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Objectives: To describe the psychometric properties of the Picture‐based Memory Impairment Screen (PMIS) in a multidisciplinary memory disorder center serving an ethnically and educationally diverse community. Design: Cross‐sectional cohort study. Setting: Montefiore Center for Aging Brain (CAB) Participants: Individuals with cognitive complaints (N=405; average age 76±10, 66% female). Measurements: A geriatrician or neurologist administered the PMIS, and a neuropsychologist administered the Blessed Information, Memory, and Concentration (BIMC) test and determined whether participants had dementia, mild cognitive impairment (MCI), or subjective cognitive complaints (SCC). Results: Mean PMIS scores were 4.0±2.6 in participants with dementia (n=194), 6.8±1.5 in those with MCI (n= 155), and 7.0±1.8 in those with SCC (n= 56) (p<.001). PMIS scores showed similar significant linear trends when analyzed according to ethnicity, education, sex, and language. The PMIS was negatively correlated with BIMC score (p<.001). The PMIS had positive predictive value of 77%, negative predictive value of 73%, sensitivity of 68%, and specificity of 81% to detect all‐cause dementia in this population of individuals with cognitive complaints. Conclusion: The PMIS is a quick, valid screening tool to identify cognitive impairment in individuals with cognitive complaints that accounts for cultural and educational differences. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to determine early developmental and cognitive outcomes of children with febrile status epilepticus (FSE) one month and one year after FSE. Methods One hundred ninety four children with FSE were evaluated on measures of cognition, receptive language, and memory as part of the FEBSTAT study and compared with 100 controls with simple febrile seizures (FSs). Results Children with FSE did not differ dramatically on tasks compared with FS controls at one month after FSE but demonstrated slightly weaker motor development (p = 0.035) and receptive language (p = 0.034) at one year after FSE. Performances were generally within the low average to average range. Within the FSE cohort, non-White children performed weaker on many of the tasks compared with Caucasian children. At the one-year visit, acute hippocampal T2 findings on MRI were associated with weaker receptive language skills (p = 0.0009), and human herpes virus 6 or 7 (HHV6/7) viremia was associated with better memory performances (p = 0.047). Conclusion Febrile status epilepticus does not appear to be associated with significant cognitive impairment on early developmental measures, although there is a trend for possible receptive language and motor delay one year after FSE. Further follow-up, which is in progress, is necessary to track long-term cognitive functioning. [ABSTRACT FROM AUTHOR]

Objective: The KCNQ2 gene mutations (KCNQ2), a known cause of neuronal potassium channel dysfunction in brain cells, causes susceptibility to seizures beginning within the first days of life. Seizure semiology, severity and cognitive sequela can vary depending on the type of KCNQ2 mutation. Cognitive impact ranges from moderate to severe; no known consistent presentation. KCNQ2 affects approximately 2.8 in 100,000 births: over 3,000 annual cases worldwide. We describe the neuropsychological findings of an 11-year-old female with a monoallelic mutation of the KCNQ2 gene, and history of seizures. EEG indicated generalized epilepsy syndrome with a right occipital focal area of dysfunction. We highlight the importance of neuropsychological evaluation in medical and psychological management of children with KCNQ2. Methods: Medical history includes multifocal seizures beginning at 2 days old and significant anxiety, both managed with medication, language delay, and a diagnosis of KCNQ2 at age 9. A comprehensive neuropsychological evaluation was conducted to assess slower processing speed, behavioral concerns, and anxiety. Results: Evaluation revealed low average overall cognition and average academic performances, with strengths in verbal comprehension, fluid reasoning, and written expression. Cognitive processing speed was atypical, with slow processing speed affecting her performance across multiple domains. Behavior assessment supports Generalized Anxiety Disorder. Conclusion: This case of a girl with KCNQ2 demonstrated an atypical cognitive and behavioral profile, contributing to our limited knowledge of how KCNQ2 presents. The patterns of her performances add to the literature of the KCNQ2 gene mutation and raise important questions regarding the role of KCNQ2 in manifestations of cognitive and behavioral symptoms. [ABSTRACT FROM AUTHOR]

Objective Spinocerebellar ataxia 29 (SCA29) is a rare autosomal dominant disorder resulting in infantile-onset hypertonia, gross motor delay and cognitive impairment. SCA29 causes cerebellar dysfunction and atrophy manifested by poor hand coordination, instability of gait, impaired articulation, poor hand-eye coordination, language delay, and a wide legged, unsteady walk. Slow improvement across childhood is common, but the limited available research suggests significant clinical heterogeneity among individuals diagnosed with SCA29. We report the case of a six-year-old first grade girl to highlight the cognitive profile of SCA29 and determine its consistency with the literature. Methods Full neuropsychological evaluation was conducted, including examination of overall cognitive ability, academic achievement, and behavior. Results The patient demonstrated delayed cognitive and motor skills, slow processing, reduced reading fluency, and weak reading comprehension. Impaired verbal comprehension and limited fund of knowledge was seen. Working memory and visual spatial ability were relative individual strengths, though normatively weak. Untimed and non-motor academic skills were well below peers. Performances met criteria for ADHD and Language Disorder. Conclusion Six-year-old girl with SCA29 with expected motor difficulties including gross motor delay, hypotonia, ataxia, poor ocular fixation evidenced global impairments with expected weakness with verbal comprehension and receptive language skills. This is consistent with the findings in the SCA29 literature. Comorbid diagnoses of ADHD and Language Disorder were present. Given clinical heterogeneity, this case serves to expand existing knowledge on case variability, and adds the consideration of wider comorbidities in this rare condition. [ABSTRACT FROM AUTHOR]

Objective Antiphospholipid Antibody Syndrome (APS), also known as Hughes Syndrome, is an autoimmune condition linked to various adverse medical and neurological outcomes affecting 5 in 100,000. APS results from antibodies (aPL) that attack blood proteins that bind to phospholipids (e.g. 2-glycoprotein I and prothrombin), which can cause blood flow problems, increased risk of blood clots, and recurrent vascular thrombotic events. Research suggests APS may lead to various neurologic/medical issues including memory loss, visual disturbances, and dementia. Method Neuropsychological evaluation of 48-year-old female with triple-positive APS and history of bilateral superior parietal chronic ischemic infarctions, multiple bilateral lacunar infarctions, and bilateral encephalomalacia. Reports progressive cognitive changes (< 1 year). Results Neuropsychological evaluation evidenced low average premorbid functioning and currently, extremely low overall cognitive ability. Memory was variable with significant visual and working memory impairment but preserved delayed recall of contextual information. While verbal abilities were intact, deficits were noted in executive functioning, attention, processing speed, visuomotor, visual–spatial, and fine motor skills. Conclusion This 48-year-old woman's cognitive profile is consistent with findings in the APS literature and is indicative of an early onset major vascular neurocognitive disorder. Retrospective studies suggest that cognitive deficits often precede somatic symptoms of APS and abnormal neuroimaging findings; she presents atypically, as somatic symptoms and abnormal neuroimaging preceded cognitive decline. This case adds to the limited body of neuropsychological data regarding the effects of APS on cognitive functioning, as the pathogenesis of cognitive impairment in APS is unclear and leads to questions regarding differences in, and trajectories of, cognitive deficits in APS. [ABSTRACT FROM AUTHOR]

Objective Developmental Discoordination Disorder (DCD) is an often overlooked and seldom diagnosed neurodevelopmental condition marked by impairments in motor skills. Lacking identifiable medical or neurological etiology, children with DCD often have preserved intellectual abilities. Comorbidity is common, including ADHD and specific learning disability. Despite extensive evidence of significant impact on daily activities and academics due to differences in motor behaviors, DCD difficulties are regularly treated as behavioral problems. Method Neuropsychological evaluation of an 8-year-old boy with a possible reading delay and inability to perform some age-appropriate academic and self-care tasks. Results Average overall ability with very strong verbal performances; intact visual perceptual processing, memory, and non-written language. Academics are within expected range, although graphomotor weakness impacted academic performances on tasks with written demands. Patient appeared clumsy and awkward with low muscle tone, poor balance, and difficulty learning new motor skills. Impaired fine motor control, handwriting, gait, gross motor skills, motor planning, coordination, and oromotor weakness as well as inferior verbal language abilities were evident. Impulsivity, inattention, poor planning, and poor self-monitoring were also evident. Conclusions DCD is evidenced by impairment in fine and gross motor skills, oromotor skills, motor planning, energy, and coordination with clear discrepancy between motor abilities and abilities in other areas, specifically language. In our case, DCD features were overlooked despite wide ranging impact. ADHD and SLD with impairment in written expression were concurrent. This case highlights the need for greater appreciation of DCD so that children can benefit from early detection and intervention considering the life-long implications of the disorder. [ABSTRACT FROM AUTHOR]

Background: Efficacy and validity of the MoCA for cognitive screening in ethnoculturally and linguistically diverse settings is unclear. We sought to examine the utility and discriminative validity of the Spanish and English MoCA versions to identify cognitive impairment among diverse community‐dwelling older adults. Methods: Participants aged ≥65 with cognitive concerns attending outpatient primary care in Bronx, NY, were recruited. MoCA and neuropsychological measures were administered in Spanish or English, and a neuropsychologist determined cognitive status (normal with subjective cognitive concerns [SCC], mild cognitive impairment [MCI], and dementia). One‐way ANOVA compared cognitive statuses. ROC analyses identified optimal MoCA cutpoints for discriminating possible cognitive impairment. Results: There were 231 participants, with mean age 73, 72% women, 43% Hispanic; 39% Black/African American; 113 (49%) completed testing in English and 118 (51%) in Spanish. Overall MoCA mean was 17.7 (SD = 4.3). Neuropsychological assessment identified 90 as cognitively normal/SCC, average MoCA 19.9 (SD = 4.1), 133 with MCI, average MoCA 16.6 (SD = 3.7), and 8 with dementia, average MoCA 10.6 (SD = 3.1). Mean English MoCA average was 18.6 (SD = 4.1) versus Spanish 16.7 (SD = 4.3). The published cutpoint ≤23 for MCI yielded a high false‐positive rate (79%). ROC analyses identified ≤18.5 as the score to identify MCI or dementia using the English MoCA (65% sensitivity; 77% specificity) and ≤16.5 for the Spanish MoCA (64% sensitivity;73% specificity) in this sample of older adults with cognitive concerns. Conclusions: Current MoCA cutpoints were inappropriately high in a culturally/linguistically diverse urban setting, leading to a high false‐positive rate. Lower Spanish and English MoCA cutpoints may improve diagnostic accuracy for identifying cognitive impairment in this group, highlighting the need for the creation and validation of accurate cognitive screeners for ethnoculturally and linguistically diverse older adults. [ABSTRACT FROM AUTHOR]

Background: Very few studies have explored the utility of subjective cognitive complaints (SCCs) in primary care settings.Objective: We aim to investigate associations between SCCs (item-level), objective cognitive function (across domains and global), and mood in a diverse primary care population, including subjects with mild cognitive impairment.Methods: We studied 199 (75.9%females; 57.8%Hispanics; 42.2%African Americans) older adults (mean age 72.5 years) with memory concerns at a primary care clinic. A five-item SCC questionnaire, and objective cognitive assessments, including the Montreal Cognitive Assessment (MoCA) and the Geriatric Depression Scale, were administered.Results: Logistic regression analyses showed associations between SCC score and depressive symptoms. A memory-specific ("memory worsening") SCC predicted scores on the MoCA (p = 0.005) in Hispanics.Conclusion: SCCs are strongly linked to depressive symptoms in African Americans and Hispanics in a primary care setting; a specific type of SCC is related to global cognitive function in Hispanics. [ABSTRACT FROM AUTHOR]

Objective: Neuropsychiatric System Lupus Erythematosus (NP-SLE) is a subtype of SLE characterized by chronic or episodic neurologic and/or psychiatric central nervous system features. The neuropsychological profile of NP-SLE is not well-established. Here we present serial evaluations of a woman with confirmed NP-SLE who underwent subsequent medical intervention. This case study adds to the growing body of literature demonstrating the role neuropsychology plays in the care of patients with NP-SLE. Method: This was an evaluation of a 25-year-old woman with NP-SLE. Initial testing took place inpatient prior to treatment with immunotherapy treatment subsequent evaluations were outpatient at 1 month, 4 months and 8 months post-treatment. Results: Inpatient evaluation revealed a woman of at least average premorbid abilities with suboptimal performances across cognitive domains including reduced speed of processing and notable difficulty with planning and organization. Evaluation 1 month later evidenced worsening cognitive and motoric performances across tasks which led to adjustment of medical management. Evaluation at 4 months demonstrated a positive trend and some improved cognitive functioning; 8-month evaluation confirmed improvement in global cognition and functioning with suspected return to premorbid abilities. Conclusions: This case provides an example of NP-SLE neuropsychological profile over time and demonstrates the beneficial impact of correct diagnosis and medical regimen. It also highlights the role of serial neuropsychological assessment in the management of complex neurological disease. [ABSTRACT FROM AUTHOR]

Introduction: Language acculturation is the process by which a bilingual individual obtains proficiency and comfort in speaking a new language while maintaining fluency in their native language. Considering the degree of language acculturation in bilingual patients is essential to choosing appropriate tests and interpreting neuropsychological assessment. The Language Acculturation Meter™ (LAM) was created for native Spanish speakers who are bilingual in English to aid in selecting and interpreting verbally-administered assessments. While the LAM was created to be completed as an interview, a Spanish version of the form exists and can be given to patients to complete independently. We sought to evaluate the feasibility and utility of self-administered LAM in a clinical older adult population in NY State. Methods: The LAM was given to Spanish-speaking older adults and their caregivers as part of their clinical neuropsychological evaluation at Montefiore's Memory Disorders Centers. 16 patient and caregiver dyads completed the LAM in either English or Spanish. Results: Patient ages ranged from 67 to 83; 75% of the patients were female, and 56% self-identified as bilingual. 18% of patients completed the LAM without caregiver assistance. Dyads did not comment on the form, but early qualitative feedback suggests that some had difficulty understanding how to complete aspects of the LAM, and others found that some items on the LAM did not apply to them. Conclusions: The LAM is a previously validated interview tool that requires further research to determine if it can be used as a self-report questionnaire in clinical populations, including older adults with cognitive complaints. [ABSTRACT FROM AUTHOR]

Objective: Anti-leucine-rich glioma-inactivated 1 limbic encephalitis (LGI1-LE) is a rare diagnosis but the second most common autoimmune encephalitis. While it has a growing body of neuropsychological literature, there is limited awareness by the lay public about this condition. As with all complex neurological conditions, caregiver/family understanding of the disorder and engagement in treatment is important for optimal recovery and dyad wellbeing. We present the case of a caregiver and patient dyad with confirmed LGI1-LE/ Voltage-Gated Potassium Channel antibodies seen for repeat neuropsychological evaluations to demonstrate the importance of education, advocacy, and multidisciplinary involvement as part of the neuropsychological assessment process. Method: Repeat neuropsychological evaluations of a 72-year-old Spanish-speaking woman with limited formal education and complex medical history, including past strokes and recent autoimmune encephalitis. Results: Initial evaluation revealed marked behavioral and cognitive fluctuations/variability with familial frustration secondary to poor understanding by caregiver until neuropsychological feedback session. Repeat evaluation was delayed four weeks due to caregiver factors but demonstrated improvement in global cognition and overall functioning. Follow up, six months later, demonstrated significant cognitive decline and new motoric symptoms with further difficulty coordinating appointments by the caregiver. In addition to assistance with medical management, neuropsychological involvement led to connection to case management, home evaluation, concrete solutions for food insecurity, and cognitive evaluation for the caregiver. Conclusions: This case adds to LG1-LE literature and demonstrates the importance of neuropsychology not only for disease tracking/ management but also as an important tool for advocacy and patient/caregiver education, specifically in culturally and educationally diverse populations with complex medical conditions. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate the validity of the Symbol Match in a diverse clinical setting. Background: To improve detection of cognitive impairment in older primary care patients, our team developed the 5-Cog, a 5-minute cognitive assessment and decision tree paradigm that can be administered by non-clinicians. The Symbol Match is a new 90-second oral symbol and digit substitution task that is one of the three tests in the 5-Cog that assesses processing speed and executive function. Methods: 50 participants (66% female; 44% Hispanic, 38% Non-Hispanic Black; 36% evaluated in Spanish) with a mean age of 77.84 ± 7.3, and 12 ± 4.7 mean years of education. Participants were recruited following clinical evaluations at the Montefiore Memory Disorder Centers and had confirmed clinical diagnoses of dementia, mild cognitive impairment (MCI), or subjective cognitive concerns (SCC). Results: Symbol Match scores were significantly different (p < 0.001) between participants with SCC (N = 5, M = 48 ± 9.7), MCI (N = 14, M = 31.7 ± 14.3), and dementia (N = 28, M = 9.6 ± 11.5). Age (p = 0.004) and education (p < 0.001) were correlated with Symbol Match score in the overall sample. Symbol Match scores were significantly different between the 3 disease states (p < 0.001) even when controlling for age and education. The Symbol Match was highly correlated (r = 0.843, p < 0.001) with the Symbol Digit Modalities Test (SDMT), an established neuropsychological measure of processing speed and executive function. Conclusion: This study provides initial validation of the Symbol Match and its utility in a clinical population. Further research on psychometric properties and construct validity of this new tool is needed. [ABSTRACT FROM AUTHOR]

Objective: Wernicke-Korsakoff syndrome (WKS) is a neurological disorder caused by the lack of thiamine (vitamin B1) and includes Wernicke encephalopathy and the later stage of Korsakoff amnesic syndrome. WKS could be secondary to malnutrition, including Hyperemesis Gravidarum (HEG), which is characterized by severe vomiting during pregnancy. We present a case of HEG resulting in suspected WKS where neuropsychological evaluation clarified cognitive status with complex cultural, language, and educational factors. Method: Repeat evaluations of a 29-year-old West-African* woman with mental status change, decreased verbal output, agitation, and inability to walk in the context of HEG. Initially referred for inpatient neuropsychological evaluation at 21 weeks gestation. MRI demonstrated mild diffuse cerebral atrophy and symmetric foci of T2 FLAIR hyperintensities in periaqueductal gray matter, hypothalamus, bilateral thalami, perirolandic cortex, and bilateral mammillary bodies. Results: Initial inpatient testing with a face-to-face language congruent interpreter demonstrated notable multidomain impairment. Possible Intellectual Disability was considered by the referring team and test performances. Attempts at re-evaluation were limited by medical complications and prolonged hospitalization. Repeat inpatient evaluation 5 months later following birth of healthy child and initiation of stimulant medication, demonstrated profound memory impairment but otherwise improved cognitive capacity and engagement. Results aided in discharge planning including cognitive remediation with goal of improving functional independence. Conclusions: Wernicke-Korsakoff syndrome due to Hyperemesis Gravidarum is an uncommon but known complication that can have profound acute and long-term consequences. This case demonstrates that repeat neuropsychological evaluations can clarify cognitive status in complex medical/cultural/language situations. *(country of origin and primary language not provided for patient privacy). [ABSTRACT FROM AUTHOR]

Objective: The Symbol Digit Modalities Test (SDMT) is a task of processing speed and executive functioning that is widely used to evaluate individuals with Multiple Sclerosis (MS) and has been shown to predict various instrumental activities of daily living. The relationship between SDMT and daily functioning has not been well explored in the aging population. The Activities of Daily Living-Prevention Instrument (ADL-PI) is a self-report measure that assesses changes in functioning and instrumental activities of daily living (IADLs). We evaluate the relationship between SDMT and ADL-PI in older adults with subjective cognitive complaints in an urban, multi-ethnic, primary care population in Bronx, New York. Methods: 300 participants (50.7% Hispanic, 43.7% non-Hispanic Black; 37% assessed in Spanish) completed the SDMT and ADL-PI as part of a larger study seeking to improve detection of cognitive impairment in primary care. The mean age of the sample was 71.35 ± 5.76 years and participants had a mean 12.26 ± 3.76 years of education. Pearson correlations were used to examine the relationship between SDMT and IADLs. Results: SDMT performance was weakly albeit significantly correlated with self-report of functional difficulties on the ADL-PI (r = −0.312, p < 0.001). The relationship between SDMT (Range = 1–51, M = 25.39) and ADL-PI was significant in both English (p < 0.0011) and Spanish (p = 0.004) speaking participants and remained significant when controlling for age, education, and depression (p = 0.002). Conclusion: Consistent with MS literature, the SDMT is a useful tool for predicting self-report of instrumental activities of daily living of older adults with cognitive concerns. [ABSTRACT FROM AUTHOR]

Aging is a complex trait characterized by a diverse spectrum of endophenotypes. By utilizing the SomaScan® proteomic platform in 1,025 participants of the LonGenity cohort (age range: 65–95, 55.7% females), we found that 754 of 4,265 proteins were associated with chronological age. Pleiotrophin (PTN; β[SE] = 0.0262 [0.0012]; p = 3.21 × 10−86), WNT1‐inducible‐signaling pathway protein 2 (WISP‐2; β[SE] = 0.0189 [0.0009]; p = 4.60 × 10−82), chordin‐like protein 1 (CRDL1; β[SE] = 0.0203[0.0010]; p = 1.45 × 10−77), transgelin (TAGL; β[SE] = 0.0215 [0.0011]; p = 9.70 × 10−71), and R‐spondin‐1(RSPO1; β[SE] = 0.0208 [0.0011]; p = 1.09 × 10−70), were the proteins most significantly associated with age. Weighted gene co‐expression network analysis identified two of nine modules (clusters of highly correlated proteins) to be significantly associated with chronological age and demonstrated that the biology of aging overlapped with complex age‐associated diseases and other age‐related traits. The correlation between proteomic age prediction based on elastic net regression and chronological age was 0.8 (p < 2.2E−16). Pathway analysis showed that inflammatory response, organismal injury and abnormalities, cell and organismal survival, and death pathways were associated with aging. The present study made novel associations between a number of proteins and aging, constructed a proteomic age model that predicted mortality, and suggested possible proteomic signatures possessed by a cohort enriched for familial exceptional longevity. [ABSTRACT FROM AUTHOR]

Objective Rogalski and colleagues (2013) use the term SuperAgers to indicate individuals aged 80 and older who have exceptional memory with the goal of clarifying factors that impact successful aging. Using a modified definition, we explored cognitive trajectories of SuperAgers within our longitudinal study of the genetic factors associated with exceptional longevity (OPEL) in individuals of Ashkenazi Jewish descent. Method LonGenity Study participants complete annual physical and cognitive assessments which include the Free and Cued Selective Reminding Test (FCSRT) and WMS-R Logical Memory (LMI). All participants who completed a visit at age 80 were included in the analysis (N = 230; 56.5% female; mean education 17.57 ± 2.74 years; 46.5% OPEL; median follow-up 4 years). Twenty-one participants met modified SuperAger criteria (FCSRT: >38 and LMI: >25; no other cognitive impairment). Descriptive statistics, t-tests, and linear mixed effects models of cognitive trajectories were used to examine the differences between SuperAgers and non-SuperAgers. Results Although there were no differences in demographics or familial history of exceptional longevity, SuperAgers were less likely to have a history of cardiac problems (p = 0.02). Overall cognitive functioning remained stable with age in the SuperAgers, whereas non-SuperAgers demonstrated declining overall cognition with age (β = −0.029, CI: −0.036—0.022). Memory task performances demonstrated a similar discrepancy in trajectories. Conclusion(s) In our unique and high functioning population, SuperAgers as defined at age 80 do not demonstrate the typical cognitive declines thought to be associated with age. Vascular risk factors appear to play a role, but further investigation including exploring genetic markers and MRI is warranted. [ABSTRACT FROM AUTHOR]

While the growth hormone/insulin-like growth factor-1 (GH/IGF-1) pathway plays essential roles in growth and development, diminished signaling via this pathway in model organisms extends lifespan and health-span. In humans, circulating IGF-1 and IGF-binding proteins 3 and 1 (IGFBP-3 and 1), surrogate measures of GH/IGF-1 system activity, have not been consistently associated with morbidity and mortality. In a prospective cohort of independently-living older adults (n = 840, mean age 76.1 ± 6.8 years, 54.5% female, median follow-up 6.9 years), we evaluated the age- and sex-adjusted hazards for all-cause mortality and incident age-related diseases, including cardiovascular disease, diabetes, cancer, and multiple-domain cognitive impairment (MDCI), as predicted by baseline total serum IGF-1, IGF-1/IGFBP-3 molar ratio, IGFBP-3, and IGFBP-1 levels. All-cause mortality was positively associated with IGF-1/IGFBP-3 molar ratio (HR 1.28, 95% CI 1.05–1.57) and negatively with IGFBP-3 (HR 0.82, 95% CI 0.680–0.998). High serum IGF-1 predicted greater risk for MDCI (HR 1.56, 95% CI 1.08–2.26) and composite incident morbidity (HR 1.242, 95% CI 1.004–1.538), whereas high IGFBP-1 predicted lower risk for diabetes (HR 0.50, 95% CI 0.29–0.88). In conclusion, higher IGF-1 levels and bioavailability predicted mortality and morbidity risk, supporting the hypothesis that diminished GH/IGF-1 signaling may contribute to human longevity and health-span. [ABSTRACT FROM AUTHOR]