Serum transthyretin and risk of cognitive decline and dementia: 22-year longitudinal study

Neurological Sciences - Serum transthyretin (TTR) may be an early biomarker for Alzheimer’s disease and related disorders (ADRD). We investigated associations of TTR measured at baseline with...     

Incidence of dementia and cognitive decline in over-75s in Cambridge: overview of cohort study

This paper summarises the methods and some of the findings of a large cohort study of dementia and cognitive decline in subjects aged over 75 years in Cambridge, particularly regarding the incidence wave. From a sample of 1968 subjects previously studied in a prevalence study in 1985–1987, survivors were restudied at 2.4 years, in a two-stage design employing the Mini; Mental State Examination (MMSE) and the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). High incidence rates of dementia were found, which rose steeply with age, particularly for Alzheimer's disease. New minimal dementia and milder cognitive impairment were also common. Cognitive decline on the MMSE showed a near normal, non-bimodal distribution. The sample has since been restudied at intervals for a total of up to 9 years to document longitudinal cognitive change. Brains have been obtained for post mortem neuropathological and molecular biological study, particularly of the early sequential changes associated with cognitive decline and dementia. Accepted: 18 February 1998     

Midlife stroke risk and cognitive decline: A 10-year follow-up of the Whitehall II cohort study

BackgroundStroke is associated with an increased risk of dementia. However, it is unclear whether risk of stroke in those free of stroke, particularly in nonelderly populations, leads to differential rates of cognitive decline. Our aim was to assess whether risk of stroke in mid life is associated with cognitive decline over 10 years of follow-up.MethodsWe studied 4153 men and 1657 women (mean age, 55.6 years at baseline) from the Whitehall II study, a longitudinal British cohort study. We used the Framingham Stroke Risk Profile (FSRP), which incorporates age, sex, systolic blood pressure, diabetes mellitus, smoking, prior cardiovascular disease, atrial fibrillation, left ventricular hypertrophy, and use of antihypertensive medication. Cognitive tests included reasoning, memory, verbal fluency, and vocabulary assessed three times over 10 years. Longitudinal associations between FSRP and its components were tested using mixed-effects models, and rates of cognitive change over 10 years were estimated.ResultsHigher stroke risk was associated with faster decline in verbal fluency, vocabulary, and global cognition. For example, for global cognition there was a greater decline in the highest FSRP quartile (−0.25 of a standard deviation; 95% confidence interval: −0.28 to −0.21) compared with the lowest risk quartile (P = .03). No association was observed for memory and reasoning. Of the individual components of FSRP, only diabetes mellitus was associated independently with faster cognitive decline (β = −0.06; 95% confidence interval, −0.01 to 0.003; P = .03).ConclusionElevated stroke risk at midlife is associated with accelerated cognitive decline over 10 years. Aggregation of risk factors may be especially important in this association.     

Vascular risk factors for incident Alzheimer disease and vascular dementia: the Cache County study

Vascular risk factors for Alzheimer disease (AD) and vascular dementia (VaD) have been evaluated; however, few studies have compared risks by dementia subtypes and sex. We evaluated relationships between cardiovascular risk factors (hypertension, high cholesterol, diabetes mellitus, and obesity), events (stroke, coronary artery bypass graft surgery, and myocardial infarction), and subsequent risk of AD and VaD by sex in a community-based cohort of 3264 Cache County residents aged 65 or older. Cardiovascular history was ascertained by self-report or proxy-report in detailed interviews. AD and VaD were diagnosed using standard criteria. Estimates from discrete-time survival models showed no association between self-reported history of hypertension and high cholesterol and AD after adjustments. Hypertension increased the risk of VaD [adjusted hazard ratio (aHR) 2.42, 95% confidence interval (CI) 0.95-7.44]. Obesity increased the risk of AD in females (aHR 2.23, 95% CI 1.09-4.30) but not males. Diabetes increased the risk of VaD in females after adjustments (aHR 3.33, 95% CI 1.03-9.78) but not males. The risk of VaD after stroke was increased in females (aHR 16.90, 95% CI 5.58-49.03) and males (aHR 10.95, 95% CI 2.48-44.78). The results indicate that vascular factors increase risks for AD and VaD differentially by sex. Future studies should focus on specific causal pathways for each of these factors with regard to sex to determine if sex differences in the prevalence of vascular factors have an influence on sex differences in dementia risk.     

FMR1 alleles in Parkinson's disease: relation to cognitive decline and hallucinations, a longitudinal study

Carriers of expanded alleles of the fragile X mental retardation (FMR1) gene may display parkinsonism, cognitive decline, and behavioral changes. The authors screened 2 male groups of patients affected with Parkinson's disease (PD) (n = 137). One group (n = 56) was followed longitudinally for up to 12 years. Length of CGG repeats in PD patients was compared with healthy controls (n = 310). In addition, the association of the number of CGG repeats with cognitive decline or hallucinations was studied in the longitudinally followed PD group. The authors found no repeats in the premutation range (55-200 CGG repeats) and no significant difference in the proportion of intermediate-size (41-54 CGG repeats) carriers between the PD and the control groups. Using linear regression, the number of CGG repeats was not related to motor or cognitive progression. However, the marked cognitive decline in 2 patients carrying intermediate-size alleles points to a possible association. More studies with larger PD samples are warranted.     

Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics: The FINGER trial

Introduction

The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated whether sociodemographics, socioeconomic status, baseline cognition, or cardiovascular factors influenced intervention effects on cognition.

Education and cognitive decline in Parkinson's disease: a study of 102 patients

OBJECTIVE: To understand the correlation between low education level (EL) and the cognitive impairment in Parkinson's disease (PD). PATIENTS AND METHODS: This is a cross-sectional study of cognitive function in 102 non-demented PD patients, from a special clinic (behavioral neurology) in a referral medical center. PD patients were divided into low, middle and high EL groups. We used the Chinese version of the Cognitive Ability Screening Instrument as a neuropsychological test, which covers nine domains of cognitive function. A full score is 100. When determining the abnormality rate of each item of CASI, we used age/education stratified normal control groups as reference to obliterate the influence of education and age on cognitive decline. RESULTS: Recent memory, language and attention are the three items in which there were differences between the groups, in terms of abnormal performance rates. The high EL group is at less risk of recent memory impairment, but at more risk of impairment in language and attention. The other six items and total score showed no differences among the groups. Thirty-eight percent of the patients had a total score below 1.5 SD of the means of the general population. CONCLUSION: This study shows that high EL exerts no protective effect on the cognitive decline in PD patients in general, except in recent memory. The rate of cognitive dysfunction in PD patients is high. This deserves more attention.     

Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: a prospective cohort study

BACKGROUND: Mild cognitive impairment has been regarded as a precursor to dementia of Alzheimer type, but not all patients with mild cognitive impairment develop dementia. OBJECTIVE: To determine whether depression may increase the risk of developing dementia. SETTING: The outpatient clinics of a community general hospital. DESIGN: Prospective cohort study. METHODS: A cohort of 114 patients with amnestic mild cognitive impairment was followed up for a mean period of 3 years. At baseline, the patients underwent memory tests, the Spanish version of the Mini-Mental State Examination, a verbal fluency test, the Geriatric Depression Scale, and the Clinical Dementia Rating Scale for staging purposes. Psychiatric examination for depression was based on structured interview and Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria. We also carried out either computed tomography or magnetic resonance imaging of the brain. MAIN OUTCOME MEASURES: We carried out periodic evaluations based on the Mini-Mental State Examination, verbal fluency test, Geriatric Depression Scale, Blessed Dementia Rating Scale, and Clinical Dementia Rating Scale. The end point was the development of probable Alzheimer disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. RESULTS: Depression was observed in 41 patients (36%) at baseline. After a mean period of 3 years, 59 patients (51.7%) developed dementia of Alzheimer type, and 6 died. Of the depressed patients, 35 (85%) developed dementia in comparison with 24 (32%) of the nondepressed patients (relative risk, 2.6; 95% confidence interval, 1.8-3.6). The survival analysis also showed that depressed patients developed dementia earlier than the nondepressed. Most patients with depression at baseline exhibited a poor response to antidepressants. CONCLUSIONS: We conclude that patients with mild cognitive impairment and depression are at more than twice the risk of developing dementia of Alzheimer type as those without depression. Patients with a poor response to antidepressants are at an especially increased risk of developing dementia.     

Disease progression in vascular cognitive impairment: cognitive, functional and behavioural outcomes in the Consortium to Investigate Vascular Impairment of Cognition (CIVIC) cohort study

BACKGROUND AND PURPOSE: Empirical studies to clarify the outcomes in Vascular Cognitive Impairment (VCI) are needed. We compared cognitive, functional, and behavioural outcomes in patients with VCI to patients with no cognitive impairment (NCI), and Alzheimer's disease (AD). METHODS: Secondary analysis of the Consortium to Investigate Vascular Impairment of Cognition (CIVIC), a multi-centre Canadian memory clinic 30-month cohort study. RESULTS: Of 1347 patients, 938 were eligible for follow-up, of whom 239 (24.5%) were lost and 29 (3%) had died. Of the remaining 697 patients, 125 had NCI, 229 had VCI, and 343 had AD at baseline. Compared to people with NCI, of whom 20-40% showed progression based on cognitive and functional measures, those with VCI were more likely to progress (50-65%), as were people with AD (50-80%) (p<0.01). More people with VCI showed progression of affective symptoms (30%) than those with NCI (12%) or AD (15% p<0.01). Progression of impaired judgment (rated clinically) in VCI (15%) was similar to AD (11%) but more common than in NCI (4%, p<0.01). CONCLUSIONS: Most people with VCI show readily detectable progression by 30 months. Depressive symptoms were more common and more progressive in VCI than in Alzheimer's disease, whereas clinical evidence of progressive executive dysfunction was common in both AD and VCI.     

Tonsillectomy and risk of Parkinson's disease: A danish nationwide population‐based cohort study

Background : We hypothesized that tonsillectomy modifies the risk of PD. Objectives: To test the hypothesis in a nationwide population‐based cohort study. Methods: We used Danish medical registries to construct a cohort of all patients in Denmark with an operation code of tonsillectomy 1980‐2010 (n = 195,169) and a matched age and sex general population comparison cohort (n = 975,845). Patients were followed until PD diagnosis, death, censoring, or end of follow‐up 30 November 2013. Using Cox regression, we computed hazard ratios for PD and corresponding 95% confidence intervals, adjusting for age and sex by study design, and potential confounders. Results: We identified 100 and 568 patients diagnosed with PD among the tonsillectomy and general population comparison cohort, respectively, finding similar risks of PD (adjusted hazard ratio = 0.95 [95% confidence interval: 0.76‐1.19]; for > 20 years' follow‐up (adjusted hazard ratio = 0.96 [95% confidence interval: 0.64‐1.41]). Conclusion: Tonsillectomy is not associated with risk of PD, especially early‐onset PD. © 2017 International Parkinson and Movement Disorder Society