Cognitive Impairment But No Dementia Research Articles

THE EFFECTS OF EARLY-LIFE ADVERSITY ON WOMEN’S COGNITIVE HEALTH AFTER AGE 50

Abstract According to the Alzheimer’s Association, 6 million people age 65 and older are living with Alzheimer’s Disease in the United States, and nearly 4 million are women. Few research studies have examined the impact of adverse childhood events (ACEs) on cognitive health among women over 50. Evaluating gender-specific differences in predictors of cognitive health can help clarify mechanisms that hinder or magnify gender-based health differences and provide information on ways to narrow gender disparities in dementia. The study examined the relationship between ACEs, cognitive impairment, and incident dementia using data from the Health and Retirement Study Cross-wave 2015-2017 Life History Mail Survey (N = 4,980; Mage = 67.6). Cognitive status was measured using the 2016 Langa-Weir three category indicator: Normal, Cognitive Impairment but No Dementia (CIND), and Dementia. Compared to women exposed to 0 ACEs, women exposed to 1 ACE had a higher relative risk for CIND and dementia (RRR=1.71, p<.05; RRR=2.44, p<.05). Women exposed to 3 ACEs had a higher relative risk for dementia (RRR=3.43, p<.05). Non-Hispanic Black women exposed to 3 ACEs had a lower relative risk for dementia (RRR=0.18, p<.05) than white women. Women with 12 years of education have a higher relative risk for CIND and dementia (RRR=2.27, p<.05; RRR=3.45, p<.05) than women with >13 years of education. Although women’s life expectancy has increased over the past few decades, women remain at risk for delayed identification of cognitive decline. Future research should examine how other critical social determinants of health influence women’s cognitive health after 50.

Association of ergothioneine with neurodegeneration and cerebrovascular disease in cognitive impairment and dementia

AbstractBackgroundErgothioneine (ET) is a dietary amino‐thione with strong antioxidant properties and therapeutic potential for neurodegenerative and vascular diseases (Halliwell et al., 2018; Smith et al., 2020). Decreased blood concentrations of ET have been found in patients with mild cognitive impairment (Cheah et al., 2016), but its status in neurodegenerative and vascular dementias are currently unclear. We thus investigated the association of plasma ET levels with (1) cognitive impairment and dementia, (2) cerebrovascular disease (CeVD), namely white matter hyperintensities (WMH), cortical infarcts and lacunes and (3) brain atrophy.MethodA cross‐sectional study was conducted in a total of 496 participants in an ongoing longitudinal study, including 88 subjects with no cognitive impairment (NCI), 201 subjects with cognitive impairment but no dementia (CIND), 207 dementia patients of whom 160 had Alzheimer’s Disease and 47 vascular dementia (VaD). All subjects underwent collection of blood samples, neuropsychological assessment, and neuroimaging. Plasma ET levels were measured with a high sensitivity liquid chromatography tandem‐mass spectrometry (LC‐MS/MS) method.ResultPlasma ET concentrations were lowest in dementia (p<0.001 vs. NCI and CIND), with intermediate levels in CIND (p<0.001 vs. NCI). In multivariate analyses, lower levels of ET were significantly associated with CIND (OR, 0.20; 95% CI, 0.07–0.56; p<0.01) and dementia (OR, 0.06; 95% CI, 0.02–0.20; p<0.001) after adjustment for demographics and risk factors. There was a positive correlation between plasma ET and MMSE scores (r=0.341, p<0.001). Lower ET levels were also strongly associated with WMH (OR, 0.44; 95% CI, 0.123–0.85); p<0.01) and brain atrophy markers (cortical atrophy: OR, 0.42; 95% CI, 0.20–0.92; central atrophy: OR, 0.46; 95% CI, 0.22–0.93; medial temporal atrophy: OR, 0.45; 95% CI, 0.24–0.99, p<0.05 for all).ConclusionThe incremental decreases in ET levels along the clinical continuum suggest that ET may be associated with disease severity and is a potential biomarker for early detection of cognitive impairment. Deficiency of ET may contribute towards neurodegeneration‐ and CeVD‐associated cognitive impairments by exacerbating the deleterious effects of oxidative stress in these conditions.

The Association Between Retinal Neuronal Layer and Brain Structure is Disrupted inPatients with Cognitive Impairment andAlzheimer's Disease.

Both healthy and pathological aging due to Alzheimer's disease (AD) are associated with decreased brain grey matter volume (GMV) and disrupted white matter (WM) microstructure. Thinner macular ganglion cell-inner plexiform layer (GC-IPL) measured by spectral-domain optical coherence tomography has been reported in patients with AD and mild cognitive impairment. Emerging evidence suggested a link between thinner GC-IPL and lower GMV in subjects with no dementia using region-of-interest-based approach. However, it remains unknown whether GC-IPL thickness is associated with brain WM microstructure and how such association differed between normal and cognitively impaired subjects. Here, for subjects with no cognitive impairment (NCI), thinner GC-IPL was associated with lower WM microstructure integrity in the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corticospinal tracts, anterior thalamic radiation, and cingulum regions, while it was weakly associated with lower GMV in visual cortex and cerebellum. Nevertheless, these retina-brain associations were disrupted in the presence of cognitive impairment. Correlations between GMV and GC-IPL were lost in patients with cognitive impairment but no dementia (CIND) and AD patients. GC-IPL was related to WM microstructural disruption in similar regions with decreased significance. In contrast, lower WM microstructure integrity in the fornix showed a trend of correlation with thinner GC-IPL in both CIND and AD but not NCI. Collectively, our findings suggest the possible physiological retina-brain relationship in healthy aging, which might be disrupted by disease-induced changes in patients with cognitive impairment. Longitudinal study with larger patient sample should follow to confirm the disease mechanism behind these retina-brain relationship changes.

White Matter Changes and Cognitive Decline in a Ten-Year Follow-Up Period: A Pilot Study on a Single-Center Cohort from the Leukoaraiosis and Disability Study

Aims: To describe the contribution of white matter lesions to the long-term neuropsychological profiles of different groups of clinical diagnoses, and to identify neuropsychological predictors of cognitive impairment in a 10-year follow-up. Methods: The Lisbon subcohort of the Leukoaraiosis and Disability (LADIS) study was re-evaluated performing a clinical, functional and cognitive evaluation [including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and ADAS-Cog with the extension for vascular impairment (VADAS-Cog), the 9-word version of the California Verbal Learning Test (CVLT-9), the Trail-Making test and the Stroop test] as well as an MRI scan. Using clinical diagnostic criteria, participants were identified as having no cognitive impairment (NI), cognitive impairment but no dementia (CIND) or dementia (DEM), and the effect of time on clinical diagnosis and neuropsychological profiles was analyzed. Results: From the initial group of 66 participants, 37 out of 41 survivors (90%) were re-evaluated (mean age 81.40 years, 57% women). Fifteen patients (41%) had DEM, 12 (32%) CIND and 10 (27%) NI. Over time, the three groups presented distinct profiles in the MMSE [F_{2, 62} = 15.85, p = 0.000], ADAS [F_{2, 62} = 15.85, p = 0.000] and VADAS [F_{2, 48} = 5.87, p = 0.008]. Logistic regression analysis identified higher scores on MMSE (β = 1.14, p = 0.03, OR = 3.13, 95% CI 1.09-8.97) as predictors of NI after 10 years of follow-up. Conclusion: Higher scores on baseline MMSE were the only neuropsychological predictors of NI after 10 years.

Cognitive impairment, oral self‐care function and dental caries severity in community‐dwelling older adults

To investigate whether oral self-care function mediates the associations between cognitive impairment and caries severity in community-dwelling older adults. Cognitive impairment affects activities of daily living and compromises oral health, systemic health and quality of life in older adults. However, the associations among cognitive impairment, oral self-care capacity and caries severity remain unclear. This increases difficulty in developing effective interventions for cognitively impaired patients. Medical, dental, cognitive and functional assessments were abstracted from the dental records of 600 community-dwelling elderly. 230 participants were selected using propensity score matching and categorised into normal, cognitive impairment but no dementia (CIND) and dementia groups based on their cognitive status and a diagnosis of dementia. Multivariable regressions were developed to examine the mediating effect of oral self-care function on the association between cognitive status and number of caries or retained roots. Cognitive impairment, oral self-care function and dental caries severity were intercorrelated. Multivariable analysis showed that without adjusting for oral self-care capacity, cognition was significantly associated with the number of caries or retained roots (p = 0.003). However, the association was not significant when oral self-care capacity was adjusted (p = 0.125). In contrast, individuals with impaired oral self-care capacity had a greater risk of having a caries or retained root (RR = 1.67, 95% CI 1.15, 2.44). Oral care capacity mediates the association between cognition and dental caries severity in community-dwelling older adults.

Rivastigmine for vascular cognitive impairment

Vascular dementia represents the second most common type of dementia after Alzheimer's disease. In older patients, in particular, the combination of vascular dementia and Alzheimer's disease is common, and is referred to as mixed dementia. The classification of vascular dementia broadly follows three clinico-pathological processes: multi-infarct dementia, single strategic infarct dementia and subcortical dementia. Not all victims fulfil strict criteria for dementia and may be significantly cognitively impaired without memory loss, when the term vascular cognitive impairment (VCI) is more useful. Currently, no established standard treatment for VCI exists. Reductions in acetylcholine and acetyltransferase activity are common to both Alzheimer's disease and VCI, raising the possibility that cholinesterase inhibitors - such as rivastigmine - which are beneficial in Alzheimer's disease, may also be beneficial for VCI. To assess the efficacy of rivastigmine compared with placebo in the treatment of people with vascular cognitive impairment (VCI), vascular dementia or mixed dementia. We searched ALOIS (the Cochrane Dementia and Cognitive Improvement Group's Specialized Register) on 12 February 2013 using the terms: rivastigmine, exelon, "SDZ ENA 713". ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS), numerous trial registries and grey literature sources. All unconfounded randomized double-blind trials comparing rivastigmine with placebo in the treatment of people with VCI, vascular dementia or mixed dementia were eligible for inclusion. Two reviewers extracted and assessed data independently, and agreement was reached after discussion. They noted results concerning adverse effects. Three trials, with a total of 800 participants, were identified for inclusion. The participants in one trial did not have dementia, while the other two studies included participants with dementia of different severities. The dose of rivastigmine was different in each study. No pooling of study results was attempted because of these differences between the studies.One trial included 40 participants with subcortical vascular dementia (age range 40 to 90 years) with a mean mini-mental state examination (MMSE) score of 13.0 and 13.4 in the rivastigmine and placebo arms, respectively. Treatment over 26 weeks was limited to 3 mg rivastigmine twice daily, or placebo. No significant difference was found on any outcome measure relevant to cognition, neuropsychiatric symptoms, function or global rating, or in the number of withdrawals before the end of treatment.Another trial included 710 participants with vascular dementia, including subcortical and cortical forms (age range 50 to 85 years). Over 24 weeks, a mean dose of rivastigmine of 9.4 mg/day was achieved versus placebo. Baseline MMSE was identical for both groups, at 19.1. Statistically significant advantage in cognitive response (but not with global impression of change or non-cognitive measures) was seen with rivastigmine treatment at 24 weeks (MMSE change from baseline MD 0.6, 95% CI 0.11 to 1.09, P value 0.02; Vascular Dementia Assessment Scale (VaDAS) change from baseline MD -1.3, 95% CI-2.62 to 0.02, P value 0.05 ). Significantly higher rates of vomiting, nausea, diarrhoea and anorexia and withdrawals from treatment were noted in the participants randomized to rivastigmine compared with placebo (withdrawals rivastigmine 90/365, placebo 48/345, OR 2.02, 95% CI 1.38 to 2.98) (withdrawals due to an adverse event rivastigmine 49/365, placebo 19/345, OR 2.66, 95% CI 1.53 to 4.62, P value 0.0005).The third study included 50 participants (age range 48 to 84 years) with mean MMSE scores of 23.7 and 23.9 in the rivastigmine and placebo arms, respectively. Over a 24-week period, participants labelled as having cognitive impairment but no dementia (CIND) following ischaemic stroke were given up to 4.5 mg rivastigmine twice daily, or placebo. Primary and secondary outcome measures showed no statistically significant difference when considering neurocognitive abilities, function, neuropsychiatric symptoms and global performance. One participant in the rivastigmine group and two in the placebo group discontinued their medication because of an adverse effect. There is some evidence of benefit of rivastigmine in VCI from trial data from three studies. However, this conclusion is based on one large study. Rivastigmine is capable of inducing side effects that lead to withdrawal in a significant proportion of patients.

Monocyte chemoattractant protein-1 promoter polymorphism and plasma levels in alzheimer’s disease

BackgroundNeurodegenerative disorders such Alzheimer's disease (AD) are often characterized by senile plaques and neurofibrillary tangle. In addition, reactive astrogliosis, microglia activation and a chronic inflammation are found in AD brain. Activated microglia has been reported to express a large number of beta chemokines including monocyte chemoattractant protein-1 (MCP-1). The potential role of MCP-1 in AD pathogenesis is supported by the over expression of MCP-1 associated with an increase of amyloid deposition in transgenic mice. MCP-1 protein may be regulated by a single nucleotide polymorphism (SNP) occurring at position −2518 of the MCP-1 gene promoter. In this paper we correlated the A-2518G MCP-1 SNP distribution in three different populations: AD, control and MCI (mild cognitive impairment) population to evaluate whether this SNP might be a risk factor for AD or for MCI-AD conversion. MCP-1 plasma levels were also measured and correlated to the cognitive impairment (CIND) and AD risk.ResultsNo differences in genotype distribution and allele frequencies of A-2518G MCP-1 SNP among AD patients, MCI subjects and controls were observed even after APOEe4 variation adjustment with logistic regression. However in MCI subjects, followed up for two years, this SNP appears to influence the progression of the disease; being the G allele slightly more frequent in MCI patients that developed AD. MCP-1 plasma levels were different among CIND (cognitive impairment but no dementia), AD and controls. The MCP-1 A-2518G promoter polymorphism did not affect MCP-1 plasma levels within the three populations.ConclusionsMCP-1 G allele did not affect the risk of AD, but slightly influenced MCI conversion to AD and MCP-1 plasma levels were increased in subjects with preclinical AD.

Cognitive Impairment in Euthymic Older Adults With Bipolar Disorder: A Controlled Study Using Cognitive Screening Tests

Cognitive impairment is a common feature of bipolar disorder (BD), with increased risk of developing dementia in late life. The aim of this study was to investigate the performance on cognitive screening tests in a sample of older adults with BD, as compared to non-BD subjects. 186 older adults (86 with BD and 100 without BD) were included. Patients were stratified according to cognitive performance (normal cognition, mild impairment, and dementia). The comparison group comprised healthy controls; subjects with cognitive impairment but no dementia (CIND); or patients with probable or possible Alzheimer disease (AD). Sixty-five subjects were cognitively unimpaired (35 BD), 65 had CIND (25 BD), and 56 AD (26 BD). In each of these levels of cognitive function, we compared the performance of BD and non-BD subjects on the Mini-Mental State Examination (MMSE), verbal fluency test (VFT), and the Clock Drawing Test (CDT). Non-demented patients with BD had a slightly worse global cognitive performance as compared with healthy controls and patients with CIND, as shown by lower scores on the MMSE. Similarly, BD patients performed worse on the VFT, both in the normal cognition range and in the dementia range. Finally, demented BD patients had a significantly worse performance on the CDT as compared with patients with dementia due to AD. Older adults with BD perform significantly worse on some cognitive screening tests as compared with those without BD across different levels of cognition.

Health numeracy and cognitive decline in advanced age

ABSTRACTThe study aimed at investigating health numeracy in cognitively well performing healthy participants aged from 50 to 95 years as well as in participants with cognitive impairment, but no dementia (CIND). In cognitively well performing participants (n = 401), demographic variables and cognitive abilities (executive functions, reading comprehension, mental calculation, vocabulary) were associated with health numeracy. Older age, lower education, female gender as well as lower cognitive functions predicted low health numeracy. The effect of older age was partly mediated by executive functions and calculation abilities. Participants with CIND (n = 51) performed significantly lower than healthy controls in health numeracy. The findings suggest that cognitively well performing old individuals have difficulties in understanding health-related numerical information. The risk of misunderstanding health-related numerical information is increased in persons with CIND. As these population groups are frequently involved in health care decisions, particular attention has to be paid to providing numerical information in comprehensible form.

The predictive validity of the 10/66 dementia diagnosis in Chennai, India: a 3-year follow-up study of cases identified at baseline.

The prevalence of dementia according to DSM-IV criteria tends to be very low in less developed settings. The 10/66 Dementia Research Group's cross-culturally validated diagnosis returns a considerably higher prevalence. Assessing the predictive validity of the 10/66 dementia diagnosis will assist in establishing the best criterion for estimating the population burden of dementia. In a population-based study in Chennai, India, we aimed to follow-up after 3 years 75 people with 10/66 dementia and 193 with cognitive impairment but no dementia (CIND), reassessing diagnostic status, clinical severity, cognitive function, disability, and needs for care. We traced 54 people with dementia of whom 25 (46.3%) had died, double the mortality rate among those with CIND. Twenty-two of the 24 people with 10/66 dementia that were reexamined still met 10/66 dementia criteria. There was clear evidence of clinical progression and increased needs for care. Only one "case" had unambiguously improved. Cognitive function had deteriorated and disability increased to a much greater extent than among those with CIND. The strong predictive validity of the 10/66 dementia diagnosis is consistent with a lack of sensitivity of the DSM-IV criteria to mild-to-moderate cases, which may underestimate prevalence in less developed regions.

Five-Year Outcomes for Dementia Defined Solely by Neuropsychological Test Performance

Cognitive impairment that does not meet criteria for dementia is common and progresses to dementia at a high rate. It is not clear how best to define this type of cognitive impairment. We assessed the predictive validity of different case definitions for cognitive impairment and dementia by comparing rates of adverse outcomes for individuals who did not meet dementia criteria but had neuropsychological test results indicating dementia (NPDementia), those who had traditional dementia diagnoses (mild and moderate-severe severity), those who had other cognitive impairment but no dementia (CIND), and those with no cognitive impairment (NCI). Our sample comprised 1,659 participants who had completed a neuropsychological assessment in the Canadian Study of Health and Aging, a prospective, cohort study of 10,263 randomly selected persons aged 65 years or older. Outcomes were determined after 5 years. Institutionalization and death rates for the NPDementia and CIND groups were higher than for the NCI group. Both groups had lower institutionalization rates than the two Dementia groups and lower death rates than the Moderate-Severe Dementia group. Rates of progression to dementia were increased in NPDementia and CIND groups, relative to the NCI group, and the NPDementia group was less likely than the CIND group to revert to a diagnosis of NCI at the 5-year follow-up. Thus, individuals with NPDementia and CIND have substantially worse outcomes over 5 years than those with NCI. The case definition of NPDementia identified individuals with cognitive impairment that is unlikely to resolve and likely to progress to dementia.

Five-year follow-up of cognitive impairment with no dementia.

The importance of early identification of dementia has prompted numerous investigations of mild cognitive impairment and the preclinical stages of progressive degenerative disorders. To date, there is limited information from large-scale studies regarding outcomes of persons specifically identified with cognitive impairment but no dementia (CIND). To investigate outcomes for persons with no cognitive impairment (NCI) or CIND, focusing on its etiologic subcategories, from the Canadian Study of Health and Aging (CSHA) and to examine the predictive validity of a set of core features thought to be early manifestations of subsequent dementia. Five-year, longitudinal follow-up of all persons without dementia examined during the first phase of the CSHA in 1991. Community and institutional settings. Population-based sample of 883 persons with NCI and 801 persons with CIND at the first phase of the CSHA. At follow-up, 517 persons with NCI (59%) and 327 persons with CIND (41%) were alive and received clinical diagnoses. Mortality, institutionalization, and clinical diagnoses using the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria for dementia. Persons with CIND were more likely than those with NCI to die (49% vs 30%), to be admitted to facility care (29% vs 14%), or to receive diagnoses of dementia (47% vs 15%) at follow-up. Those subsequently diagnosed as having dementia were more likely to have had impaired memory, informant-reported change in memory, and functional impairment at baseline. Persons with CIND were more likely to have a negative outcome than persons with NCI during a 5-year interval. This was true across etiologic subcategories and suggests that the use of specific diagnostic criteria sets does not improve our identification of those who develop dementia compared with a broader, more inclusive approach. More factors contributed to the prediction of all forms of dementia than to AD, but the most accurate prediction was for those who remained dementia free.

Mild dementia or cognitive impairment: the Modified Mini-Mental State examination (3MS) as a screen for dementia.

To examine the Modified Mini-Mental State Examination (3MS) as a screen for dementia. A group of 1092 elderly Edmonton community residents completed the 3MS and the Geriatric Mental State Examination (GMS). 3MS sensitivity and specificity were determined by comparing positive 3MS screens (score < or = 77) with those classified as GMS "organic" (severity level 3, equivalent to a clinical diagnosis). In the Canadian Study of Health and Aging (CSHA), 2914 subjects received the 3MS and a clinical examination. A group described as having "cognitive impairment but no dementia (CIND)" was identified. In Edmonton, the 3MS showed 88% sensitivity, 90% specificity, 29% positive predictive value (PPV), and 99% negative predictive value (NPV). In the CSHA, 30% of subjects receiving both the 3MS and a clinical examination were classified as CIND. One-half of these were classified as having "age associated memory impairment (AAMI)" or as "unspecified." The 3MS with a cutting score of 77/78 proved a reasonable screening instrument; 1 case in 3 screening "positive" has dementia, but few (0.64%) will be missed by screening "negative." CIND, accounting for 2 out of 3 cases screened positive by the 3MS in the Edmonton study, is a substantial, heterogeneous group that is not necessarily "predementia" but that in many cases merits further investigation.