Functioning In Nondemented Older Adults Research Articles

Associations between IL-1β, IL-6, and TNFα polymorphisms and longitudinal trajectories of cognitive function in non-demented older adults

Inflammation is implicated in Alzheimer's disease (AD), and specific single nucleotide polymorphisms (SNPs) in inflammatory cytokine genes are associated with increased AD risk. Whether the same polymorphisms also predict domain-specific cognitive change in cognitively healthy older adults is unclear. Specific SNPs in three cytokine genes, IL-1β (rs16944), IL-6 (rs1800795), and TNFα (rs1800629) were assessed for association with longitudinal trajectories spanning up to 16 years of global cognitive function, episodic memory, attention and working memory, and executive function in a sample of 324 non-demented older adults. Only rs1800629 (TNFα) was associated with significant change in global cognitive function over time [γ = 5.22; 95% CI: 0.61, 9.83; p = 0.027]. Despite an association with AD risk, rs16944 and rs1800795 may not predict cognitive decline in cognitively healthy older adults. The presence of an A at rs1800629 (TNFα) may have broad, protective effects on cognitive function, over time. More validation studies are needed to determine whether specific cytokine SNPs are associated with respective serum levels to further understanding of AD biomarkers that may also serve as markers of cognitive decline.

Amyloid deposition and small vessel disease are associated with cognitive function in older adults with type 2 diabetes.

Diabetes is associated with cognitive decline, but the underlying mechanisms are complex and their relationship with Alzheimer's Disease biomarkers is not fully understood. We assessed the association of small vessel disease (SVD) and amyloid burden with cognitive functioning in 47 non-demented older adults with type-2 diabetes from the Israel Diabetes and Cognitive Decline Study (mean age 78Y, 64% females). FLAIR-MRI, Vizamyl amyloid-PET, and T1W-MRI quantified white matter hyperintensities as a measure of SVD, amyloid burden, and gray matter (GM) volume, respectively. Mean hemoglobin A1c levels and duration of type-2 diabetes were used as measures of diabetic control. Cholesterol level and blood pressure were used as measures of cardiovascular risk. A broad neuropsychological battery assessed cognition. Linear regression models revealed that both higher SVD and amyloid burden were associated with lower cognitive functioning. Additional adjustments for type-2 diabetes-related characteristics, GM volume, and cardiovascular risk did not alter the results. The association of amyloid with cognition remained unchanged after further adjustment for SVD, and the association of SVD with cognition remained unchanged after further adjustment for amyloid burden. Our findings suggest that SVD and amyloid pathology may independently contribute to lower cognitive functioning in non-demented older adults with type-2 diabetes, supporting a multimodal approach for diagnosing, preventing, and treating cognitive decline in this population.

A - 12 Investigating Relationships between Theory of Mind, Executive Functioning, and Adaptive Functioning in Non-Demented Older Adults.

Theory of mind (ToM) is a facet of social cognition that relies on the ability to infer the mental states of others and is a cognitive and emotional capacity that may become compromised in the context of neurodegeneration. This may put older adults at greater risk for financial exploitation or susceptibility to scams. We investigated relationships among executive functioning, financial capacity, and ToM in a sample of older adults who did not have a diagnosis of dementia. Participants were cognitively unimpaired or presented with subjective cognitive decline or mild cognitive impairment. As part of a comprehensive neuropsychological battery, participants completed the Reading the Mind in the Eyes Test (RMET), a measure of ToM in which participants view photos of the eye region of the face and select which social emotion they perceive to be depicted in each photo. Pearson correlations were calculated to test relationships among RMET performance and select measures of executive functioning (D-KEFS Trail Making Test 4, Letter Fluency) and basic financial skills (Financial Capacity Instrument, short form). Participants' (n = 72; M age = 75.36; M education = 15.676; 69% female) RMET performance was significantly associated with measures of executive functioning (r = 0.243, p = 0.041), mental flexibility (r = -0.283, p = 0.017), and financial skills (r = 0.291, p = 0.015). Capacity for ToM is linked with integrity of executive functioning skills and financial capacity in older adults with varying degrees of cognitive compromise. Older adults who demonstrate deficits in aspects of social cognition may be at risk for poor outcomes in key cognitive and adaptive skills in daily life.

Sleep Duration Positively Correlates with Global Cognition in the Non-Demented Older Adults with High School or above Education.

Sleep disturbance is common in the elderly. The effect of sleep duration on cognitive function in the non-demented older adults with high school or above education needs to be clarified. Here, we conducted a cross-sectional study to explore the correlation between sleep duration and multi-domain cognitive function in non-demented older adults. A total of 226 adults aged 60 years and over who have an educational background over 9 years, received a battery of neuropsychological evaluations. The Mini-Mental State Examination (MMSE) was used to assess global cognitive function, the Auditory Verbal Learning Test (AVLT), Verbal Fluent Test (VFT), Trial Making Test-A/B (TMT-A/B), Symbol Digit Modalities Test (SDMT), and Rey-Osterriech Complex Figure Test (CFT) were used to assess the memory, language, attention and executive, and visuospatial functions respectively. Sleep characteristics were collected by questionnaire. Subjects with sleep disturbance performed worse in visuospatial ability as compared with those with normal sleep. A significant correlation between nocturnal/total sleep duration and MMSE scores and CFT scores was found in overall subjects using linear regression models after adjusting for age, gender, education and BMI. Consistently, the nocturnal/total sleep duration positively correlated with MMSE scores after controlling for age, gender, education, BMI, hypertension, diabetes, hyperlipidemia, coronary artery disease and household conditions. The results indicate that shorter sleep duration impairs the global cognition and visuospatial ability in the older adults with high school or above education, even in the very early non-demented stage.

The Relationship Between Depressive Symptoms and Cognitive Function in Non-Demented Older Adults Across Different Alzheimer’s Disease Biomarker Profiles (2905)

The Relationship Between Depressive Symptoms and Cognitive Function in Non-Demented Older Adults Across Different Alzheimer’s Disease Biomarker Profiles (2905)

Lower brain-derived neurotrophic factor levels are associated with age-related memory impairment in community-dwelling older adults: the Sefuri study

The beneficial effects of brain-derived neurotrophic factor (BDNF)—a member of the neurotrophin family—on cognitive function or dementia are well established in both rodents and human beings. In contrast, little is known about the association of proBDNF—a precursor protein with opposing neuronal effects of BDNF—with cognitive function in non-demented older adults. We analyzed brain magnetic resonance imaging findings of 256 community-dwelling older adults (mean age of 68.4 years). Serum BDNF and proBDNF levels were measured by quantitative enzyme-linked immunosorbent assay. Logistic regression analysis revealed that older age, less physical activity, hippocampal atrophy, and lower BDNF levels were independently associated with memory impairment determined by the Rivermead Behavioral Memory Test. Path analysis based on structural equation modeling indicated that age, sport activity, hippocampal atrophy and BDNF but not proBDNF were individually associated with Rivermead Behavioral Memory Test scores. These findings suggest that impaired BDNF function, in addition to physical inactivity and hippocampal atrophy, is associated with age-related memory impairment. Therefore, BDNF may be a potential target for dementia prevention.

Sleep Quality, Depression, and Cognitive Function in Non-Demented Older Adults.

Both sleep quality and depression could affect cognitive performance in older adults. Previous studies have suggested that there are bi-directional relationships between sleep quality and depression. Possibly, the influence of sleep quality on cognition is partly mediated by depression, and vice versa. We aimed to assess the mediation effects of sleep quality and depression on each other's relationship with various cognitive functions in non-demented older adults. Correlations were examined among sleep quality indices, depressive severity score, and five cognitive functions in 206 cognitively normal (CN) older adults and all participants that included these CN and 40 mild cognitive impairment (MCI) individuals. We then analyzed the mediation effects for the significant cognitive correlations of sleep disturbance and depression using the bias-corrected Bootstrap method in the two populations. Both sleep disturbance and depression were significantly correlated with memory recall and processing speed. In CN, depression could mediate the relationships of sleep disturbance with both cognitive functions, while sleep disturbance could only mediate the relationship of depression with processing speed, but not memory recall. However, in all participants, sleep disturbance could mediate the relationships of depression with both cognitive functions. Different mediation effects in the two models in CN older adults might suggest differential mechanisms underlying the pathways from sleep disturbance and depression to various cognitive functions. The mediation results in all participants might indicate that the mechanisms underlying the pathways from sleep disturbance and depression to memory recall were different between MCI and CN older adults.

Long-chain omega-3 polyunsaturated fatty acids and cognitive decline in non-demented adults: a systematic review and meta-analysis.

Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs) are widely considered as nootropic agents that may be beneficial in reversing cognitive impairment. The present systematic review of randomized controlled trials was conducted to determine the changes in cognitive function after intervention with LCn-3PUFA supplementation in non-demented adults, including those with mild cognitive impairment. Five databases (MEDLINE, CINAHL, Scopus, EMBASE, and the Cochrane Library) were searched systematically along with reference lists of selected articles. Studies were eligible for inclusion if they measured the effect of LCn-3PUFA supplementation on cognition in non-demented adults. A total of 787 records were screened, of which 25 studies were eligible for inclusion. Treatment effects were summarized as global cognitive function for primary outcome and measured using the Mini-Mental State Examination and individual cognitive domains for secondary outcome. The pooled effect sizes were estimated using Hedge's g and random-effects modeling. Results from randomized controlled trials indicate that LCn-3PUFAs have no effect on global cognitive function (Hedge's g = 0.02; 95% confidence interval, -0.12 to 0.154), and among the specific cognitive domains, only memory function showed a mild benefit (Hedge's g = 0.31; P = 0.003; z = 2.945). The existing literature suggests that LCn-3PUFA supplementation could provide a mild benefit in improving memory function in non-demented older adults. PROSPERO registration no. CRD42017078664.

Cognitive dispersion is a sensitive marker for early neurodegenerative changes and functional decline in nondemented older adults.

Intraindividual cognitive variability (IIV), a measure of within-person variability across cognitive measures at a single time point, is associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Little is known regarding brain changes underlying IIV, or the relationship between IIV and functional ability. Therefore, we investigated the association between IIV and cerebral atrophy in AD-vulnerable regions and everyday functioning in nondemented older adults. 736 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (285 cognitively normal [CN]; 451 MCI) underwent neuropsychological testing and serial MRI over 2 years. Linear mixed effects models examined the association between baseline IIV and change in entorhinal cortex thickness, hippocampal volume, and everyday functioning. Adjusting for age, sex, apolipoprotein E genotype, amyloid-β positivity, and mean level of cognitive performance, higher baseline IIV predicted faster rates of entorhinal and hippocampal atrophy, as well as functional decline. Higher IIV was associated with both entorhinal and hippocampal atrophy among MCI participants but selective vulnerability of the entorhinal cortex among CN individuals. IIV was associated with more widespread medial temporal lobe (MTL) atrophy in individuals with MCI relative to CN, suggesting that IIV may be tracking advancing MTL pathologic changes across the continuum of aging, MCI, and dementia. Findings suggest that cognitive dispersion may be a sensitive marker of neurodegeneration and functional decline in nondemented older adults. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Effect of Multidomain Intervention, Omega-3 Polyunsaturated Fatty Acids Supplementation or their Combinaison on Cognitive Function in Non-Demented Older Adults According to Frail Status: Results from the MAPT Study.

Aim: The aim of this study was to explore whether multidomain intervention (MI) and Omega-3 Polyunsaturated Fatty Acids supplementation can modify the cognitive function on elderly according to frail status. Data are from a secondary exploratory analysis of the Multidomain Alzheimer Preventive Trial (MAPT), a French community-dwellers aged 70 or over reporting subjective memory complaints, but free from clinical dementia. The multidomain intervention consisted of 2 hours group sessions focusing on three domains (cognitive stimulation, physical activity, and nutrition) and a preventive consultation (at baseline, 12 months, and 24 months). For Omega-3 Polyunsaturated Fatty Acids supplementation, participants took two capsules of either placebo or polyunsaturated fatty acids daily. Linear mixed-model repeated-measures analyses were used including baseline, 6, 12, 24 and 36-month follow-up data to assess between-group differences in the change in cognitive tests over 36 months. The overall mean age of the MAPT study population was 75.25(±4.38). A tend toward significant differences in TMT-A were found for the effect of the multidomain intervention on the prefrail group compared to non-frail group. The MI and n3 PUFA program could not significantly have reduced cognitive function in a sample of pre-frailty elders. This population-based study in community-dwellers aged 70 years or over suggested that multidomain intervention and n3 PUFA supplementation have not significant effects on cognitive function change in frail older adults with memory complaints. The beneficial effect of multidomain intervention and n3 PUFA supplementation on cognitive function did not differ between frail and nonfrail participants.

Physical Activity and Hippocampal Sub-Region Structure in Older Adults with Memory Complaints.

Background:Physical activity (PA) plays a major role in maintaining cognition in older adults. PA has been shown to be correlated with total hippocampal volume, a memory-critical region within the medial temporal lobe (MTL). However, research on associations between PA and MTL sub-region integrity is limited.Objective:To examine the relationship between PA, MTL thickness, and its sub-regions, and cognitive function in non-demented older adults with memory complaints.Methods:Twenty-nine subjects aged ≥60 years, with memory complaints were recruited for this cross-sectional study. PA was tracked for 7 days using accelerometers, and average number of steps/day determined. Subjects were categorized into two groups: those who walked ≤4000 steps/day (lower PA) and those with >4000 steps/day (higher PA). Subjects received neuropsychological testing and 3T MRI scans. Nonparametric ANCOVAs controlling for age examined differences between the two groups.Results:Twenty-six subjects aged 72.7(8.1) years completed the study. The higher PA group (n=13) had thicker fusiform gyrus (median difference=0.11mm, effect size (ES)=1.43, p=0.001) and parahippocampal cortex (median difference=0.12mm, ES=0.93, p=0.04) compared to the lower PA group. The higher PA group also exhibited superior performance in attention and information-processing speed (median difference=0.90, ES=1.61, p=0.003) and executive functioning (median difference=0.97, ES=1.24, p=0.05). Memory recall was not significantly different between the two groups.Conclusion:Older non-demented individuals complaining of memory loss who walked>4000 steps each day had thicker MTL sub-regions and better cognitive functioning than those who walked ≤4000 steps. Future studies should include longitudinal analyses and explore mechanisms mediating hippocampal related atrophy.

Physical Frailty Is Associated with Longitudinal Decline in Global Cognitive Function in Non-Demented Older Adults: A Prospective Study.

To assess the relationship between physical frailty and subsequent decline in global cognitive function in the non-demented elderly. A prospective population-based study in a west Japanese suburban town, with two-year follow-up. Community-dwellers aged 65 and older without placement in long-term care, and not having a history of dementia, Parkinson's disease and depression at baseline, who participated in the cohort of the Sasaguri Genkimon Study and underwent follow-up assessments two years later (N = 1,045). Global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Physical frailty was identified according to the following five components: weight loss, low grip strength, exhaustion, slow gait speed and low physical activities. Linear regression models were used to examine associations between baseline frailty status and the MoCA scores at follow-up. Logistic regression models were used to estimate the risk of cognitive decline (defined as at least two points decrease of MoCA score) according to baseline frailty status. Seven hundred and eight non-demented older adults were included in the final analyses (mean age: 72.6 ± 5.5 years, male 40.3%); 5.8% were frail, and 40.8% were prefrail at baseline. One hundred and fifty nine (22.5%) participants experienced cognitive decline over two years. After adjustment for baseline MoCA scores and all confounders, being frail at baseline was significantly associated with a decline of 1.48 points (95% confidence interval [CI], -2.37 to -0.59) in MoCA scores, as compared with non-frailty. Frail persons were over two times more likely to experience cognitive decline (adjusted odds ratio 2.28; 95% CI, 1.02 to 5.08), compared to non-frail persons. Physical frailty is associated with longitudinal decline in global cognitive function in the non-demented older adults over a period of two years. Physically frail older community-dwellers should be closely monitored for cognitive decline that can be sensitively captured by using the MoCA.

Associations between white matter hyperintensities and cognitive decline over three years in non-dementia older adults with memory complaints

We investigated whether the baseline level and overtime changes of white matter hyperintensities (WMH) would be associated with cognitive decline over three years in non-demented older adults with memory complaints. 109 participants with baseline magnetic resonance imaging (MRI) and follow-up cognitive assessments up to 3-year were included; among them, 82 also had a follow-up MRI assessment over three years. WMH volume was obtained by an automated segmentation algorithm. Baseline WMH volumes and change between baseline and follow-up WMH were related to cognitive scores over time using mixed-effect linear regressions. Secondary stratified analyses according to Clinical Dementia Rating (CDR) status, APOE4 status, and presence of amyloid in the brain were conducted using similar regression models. Change in WMH volume overtime was associated with declines in COWAT (β=−0.239; 95% CI=−0.381, −0.096, p=0.001). Baseline WMH was not associated to any of the cognitive tests. Secondary analysis found that baseline WMH was associated to declines in TMT-A in APOE4 non-carriers (β=0.343; 95% CI=0.121, 0.564, p=0.003) and CDR 0 groups (β=0.307; 95% CI=0.095, 0.519, p=0.005); in CDR 0 group, overtime changes in WMH was associated to declines on both TMT-A (β=0.698; 95% CI=0.270, 1.126, p=0.002) and TMT-B (β=2.573; 95% CI=1.200, 3.947, p<0.001). Changes in WMH volume are associated with declines in information processing speed and executive function in non-demented older adults with memory complaints. Overtime changes in WMH volume is probably a better determinant of cognitive function in the elderly than baseline WMH volume.

Association between Toxoplasma gondii seropositivity and memory function in nondemented older adults

Toxoplasma gondii (T. gondii) seropositivity may be associated with decreased memory in older adults. To further investigate the association between T. gondii seropositivity and memory in nondemented older adults, we obtained serum samples from 114 nondemented older adults evaluated by the Alzheimer's Disease and Research Center at Washington University in St. Louis, Missouri, USA. We determined T. gondii seropositivity and anti-T. gondii IgG antibody titer and examined associations with memory function while controlling for socioeconomic status, education level, age, and apolipoprotein E4 status. There were few associations between T. gondii seropositivity or anti-T. gondii IgG antibodies and memory, although there was some support suggesting an interaction between anti-T. gondii and sex. In the seropositive-only sample, there was an inverse relationship between anti-T. gondii titer and performance on the selective reminding test. Overall, we found little evidence of an association between impaired memory function and T. gondii seropositivity and anti-T. gondii IgG antibodies in this sample of nondemented older adults.

P.2.f.005 Plasma levels of IL-6, 5-HTT gene polymorphism, and SSRIs responses in patients with major depressive disorder

We investigated whether the baseline level and overtime changes of white matter hyperintensities (WMH) would be associated with cognitive decline over three years in non-demented older adults with memory complaints. 109 participants with baseline magnetic resonance imaging (MRI) and follow-up cognitive assessments up to 3-year were included; among them, 82 also had a follow-up MRI assessment over three years. WMH volume was obtained by an automated segmentation algorithm. Baseline WMH volumes and change between baseline and follow-up WMH were related to cognitive scores over time using mixed-effect linear regressions. Secondary stratified analyses according to Clinical Dementia Rating (CDR) status, APOE4 status, and presence of amyloid in the brain were conducted using similar regression models. Change in WMH volume overtime was associated with declines in COWAT (β = − 0.239; 95% CI = − 0.381, − 0.096, p = 0.001). Baseline WMH was not associated to any of the cognitive tests. Secondary analysis found that baseline WMH was associated to declines in TMT-A in APOE4 non-carriers (β = 0.343; 95% CI = 0.121, 0.564, p = 0.003) and CDR 0 groups (β = 0.307; 95% CI = 0.095, 0.519, p = 0.005); in CDR 0 group, overtime changes in WMH was associated to declines on both TMT-A (β = 0.698; 95% CI = 0.270, 1.126, p = 0.002) and TMT-B (β = 2.573; 95% CI = 1.200, 3.947, p < 0.001). Changes in WMH volume are associated with declines in information processing speed and executive function in non-demented older adults with memory complaints. Overtime changes in WMH volume is probably a better determinant of cognitive function in the elderly than baseline WMH volume.

Amyloid deposition and cognition in older adults: the effects of premorbid intellect.

Although amyloid deposition remains a marker of the development of Alzheimer's disease, results linking amyloid and cognition have been equivocal. Twenty-five community-dwelling non-demented older adults were examined with (18)F-flutemetamol, an amyloid imaging agent, and a cognitive battery, including an estimate of premorbid intellect and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). In the first model, (18)F-flutemetamol uptake significantly correlated with the Delayed Memory Index of the RBANS (r = -.51, p = .02) and premorbid intellect (r = .43, p = .03). In the second model, the relationship between (18)F-flutemetamol and cognition was notably stronger when controlling for premorbid intellect (e.g., three of the five RBANS Indexes and its Total score significantly correlated with (18)F-flutemetamol, r's = -.41 to -.58). Associations were found between amyloid-binding (18)F-flutemetamol and cognitive functioning in non-demented older adults. These associations were greatest with delayed memory and stronger when premorbid intellect was considered, suggesting that cognitive reserve partly compensates for the symptomatic expression of amyloid pathology in community-dwelling elderly.

Sleep onset/maintenance difficulties and cognitive function in nondemented older adults: the role of cognitive reserve.

This study examined the relationship between cognitive function and sleep onset/maintenance difficulties (SO/MD) in nondemented older adults. We hypothesized that SO/MD negatively impacts cognition and that older adults with lower education would be especially vulnerable to its effects. The sample comprised 549 older adults from the Einstein Aging Study (EAS), a community-based cohort. Participants completed neuropsychological assessment and a sleep questionnaire. Univariate ANCOVAs were performed with cognitive performance as a dependent variable, SO/MD (present or absent) and education (lower: ≤ 12 years; higher: >12 years) as between-subjects factors, and age, ethnicity, gender, depression, and cardiovascular comorbidies as covariates. Participants were an average age of 79.7 ± 5.0 years (range = 71-97 years). Fifty-seven percent (n = 314) of the sample met criteria for SO/MD. Among participants with SO/MD, those with lower education performed more poorly on a test of category fluency than participants with higher education (means: 35.2 vs. 41.0; p < .001); among older adults without SO/MD, educational attainment had no measurable effect on cognition (SO/MD × education interaction (F(1,536) = 14.5; p = .00)). Consistent with the cognitive reserve hypothesis, older adults with lower education appear selectively vulnerable to the negative effects of sleep onset/maintenance difficulties on tests of verbal fluency.

Anxious symptoms and cognitive function in non-demented older adults: an inverse relationship.

The goals of this study were to determine the relationship between anxious symptoms and cognitive functioning in a non-demented, community-dwelling older adults sample (n = 48), and to determine the effect of depressive symptoms upon this relationship. Anxious and depressive symptoms were assessed using the Symptom Checklist 90--Revised. Cognitive functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status. Results indicated that although both cognitive functioning and anxious symptoms were within normal limits in this sample, anxious symptoms showed a significant, inverse relationship with global cognitive function [r(47) = -0.400, p = 0.005]. In addition, specific relationships were noted between severity of anxious symptoms and visuospatial/constructional ability as well as immediate and delayed memory. With regard to the secondary objective, both anxiety and depressive symptoms together accounted for the highest level of variance [R(2) = 0.175, F(2, 45) = 4.786, p = 0.013] compared with anxiety [R(2) (47) = 0.160, p = 0.005] and depression [R(2) (47) = 0.106, p = 0.024] alone. Nevertheless, neither anxious nor depressive symptoms emerged as a unique correlate with cognitive ability [r(47) = -0.278, p = 0.058; r(48) = -0.136, p = 0.363, respectively]. This study demonstrates that subthreshold anxiety symptoms and cognitive functioning are significantly related even among generally healthy older adults whose cognitive ability and severity of anxious symptoms are within broad normal limits. These findings have implications both for clinical care of older patients, as well as for cognitive research studies utilizing this population.

Ambulatory blood pressure and cognitive function in nondemented older adults: Findings of the maracaibo aging study

Ambulatory blood pressure and cognitive function in nondemented older adults: Findings of the maracaibo aging study

Cognitive function in non-demented older adults with hypothyroidism.

(1) to evaluate objectively changes in cognitive function and electrophysiologic characteristics associated with hypothyroidism of varying severity and duration in primarily older persons; (2) to determine whether these changes are reversible when a euthyroid state has been attained after treatment with thyroid hormone. We enrolled 54 non-demented hypothyroid patients (31-99, mean 68.6 +/- 16.4 years) with biochemical evidence of hypothyroidism (38 had overt and 14 had minimal hypothyroidism) and 30 euthyroid controls (31-96, mean 63.7 +/- 18.4 years) screened for good general health. We evaluated attention, orientation, memory, learning, visual-spatial abilities, calculation, language, visual scanning, and motor speed using standardized neuropsychological tests. Electrophysiological measures of neurocognitive function included the P300 latency component of the auditory Event-Related Potentials (ERP) and conduction speed from eye to cortex, the P100 latency component of the Patterned Visual-Evoked Potential (PVEP). All patients were studied when hypothyroid. A subset of patients with minimal initial test abnormalities were available to be retested when euthyroid, 5 and 9 months after onset of thyroid replacement therapy. Hypothyroid patients showed significantly lower scores on the Mini-Mental Status Test (MMS) and on five of 14 neuropsychological tests as compared to controls. The neuropsychological tests affected were copying a cube (visual-spatial function), the Inglis Paired Associates Learning Test-Low and Medium association items (memory and learning), Animal Naming (word fluency/production), and the Trail Making A test (attention, visual scanning and psychomotor function. Hypothyroidism also was associated with longer P100 latencies of PVEPs to 20' checks, but showed no significant differences in PVEP P100 latency to 50' checks, nor in the latency of the auditory ERP component P300. There was a statistically significant correlation between a laboratory index of the severity of hypothyroidism (serum T4) and the Inglis Medium Association items and Animal Naming. There was a statistically significant improvement after 5 months of treatment on three of the timed performance tests that previous studies have shown to be most sensitive to brain dysfunction. Hypothyroidism in non-demented older adults is associated with impairments in learning, word fluency, visual-spatial abilities, and some aspect of attention, visual scanning, and motor speed. The MMS by itself was sensitive in differentiating hypothyroid patients with cognitive deficits from controls, while electrophysiological measures did not generally differentiate the hypothyroid patients from normal controls. The MMS was not sensitive to treatment effects, but treatment was associated with significant improvements in three of the most sensitive measures of cognitive dysfunction.