Coffee and tea consumption and dementia risk: The role of sex and vascular comorbidities.

BACKGROUND: Coffee and tea consumption has been linked to dementia. However, it remained unknown how sex and vascular risk factors modify the association. We aimed to investigate the association of coffee and tea consumption with dementia and whether sex and vascular comorbidities modified the association. METHODS: We included 278 elderly patients with Alzheimer's disease (AD) and 102 patients with vascular dementia (VaD) from three hospitals; controls (N = 468) were recruited during the same period. We collected the frequency and amount of coffee and tea consumption and the presence of vascular comorbidities. The multinomial logistic regression model was utilized to evaluate the association of coffee and tea consumption with dementia, stratified by sex and vascular comorbidities. RESULTS: Different combinations and quantities of coffee and tea consumption protected against AD and VaD. Consumption of ≥3 cups of coffee or tea per day was protective against AD [adjusted odds ratio (aOR) = 0.42; 95% confidence interval (CI) = 0.22-0.78)] and VaD (aOR = 0.42; 95% CI = 0.19-0.94). Stratified analyses showed that the protective effects of a higher quantity of coffee and tea against AD were more pronounced among females and individuals with hypertension. Consumption of either coffee or tea was associated with a decreased risk of VaD among diabetic participants (aOR = 0.23; 95% CI = 0.06-0.98). Hyperlipidemia modified the association of coffee or tea consumption on the risk of AD and VaD (both Pinteraction < 0.01). CONCLUSION: The risk of AD and VaD was lower with increased consumption of coffee and tea; the impact differed by sex and vascular comorbidities including hypertension, hyperlipidemia, and diabetes.

More than a piece of cake: Noun classifier processing in primary progressive aphasia.

INTRODUCTION: Clinical understanding of primary progressive aphasia (PPA) has been primarily derived from Indo-European languages. Generalizing certain linguistic findings across languages is unfitting due to contrasting linguistic structures. While PPA patients showed noun classes impairments, Chinese languages lack noun classes. Instead, Chinese languages are classifier language, and how PPA patients manipulate classifiers is unknown. METHODS: We included 74 native Chinese speakers (22 controls, 52 PPA). For classifier production task, participants were asked to produce the classifiers of high-frequency items. In a classifier recognition task, participants were asked to choose the correct classifier. RESULTS: Both semantic variant (sv) PPA and logopenic variant (lv) PPA scored significantly lower in classifier production task. In classifier recognition task, lvPPA patients outperformed svPPA patients. The classifier production scores were correlated to cortical volume over left temporal and visual association cortices. DISCUSSION: This study highlights noun classifiers as linguistic markers to discriminate PPA syndromes in Chinese speakers. HIGHLIGHTS: Noun classifier processing varies in the different primary progressive aphasia (PPA) variants. Specifically, semantic variant PPA (svPPA) and logopenic variant PPA (lvPPA) patients showed significantly lower ability in producing specific classifiers. Compared to lvPPA, svPPA patients were less able to choose the accurate classifiers when presented with choices. In svPPA, classifier production score was positively correlated with gray matter volume over bilateral temporal and left visual association cortices in svPPA. Conversely, classifier production performance was correlated with volumetric changes over left ventral temporal and bilateral frontal regions in lvPPA. Comparable performance of mass and count classifier were noted in Chinese PPA patients, suggesting a common cognitive process between mass and count classifiers in Chinese languages.

Association of subclinical depressive symptoms and sleep with cognition in the community-dwelling older adults.

BACKGROUND: /Purpose: This study aimed to explore the association of subclinical depressive symptoms and sleep with cognition in community-dwelling Taiwanese older adults. METHODS: This four-year prospective cohort study (2015-2019) included 379 participants aged 65 years or older from the annual senior health checkup program at National Taiwan University Hospital who were followed up two years later. Global and domain cognitive functions were assessed using validated neuropsychological tests. Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression (CES-D) Scale. Sleep quality was evaluated using the Pittsburg Sleep Quality Index (PSQI). Excessive daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Generalized linear mixed models were used to explore the associations of subclinical depressive symptoms and sleep variables with cognition, adjusting for important covariates. Stratification analyses were performed using the sleep variables. RESULTS: Over time, depressive symptoms were associated with poor performance of memory (߈ = 0.24, P = 0.04) and executive function (߈ = -0.24, P = 0.03). Poor sleep quality (elevated PSQI score) was associated with poor memory performance (߈ = -0.04 to -0.03, P < 0.05). Excessive daytime sleepiness (elevated ESS score) was associated with poor performance of memory (߈ = -0.02, P < 0.05) and executive function (߈ = -0.02, P = 0.001). At baseline, better sleep quality and no excessive daytime sleepiness were associated with better memory performance over time. CONCLUSION: Subclinical depressive symptoms, worse sleep quality, and excessive daytime sleepiness were differentially associated with impairment of cognitive domains (mainly memory and executive function).

The association between retinal vascular fractal dimension and cognitive function in the community-dwelling older adults cohort TIGER.

BACKGROUND/PURPOSE: The small retinal vessels reflect cerebral microcirculation and its fractal dimension (Df), representing the complexity of the retinal microcirculation. However, the connection between retinal circulation and cognitive function lacked consistent and longitudinal evidence. This study aimed to explore the association between retinal vascular complexity and cognitive impairment over time in non-demented community-dwelling older adults. METHODS: This four-year prospective cohort study (2015-2019) is part of the ongoing Taiwan Initiative for Geriatric Epidemiological Research (TIGER, 2011 to present). Of the 434 older adults (age >65) recruited, 207 participants were included for analysis. The retinal vascular Df was assessed by baseline images from fundus photography (2015-2017). Global (Montreal Cognitive Assessment-Taiwanese version, MoCA-T) and domain-specific cognition were assessed at the baseline and 2-year follow-up (2017-2019). The multivariable linear regression models and generalized linear mixed models were used to evaluate the association of Df with cognitive decline/impairment over time. RESULTS: Decreased left retinal vascular complexity was associated with poor attention performance (ß = -0.40). As follow-up time increased, decreased vascular complexity was associated with poor memory performance (right: ß = -0.25; left: ß = -0.19), and decreased right vascular complexity was associated with poor attention performance (ß = -0.18). CONCLUSION: Low retinal vascular complexity of the right or left eye may be differentially associated with cognitive domains in community-dwelling older adults over two years. The retinal vascular Df of either eye may be served as a screening tool for detecting cognitive impairment in the preclinical phase of dementia.

White matter pathology in alzheimer's transgenic mice with chronic exposure to low-level ambient fine particulate matter.

BACKGROUND: Air pollution, especially fine particulate matter (PM), can cause brain damage, cognitive decline, and an increased risk of neurodegenerative disease, especially alzheimer's disease (AD). Typical pathological findings of amyloid and tau protein accumulation have been detected in the brain after exposure in animal studies. However, these observations were based on high levels of PM exposure, which were far from the WHO guidelines and those present in our environment. In addition, white matter involvement by air pollution has been less reported. Thus, this experiment was designed to simulate the true human world and to discuss the possible white matter pathology caused by air pollution. RESULTS: 6 month-old female 3xTg-AD mice were divided into exposure and control groups and housed in the Taipei Air Pollutant Exposure System (TAPES) for 5 months. The mice were subjected to the Morris water maze test after exposure and were then sacrificed with brain dissection for further analyses. The mean mass concentration of PM2.5 during the exposure period was 13.85 µg/m3. After exposure, there was no difference in spatial learning function between the two groups, but there was significant decay of memory in the exposure group. Significantly decreased total brain volume and more neuronal death in the cerebral and entorhinal cortex and demyelination of the corpus callosum were noted by histopathological staining after exposure. However, there was no difference in the accumulation of amyloid or tau on immunohistochemistry staining. For the protein analysis, amyloid was detected at significantly higher levels in the cerebral cortex, with lower expression of myelin basic protein in the white matter. A diffuse tensor image study also revealed insults in multiple white matter tracts, including the optic tract. CONCLUSIONS: In conclusion, this pilot study showed that even chronic exposure to low PM2.5 concentrations still caused brain damage, such as gross brain atrophy, cortical neuron damage, and multiple white matter tract damage. Typical amyloid cascade pathology did not appear prominently in the vulnerable brain region after exposure. These findings imply that multiple pathogenic pathways induce brain injury by air pollution, and the optic nerve may be another direct invasion route in addition to olfactory nerve.

Genetic study of young-onset dementia using targeted gene panel sequencing in Taiwan.

Recent genetic progress allows the molecular diagnosis of young-onset dementia, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). We aimed to identify the mutational and clinical spectra of causal genes in a Taiwanese cohort of young-onset dementia. Ninety-one patients with young-onset dementia and 22 age/gender-matched controls were recruited. Genetic causes were identified by a targeted panel containing 90 causative genes for AD, FTD, and related neurodegenerative disorders. Plasma biomarkers, including total tau, Aß42, and Aß40, were assayed. Molecular amyloid and tau PET scans were performed in some patients carrying mutations. Nine of 52 patients (17.3%) with young-onset AD had mutations: 2 (22.2%), 4 (44.5%), 2 (22.2%), and 1 (11.1%) in APP, PSEN1, PSEN2, and TREM2, respectively. Two of 33 patients (6.1%) with young-onset FTD had mutations in MAPT and LRRK2. Three of the 6 patients (50.0%) with possible FTD combined with other neurodegenerative disorders had individual mutations in APP, PSEN2, or MAPT. Patients with PSEN1 mutations had earlier onset of disease than those without mutations (p = .02). Plasma level of total tau was increased and Aß42 and Aß40 levels decreased in all groups of dementia patients compared to controls. Our findings provide a genetic spectrum of young-onset dementia in our population.

Neuropathology changed by 3- and 6-months low-level PM2.5 inhalation exposure in spontaneously hypertensive rats.

BACKGROUND: Epidemiological evidence has linked fine particulate matter (PM2.5) to neurodegenerative diseases; however, the toxicological evidence remains unclear. The objective of this study was to investigate the effects of PM2.5 on neuropathophysiology in a hypertensive animal model. We examined behavioral alterations (Morris water maze), lipid peroxidation (malondialdehyde (MDA)), tau and autophagy expressions, neuron death, and caspase-3 levels after 3 and 6 months of whole-body exposure to urban PM2.5 in spontaneously hypertensive (SH) rats. RESULTS: SH rats were exposed to S-, K-, Si-, and Fe-dominated PM2.5 at 8.6 ± 2.5 and 10.8 ± 3.8 µg/m3 for 3 and 6 months, respectively. We observed no significant alterations in the escape latency, distance moved, mean area crossing, mean time spent, or mean swimming velocity after PM2.5 exposure. Notably, levels of MDA had significantly increased in the olfactory bulb, hippocampus, and cortex after 6 months of PM2.5 exposure (p < 0.05). We observed that 3 months of exposure to PM2.5 caused significantly higher expressions of t-tau and p-tau in the olfactory bulb (p < 0.05) but not in other brain regions. Beclin 1 was overexpressed in the hippocampus with 3 months of PM2.5 exposure, but significantly decreased in the cortex with 6 months exposure to PM2.5. Neuron numbers had decreased with caspase-3 activation in the cerebellum, hippocampus, and cortex after 6 months of PM2.5 exposure. CONCLUSIONS: Chronic exposure to low-level PM2.5 could accelerate the development of neurodegenerative pathologies in subjects with hypertension.

Nanoparticle-based immunomagnetic assay of plasma biomarkers for differentiating dementia and prodromal states of Alzheimer's disease - A cross-validation study.

Blood-based biomarker assays of plasma ß-amyloid (Aß) and tau have the advantages of cost-effective and less invasive for the diagnosis of Alzheimer's disease (AD). We used two independent cohorts to cross-validate the clinical use of the nanoparticle-based immunomagnetic assay of plasma biomarkers to assist in the differential diagnosis of early AD. There were in total 160 subjects in the derivation cohort, and 242 in the validation cohort both containing controls, mild cognitive impairment due to AD and AD dementia diagnosed according to the 2011 NIA-AA guidelines. The cutoff value for plasma Aß1-42 (16.4 pg/ml) performed the best in differentiating between controls and patients with prodromal or clinical AD, with 92.5% for positive percent agreement (PPA), negative percent agreement (NPA), and overall rate of agreement (ORA). Aß1-42 × tau (642.58) was useful for separating patients with dementia and prodromal states of AD, with 84.9% PPA, 78.8% NPA and 83% ORA.

Classifications of Neurodegenerative Disorders Using a Multiplex Blood Biomarkers-Based Machine Learning Model.

Easily accessible biomarkers for Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and related neurodegenerative disorders are urgently needed in an aging society to assist early-stage diagnoses. In this study, we aimed to develop machine learning algorithms using the multiplex blood-based biomarkers to identify patients with different neurodegenerative diseases. Plasma samples (n = 377) were obtained from healthy controls, patients with AD spectrum (including mild cognitive impairment (MCI)), PD spectrum with variable cognitive severity (including PD with dementia (PDD)), and FTD. We measured plasma levels of amyloid-beta 42 (Aß42), Aß40, total Tau, p-Tau181, and α-synuclein using an immunomagnetic reduction-based immunoassay. We observed increased levels of all biomarkers except Aß40 in the AD group when compared to the MCI and controls. The plasma α-synuclein levels increased in PDD when compared to PD with normal cognition. We applied machine learning-based frameworks, including a linear discriminant analysis (LDA), for feature extraction and several classifiers, using features from these blood-based biomarkers to classify these neurodegenerative disorders. We found that the random forest (RF) was the best classifier to separate different dementia syndromes. Using RF, the established LDA model had an average accuracy of 76% when classifying AD, PD spectrum, and FTD. Moreover, we found 83% and 63% accuracies when differentiating the individual disease severity of subgroups in the AD and PD spectrum, respectively. The developed LDA model with the RF classifier can assist clinicians in distinguishing variable neurodegenerative disorders.

Diminution of context association memory structure in subjects with subjective cognitive decline.

Alzheimer's disease (AD) progresses insidiously from the preclinical stage to dementia. While people with subjective cognitive decline (SCD) have normal cognitive performance, some may be in the preclinical stage of AD. Neurofibrillary tangles appear first in the transentorhinal cortex, followed by the entorhinal cortex in the clinically silent stage of AD. We expected the earliest changes in subjects with SCD to occur in medial temporal subfields other than the hippocampal proper. These selective structural changes would affect specific memory subcomponents. We used the Family Picture subtest of the Wechsler Memory Scale-III, which was modified to separately compute character, activity, and location subscores for episodic memory subcomponents. We recruited 43 subjects with SCD, 44 subjects with amnesic mild cognitive impairment, and 34 normal controls. MRI was used to assess cortical thickness, subcortical gray matter volume, and fractional anisotropy. The results demonstrated that SCD subjects showed significant cortical atrophy in their bilateral parahippocampus and perirhinal and the left entorhinal cortices but not in their hippocampal regions. SCD subjects also exhibited significantly decreased mean fractional anisotropy in their bilateral uncinate fasciculi. The diminution of cortical thickness over the mesial temporal subfields corresponded to brain areas with early tangle deposition, and early degradation of the uncinate fasciculus was in accordance with the retrogenesis hypothesis. The parahippocampus and perirhinal cortex contribute mainly to context association memory while the entorhinal cortex, along with the uncinate fasciculus, contributes to content-related contextual memory. We proposed that context association and related memory structures are vulnerable in the SCD stage.

Diagnostic accuracy of Instrumental Activities of Daily Living for dementia in community-dwelling older adults.

BACKGROUND: many people living with dementia remain underdiagnosed and unrecognised. Screening strategies are important for early detection. OBJECTIVE: to examine whether the Lawton's Instrumental Activities of Daily Living (IADL) scale, compared with other cognitive screening tools-the Mini-Mental State Examination (MMSE), and the Ascertain Dementia 8-item Informant Questionnaire (AD8)-can identify older (≥ 65 years) adults with dementia. DESIGN: population-based cross-sectional observational study. SETTING: all 19 counties in Taiwan. PARTICIPANTS: community-dwelling older adults (n = 10,340; mean age 74.87 ± 6.03). METHODS: all participants underwent a structured in-person interview. Dementia was identified using National Institute on Aging-Alzheimer's Association core clinical criteria for all-cause dementia. Receiver operator characteristic curves were used to determine the discriminant abilities of the IADL scale, MMSE and AD8 to differentiate participants with and without dementia. RESULTS: we identified 917 (8.9%) participants with dementia, and 9,423 (91.1%) participants without. The discriminant abilities of the MMSE, AD8 and IADL scale (cutoff score: 6/7; area under curve = 0.925; sensitivity = 89%; specificity = 81%; positive likelihood ratio = 4.75; accuracy = 0.82) were comparable. Combining IADL with AD8 scores significantly improved overall accuracy: specificity = 93%; positive likelihood ratio = 11.74; accuracy = 0.92. CONCLUSIONS: our findings support using IADL scale to screen older community-dwelling residents for dementia: it has discriminant power comparable to that of the AD8 and MMSE. Combining the IADL and the AD8 improves specificity.

Arbitrary and semantic associations in subjective memory impairment and amnestic mild cognitive impairment among Taiwanese individuals: A cross-sectional study.

BACKGROUND/PURPOSE: Researchers have recently proposed a preclinical stage of dementia of Alzheimer's type (DAT), referred to as subjective memory impairment (SMI), with the aim of developing methods for the early detection of DAT and subsequent intervention. It has been proposed that the objective memory functions of individuals with SMI are normal; however, arbitrary and semantic associations are both used to describe the processes of memory. No previous studies have investigated these processes among individuals with SMI. METHODS: Cross-sectional analysis was used to compare the memory function of individuals with SMI, amnestic mild cognitive impairment (aMCI), or DAT. One hundred and eighty-three participants were recruited from the Memory Clinic of National Taiwan University Hospital and communities in northern Taiwan, including individuals with no memory complaints (HC, n = 30) and individuals with SMI (n = 61), aMCI-single domain (n = 24), aMCI-multiple domain (n = 33), or DAT (n = 35). The Word Sequence Learning Test (WSLT) was used to assess the formation of arbitrary associations and the Logical Memory subtest of the Wechsler Memory Scale-Third Edition was used to assess the formation of semantic associations. RESULTS: Compared to the HC group, the SMI group performed poorly only on the WSLT, whereas the other groups performed poorly on both of the memory tasks. This study demonstrated that SMI individuals tend to perform poorly in the formation of arbitrary associations. CONCLUSION: Our findings suggest that tasks requiring arbitrary associations may provide greater sensitivity in the detection cognitive changes associated with preclinical DAT.

Genetic polymorphisms of lipid metabolism gene SAR1 homolog B and the risk of Alzheimer's disease and vascular dementia.

BACKGROUND/PURPOSE: Lipid metabolism is involved in beta amyloid generation, which has been related with the progression of Alzheimer's disease (AD). No study has explored the association between polymorphisms of SAR1 homolog B (SAR1B) and the risk of dementia previously. METHODS: This is a case-control study. A total of 279 AD and 117 vascular dementia (VaD) patients were recruited from neurology clinics at three teaching hospitals in Taiwan from 2007 to 2010. Controls (n = 466) were recruited from the elderly health checkup program and volunteers in the hospital during the same time interval. Three common (frequency ≥ 5%) haplotype-tagging single nucleotide polymorphisms were selected from the lipid metabolism gene SAR1B to assess its association with AD and VaD. RESULTS: Homozygous variants of rs11948613 were associated with a decreased AD risk (CC vs. TT: adjusted odds ratio = 0.39, 95% confidence interval = 0.15-0.98) with a population attributable risk of 26.7%. This association decreased further in apolipoprotein E ε4 (ApoE ε4) noncarriers (adjusted odds ratio = 0.28, 95% confidence interval = 0.09-0.91). No association was found for VaD. Two common haplotypes (with a cumulative frequency of 95.7% in controls) were identified for SAR1B, and no association was found for AD or VaD. Simultaneous screening using rs11948613 and ApoE ε4 significantly improved the sensitivity of ApoE ε4 alone (from 0.40 to 0.75). CONCLUSION: SAR1B polymorphisms were associated with AD risk; results were not significant after correction for multiple tests. Simultaneous screening using SAR1B rs11948613 and ApoE ε4 status offered a better sensitivity for AD screening.

Distinct Patterns and Clinical Implications of Semantic Memory Deterioration Among Patients With MCI.

Limited research has investigated the effects of executive dysfunction on semantic memory deterioration among patients with amnestic mild cognitive impairment (aMCI). This study examined the cognitive performance of 181 participants from various MCI subgroups, a group of mildly impaired individuals with dementia of the Alzheimer type (DAT) and a group of individuals with subjective memory impairment on various semantic memory tasks. The aMCI-single domain (aMCI-sd) group displayed poor performance on a semantic memory task requiring relatively higher degrees of effortful retrieval, and participants in the aMCI-multiple domain (aMCI-md) group, who also suffered with mild executive dysfunction displayed poor performance on all semantic memory tasks, similar to the DAT group. The nonamnestic MCI (non-a-MCI)-single domain group displayed normal performance across all semantic tasks, whereas the non-a-MCI-multiple domain group displayed a pattern similar to that of the aMCI-sd group. aMCI-sd patients who displayed poor performance on the semantic memory task had higher risk of conversion to DAT, whereas poor performance on tasks requiring relatively less effortful retrieval was associated with higher risk of conversion in the aMCI-md group. Thus, executive function may relate to deterioration of semantic memory retrieval processes. Such patterns of semantic memory impairment could be valuable for characterization of cognitive differences among MCI patients.

Sequence variants of the aging gene CISD2 and the risk for Alzheimer's disease.

BACKGROUND/PURPOSE: The CISD2 gene has been related to life span control and mitochondrial dysfunction in animals. In addition, inhibition of mitochondrial enzymes due to an accumulation of beta-amyloid peptide has been related to Alzheimer's disease (AD). This study aimed to explore the association between sequence variants of the CISD2 gene and risk for AD, which has not been explored previously. METHODS: This was a case-control study involving a total of 276 patients with AD who were recruited from three teaching hospitals in Taiwan from 2007 to 2010; 460 controls were recruited from elderly individuals attending for health check-ups and volunteers in the hospital during the same period of time. All participants were aged 60 years or older. Two haplotype-tagging single nucleotide polymorphisms (htSNPs), rs223330 and rs223331, were selected from the CISD2 gene to test the association between their polymorphisms and the risk for dementia, and how ApoE ɛ4 status, sex, hypertension, and type 2 diabetes mellitus might modify this association. RESULTS: rs223330 variant carriage was not associated with risk for AD [TT versus CC: adjusted odds ratio (AOR) = 0.98, 95% confidence interval (CI) = 0.59-1.62; TC versus CC: AOR = 0.72, 95% CI = 0.47-1.11]. Similar findings were observed for rs223331 (AA versus TT: AOR = 1.12; AT versus TT: AOR = 0.99). In addition, hypertension significantly modified the association between rs223331 and risk for AD (p = 0.005).Three common haplotypes (with a frequency of 99.8%) were observed for CISD2. Common CISD2 haplotypes were not associated with the risk for AD. CONCLUSION: Our findings suggested that CISD2 htSNPs are not associated with AD risk.

Leisure activities, apolipoprotein E e4 status, and the risk of dementia.

BACKGROUND/PURPOSE: Leisure activities have been associated with a decreased risk of dementia. However, to date, no study has explored how apolipoprotein E (ApoE) e4 status or vascular risk factors modified the association between leisure activities and dementia risks. METHODS: This case-control study recruited patients (age ≥ 60 years) with Alzheimer's disease (AD; n = 292) and vascular dementia (VaD; n = 144) and healthy controls (n = 506) from three teaching hospitals in Taiwan between 2007 and 2010. Information on patient's leisure activities were obtained through a questionnaire. Conditional logistic regression models were used to assess the association of leisure activities and ApoE e4 status with the risk of dementia. RESULTS: High-frequency physical activity was associated with a decreased risk of AD [adjusted odds ratio (AOR) = 0.45], and the results become more evident among ApoE e4 carriers with AD (AOR = 0.30) and VaD (AOR = 0.26). Similar findings were observed for cognitive (AOR = 0.42) and social activities (AOR = 0.55) for AD. High-frequency physical, cognitive, and social activities were associated with a decreased risk of VaD (AOR = 0.29-0.60). Physical and social activities significantly interacted with each other on the risk of VaD (pinteraction = 0.04). CONCLUSION: Physical activity consistently protects against AD and VaD. Significant interactions were identified across different types of leisure activities in lowering dementia risk.

Plasma tau as a window to the brain-negative associations with brain volume and memory function in mild cognitive impairment and early Alzheimer's disease.

Neurofibrillary tangles are associated with cognitive dysfunction, and hippocampal atrophy with increased CSF tau markers. However, the plasma tau levels of Alzheimer's disease (AD) have not been well studied. We investigated plasma tau by using an immunomagnetic reduction assay in 20 patients with mild cognitive impairment (MCI) due to AD, 10 early AD dementia, and 30 healthy elders (HE). All received a 3D-brain MRI scan and a set of cognitive function test. We explored their relationships with both brain structure and cognitive functions. Images were analyzed to determine the brain volumes and gray matter densities. Patients with MCI or early AD had significantly increased plasma tau levels compared with HE. Plasma tau levels were negatively associated with the performance of logical memory, visual reproduction, and verbal fluency; also negatively associated with volume of total gray matter, hippocampus, amygdala; and gray matter densities of various regions. Regression analyses indicated that logical memory explained 0.394 and hippocampus volume predicted .608 of the variance of plasma tau levels, both P < 0.001. Education years were negatively associated with the gray matter densities of the supramarginal (r = -0.407), middle temporal gyrus (r = -0.40) and precuneus (r = -0.377; all P < 0.05) in HE; and negatively associated with plasma tau levels in patients (r = -0.626). We propose that plasma tau may serve as a window to both structure and function of the brain. Higher education is a protective factor against AD and is associated with lower plasma tau levels in patients.

Cingulum correlates of cognitive functions in patients with mild cognitive impairment and early Alzheimer's disease: a diffusion spectrum imaging study.

Diffusion spectrum imaging (DSI) of MRI can detect neural fiber tract changes. We investigated integrity of cingulum bundle (CB) in patients with mild cognitive impairment (MCI) and early Alzheimer's disease (EAD) using DSI tractography and explored its relationship with cognitive functions. We recruited 8 patients with MCI, 9 with EAD and 15 healthy controls (HC). All subjects received a battery of neuropsychological tests to access their executive, memory and language functions. We used a 3.0-tesla MRI scanner to obtain T1- and T2-weighted images for anatomy and used a pulsed gradient twice-refocused spin-echo diffusion echo-planar imaging sequence to acquire DSI. Patients with EAD performed significantly poorer than the HC on most tests in executive and memory functions. Significantly smaller general fractional anisotropy (GFA) values were found in the posterior and inferior segments of left CB and of the anterior segment of right CB of the EAD compared with those of the HC. Spearman's correlation on the patient groups showed that GFA values of the posterior segment of the left CB were significantly negatively associated with the time used to complete Color Trails Test Part II and positively correlated with performance of the logical memory and visual reproduction. GFA values of inferior segment of bilateral CB were positively associated with the performance of visual recognition. DSI tractography demonstrates significant preferential degeneration of the CB on the left side in patients with EAD. The location-specific degeneration is associated with corresponding declines in both executive and memory functions.

Grip Strength and Sarcopenia Predict 2-Year Cognitive Impairment in Community-Dwelling Older Adults.

OBJECTIVES: Using the Asian Working Group for Sarcopenia (AWGS2019) and the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, this study examined associations of sarcopenia and its components with specific domains of cognitive impairment over time. DESIGN: A prospective cohort study with a 2-year follow-up. SETTING AND PARTICIPANTS: This study is part of the Taiwan Initiatives for Geriatric Epidemiological Research (TIGER), which recruited participants aged 65 years old who attended the senior health checkup program at National Taiwan University Hospital (NTUH). METHODS: Grip strength was measured using a handgrip dynamometer. Walking speed (m/s) was measured as the time required to walk 8 feet. Muscle mass was measured by performing a bioelectrical impedance analysis. Global cognition (assessed using the Taiwanese version of the Montreal Cognitive Assessment) and 4 cognitive domains (memory, executive function, verbal fluency, and attention) were assessed over time. Associations of sarcopenia and its components with cognitive impairment were evaluated after stratification by sex using generalized linear mixed models adjusted for essential covariates for cognitive impairment. RESULTS: Compared with robust women, those with severe sarcopenia were more likely to have a global cognitive impairment over time (ß = -0.87, P = .03 based on AWGS2019 criteria and ß = -1.07, P = .02 based on the EWGSOP2 criteria). Among men, low grip strength was associated with poor scores on measures of global cognition (ß = -0.80, P = .03), executive function (ß = -0.35, P = .001), verbal fluency (ß = -0.31, P = .02), and attention (ß = -0.34, P = .008) over time. CONCLUSIONS AND IMPLICATIONS: Severe sarcopenia predicted global and specific domains of cognitive impairment in older adults. Poor grip strength predicted cognitive impairment in men but not in women. A screen for sarcopenia severity and low muscle strength may be used to identify the risk of cognitive impairment.

Multimorbid Patterns and Cognitive Performance in the Presence of Informative Dropout Among Community-Dwelling Taiwanese Older Adults.

Background and Objectives: Longitudinal studies among older adults often feature elevated dropout rates and multiple chronic conditions. How Taiwanese multimorbid patterns relate to different cognitive domains remains unclear. This study aims to identify sex-specific multimorbid patterns and associate them with cognitive performance while modeling the risk for dropout. Research Design and Methods: A prospective cohort study (2011-19) in Taiwan recruited 449 Taiwanese older adults without dementia. Global and domain-specific cognition were assessed biennially. We used exploratory factor analysis to identify baseline sex-specific multimorbid patterns of 19 self-reported chronic conditions. We utilized a joint model incorporating longitudinal and time-to-dropout data to examine the association between multimorbid patterns and cognitive performance accounting for the informative dropout via the shared random effect. Results: At the end of the study, 324 participants (72.1%) remained in the cohort, with an average annual attrition rate of 5.5%. We found that advanced age, low levels of physical activities, and poor cognition at baseline were associated with increased dropout risks. Besides, 6 multimorbid patterns were identified, labeled Mental, Renal-vascular, and Cancer-urinary patterns in men, and Mental, Cardiometabolic, and Cancer-endocrine patterns in women. For men, as the follow-up time increased, the Mental pattern was associated with poor global cognition and attention; the Renal-vascular pattern was associated with poor executive function. For women, the Mental pattern was associated with poor memory; as follow-up time increased, and Cardiometabolic patterns were related to poor memory. Discussion and Implications: Sex-specific multimorbid patterns identified in the Taiwanese older population showed differences (notably Renal-vascular pattern in men) from patterns found in Western countries and were differentially associated with cognitive impairment over time. When informative dropout is suspected, appropriate statistical methods should be applied.