistic diagnostic system can also be applied to participants that exhibit more heterogeneous profiles or with missing responses for some NP tests. ConclusionsWe developed a probabilistic dependency network for AD diagnosis from 11 NP tests. Our study revealed important psychological functional segregations and precursor evidence of AD development and heterogeneity.

INTRODUCTION: Tau is a key pathology in chronic traumatic encephalopathy (CTE). Here, we report our findings in tau positron emission tomography (PET) measurements from the DIAGNOSE CTE Research Project. METHOD: We compare flortaucipir PET measures from 104 former professional players (PRO), 58 former college football players (COL), and 56 same-age men without exposure to repetitive head impacts (RHI) or traumatic brain injury (unexposed [UE]); characterize their associations with RHI exposure; and compare players who did or did not meet diagnostic criteria for traumatic encephalopathy syndrome (TES). RESULTS: Significantly elevated flortaucipir uptake was observed in former football players (PRO+COL) in prespecified regions (p

IntroductionClinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population.MethodsThe ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites. We developed a comprehensive study protocol for outreach and recruitment, an extensive data collection packet, and a centralized data management system, in English, Chinese, Korean, and Vietnamese.ResultsACAD has recruited 606 participants with an additional 900 expressing interest in enrollment since program inception.DiscussionACAD's traction indicates the feasibility of recruiting Asians for clinical research to enhance understanding of AD risk factors. ACAD will recruit > 5000 participants to identify genetic and non-genetic/lifestyle AD risk factors, establish blood biomarker levels for AD diagnosis, and facilitate clinical trial readiness.HighlightsThe Asian Cohort for Alzheimer's Disease (ACAD) promotes awareness of under-investment in clinical research for Asians. We are recruiting Asian Americans and Canadians for novel insights into Alzheimer's disease. We describe culturally appropriate recruitment strategies and data collection protocol. ACAD addresses challenges of recruitment from heterogeneous Asian subcommunities. We aim to implement a successful recruitment program that enrolls across three Asian subcommunities.

Recent advancements in generative artificial intelligence, particularly using large language models (LLMs), are gaining increased public attention. We provide a perspective on the potential of LLMs to analyze enormous amounts of data from medical records and gain insights on specific topics in neurology. In addition, we explore use cases for LLMs, such as early diagnosis, supporting patient and caregivers, and acting as an assistant for clinicians. We point to the potential ethical and technical challenges raised by LLMs, such as concerns about privacy and data security, potential biases in the data for model training, and the need for careful validation of results. Researchers must consider these challenges and take steps to address them to ensure that their work is conducted in a safe and responsible manner. Despite these challenges, LLMs offer promising opportunities for improving care and treatment of various neurologic disorders.

BackgroundDeep learning has shown potential in various scientific domains but faces challenges when applied to complex, high-dimensional multi-omics data. Alzheimer's Disease (AD) is a neurodegenerative disorder that lacks targeted therapeutic options. This study introduces the Circular-Sliding Window Association Test (c-SWAT) to improve the classification accuracy in predicting AD using serum-based metabolomics data, specifically lipidomics.MethodsThe c-SWAT methodology builds upon the existing Sliding Window Association Test (SWAT) and utilizes a three-step approach: feature correlation analysis, feature selection, and classification. Data from 997 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) served as the basis for model training and validation. Feature correlations were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA), and Convolutional Neural Networks (CNN) were employed for feature selection. Random Forest was used for the final classification.FindingsThe application of c-SWAT resulted in a classification accuracy of up to 80.8% and an AUC of 0.808 for distinguishing AD from cognitively normal older adults. This marks a 9.4% improvement in accuracy and a 0.169 increase in AUC compared to methods without c-SWAT. These results were statistically significant, with a p-value of 1.04 × 10ˆ-4. The approach also identified key lipids associated with AD, such as Cer(d16:1/22:0) and PI(37:6).InterpretationOur results indicate that c-SWAT is effective in improving classification accuracy and in identifying potential lipid biomarkers for AD. These identified lipids offer new avenues for understanding AD and warrant further investigation.FundingThe specific funding of this article is provided in the acknowledgements section.

Clinical trials for Alzheimers disease (AD) are slower to enroll study participants, take longer to complete, and are more expensive than trials in most other therapeutic areas. The recruitment and retention of a large number of qualified, diverse volunteers to participate in clinical research studies remain among the key barriers to the successful completion of AD clinical trials. An advisory panel of experts from academia, patient-advocacy organizations, philanthropy, non-profit, government, and industry convened in 2020 to assess the critical challenges facing recruitment in Alzheimers clinical trials and develop a set of recommendations to overcome them. This paper briefly reviews existing challenges in AD clinical research and discusses the feasibility and implications of the panels recommendations for actionable and inclusive solutions to accelerate the development of novel therapies for AD.

BackgroundIt remains unclear whether persistent loneliness is related to brain structures that are associated with cognitive decline and development of Alzheimer's disease (AD). This study aimed to investigate the relationships between different loneliness types, cognitive functioning, and regional brain volumes.MethodsLoneliness was measured longitudinally, using the item from the Center for Epidemiologic Studies Depression Scale in the Framingham Heart Study, Generation 3, with participants' average age of 46·3 ± 8·6 years. Robust regression models tested the association between different loneliness types with longitudinal neuropsychological performance (n = 2,609) and regional magnetic resonance imaging brain data (n = 1,829) (2002-2019). Results were stratified for sex, depression, and Apolipoprotein E4 (ApoE4).FindingsPersistent loneliness, but not transient loneliness, was strongly associated with cognitive decline, especially memory and executive function. Persistent loneliness was negatively associated with temporal lobe volume (β = -0.18, 95%CI [-0.32, -0.04], P = 0·01). Among women, persistent loneliness was associated with smaller frontal lobe (β = -0.19, 95%CI [-0.38, -0.01], P = 0·04), temporal lobe (β = -0.20, 95%CI [-0.37, -0.03], P = 0·02), and hippocampus volumes (β = -0.23, 95%CI [-0.40, -0.06], P = 0·007), and larger lateral ventricle volume (β = 0.15, 95%CI [0.02, 0.28], P = 0·03). The higher cumulative loneliness scores across three exams, the smaller parietal, temporal, and hippocampus volumes and larger lateral ventricle were evident, especially in the presence of ApoE4.InterpretationPersistent loneliness in midlife was associated with atrophy in brain regions responsible for memory and executive dysfunction. Interventions to reduce the chronicity of loneliness may mitigate the risk of age-related cognitive decline and AD.FundingUS National Institute on Aging.

AimImpaired sleep quality and sleep oxygenation are common sleep pathologies. This study assessed the impact of these abnormalities on white matter (WM) integrity in an epidemiological cohort.MethodsThe target population was the Framingham Heart Study Generation-2/Omni-1 Cohorts. Magnetic resonance imaging (diffusion tensor imaging) was used to assess WM integrity. Wearable digital devices were used to assess sleep quality: the (M1-SleepImage™ system) and the Nonin WristOx for nocturnal oxygenation. The M1 device collects trunk actigraphy and the electrocardiogram (ECG); sleep stability indices were computed using cardiopulmonary coupling using the ECG. Two nights of recording were averaged.ResultsStable sleep was positively associated with WM health. Actigraphic periods of wake during the sleep period were associated with increased mean diffusivity. One marker of sleep fragmentation which covaries with respiratory chemoreflex activation was associated with reduced fractional anisotropy and increased mean diffusivity. Both oxygen desaturation index and oxygen saturation time under 90% were associated with pathological directions of diffusion tensor imaging signals. Gender differences were noted across most variables, with female sex showing the larger and significant impact.ConclusionsSleep quality assessed by a novel digital analysis and sleep hypoxia was associated with WM injury, especially in women.

‘I have not found among my possessions anything which I hold more dear than, or value so much as, my knowledge of the actions of great people, acquired by long experience in contemporary affairs, and a continual study of antiquity.’ The Prince, Machiavelli

BackgroundAlthough greater flavonoid intake is associated with a reduced risk of Alzheimer's disease (AD) and related dementias (ADRD), evidence relating dietary flavonoid intake to brain health based on MRI is lacking.ObjectiveThe objective of this study was to explore the association between dietary flavonoid intake and MRI measures of brain health, including total brain tissue volume (TBV), white matter hyperintensities volume (WMHV), and hippocampal volume (HV).MethodsEligible subjects included members of the Framingham Heart Study Offspring Cohort who were free of stroke at exam 7 and had at least 1 valid food frequency questionnaire from exams 5, 6, or 7 (n = 2086; mean age at exam 7, 60.6 y). Flavonoid intakes represented the cumulative mean of intakes across the 3 exams and were categorized based on quartiles categories of intake. TBV, WMHV, and HV were assessed at exam 7. Multiple linear regression models were used to examine the cross-sectional association between total and the 6 classes of flavonoids and the 3 aforementioned MRI measures.ResultsThe mean (95% CI) of the WMHV of subjects in the highest quartile category of flavan-3-ols [0.56 (0.52, 0.61)] and flavonoid polymers [0.57 (0.52, 0.61)] intake was significantly smaller relative to that of subjects in the lowest quartile category of flavan-3-ols [0.65 (0.60, 0.71)] and flavonoid polymers [0.66 (0.60, 0.71)] after accounting for important demographic, lifestyle, and clinical factors. Inverse trend associations with WMHV were also seen for flavan-3-ols (P = 0.01) and flavonoid polymers (P = 0.01) as well as for total flavonoids (P = 0.01). TBV and HV were not associated with dietary flavonoid intake following the adjustment for potential confounders.ConclusionsOur results contribute to the literature on flavonoids and ADRD as they suggest that higher flavonoid intakes may affect ADRD risk in middle-aged and older adults by reducing WMHV, a marker strongly associated with ADRD.

BackgroundThere is growing interest in the pathophysiological processes of preclinical Alzheimer's disease (AD), including the potential role of leptin. Human studies have shown that both low and high levels of leptin can be associated with worse neurocognitive outcomes, suggesting this relationship may be moderated by another risk factor.ObjectiveWe examined the association between plasma leptin levels and both neuropsychological test performance and structural neuroimaging and assessed whether body mass index (BMI) is an effect modifier of these associations.MethodsOur study sample consisted of 2,223 adults from the Framingham Heart Study Third Generation Cohort (average age = 40 years, 53% women).ResultsAmong the entire sample, there was no association between leptin and any of the neuropsychological domain measures or any of the MRI brain volume measures, after adjustment for BMI, APOE4, and other clinical factors. However, we did observe that BMI category was an effect modifier for the association between leptin and verbal memory (p for interaction = 0.03), where higher levels of leptin were associated with better performance among normal weight participants (BMI 18.5-24.9) kg/m2 (beta = 0.12, p = 0.02). No association was observed between leptin level and verbal memory test performance among participants who were overweight or obese.ConclusionThese findings suggest that the association between leptin and cognitive function is moderated by BMI category. Prospective examination of individuals transitioning from middle age to older adulthood will help to clarify the contribution of leptin to AD and other neurodegenerative conditions.

IntroductionRecent research with neuropathologic or biomarker evidence of Alzheimer's disease (AD) casts doubt on traumatic brain injury (TBI) as a risk factor for AD. We leveraged the National Alzheimer's Coordinating Center to examine the association between self-reported TBI with loss of consciousness and AD neuropathologic changes, and with baseline and longitudinal clinical status.MethodsThe sample included 4761 autopsy participants (453 with remote TBI with loss of consciousness; 2822 with AD neuropathologic changes) from National Alzheimer's Coordinating Center.ResultsSelf-reported TBI did not predict AD neuropathologic changes (P > .10). Reported TBI was not associated with baseline or change in dementia severity or cognitive function in participants with or without autopsy-confirmed AD.DiscussionSelf-reported TBI with loss of consciousness may not be an independent risk factor for clinical or pathological AD. Research that evaluates number and severity of TBIs is needed to clarify the neuropathological links between TBI and dementia documented in other large clinical databases.

This cohort study investigates the risk of mild cognitive impairment, Alzheimer disease, and all-cause dementia associated with subjective cognitive decline using the subjective cognitive decline–plus criteria among cognitively normal adults in the community. Key Points: Question: Among cognitively normal adults in the community, what is the risk from subjective cognitive decline (SCD), using SCD-plus (SCD+) criteria and assessed longitudinally, associated with mild cognitive impairment (MCI), Alzheimer disease (AD), and all-cause dementia? Findings: In this cohort study using longitudinal data from the Framingham Heart Study including 3585 participants, SCD+ was significantly associated with survival time to MCI, AD, and all-cause dementia. Associations were independent of APOE status and an AD polygenic risk score. Meaning: In a community setting, SCD+ was associated with an increased risk of future MCI, AD, and all-cause dementia with similar hazards estimated in clinic-based settings. Importance: Subjective cognitive decline (SCD) is recognized to be in the Alzheimer disease (AD) cognitive continuum. The SCD Initiative International Working Group recently proposed SCD-plus (SCD+) features that increase risk for future objective cognitive decline but that have not been assessed in a large community-based setting. Objective: To assess SCD risk for mild cognitive impairment (MCI), AD, and all-cause dementia, using SCD+ criteria among cognitively normal adults. Design, Setting, and Participants: The Framingham Heart Study, a community-based prospective cohort study, assessed SCD between 2005 and 2019, with up to 12 years of follow-up. Participants 60 years and older with normal cognition at analytic baseline were included. Cox proportional hazards (CPH) models were adjusted for baseline age, sex, education, APOE ε4 status, and tertiles of AD polygenic risk score (PRS), excluding the APOE region. Data were analyzed from May 2021 to November 2023. Exposure: SCD was assessed longitudinally using a single question and considered present if endorsed at the last cognitively normal visit. It was treated as a time-varying variable, beginning at the first of consecutive, cognitively normal visits, including the last, at which it was endorsed. Main Outcomes and Measures: Consensus-diagnosed MCI, AD, and all-cause dementia. Results: This study included 3585 participants (mean [SD] baseline age, 68.0 [7.7] years; 1975 female [55.1%]). A total of 1596 participants (44.5%) had SCD, and 770 (21.5%) were carriers of APOE ε4. APOE ε4 and tertiles of AD PRS status did not significantly differ between the SCD and non-SCD groups. MCI, AD, and all-cause dementia were diagnosed in 236 participants (6.6%), 73 participants (2.0%), and 89 participants (2.5%), respectively, during follow-up. On average, SCD preceded MCI by 4.4 years, AD by 6.8 years, and all-cause dementia by 6.9 years. SCD was significantly associated with survival time to MCI (hazard ratio [HR], 1.57; 95% CI, 1.22-2.03; P <.001), AD (HR, 2.98; 95% CI, 1.89-4.70; P <.001), and all-cause dementia (HR, 2.14; 95% CI, 1.44-3.18; P <.001). After adjustment for APOE and AD PRS, the hazards of SCD were largely unchanged. Conclusions and Relevance: Results of this cohort study suggest that in a community setting, SCD reflecting SCD+ features was associated with an increased risk of future MCI, AD, and all-cause dementia with similar hazards estimated in clinic-based settings. SCD may be an independent risk factor for AD and other dementias beyond the risk incurred by APOE ε4 and AD PRS. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Type 2 diabetes and glucose metabolism have previously been linked to Alzheimer disease (AD). Yet, findings on the relation of glucose metabolism with amyloid-β and tau pathology later in life remain unclear. RESEARCH DESIGN AND METHODS: We included 288 participants (mean age 43.1 years, SD 10.7, range 20–70 years) without dementia, from the Framingham Heart Study, who had available measures of glucose metabolism (i.e., one-time fasting plasma glucose and insulin) and positron emission tomography (PET) measures of amyloid-β and/or tau 14 years later. We performed linear regression analyses to test associations of plasma glucose (continuously and categorically; elevated defined as >100 mg/dL), plasma insulin, homeostatic model assessment for insulin resistance (HOMA-IR) with amyloid-β or tau load on PET. When significant, we explored whether age, sex, and APOE ε4 allele carriership (AD genetic risk) modified these associations. RESULTS: Our findings indicated that elevated plasma glucose was associated with greater tau load 14 years later (B [95% CI] = 0.03 [0.01–0.05], P = 0.024 after false discovery rate [FDR] correction) but not amyloid-β. APOE ε4 carriership modified this association (B [95% CI] = −0.08 [−0.12 to −0.03], P = 0.001), indicating that the association was only present in APOE ε4 noncarriers (n = 225). Plasma insulin and HOMA-IR were not associated with amyloid-β or tau load 14 years later after FDR correction. CONCLUSIONS: Our findings suggest that glucose metabolism is associated with increased future tau but not amyloid-β load. This provides relevant knowledge for prevention strategies and prognostics to improve health care. [ABSTRACT FROM AUTHOR]

ObjectivePreclinical Alzheimer's disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI.MethodCognitively normal participants (n = 525) from the Alzheimer's Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220). Cox regressions were used to determine whether baseline process scores on the Rey Auditory Verbal Learning Test (AVLT; intrusion errors, learning slope, proactive interference, retroactive interference) predicted progression to MCI and a Clinical Dementia Rating (CDR) score of 1 after considering demographic characteristics, apolipoprotein E ε4 status, cerebrospinal fluid AD biomarkers, ischemia risk, mood, functional difficulty, and standard neuropsychological total test scores for the model.ResultsBaseline AVLT intrusion errors predicted progression to MCI (hazard ratio = 1.04, 95% confidence interval 1.01-1.07, p = .008) and improved model fit after the other valuable predictors were already in the model, χ2(df = 1) = 6.330, p = .012. AVLT intrusion errors also predicted progression to CDR = 1 (hazard ratio = 1.10, 95% confidence interval 1.02-1.18, p = .016) and again improved model fit, χ2(df = 1) = 4.682, p = .030.ConclusionsIntrusion errors on the AVLT contribute unique value for predicting progression from normal cognition to MCI and normal cognition to mild dementia (CDR = 1). Intrusion errors appear to reflect subtle change and inefficiencies in cognition that precede impairment detected by neuropsychological total scores. (PsycINFO Database Record

IntroductionWe examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up.MethodsFramingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified.ResultsBaseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion from normal cognition to MCI at 6.5-year follow-up. Annualized change rates in total cerebral brain volume and hippocampal volume were associated with conversion from normal cognition to MCI to follow-up.DiscussionBaseline WMH and hippocampal volume are markers that are both associated with conversion from normal cognition to MCI, highlighting the role of both vascular lesions and neurodegeneration in MCI.

BackgroundWorking memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span Test (BDT), only aggregate test performance was examined.ObjectiveThe current research tallied primacy/recency effects, out-of-sequence transposition errors, perseverations, and omissions to assess WM deficits in patients with mild cognitive impairment (MCI).MethodsMemory clinic patients (n = 66) were classified into three groups: single domain amnestic MCI (aMCI), combined mixed domain/dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/WM ability was assessed by asking participants to repeat 7 trials of five digits backwards. Serial order position accuracy, transposition errors, perseverations, and omission errors were tallied.ResultsA 3 (group)×5 (serial position) repeated measures ANOVA yielded a significant group×trial interaction. Follow-up analyses found attenuation of the recency effect for mixed/dys MCI patients. Mixed/dys MCI patients scored lower than non-MCI patients for serial position 3 (p

BackgroundWhite matter hyperintensities (WMH) on magnetic resonance imaging (MRI) have been postulated to be a core feature of Alzheimer's disease. Clinicopathological studies are needed to elucidate and confirm this possibility.ObjectiveThis study examined: 1) the association between antemortem WMH and autopsy-confirmed Alzheimer's disease neuropathology (ADNP), 2) the relationship between WMH and dementia in participants with ADNP, and 3) the relationships among cerebrovascular disease, WMH, and ADNP.MethodsThe sample included 82 participants from the National Alzheimer's Coordinating Center's Data Sets who had quantitated volume of WMH from antemortem FLAIR MRI and available neuropathological data. The Clinical Dementia Rating (CDR) scale (from MRI visit) operationalized dementia status. ADNP+ was defined by moderate to frequent neuritic plaques and Braak stage III-VI at autopsy. Cerebrovascular disease neuropathology included infarcts or lacunes, microinfarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy.Results60/82 participants were ADNP+. Greater volume of WMH predicted increased odds for ADNP (p = 0.037). In ADNP+ participants, greater WMH corresponded with increased odds for dementia (CDR≥1; p = 0.038). WMH predicted cerebral amyloid angiopathy, microinfarcts, infarcts, and lacunes (ps

Background/aimsMild cognitive impairment (MCI) lacks a "gold standard" operational definition. The Jak/Bondi actuarial neuropsychological criteria for MCI are associated with improved diagnostic stability and prediction of progression to dementia compared to conventional MCI diagnostic approaches, although its utility in diagnosing MCI in old-old individuals (age 75+) is unknown. Therefore, we investigated the applicability of neuropsychological MCI criteria among old-old from the Framingham Heart Study.MethodsA total of 347 adults (ages 79-102) were classified as cognitively normal or MCI via Jak/Bondi and conventional Petersen/Winblad criteria, which differ on cutoffs for cognitive impairment and number of impaired scores required for a diagnosis. Cox models examined MCI status in predicting risk of progression to dementia.ResultsMCI diagnosed by both the Jak/Bondi and Petersen/Winblad criteria was associated with incident dementia; however, when both criteria were included in the regression model together, only the Jak/Bondi criteria remained statistically significant. At follow-up, the Jak/Bondi criteria had a lower MCI-to-normal reversion rate than the Petersen/Winblad criteria.ConclusionsOur findings are consistent with previous research on the Jak/Bondi criteria and support the use of a comprehensive neuropsychological diagnostic approach for MCI among old-old individuals.