Faster Decline In Global Cognition Research Articles

Consumption of ultra‐processed food and cognitive decline among older adults with type‐2 diabetes

AbstractBackgroundUltra‐processed foods (UPF) are ready‐to‐eat/heat foods that derive from a series of industrial processes. These products constitute a large and increasing amount of the food supply in high and middle‐income countries. Accumulating evidence point to an association of UPF intake with increased mortality and adverse health outcomes, including cardiovascular and metabolic diseases. However, whether UPF consumption is associated with cognitive function is not clear. We investigated the associations between UPF intake and cognitive decline, in a cohort of older adults at high‐risk for dementia due to type‐2 diabetes (T2D).MethodThe study sample included initially non‐demented T2D older adults (≥65y), from the Israel Diabetes and Cognitive Decline (IDCD) study, who had complete information on nutrition at baseline and at least three cognitive assessments (mean follow‐up 5.3±1.5y). Nutritional intake was evaluated by a validated Food‐Frequency Questionnaire and foods were categorized as UPF based on NOVA classification. Percent of calories from UPF were calculated from total caloric consumption, first as overall UPF intake and then for specific food groups. Global cognitive functioning and four cognitive domains (episodic memory, working memory/attention, semantic categorization, and executive functions) were assessed. Mixed effect models were used to examine the link between UPF intake (top vs. bottom quartiles) and change in cognitive function while adjusting for age, sex, education, smoking, physical activity, BMI, HbA1C, duration of diabetes, total cholesterol and blood pressure.ResultOf the total sample (N=578; mean age at baseline 71.3±4.5y, 61% men), 144 (top quartile) consumed >31% kcal from UPF out of total kcal. Total UPF consumption was not related to cognitive function. However, consumption of ultra‐processed fat (e.g. mayonnaise) was associated with faster decline in global cognition, executive function and memory (ß=‐0.028±0.010; p=0.009, ß=‐0.031±0.014; p=0.022 and ß=‐0.035±0.017; p=0.046, respectively). Additionally, increased intake of ultra‐processed meat (e.g. sausages) was associated with a faster decline in executive functions (ß=‐0.029±0.013; p=0.031). UPF derived from dairy products and carbohydrates were not associated with cognitive change.ConclusionThis pioneering study suggests a possible association of ultra‐processed meat and fat intake with accelerated cognitive decline in older individuals with T2D, independently of sociodemographic, lifestyle, cardiovascular and T2D‐related factors.

Brain insulin signaling in persons with and without diabetes is associated with cognitive decline

AbstractBackgroundPeripheral insulin resistance is associated with increased risk of AD dementia, and postmortem measures of reduced insulin signaling in the brain have been linked to poorer cognition in AD‐related domains proximal to death. However, the relationship between brain insulin signaling and longitudinal cognitive decline over the years leading up to death is under‐studied. This study assessed the relationship between longitudinal change in domain‐specific cognition and brain insulin signaling in a clinical‐pathologic, community‐based cohort.MethodUsing a subsample of participants in the Religious Orders Study (75 with diabetes matched to 75 without diabetes), we examined data derived from annual cognitive assessments (mean age (years) baseline: 77.25 ± 6.34; final: 86.03 ± 6.14) and postmortem measures of brain insulin signaling. Neuropsychological testing was grouped to form a primary measure of global cognition, and five separate cognitive domains. Brain insulin receptor signaling was quantified via ELISA for the ratio of pS307IRS1 /total IRS1 (insulin receptor substrate‐1) “IRS1 phosphorylation”, ratio of pT308AKT1/total AKT1 (serine/threonine‐protein kinase) “AKT phosphorylation”, and immunohistochemistry for IRS1 cells/mm2, and pIRS1 at S616. Mixed effects regression models assessed per‐person mean level and rate of change (slope) in each cognitive domain, along with effects of brain variables, age at death, sex, and education on mean level, and effects of brain variables on change (the α was set at 0.025).ResultGreater AKT phosphorylation had a trend‐level association with faster decline in global cognition (‐0.02 (0.01) 0.035). Greater AKT phosphorylation was associated with faster declines in working memory (‐0.02 (0.01) 0.015) and visuospatial ability (‐0.01 (0.01) 0.023) and at a trend level with faster episodic memory decline (‐0.03 (0.01) 0.026). Greater IRS1 phosphorylation was associated with slower decline in perceptual speed (0.02 (0.01) 0.023). Greater staining for pS616IRS1 was associated with faster visuospatial ability decline (‐0.02 (0.01) 0.020).ConclusionBrain insulin signaling measures are associated with cognitive decline in the years prior to death. Future work should further characterize these relationships and explore links of peripheral insulin resistance and cognitive decline and dementia.

Dementia in Southeast Asia: influence of onset-type, education, and cerebrovascular disease

BackgroundSoutheast Asia represents 10% of the global population, yet little is known about regional clinical characteristics of dementia and risk factors for dementia progression. This study aims to describe the clinico-demographic profiles of dementia in Southeast Asia and investigate the association of onset-type, education, and cerebrovascular disease (CVD) on dementia progression in a real-world clinic setting.MethodsIn this longitudinal study, participants were consecutive series of 1606 patients with dementia from 2010 to 2019 from a tertiary memory clinic from Singapore. The frequency of dementia subtypes stratified into young-onset (YOD; <65 years age-at-onset) and late-onset dementia (LOD; ≥65 years age-at-onset) was studied. Association of onset-type (YOD or LOD), years of lifespan education, and CVD on the trajectory of cognition was evaluated using linear mixed models. The time to significant cognitive decline was investigated using Kaplan-Meier analysis.ResultsDementia of the Alzheimer’s type (DAT) was the most common diagnosis (59.8%), followed by vascular dementia (14.9%) and frontotemporal dementia (11.1%). YOD patients accounted for 28.5% of all dementia patients. Patients with higher lifespan education had a steeper decline in global cognition (p<0.001), with this finding being more pronounced in YOD (p=0.0006). Older patients with a moderate-to-severe burden of CVD demonstrated a trend for a faster decline in global cognition compared to those with a mild burden.ConclusionsThere is a high frequency of YOD with DAT being most common in our Southeast Asian memory clinic cohort. YOD patients with higher lifespan education and LOD patients with moderate-to-severe CVD experience a steep decline in cognition.

Pulmonary function is associated with cognitive decline and structural brain differences.

The association of poor pulmonary function (PF) with cognitive trajectories and structural brain differences remains unclear. Within the Rush Memory and Aging Project, 1377 dementia-free subjects were followed up to 21 years. PF was assessed with a composite score measured at baseline. Global and domain-specific cognitive function was assessed annually constructed from 19 cognitive tests. A subsample of 351 participants underwent brain magnetic resonance imaging to investigate the cross-sectional association between PF and structural brain volumes. We found that low PF was related to faster decline in global cognition, and domain-specific function including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed. In addition, low PF was associated with smaller volumes of total brain, white matter and gray matter, and larger white matter hyperintensities volume. Our results suggest that low PF is associated with faster cognitive decline, and both neurodegeneration and vascular brain lesions may underlie the association.

TOMM40-APOE haplotypes are associated with cognitive decline in non-demented Blacks.

The goal was to investigate effects of APOE-TOMM40-'523 haplotypes on cognitive decline in non-demented non-Hispanic Blacks (NHB), and determine whether effects differ from non-Hispanic Whites (NHW). The impact of zero to two copies of the '523-Short variant (S; poly-T alleles<20) within apolipoprotein E (APOE) genotype on a composite measure of global cognition and five domains was examined. In NHB with ε3/ε3 (N=294), '523-S/S was associated with faster decline in global cognition (β=-0.048, P=0.017), episodic memory (β=-0.05, P=0.031), and visuospatial ability (β=-0.037, P=0.034) relative to those without '523-S. For NHB ε4+ (N=182), '523-S/S had slower decline in global cognition (β=0.047, P=0.042) and visuospatial ability (β=0.07, P=0.0005) relative to '523-S non-carriers. NHB ε4+ with '523-S also had a slower rate of decline than NHWs ε4+ with '523-S. '523-S/S has a different effect on cognitive decline among NHB dependent on APOE allele. Differences in the effect of ε4-'523-S in NHB may explain prior mixed findings on ε4 and decline in this population.

TAR DNA-Binding Protein 43 Is Associated with Rate of Memory, Functional and Global Cognitive Decline in the Decade Prior to Death.

Background:Transactive response DNA-binding protein of 43 kDa (TDP-43) is associated with memory impairment and overall cognitive decline. It is unclear how TDP-43 contributes to the rate of clinical decline.Objective:To determine whether cross-sectional and longitudinal cognitive and functional decline are associated with anatomical distribution of TDP-43 in the brain.Methods:Longitudinal clinical-neuropathologic autopsy cohort study of 385 initially cognitively normal/mildly impaired older adults prospectively followed until death. We investigated how TDP-43, amyloid-β (Aβ), tau neurofibrillary tangles (NFT), Lewy body disease (LBD), age, sex, and genetics are associated with clinical scores and rates of their longitudinal decline.Results:Of 385 participants, 260 (68%) had no TDP-43, 32 (8%) had TDP-43 limited to amygdala, and 93 (24%) had TDP-43 in the hippocampus and beyond. Higher TDP-43 and Braak NFT stages independently were associated with faster decline in global cognition, functional performance measured by Clinical Dementia Rating scale, and naming and episodic memory, whereas older age was associated with slower rate of cognitive, psychiatric, and functional decline. Cross-sectionally the following associations were found: higher TDP-43 and Braak NFT - worse performance; higher Aβ burden - worse global cognition, more behavioral changes, the latter also with higher LBD; older age - worse naming, lower frequency of behavioral changes; female sex - more impaired naming and better preserved episodic memory. There were no genetic associations.Conclusion:The association of TDP-43 distribution with decline in cognitive and functional performance suggests that TDP-43 is playing a role in the clinical progression to dementia. Further characterization of clinical features associated with TDP-43 can facilitate establishment of antemortem diagnosis.

Association of cardiovascular risk burden with cognitive trajectories and structural brain differences

AbstractBackgroundThe impact of cardiovascular risk burden on cognitive trajectories and brain structure changes remains unclear.MethodWithin the Rush Memory and Aging Project, 1,588 dementia‐free participants (mean age=79.5 years) were followed for up to 21 years. FGCRS was assessed at baseline and categorized into tertiles (the lowest, middle, and the highest). Episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with a battery of 19 tests, from which composite scores were derived. A subsample (n=378) of the participants underwent magnetic resonance imaging (MRI). Structural total and regional brain volumes were estimated. Data were analyzed using linear mixed‐effects models and linear regression models.ResultIn all participants, FGCRS ranged from 4 to 28 (mean score=15.6±3.7). Compared with the lowest tertile of FGCRS, the highest was associated with faster decline in global cognition (β=‐0.019, 95% confidence interval [CI] ‐0.035 to ‐0.003), episodic memory (β=‐0.023, 95% CI ‐0.041 to ‐0.004), working memory (β=‐0.021, 95% CI ‐0.035 to ‐0.007), and perceptual speed (β=‐0.027, 95% CI ‐0.042 to ‐0.011) over the follow‐up. In MRI data analyses, higher FGCRS was related to smaller volumes of the hippocampus (β=‐0.021, 95% CI ‐0.042 to ‐0.000), total gray matter (β=‐1.569 95% CI ‐2.757 to ‐0.382), and total brain (β=‐1.588, 95% CI ‐2.832 to ‐0.344), and greater volume of white matter hyperintensities (β=0.035, 95% CI 0.001 to 0.069).ConclusionHigher cardiovascular risk burden may predict decline in episodic memory, working memory and perceptual speed, and is associated with neurodegeneration and vascular lesions in the brain.

Limbic-predominant age-related TDP-43 encephalopathy, ADNC pathology, and cognitive decline in aging.

To examine the impact of 3 pathologic groups, pure limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy (LATE) neuropathologic changes (NC), pure Alzheimer disease neuropathologic change (ADNC), and mixed ADNC with LATE-NC, on late-life cognitive decline. Data came from 1,356 community-based older persons who completed detailed annual cognitive testing and systematic neuropathologic examination at autopsy to identify LATE-NC, ADNC, and other age-related pathologies. Persons were categorized into (0) a group without a pathologic diagnosis of LATE or ADNC (n = 378), (1) LATE-NC without ADNC (n = 91), (2) ADNC without LATE-NC (n = 535), and (3) mixed ADNC with LATE-NC (n = 352). We used mixed-effect models to examine the group associations with rate of decline in global cognition and 5 cognitive domains and then examined whether age modified associations. Compared to those without LATE-NC or ADNC, those with pure LATE-NC had a faster decline in global cognition (p = 0.025) and episodic memory (p = 0.002); however, compared to persons with pure ADNC, those with pure LATE-NC showed a slower decline. Those with mixed ADNC with LATE-NC showed the fastest decline compared to those with either pathology alone. Persons ≥90 years of age with mixed ADNC with LATE-NC had slower cognitive decline compared to those ≤89 years of age. Persons with pure LATE-NC follow a slower trajectory compared to those with pure ADNC. Those with mixed LATE/ADNC have a steeper decline than individuals with either pathology alone. In addition, age may modify the effect of pathology on cognitive decline. These findings have important implications for the development of biomarkers and prognosis for late-life cognitive decline. This study provides Class I evidence that LATE-NC and Alzheimer disease pathologic changes are associated with different trajectories of late-life cognitive decline.

Associations Between Cardiovascular Risk, Structural Brain Changes, and Cognitive Decline

BackgroundThe impact of cardiovascular risk burden on cognitive trajectories and brain structure changes remains unclear. ObjectivesThis study aimed to examine whether cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) is associated with cognitive decline and structural brain differences. MethodsWithin the Rush Memory and Aging Project, 1,588 dementia-free participants (mean age: 79.5 years) were followed for up to 21 years. FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with a battery of 19 tests, from which composite scores were derived. A subsample (n = 378) of participants underwent magnetic resonance imaging. Structural total and regional brain volumes were estimated. Data were analyzed using linear mixed-effects models and linear regression models. ResultsIn all participants, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Compared with the lowest tertile of FGCRS, the highest tertile was associated with faster decline in global cognition (β = −0.019; 95% confidence interval [CI]: −0.035 to −0.003), episodic memory (β = −0.023; 95% CI: −0.041 to −0.004), working memory (β = −0.021; 95% CI: −0.035 to −0.007), and perceptual speed (β = −0.027; 95% CI: −0.042 to −0.011) over the follow-up. In magnetic resonance imaging data analyses, higher FGCRS was related to smaller volumes of the hippocampus (β = −0.021; 95% CI: −0.042 to −0.000), gray matter (β = −1.569; 95% CI: −2.757 to −0.382), and total brain (β = −1.588; 95% CI: −2.832 to −0.344), and greater volume of white matter hyperintensities (β = 0.035; 95% CI: 0.001 to 0.069). ConclusionsHigher cardiovascular risk burden may predict decline in episodic memory, working memory, and perceptual speed and is associated with neurodegeneration and vascular lesions in the brain.

IMPACT OF TDP-43 AND HIPPOCAMPAL SCLEROSIS ON LATE-LIFE COGNITIVE DECLINE

There is increasing recognition of the role of TAR-DNA binding protein 43kDa (TDP-43) and hippocampal sclerosis (HS) pathology in AD and dementia. We studied TDP-43/HS pathology and the rate of decline in global cognition and 5 specific cognitive domains, and determined the impact of AD mixed with TDP-43 pathology on late-life cognitive decline Data came from 1,374 community-based older persons from the Religious Orders Study and the Rush Memory and Aging Project who completed detailed annual cognitive testing and systematic neuropathological examination to identify AD, TDP-43, HS, and other age-related pathologies. To assess distinct rates of cognitive decline in single and mixed pathology profiles, persons were categorized into 4 groups; (1) a group without TDP, HS, or AD pathology (n=378), (2) TDP with or without HS, and no AD (TDP/HS) (n=91), (3) AD without TDP/HS (n=535), and (4) AD with TDP/HS (AD/TDP or AD/TDP/HS) (n=352). Rates of cognitive decline by pathologic groupings were examined using mixed-effect models adjusted for age, sex, education, and other pathologies, followed by post-hoc comparisons. Compared to those without TDP, HS, or AD, those with TDP/HS and no AD had a faster decline in global cognition (p=0.007) and episodic memory (p<0.001); however compared to persons with isolated AD, the TDP/HS without AD group had slower decline in global cognition (p=0.02) and episodic memory (p=0.01). The mixed AD with TDP/HS group had faster decline in global cognition and all 5 cognitive domains, compared to the AD alone and TDP/HS groups. In subsequent analyses, persons with mixed AD/TDP/HS had significantly faster decline in global cognition (p=0.02) and individual cognitive domains, specifically episodic (p=0.01) and semantic memory (p=0.006), than those with mixed AD/TDP. These data show that TDP/HS without AD pathology contributes to late-life memory decline but this decline is slower than that seen in those with AD only. Mixed AD and TDP pathologies show an additive effect on decline, with mixed AD/TDP/HS showing faster decline in memory and language. These findings have important implications for the development of biomarkers and for prognosis of late-life cognitive decline.

A comparison of short- and long-term cortisol levels in melancholic and non-melancholic major depressive episodes using hair and saliva specimens

Brain proteins, including Insulin-like Growth Factor Binding Protein 5 (IGFBP-5), have been associated with cognitive dysfunction in aging. Mechanisms linking depression with cognition are poorly understood. We hypothesize that the association of depressive symptoms with cognition is mediated or modified by brain proteins.IGFBP-5, HSPB2, AK4, ITPK1 and PLXNB1 were measured in dorsolateral prefrontal cortex in 1057 deceased participants, who underwent annual assessments of depressive symptoms and cognition for a mean of 8.9 years. The average number of depressive symptoms per year before a dementia diagnosis was calculated for each person.A one standard deviation above the mean IGFBP-5 was associated with a 14% higher odds of having more depressive symptoms (p < 0.031). Higher IGFBP-5 was associated with faster decline in global cognition (p < 0.001) and five cognitive domains (p < 0.008), controlling for depressive symptoms. IGFBP-5 moderated the association of depressive symptoms with decline in global cognition (p = 0.045). IGFBP-5 mediated ten percent or less of the total effect of depressive symptoms on decline in global cognition and the cognitive domains (p > 0.070).Participants were volunteers and self-selection bias limits the generalizability of our findings. In addition, we used self-reported data on depressive symptoms. However, we also used data on depression medications as sensitivity analyses to confirm findings.In old age, brain IGFBP-5 is associated with depressive symptoms and cognition. The association of depressive symptoms with cognitive decline is conditional on IGFBP-5.

Surgical menopause in association with cognitive function and risk of dementia: A systematic review and meta-analysis

IntroductionExperimental and epidemiological studies suggest female sex hormones to have long-lasting neuroprotective and anti-ageing properties. Surgically-induced menopause leads to a premature cessation of exposure to female sex hormones and could thus impact late-life cognitive function. Yet, evidence remains controversial. MethodsWe systematically reviewed literature for articles investigating the association of surgical menopause (defined as bilateral oophorectomy before the onset of menopause) with risk of dementia, cognitive performance, cognitive decline, and Alzheimer’s disease neuropathological indices later in life. We evaluated study quality with the Newcastle-Ottawa scale and performed random-effects meta-analyses. ResultsWe identified 11 eligible studies (N = 18,867). Although surgical menopause at any age was not associated with risk of dementia (4 studies; HR: 1.16, 95%CI: 0.96–1.43), early surgical menopause (≤45 years of age) was associated with a statistically significantly higher risk (2 studies; HR: 1.70, 95%CI: 1.07–2.69). Surgical menopause at any age was associated with faster decline in verbal memory, semantic memory, and processing speed, whereas early surgical menopause was further associated with faster global cognitive decline. No heterogeneity was noted. Among women undergoing surgical menopause, a younger age at surgery was associated with faster decline in global cognition, semantic and episodic memory, worse performance in verbal fluency and executive function, and accumulation of Alzheimer’s neuropathology. ConclusionsCurrent evidence is limited, but suggests surgical menopause induced by bilateral oophorectomy at ≤45 years of age to be associated with higher risk of dementia and cognitive decline. Additional large-scale cohort studies are necessary to replicate these findings.

Brain IGFBP-5 modifies the relation of depressive symptoms to decline in cognition in older persons

BackgroundBrain proteins, including Insulin-like Growth Factor Binding Protein 5 (IGFBP-5), have been associated with cognitive dysfunction in aging. Mechanisms linking depression with cognition are poorly understood. We hypothesize that the association of depressive symptoms with cognition is mediated or modified by brain proteins. MethodsIGFBP-5, HSPB2, AK4, ITPK1 and PLXNB1 were measured in dorsolateral prefrontal cortex in 1057 deceased participants, who underwent annual assessments of depressive symptoms and cognition for a mean of 8.9 years. The average number of depressive symptoms per year before a dementia diagnosis was calculated for each person. ResultsA one standard deviation above the mean IGFBP-5 was associated with a 14% higher odds of having more depressive symptoms (p < 0.031). Higher IGFBP-5 was associated with faster decline in global cognition (p < 0.001) and five cognitive domains (p < 0.008), controlling for depressive symptoms. IGFBP-5 moderated the association of depressive symptoms with decline in global cognition (p = 0.045). IGFBP-5 mediated ten percent or less of the total effect of depressive symptoms on decline in global cognition and the cognitive domains (p > 0.070). LimitationsParticipants were volunteers and self-selection bias limits the generalizability of our findings. In addition, we used self-reported data on depressive symptoms. However, we also used data on depression medications as sensitivity analyses to confirm findings. ConclusionsIn old age, brain IGFBP-5 is associated with depressive symptoms and cognition. The association of depressive symptoms with cognitive decline is conditional on IGFBP-5.

Atrial fibrillation, antithrombotic treatment, and cognitive aging: A population-based study.

ObjectiveTo examine the association of atrial fibrillation (AF) with cognitive decline and dementia in old age, and to explore the cognitive benefit of antithrombotic treatment in patients with AF.MethodsThis population-based cohort study included 2,685 dementia-free participants from the Swedish National Study on Aging and Care in Kungsholmen, who were regularly examined from 2001–2004 to 2010–2013. AF was ascertained from clinical examination, ECG, and patient registry. Global cognitive function was assessed using the Mini-Mental State Examination. We followed the DSM-IV criteria for the diagnosis of dementia, the NINDS-AIREN (National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences) criteria for vascular dementia, and the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for Alzheimer disease. Data were analyzed using multiple linear mixed-effects and Cox regression models.ResultsWe identified 243 participants (9.1%) with AF at baseline. During the 9-year follow-up period, 279 participants (11.4%) developed AF and 399 (14.9%) developed dementia. As a time-varying variable, AF was significantly associated with a faster annual Mini-Mental State Examination decline (β coefficient = −0.24, 95% confidence interval [CI]: −0.31 to −0.16) and an increased hazard ratio (HR) of all-cause dementia (HR = 1.40, 95% CI: 1.11–1.77) and vascular and mixed dementia (HR = 1.88, 95% CI: 1.09–3.23), but not Alzheimer disease (HR = 1.33, 95% CI: 0.92–1.94). Among people with either prevalent or incident AF, use of anticoagulant drugs, but not antiplatelet treatment, was associated with a 60% decreased risk of dementia (HR = 0.40, 95% CI: 0.18–0.92).ConclusionAF is associated with a faster global cognitive decline and an increased risk of dementia in older people. Use of anticoagulant drugs may reduce dementia risk in patients with AF.

Apathy is associated with faster global cognitive decline and early nursing home admission in dementia with Lewy bodies

BackgroundLittle is known about the consequences of apathy in dementia with Lewy bodies (DLB), because previous research on apathy in dementia focused mainly on Alzheimer’s disease (AD).MethodsIn this longitudinal study, we included patients with AD (n = 128) and patients with DLB (n = 81). At baseline, we analyzed the associations between apathy and cognition in the total sample and in AD and DLB separately. Generalized linear mixed models were used to investigate the association between apathy and Mini Mental State Examination (MMSE) over 4 years, and the Kaplan-Meier method was used to assess the association between apathy and survival or nursing home admission.ResultsIn patients with DLB, apathy was associated with a faster global cognitive decline (MMSE) over 4 years. Patients with DLB and apathy had shorter time until nursing home admission than DLB patients without apathy and patients with AD, regardless of apathy. At baseline, patients with apathy had decreased performance on the Stroop color test and a composite executive function score. Neurocognition was unaffected by apathy in AD, but DLB patients with apathy had more verbal learning difficulties.ConclusionsApathy seems to be associated with more serious symptomatology in DLB than in AD. It is important to focus on apathy in dementia because it is one of the most prevalent and disturbing behavioral and psychological symptoms.

Body Mass Index and Decline in Cognitive Function in Older Black and White Persons.

While body mass index (BMI) is higher in black compared to white persons, little is known about BMI and change in cognition in cohorts with a large proportion of blacks. We examine relations of BMI with decline in global cognition and five cognitive domains, in older blacks and whites, and determine whether relations differ by race. Participants were 2,134 persons without baseline dementia (33% black; 75% women; mean age =77.9 [range 53-100] and education = 14.7 years, Mini-Mental State Examination = 28.0), enrolled in one of two longitudinal, community-based cohort studies of aging (Minority Aging Research Study; Rush Memory and Aging Project). Summary scores of global cognition and five domains were based on 19 neuropsychological tests administered annually. Mixed-effects models, controlling for age, sex, education, and race, were used to examine the relation of baseline BMI to change in cognition. Baseline BMI = 28.4 units (30.3 in blacks [95% confidence interval (CI): 27.2-27.7]; 27.4 in whites [95% CI: 29.8-30.7]). During a mean annual follow-up of 6 years (SD = 4), lower baseline BMI was related to faster decline in global cognition (p = .002), and semantic memory (p < .001) and episodic memory (p = .004), but not working memory, perceptual speed, or visuospatial ability (all p > .08). The relationship of BMI with change in cognition was not modified by race (all p > .09). Late-life lower BMI relates to faster rates of decline in cognition, specifically semantic memory and episodic memory, in both blacks and whites. The effect of BMI on cognition appears to be similar in both racial groups.

Change of Cognitive Function in U.S. Chinese Older Adults: A Population-Based Study.

This study aims to assess cognitive change in a 2-year period among U.S. Chinese older adults and examine sociodemographic characteristics associated with the change. Data were from the Population Study of Chinese Elderly (PINE) in which 2,713 participants (aged 60 and older) received in-home interviews at both the baseline and 2-year follow-up. A battery of cognitive tests that assessed episodic memory, working memory, perceptual speed, and overall cognitive status were administered in both times. A composite global cognition was constructed using all tests. Mixed-effect regression was conducted. Older age was associated with worse baseline cognition (ie, in all cognitive abilities) and faster decline in global cognition, episodic memory, and perceptual speed-rates of decline increased by .006, .004, and .009 standard score units, respectively, for each year older. More education was associated with better baseline cognition, but each year of additional schooling increased rates of decline in global cognition and episodic memory by .004 and .012 standard score units, respectively. Men performed better than women in most cognitive abilities at baseline but had faster rates of decline in working memory. Higher income was associated with better cognition at baseline and reduced rates of decline in working memory. Findings suggest differences in the rates of cognitive change by age, sex, education, and income. Those in advancing age are vulnerable to cognitive decline. The effects of education and sex on baseline performance versus change suggest a role for life experiences in cognition.

Blood cholesterol in late-life and cognitive decline: a longitudinal study of the Chinese elderly

BackgroundPrevious studies regarding the lipid-cognition relation in older adults are limited and have generated mixed results. We thus examined whether higher blood cholesterol concentrations were associated with faster cognitive decline in a community-based longitudinal study of Chinese elderly.MethodsThe study included 1,159 Chinese adults aged over 60 years (women: 48.7%, mean age: 79.4 years), who were free of dementia, Parkinson disease and stroke at the baseline. Blood concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), were assessed at the baseline. Global cognitive functions were assessed using the Chinese Mini-Mental State Examination (MMSE) at in 2009, 2012 and 2014. Association between blood cholesterol and repeated cognitive function was analyzed with linear mixed models, adjusting for sociodemographic information, behavior and lifestyle, depression symptoms, physical examination, hypertension, and laboratory indexes.ResultsHigher baseline TC and LDL-C concentrations were significantly associated with greater cognitive decline. Adjusted mean difference in cognitive decline rate, comparing two extreme quartiles, was 0.28 points (MMSE score) per year (95% confident interval (CI): -0.54,–0.02; P-trend = 0.005) for TC and 0.42 points per year (95% CI: -0.69, -0.16; P-trend = 0.006) for LDL-C. In a subgroup analysis, the associations between all lipids and cognitive decline appeared to be more pronounced among individuals aged 100 years or older (n = 90), relative to others.ConclusionsHigher blood concentrations of TC and LDL-C in late-life were associated with faster global cognitive decline.

TOMM40'523 variant and cognitive decline in older persons with APOE ε3/3 genotype.

To interrogate a poly-T variant (rs10524523, '523) in TOMM40, a gene adjacent to the APOE gene on chromosome 19, in older persons with APOE ε3/3 homozygosity for association with cognitive decline, the clinical hallmark of Alzheimer disease (AD). Data came from participants in 2 cohort studies of aging and dementia who underwent annual clinical evaluations for up to 21 years. APOE and TOMM40'523 genotypes were determined from DNA from blood or brain samples. Linear mixed models compared the rates of decline in cognition among APOE ε3/3 carriers with different '523 genotypes. The 1,170 APOE ε3/3 homozygotes were of European ancestry, were free of dementia at baseline, and had an average age of 78.5 years at baseline. Three major genotypes at the '523 variant were linked to APOE ε3/3; 26.5% had 2 short poly-Ts (S/S), 48.5% had 1 short and 1 very long poly-T (S/VL), and 24.0% had 2 very long poly-Ts (VL/VL). Participants with '523-S/S had faster decline in global cognition than participants with '523-S/VL or VL/VL (p = 0.002). The same association was observed for episodic memory (p < 0.001) and semantic memory (p = 0.003) but not for working memory, perceptual speed, or visuospatial ability. Our data reveal an association of APOE ε3/3-TOMM40'523 haplotypes with cognitive decline in community-based older persons such that the S/S poly-T genotype is related to faster cognitive decline, primarily in the domains of episodic and semantic memory.

Longitudinal brain structure and cognitive changes over 8 years in an East Asian cohort

Although East Asia harbors the largest number of aging adults in the world, there is currently little data clarifying the longitudinal brain-cognition relationships in this group. Here, we report structural MRI and neuropsychological findings from relatively healthy Chinese older adults of the Singapore-Longitudinal Aging Brain Study cohort over 8 years of follow up (n=111, mean age=67.1 years, range=56.1–83.1 years at baseline). Aging-related change in structural volume was observed, with total cerebral atrophy at −0.56%/year, hippocampal atrophy at −0.94%/year and ventricular expansion at 3.56%/year. Only speed of processing showed an aging-related decline, while other cognitive domains were relatively maintained. Faster decline in global cognition was associated with total cerebral, hippocampal and gray matter volume losses over time. Faster total cerebral atrophy and white matter atrophy (frontal and parietal regions) was associated with faster decline in verbal memory. Hippocampal atrophy and ventricular expansion were both associated with greater decline in verbal memory and executive function. Our findings provide a benchmark for research on brain structural and cognitive changes with aging in East Asians.