Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies.

INTRODUCTION: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD). METHODS: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years). RESULTS: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes. DISCUSSION: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia.

Association between metabolic syndrome and risk of incident dementia in UK Biobank.

INTRODUCTION: The association between metabolic syndrome (MetS) and incident dementia remains inconclusive. METHODS: In 176,249 dementia-free UK Biobank participants aged ≥60 years at baseline, Cox proportional-hazards models were used to investigate the association between MetS and incident dementia. MetS was defined as the presence of ≥3 of the following: elevated waist circumference, triglycerides, blood pressure, blood glucose, and reduced high-density lipoprotein cholesterol. RESULTS: Over 15 years of follow-up (median = 12.3), 5255 participants developed dementia. MetS was associated with an increased risk of incident dementia (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.06, 1.18). The association remained consistent when restricting to longer follow-up intervals: >5 to 10 years (HR: 1.17, 95% CI: 1.07, 1.27) and >10 years (HR: 1.22, 95% CI: 1.12, 1.32). Stronger associations were observed in those with ≥4 MetS components and in apolipoprotein-E (APOE)-ε4 non-carriers. DISCUSSION: In this large population-based prospective cohort, MetS was associated with an increased risk of dementia. HIGHLIGHTS: MetS was associated with a 12% increased risk of incident all-cause dementia. Associations remained similar after restricting the analysis to those with longer follow-up. The presence of four or five MetS components was significantly associated with dementia. Stronger associations were observed in those with a low genetic risk for dementia.

Association Between Retinal Nerve Fiber Layer Thickness and Incident Dementia in the European Prospective Investigation into Cancer in Norfolk Cohort.

BACKGROUND: Retinal nerve fiber layer (RNFL) thickness may reflect cerebral status. OBJECTIVE: This study assessed the relationship between RNFL thickness and incident all-cause dementia in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) Eye Study. METHODS: Glaucoma detection with variable corneal compensation (GDx-VCC) and Heidelberg Retinal Tomograph II (HRT II) derived global mean RNFL thickness from dementia-free participants at baseline within the EPIC-Norfolk Eye Study were analyzed. Incident dementia was identified through linkage to electronic medical records. Cox proportional hazard mixed-effects regression models adjusted for key confounders were used to examine the associations between RNFL thickness and incident dementia in four separate models. RESULTS: 6,239 participants were included with 322 cases of incident dementia and mean age of 67.5-years old, with 49.7% women (median follow-up 13.2-years, interquartile range (11.7 to 14.6 years). Greater RNFL thickness (GDx-VCC) was not significantly associated with a lower risk of incident dementia in the full adjusted model [HR per quartile increase 0.95; 95% CI 0.82-1.10]. Similarly, RNFL thickness assessed with HRT II was also not associated with incident dementia in any model (full adjusted model; HR per quartile increase: 1.06; [95% CI 0.93-1.19]. Gender did not modify any associations under study. CONCLUSION: GDx-VCC and HRT II derived RNFL thickness are unlikely to be useful predictors of incident dementia. Higher resolution optical imaging technologies may clarify whether there are useful relationships between neuro-retinal morphology and brain measures.

Association of Multimorbidity, Disease Clusters, and Modification by Genetic Factors With Risk of Dementia.

Importance: Individual conditions have been identified as risk factors for dementia; however, it is important to consider the role of multimorbidity, as conditions often co-occur. Objective: To investigate whether multimorbidity is associated with incident dementia and whether associations vary by different clusters of disease and genetic risk for dementia. Design, Setting, and Participants: This population-based prospective cohort study used data from the UK Biobank cohort, with baseline data collected between 2006 and 2010 and with up to 15 years of follow-up. Participants included women and men without dementia and aged at least 60 years at baseline. Medical conditions were captured as part of nurse-led verbal interviews conducted at baseline assessment centers. Data were analyzed from October 2020 to July 2022. Exposures: The presence of at least 2 long-term conditions from a preselected list of 42 conditions was used to define multimorbidity. High genetic risk for dementia was based on presence of 1 or 2 apolipoprotein (APOE) ε4 alleles. Main Outcomes and Measures: The main outcome, incident dementia, was derived from hospital inpatient and death registry records. Associations of multimorbidity with dementia were assessed with Cox proportional hazards models. Results: A total of 206 960 participants (mean [SD] age, 64.1 [2.9] years, 108 982 [52.7%] women) were included in the final sample, of whom 89 201 participants (43.1%) had multimorbidity. Over a mean (SD) of 11.8 (2.2) years of follow-up, 6182 participants (3.0%) developed dementia. The incidence rate was 1.87 (95% CI, 1.80-1.94) per 1000 person-years for those without multimorbidity and 3.41 (95% CI, 3.30-3.53) per 1000 person-years for those with multimorbidity. In Cox proportional hazards models adjusted for age, sex, ethnicity, education, socioeconomic status, and APOE-ε4 carrier status, multimorbidity was associated with an increased risk of incident dementia (hazard ratio [HR], 1.63 [95% CI, 1.55-1.71]). The highest dementia risk was observed for the hypertension, diabetes, and coronary heart disease cluster (HR, 2.20 [95% CI, 1.98-2.46]) and pain, osteoporosis, and dyspepsia cluster (HR, 2.00 [95% CI, 1.68-2.37]) in women and in the diabetes and hypertension cluster (HR, 2.24 [95% CI, 1.97-2.55]) and coronary heart disease, hypertension, and stroke cluster (HR, 1.94 [95% CI, 1.71-2.20]) in men, compared with no multimorbidity. The associations between multimorbidity and dementia were greater in those with a lower genetic risk of dementia (HR, 1.96 [95% CI, 1.81-2.11]) than in those with a higher genetic risk of dementia (HR, 1.39 [95% CI, 1.30-1.49]). Similar findings were observed when stratifying diseases clusters by genetic risk for dementia. Conclusions and Relevance: These findings suggest that multimorbidity was associated with an increased risk of dementia. The associations varied by clusters of disease and genetic risk for dementia. These findings could help with the identification of individuals at high risk of dementia as well as the development of targeted interventions to reduce or delay dementia incidence.

Speech-in-noise hearing impairment is associated with an increased risk of incident dementia in 82,039 UK Biobank participants.

INTRODUCTION: Little is known about the association between speech-in-noise (SiN) hearing impairment and dementia. METHODS: In 82,039 dementia-free participants aged ≥60 years were selected from the UK Biobank. Cox proportional-hazards models were used to investigate whether SiN hearing impairment is associated with an increased risk of incident dementia. RESULTS: Over 11 years of follow-up (median = 10.1), 1285 participants developed dementia. Insufficient and poor SiN hearing were associated with a 61% (hazard ratio [HR] = 1.61, 95% confidence [CI] 1.41-1.84) and 91% (HR = 1.91, 95% CI 1.55-2.36) increased risk of developing dementia, respectively, compared to normal SiN hearing. The association remained similar when restricting to follow-up intervals of ≤3, >3 to  <6, >6 to <9, and >9 years. There was limited evidence for mediation through depressive symptoms and social isolation. DISCUSSION: SiN hearing impairment is independently associated with incident dementia, providing further evidence for hearing impairment as a potential modifiable dementia risk factor.

Visual Impairment and Risk of Dementia in 2 Population-Based Prospective Cohorts: UK Biobank and EPIC-Norfolk.

Visual impairment has emerged as a potential modifiable risk factor for dementia. However, there is a lack of large studies with objective measures of vision and with more than 10 years of follow-up. We investigated whether visual impairment is associated with an increased risk of incident dementia in UK Biobank and European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk). In both cohorts, visual acuity was measured using a "logarithm of the minimum angle of resolution" (LogMAR) chart and categorized as no (≤0.30 LogMAR), mild (>0.3 to ≤0.50 LogMAR), and moderate to severe (>0.50 LogMAR) impairment. Dementia was ascertained through linkage to electronic medical records. After restricting to those aged ≥60 years, without prevalent dementia and with eye measures available, the analytic samples consisted of 62 206 UK Biobank and 7 337 EPIC-Norfolk participants, respectively. In UK Biobank and EPIC-Norfolk, respectively, 1 113 and 517 participants developed dementia over 11 and 15 years of follow-up. Using multivariable Cox proportional-hazards models, the hazard ratios for mild and moderate to severe visual impairment were 1.26 (95% confidence interval [CI]: 0.92-1.72) and 2.16 (95% CI: 1.37-3.40), in UK Biobank, and 1.05 (95% CI: 0.72-1.53) and 1.93 (95% CI: 1.05-3.56) in EPIC-Norfolk, compared to no visual impairment. When excluding participants censored within 5 years of follow-up or with prevalent poor or fair self-reported health, the direction of the associations remained similar for moderate impairment but was not statistically significant. Our findings suggest visual impairment might be a promising target for dementia prevention; however, the possibility of reverse causation cannot be excluded.

Visual Impairment, Eye Diseases, and Dementia Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: Visual impairment and eye diseases have been associated with dementia, though with mixed findings and often in cross-sectional studies. OBJECTIVE: To identify prospective studies investigating associations between visual impairment or common eye diseases and risk of all-cause dementia or key dementia subtypes. METHODS: We searched Medline, PsycINFO, and Embase from inception to January 2020. We also conducted backward and forward citation searches of included studies and set up alerts to identify studies published after the search date. Random-effects meta-analysis was used to combine adjusted estimates across studies. RESULTS: Thirty studies met our eligibility criteria. For visual impairment, pooled estimates indicated an increased risk of all-cause dementia (37,705 participants, 3,415 cases, risk ratio [RR] = 1.38, 95% confidence interval [CI]: 1.19-1.59, I2 = 28.6%). Pooled estimates also suggested an increased dementia risk associated with cataract (6,659 participants, 1,312 cases, hazard ratio [HR] = 1.17, 95% CI: 1.00-1.38, I2 = 0.0%) and diabetic retinopathy (43,658 participants, 7,060 cases, HR = 1.34, 95% CI: 1.11-1.61, I2 = 63.9%), respectively. There was no evidence of an association between glaucoma (175,357 participants, 44,144 cases, HR = 0.97, 95% CI: 0.90-1.04, I2 = 51.5%) or age-related macular degeneration (7,800,692 participants, > 2,559 cases, HR = 1.15, 95% CI: 0.88-1.50, I2 = 91.0%) and risk of dementia, respectively. CONCLUSION: As visual impairment, cataract, and diabetic retinopathy are associated with an increased likelihood of developing dementia, early diagnosis may help identify those at risk of dementia. Given most causes of visual impairment are treatable or preventable, the potential for dementia prevention warrants further investigation.

Association of Lifestyle and Genetic Risk With Incidence of Dementia.

IMPORTANCE: Genetic factors increase risk of dementia, but the extent to which this can be offset by lifestyle factors is unknown. OBJECTIVE: To investigate whether a healthy lifestyle is associated with lower risk of dementia regardless of genetic risk. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study that included adults of European ancestry aged at least 60 years without cognitive impairment or dementia at baseline. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016 or 2017. EXPOSURES: A polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption, categorized into favorable, intermediate, and unfavorable lifestyles. MAIN OUTCOMES AND MEASURES: Incident all-cause dementia, ascertained through hospital inpatient and death records. RESULTS: A total of 196 383 individuals (mean [SD] age, 64.1 [2.9] years; 52.7% were women) were followed up for 1 545 433 person-years (median [interquartile range] follow-up, 8.0 [7.4-8.6] years). Overall, 68.1% of participants followed a favorable lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Twenty percent had high polygenic risk scores, 60% had intermediate risk scores, and 20% had low risk scores. Of the participants with high genetic risk, 1.23% (95% CI, 1.13%-1.35%) developed dementia compared with 0.63% (95% CI, 0.56%-0.71%) of the participants with low genetic risk (adjusted hazard ratio, 1.91 [95% CI, 1.64-2.23]). Of the participants with a high genetic risk and unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) developed dementia compared with 0.56% (95% CI, 0.48%-0.66%) of participants with low genetic risk and favorable lifestyle (hazard ratio, 2.83 [95% CI, 2.09-3.83]). There was no significant interaction between genetic risk and lifestyle factors (P = .99). Among participants with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) of those with a favorable lifestyle developed dementia compared with 1.78% (95% CI, 1.38%-2.28%) with an unfavorable lifestyle (hazard ratio, 0.68 [95% CI, 0.51-0.90]). CONCLUSIONS AND RELEVANCE: Among older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk. A favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk.

Predictors of dementia misclassification when using brief cognitive assessments.

BACKGROUND: Brief cognitive assessments can result in false-positive and false-negative dementia misclassification. We aimed to identify predictors of misclassification by 3 brief cognitive assessments; the Mini-Mental State Examination (MMSE), Memory Impairment Screen (MIS) and animal naming (AN). METHODS: Participants were 824 older adults in the population-based US Aging, Demographics and Memory Study with adjudicated dementia diagnosis (DSM-III-R and DSM-IV criteria) as the reference standard. Predictors of false-negative, false-positive and overall misclassification by the MMSE (cut-point <24), MIS (cut-point <5) and AN (cut-point <9) were analysed separately in multivariate bootstrapped fractional polynomial regression models. Twenty-two candidate predictors included sociodemographics, dementia risk factors and potential sources of test bias. RESULTS: Misclassification by at least one assessment occurred in 301 (35.7%) participants, whereas only 14 (1.7%) were misclassified by all 3 assessments. There were different patterns of predictors for misclassification by each assessment. Years of education predicts higher false-negatives (odds ratio [OR] 1.23, 95% confidence interval [95% CI] 1.07-1.40) and lower false-positives (OR 0.77, 95% CI 0.70-0.83) by the MMSE. Nursing home residency predicts lower false-negatives (OR 0.15, 95% CI 0.03-0.63) and higher false-positives (OR 4.85, 95% CI 1.27-18.45) by AN. Across the assessments, false-negatives were most consistently predicted by absence of informant-rated poor memory. False-positives were most consistently predicted by age, nursing home residency and non-Caucasian ethnicity (all p < 0.05 in at least 2 models). The only consistent predictor of overall misclassification across all assessments was absence of informant-rated poor memory. CONCLUSIONS: Dementia is often misclassified when using brief cognitive assessments, largely due to test specific biases.

Stroke and dementia risk: A systematic review and meta-analysis.

INTRODUCTION: Stroke is an established risk factor for all-cause dementia, though meta-analyses are needed to quantify this risk. METHODS: We searched Medline, PsycINFO, and Embase for studies assessing prevalent or incident stroke versus a no-stroke comparison group and the risk of all-cause dementia. Random effects meta-analysis was used to pool adjusted estimates across studies, and meta-regression was used to investigate potential effect modifiers. RESULTS: We identified 36 studies of prevalent stroke (1.9 million participants) and 12 studies of incident stroke (1.3 million participants). For prevalent stroke, the pooled hazard ratio for all-cause dementia was 1.69 (95% confidence interval: 1.49-1.92; P < .00001; I2 = 87%). For incident stroke, the pooled risk ratio was 2.18 (95% confidence interval: 1.90-2.50; P < .00001; I2 = 88%). Study characteristics did not modify these associations, with the exception of sex which explained 50.2% of between-study heterogeneity for prevalent stroke. DISCUSSION: Stroke is a strong, independent, and potentially modifiable risk factor for all-cause dementia.

Case-finding in clinical practice: An appropriate strategy for dementia identification?

Earlier diagnosis of dementia is increasingly being recognized as a public health priority. As screening is not generally recommended, case-finding in clinical practice is encouraged as an alternative dementia identification strategy. The approaches of screening and case-finding are often confused, with uncertainty about what case-finding should involve and under what circumstances it is appropriate. We propose a formal definition of dementia case-finding with a clear distinction from screening. We critically examine case-finding policy and practice and propose evidence requirements for implementation in clinical practice. Finally, we present a case-finding pathway and discuss the available evidence for best practice at each stage, with recommendations for research and practice. In conclusion, dementia case-finding is a promising strategy but currently not appropriate due to the substantial gaps in the evidence base for several components of this approach.

Which Risk Factors Causally Influence Dementia? A Systematic Review of Mendelian Randomization Studies.

BACKGROUND: Numerous risk factors for dementia are well established, though the causal nature of these associations remains unclear. OBJECTIVE: To systematically review Mendelian randomization (MR) studies investigating causal relationships between risk factors and global cognitive function or dementia. METHODS: We searched five databases from inception to February 2017 and conducted citation searches including MR studies investigating the association between any risk factor and global cognitive function, all-cause dementia or dementia subtypes. Two reviewers independently assessed titles and abstracts, full-texts, and study quality. RESULTS: We included 18 MR studies investigating education, lifestyle factors, cardiovascular factors and related biomarkers, diabetes related and other endocrine factors, and telomere length. Studies were of predominantly good quality, however eight received low ratings for sample size and statistical power. The most convincing causal evidence was found for an association of shorter telomeres with increased risk of Alzheimer's disease (AD). Causal evidence was weaker for smoking quantity, vitamin D, homocysteine, systolic blood pressure, fasting glucose, insulin sensitivity, and high-density lipoprotein cholesterol. Well-replicated associations were not present for most exposures and we cannot fully discount survival and diagnostic bias, or the potential for pleiotropic effects. CONCLUSIONS: Genetic evidence supported a causal association between telomere length and AD, whereas limited evidence for other risk factors was largely inconclusive with tentative evidence for smoking quantity, vitamin D, homocysteine, and selected metabolic markers. The lack of stronger evidence for other risk factors may reflect insufficient statistical power. Larger well-designed MR studies would therefore help establish the causal status of these dementia risk factors.

Vitamin D and cognitive function: A Mendelian randomisation study.

The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.

Coronary Artery Bypass Graft Surgery and Dementia Risk in the Cardiovascular Health Study.

INTRODUCTION: The association between history of coronary artery bypass graft surgery (CABG) and dementia risk remains unclear. METHODS: We conducted a prospective cohort analysis using data on 3155 elderly adults free from prevalent dementia from the US population-based Cardiovascular Health Study (CHS) with adjudicated incident all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia. RESULTS: In the CHS, the hazard ratio (HR) for all-cause dementia was 1.93 [95% confidence interval (CI), 1.36-2.74] for those with CABG history compared with those with no CABG history after adjustment for potential confounders. Similar HRs were observed for AD (HR=1.71; 95% CI, 0.98-2.98), VaD (HR=1.42; 95% CI, 0.56-3.65), and mixed dementia (HR=2.73; 95% CI, 1.55-4.80). The same pattern of results was observed when these CHS findings were pooled with a prior prospective study, the pooled HRs were 1.96 (95% CI, 1.42-2.69) for all-cause dementia, 1.71 (95% CI, 1.04-2.79) for AD and 2.20 (95% CI, 0.78-6.19) for VaD. DISCUSSION: Our results suggest CABG history is associated with long-term dementia risk. Further investigation is warranted to examine the causal mechanisms which may explain this relationship or whether the association reflects differences in coronary artery disease severity.

The interplay between personality and cognitive ability across 12 years in middle and late adulthood: Evidence for reciprocal associations.

Research on relationships between personality and cognitive abilities has so far resulted in inconsistent findings regarding the strength of the associations. Moreover, relationships have rarely been compared longitudinally and bidirectionally between midlife versus late-life cohorts by considering different personality traits as well as multiple cognitive domains over a long-term follow-up period. We hypothesize that the interplay between the "Big Five" personality traits (Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness) and cognitive abilities (information processing speed, crystallized intelligence, fluid intelligence) may change from midlife to old age due to age-associated changes in cognitive and personality plasticity. We used data from the German Interdisciplinary Longitudinal Study of Adult Development (ILSE study; n = 1,002). Participants were either born in 1950/52 (midlife sample, n = 502) or in 1930/32 (late-life sample, n = 500) and followed up for up to 12 years. Based on bivariate latent change score regression models (adjusted for gender, education, self-rated and physician-rated health), we observed that, apart from very few exceptions, the intervariable cross-lagged associations between personality traits and cognitive abilities were generally similar between cohorts. Moreover, in case of neuroticism, extraversion, and openness, the effects of cognitive abilities on change in personality were stronger than the reversed effects. Our findings thus suggest that the so far predominant perspective of personality in middle adulthood and late-life as a predictor, rather than as an outcome, of cognitive abilities needs more differentiation and reconsideration. (PsycINFO Database Record

Vitamin D and Memory Decline: Two Population-Based Prospective Studies.

BACKGROUND: Vitamin D deficiency has been linked with dementia risk, cognitive decline, and executive dysfunction. However, the association with memory remains largely unknown. OBJECTIVE: To investigate whether low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with memory decline. METHODS: We used data on 1,291 participants from the US Cardiovascular Health Study (CHS) and 915 participants from the Dutch Longitudinal Aging Study Amsterdam (LASA) who were dementia-free at baseline, had valid vitamin D measurements, and follow-up memory assessments. The Benton Visual Retention Test (in the CHS) and Rey's Auditory Verbal Learning Test (in the LASA) were used to assess visual and verbal memory, respectively. RESULTS: In the CHS, those moderately and severely deficient in serum 25(OH)D changed -0.03 SD (95% CI: -0.06 to 0.01) and -0.10 SD (95% CI: -0.19 to -0.02) per year respectively in visual memory compared to those sufficient (p = 0.02). In the LASA, moderate and severe deficiency in serum 25(OH)D was associated with a mean change of 0.01 SD (95% CI: -0.01 to 0.02) and -0.01 SD (95% CI: -0.04 to 0.02) per year respectively in verbal memory compared to sufficiency (p = 0.34). CONCLUSIONS: Our findings suggest an association between severe vitamin D deficiency and visual memory decline but no association with verbal memory decline. They warrant further investigation in prospective studies assessing different memory subtypes.

Cross-sectional and longitudinal relationship between neuroticism and cognitive ability in advanced old age: the moderating role of severe sensory impairment.

OBJECTIVES: Gaining a comprehensive picture of the network of constructs in which cognitive functioning is embedded is crucial across the full lifespan. With respect to personality, previous findings support a relationship between neuroticism and cognitive abilities. However, findings regarding old age are inconsistent. In particular, little is known about potentially moderating variables which might explain some of the inconsistency. Our aim was to examine the moderating effect of severe sensory impairment on cross-sectional and longitudinal associations between neuroticism and cognitive functioning. METHOD: The study sample consisted of 121 visually impaired (VI), 116 hearing impaired (HI), and 150 sensory unimpaired older adults (UI). Mean age was 82.50 years (SD = 4.71 years). Neuroticism was assessed by the NEO Five Factor Inventory, and multiple established tests were used for the assessment of cognitive performance (e.g., subtests of the revised Wechsler Adult Intelligence Scale). RESULTS: Bivariate correlations and multi-group structural equation models indicated stronger relationships between cognitive abilities and neuroticism in both sensory impaired groups (VI and HI) compared to UI older individuals. This relationship was attenuated but still significant in both sensory impaired groups when controlling for age, education and health (number of chronic conditions). In cross-lagged panel models, higher baseline neuroticism was significantly associated with lower cognitive performance four years later in VI and HI individuals. CONCLUSION: Our results suggest that sensory impairment moderates both cross-sectional and longitudinal associations between neuroticism and cognitive function in advanced old age.

Parathyroid hormone, cognitive function and dementia: a systematic review.

BACKGROUND: Metabolic factors are increasingly recognized to play an important role in the pathogenesis of Alzheimer's disease and dementia. Abnormal parathyroid hormone (PTH) levels play a role in neuronal calcium dysregulation, hypoperfusion and disrupted neuronal signaling. Some studies support a significant link between PTH levels and dementia whereas others do not. METHODS: We conducted a systematic review through January 2014 to evaluate the association between PTH and parathyroid conditions, cognitive function and dementia. Eleven electronic databases and citation indexes were searched including Medline, Embase and the Cochrane Library. Hand searches of selected journals, reference lists of primary studies and reviews were also conducted along with websites of key organizations. Two reviewers independently screened titles and abstracts of identified studies. Data extraction and study quality were performed by one and checked by a second reviewer using predefined criteria. A narrative synthesis was performed due to the heterogeneity of included studies. RESULTS: The twenty-seven studies identified were of low and moderate quality, and challenging to synthesize due to inadequate reporting. Findings from six observational studies were mixed but suggest a link between higher serum PTH levels and increased odds of poor cognition or dementia. Two case-control studies of hypoparathyroidism provide limited evidence for a link with poorer cognitive function. Thirteen pre-post surgery studies for primary hyperparathyroidism show mixed evidence for improvements in memory though limited agreement in other cognitive domains. There was some degree of cognitive impairment and improvement postoperatively in observational studies of secondary hyperparathyroidism but no evident pattern of associations with specific cognitive domains. CONCLUSIONS: Mixed evidence offers weak support for a link between PTH, cognition and dementia due to the paucity of high quality research in this area.

History of alcohol use disorders and risk of severe cognitive impairment: a 19-year prospective cohort study.

OBJECTIVE: To assess the effects of a history of alcohol use disorders (AUDs) on risk of severe cognitive and memory impairment in later life. METHODS: We studied the association between history of AUDs and the onset of severe cognitive and memory impairment in 6,542 middle-aged adults born 1931 through 1941 who participated in the Health and Retirement Study, a prospective nationally representative U.S. cohort. Participants were assessed at 1992 baseline and follow-up cognitive assessments were conducted biannually from 1996 through 2010. History of AUDs was identified using the three-item modified CAGE questionnaire. Cognitive outcomes were assessed using the 35-item modified Telephone Interview for Cognitive Status at last follow-up with incident severe cognitive impairment defined as a score ≤ 8, and incident severe memory impairment defined as a score ≤ 1 on a 20-item memory subscale. RESULTS: During up to 19 years of follow-up (mean: 16.7 years, standard deviation: 3.0, range: 3.5-19.1 years), 90 participants experienced severe cognitive impairment and 74 participants experienced severe memory impairment. History of AUDs more than doubled the odds of severe memory impairment (odds ratio [OR] = 2.21, 95% confidence interval [CI] = 1.27-3.85, t = 2.88, df = 52, p = 0.01). The association with severe cognitive impairment was statistically non-significant but in the same direction (OR = 1.80, 95% CI = 0.97-3.33, t = 1.92, df = 52, p = 0.06). CONCLUSION: Middle-aged adults with a history of AUDs have increased odds of developing severe memory impairment later in life. These results reinforce the need to consider the relationship between alcohol consumption and cognition from a multifactorial lifespan perspective.