Is white matter hyperintensity burden associated with cognitive and motor impairment in patients with parkinson's disease? A systematic review and meta-analysis.

White matter damage quantified as white matter hyperintensities (WMH) may aggravate cognitive and motor impairments, but whether and how WMH burden impacts these problems in Parkinson's disease (PD) is not fully understood. This study aimed to examine the association between WMH and cognitive and motor performance in PD through a systematic review and meta-analysis. We compared the WMH burden across the cognitive spectrum (cognitively normal, mild cognitive impairment, dementia) in PD including controls. Motor signs were compared in PD with low/negative and high/positive WMH burden. We compared baseline WMH burden of PD who did and did not convert to MCI or dementia. MEDLINE and EMBASE databases were used to conduct the literature search resulting in 50 studies included for data extraction. Increased WMH burden was found in individuals with PD compared with individuals without PD (i.e. control) and across the cognitive spectrum in PD (i.e. PD, PD-MCI, PDD). Individuals with PD with high/positive WMH burden had worse global cognition, executive function, and attention. Similarly, PD with high/positive WMH presented worse motor signs compared with individuals presenting low/negative WMH burden. Only three longitudinal studies were retrieved from our search and they showed that PD who converted to MCI or dementia, did not have significantly higher WMH burden at baseline, although no data was provided on WMH burden changes during the follow up. We conclude, based on cross-sectional studies, that WMH burden appears to increase with PD worse cognitive and motor status in PD.

20-year depressive symptoms, dementia, and structural neuropathology in older women.

INTRODUCTION: The course of depressive symptoms and dementia risk is unclear, as are potential structural neuropathological common causes. METHODS: Utilizing joint latent class mixture models, we identified longitudinal trajectories of annually assessed depressive symptoms and dementia risk over 21 years in 957 older women (baseline age 72.7 years old) from the Women's Health Initiative Memory Study. In a subsample of 569 women who underwent structural magnetic resonance imaging, we examined whether estimates of cerebrovascular disease and Alzheimer's disease (AD)-related neurodegeneration were associated with identified trajectories. RESULTS: Five trajectories of depressive symptoms and dementia risk were identified. Compared to women with minimal symptoms, women who reported mild and stable and emerging depressive symptoms were at the highest risk of developing dementia and had more cerebrovascular disease and AD-related neurodegeneration. DISCUSSION: There are heterogeneous profiles of depressive symptoms and dementia risk. Common neuropathological factors may contribute to both depression and dementia. Highlights The progression of depressive symptoms and concurrent dementia risk is heterogeneous. Emerging depressive symptoms may be a prodromal symptom of dementia. Cerebrovascular disease and AD are potentially shared neuropathological factors.

A dynamic computational model of the parallel circuit on the basal ganglia-cortex associated with Parkinson's disease dementia.

The cognitive impairment will gradually appear over time in Parkinson's patients, which is closely related to the basal ganglia-cortex network. This network contains two parallel circuits mediated by putamen and caudate nucleus, respectively. Based on the biophysical mean-field model, we construct a dynamic computational model of the parallel circuit in the basal ganglia-cortex network associated with Parkinson's disease dementia. The simulated results show that the decrease of power ratio in the prefrontal cortex is mainly caused by dopamine depletion in the caudate nucleus and is less related to that in the putamen, which indicates Parkinson's disease dementia may be caused by a lesion of the caudate nucleus rather than putamen. Furthermore, the underlying dynamic mechanism behind the decrease of power ratio is investigated by bifurcation analysis, which demonstrates that the decrease of power ratio is due to the change of brain discharge pattern from the limit cycle mode to the point attractor mode. More importantly, the spatiotemporal course of dopamine depletion in Parkinson's disease patients is well simulated, which states that with the loss of dopaminergic neurons projecting to the striatum, motor dysfunction of Parkinson's disease is first observed, whereas cognitive impairment occurs after a period of onset of motor dysfunction. These results are helpful to understand the pathogenesis of cognitive impairment and provide insights into the treatment of Parkinson's disease dementia.

Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles.

Glial fibrillary acidic protein (GFAP), a proxy of astrocyte reactivity, has been proposed as biomarker of Alzheimer's disease. However, there is limited information about the correlation between blood biomarkers and post-mortem neuropathology. In a single-centre prospective clinicopathological cohort of 139 dementia patients, for which the time-frame between GFAP level determination and neuropathological assessment was exceptionally short (on average 139 days), we analysed this biomarker, measured at three time points, in relation to proxies of disease progression such as cognitive decline and brain weight. Most importantly, we investigated the use of blood GFAP to detect the neuropathological hallmarks of Alzheimer's disease, while accounting for potential influences of the most frequent brain co-pathologies. The main findings demonstrated an association between serum GFAP level and post-mortem tau pathology (ß = 12.85; P < 0.001) that was independent of amyloid deposits (ß = 13.23; P = 0.02). A mediation analysis provided additional support for the role of astrocytic activation as a link between amyloid and tau pathology in Alzheimer's disease. Furthermore, a negative correlation was observed between pre-mortem serum GFAP and brain weight at post-mortem (r = -0.35; P < 0.001). This finding, together with evidence of a negative correlation with cognitive assessments (r = -0.27; P = 0.005), supports the role of GFAP as a biomarker for disease monitoring, even in the late phases of Alzheimer's disease. Moreover, the diagnostic performance of GFAP in advanced dementia patients was explored, and its discriminative power (area under the receiver operator characteristic curve at baseline = 0.91) in differentiating neuropathologically-confirmed Alzheimer's disease dementias from non-Alzheimer's disease dementias was determined, despite the challenging scenario of advanced age and frequent co-pathologies in these patients. Independently of Alzheimer's disease, serum GFAP levels were shown to be associated with two other pathologies targeting the temporal lobes-hippocampal sclerosis (ß = 3.64; P = 0.03) and argyrophilic grain disease (ß = -6.11; P = 0.02). Finally, serum GFAP levels were revealed to be correlated with astrocyte reactivity, using the brain GFAP-immunostained area as a proxy (ρ = 0.21; P = 0.02). Our results contribute to increasing evidence suggesting a role for blood GFAP as an Alzheimer's disease biomarker, and the findings offer mechanistic insights into the relationship between blood GFAP and Alzheimer's disease neuropathology, highlighting its ties with tau burden. Moreover, the data highlighting an independent association between serum GFAP levels and other neuropathological lesions provide information for clinicians to consider when interpreting test results. The longitudinal design and correlation with post-mortem data reinforce the robustness of our findings. However, studies correlating blood biomarkers and neuropathological assessments are still scant, and further research is needed to replicate and validate these results in diverse populations.

Profiles of Lifestyle Health Behaviors and Postmortem Dementia-Related Neuropathology.

High engagement in lifestyle health behaviors appears to be protective against cognitive decline in aging. We investigated the association between patterns of modifiable lifestyle health behaviors and common brain neuropathologies of dementia as a possible mechanism. We examined 555 decedents from the Rush Memory and Aging Project, free of dementia at their initial concurrent report of lifestyle health behaviors of interest (physical, social, and cognitive activities, and healthy diet), and who underwent a postmortem neuropathology evaluation. First, we used latent profile analysis to group participants based on baseline behavior patterns. Second, we assessed the associations of profile membership with each neurodegenerative (global Alzheimer's disease [AD] pathology, amyloid-beta load, density of neurofibrillary tangles, and presence of cortical Lewy bodies and TAR DNA-binding protein 43 cytoplasmic inclusions) and neurovascular pathologies (presence of chronic gross or microscopic infarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy), using separate linear or logistic regression models, adjusted for age at death, sex (core model), vascular disease risk factors, and vascular conditions (fully adjusted model). Participants had either consistently lower (N = 224) or consistently higher (N = 331) engagement across 4 lifestyle health behaviors. We generally found no differences in neuropathologies between higher and lower engagement groups in core or fully adjusted models; for example, higher engagement in lifestyle health behaviors was not associated with global AD pathology after core or full adjustment (both p > .8). In conclusion, we found no evidence of associations between patterns of lifestyle health behaviors and neuropathology. Other mechanisms may underlie protective effects of health behaviors against dementia.

Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients.

INTRODUCTION: White matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-ß1-42 (Aß42)-positive status. METHODS: Individual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume. RESULTS: VRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p < 0.001), external capsule (B = 0.052, p < 0.001), and middle cerebellar peduncle (B = 0.067, p < 0.001), and Aß42-positive status with WMH in posterior thalamic radiation (B = 0.097, p < 0.001) and splenium (B = 0.103, p < 0.001). DISCUSSION: Vascular risk factors and Aß42 pathology have distinct signature WMH patterns. This regional vulnerability may incite future studies into how arteriolosclerosis and Aß42 pathology affect the brain's white matter. HIGHLIGHTS: Key dementia etiologies may be associated with specific patterns of white matter hyperintensities (WMH). We related WMH locations to vascular risk and cerebral Aß42 status in 11 memory clinic cohorts. Aß42 positive status was associated with posterior WMH in splenium and posterior thalamic radiation. Vascular risk was associated with anterior and infratentorial WMH. Amyloid pathology and vascular risk have distinct signature WMH patterns.

Chronic traumatic encephalopathy neuropathologic change in former Australian rugby players.

AIMS: We applied the 2021 consensus criteria for both chronic traumatic encephalopathy neuropathological change and traumatic encephalopathy syndrome in a small case series of six former elite-level Australian rugby code players. METHODS: Neuropathological assessment of these cases was carried out at the Sydney and Victorian Brain Banks. Clinical data were collected via clinical interviews and health questionnaires completed by the participants and/or their next of kin, and neuropsychological testing was conducted with participants who were capable of completing this testing. RESULTS: All cases exhibited progressive cognitive impairment during life. Chronic traumatic encephalopathy neuropathological change was identified in four out of the six cases. However, coexisting neuropathologies were common, with limbic-predominant age-related TDP-43 encephalopathy and ageing-related tau astrogliopathy seen in all cases, intermediate or high Alzheimer's disease neuropathological change seen in four cases and hippocampal sclerosis seen in two of the six cases. CONCLUSION: The presence of multiple neuropathologies in these cases complicates clinical diagnostic efforts for traumatic encephalopathy syndrome. It will be important for further clinicopathological studies on larger groups to report all neuropathological comorbidities found in cases diagnosed with either chronic traumatic encephalopathy neuropathological change and/or traumatic encephalopathy syndrome.

Prevalence, distribution, and severity of cerebral amyloid angiopathy differ between Lewy body diseases and Alzheimer's disease.

Dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and Parkinson's disease (PD) collectively known as Lewy body diseases (LBDs) are neuropathologically characterised by α-synuclein deposits (Lewy bodies and Lewy neurites). However, LBDs also exhibit pathology associated with Alzheimer's disease (AD) (i.e. hyperphosphorylated tau and amyloid ß (Aß). Aß can be deposited in the walls of blood vessels in the brains of individuals with AD, termed cerebral amyloid angiopathy (CAA). The aim of this study was to investigate the type and distribution of CAA in DLB, PDD, and PD and determine if this differs from AD. CAA type, severity, and topographical distribution was assessed in 94 AD, 30 DLB, 17 PDD, and 11 PD cases, and APOE genotype evaluated in a subset of cases where available. 96.3% AD cases, 70% DLB cases and 82.4% PDD cases exhibited CAA (type 1 or type 2). However only 45.5% PD cases had CAA. Type 1 CAA accounted for 37.2% of AD cases, 10% of DLB cases, and 5.9% of PDD cases, and was not observed in PD cases. There was a hierarchical topographical distribution in regions affected by CAA where AD and DLB displayed the same distribution pattern that differed from PDD and PD. APOE ε4 was associated with severity of CAA in AD cases. Topographical patterns and severity of CAA in DLB more closely resembled AD rather than PDD, and as type 1 CAA is associated with clinical dementia in AD, further investigations are warranted into whether the increased presence of type 1 CAA in DLB compared to PDD are related to the onset of cognitive symptoms and is a distinguishing factor between LBDs. Possible alignment of the the topographical distribution of CAA and microbleeds in DLB warrants further investigation. CAA in DLB more closely resembles AD rather than PDD or PD, and should be taken into consideration when stratifying patients for clinical trials or designing disease modifying therapies.

Association of peripheral immunity and cerebral small vessel disease in older adults without dementia: A longitudinal study.

This study explored the associations between peripheral immunity with cerebral small vessel diseases. Older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative were investigated. Peripheral blood was obtained, and magnetic resonance imaging was performed to measure cerebral microbleeds (CMB), lacunar infarctions (LI), and white matter hyperintensities (WMH). Multivariable-adjusted regression models, linear mixed-effects models, and the Spearman correlations were used to evaluate the associations. At baseline, individuals with greater neutrophils (odds ratio [OR] =1.10, 95% confidence interval [CI] 1.00-1.20, p=0.042) and monocytes (OR=1.12, 95% CI 1.02-1.22, p=0.016) had higher WMH volume. On the contrary, a higher lymphocyte-to-monocyte ratio (LMR) was related to lower WMH volume (OR=0.91, 95% CI 0.82-1.00, p=0.041). Longitudinally, higher neutrophils (ρ=0.084, p=0.049) and NLR (ρ=0.111, p=0.009) predicted accelerated progression of WMH volume, while a greater LMR (ρ=-0.101, p=0.018) was linked to slower growth of WMH volume. Nevertheless, associations between peripheral immunity with CMB or LI were not observed at baseline and follow-up. Our study found that peripheral immune indexes could serve as convenient noninvasive biomarkers of WMH.

Apolipoprotein E Gene in α-Synucleinopathies: A Narrative Review.

In this narrative review, we delved into the intricate interplay between Apolipoprotein E (APOE) alleles (typically associated with Alzheimer's disease-AD) and alpha-synucleinopathies (aS-pathies), involving Parkinson's disease (PD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple-system atrophy (MSA). First, in-vitro, animal, and human-based data on the exacerbating effect of APOE4 on LB pathology were summarized. We found robust evidence that APOE4 carriage constitutes a risk factor for PDD-APOE2, and APOE3 may not alter the risk of developing PDD. We confirmed that APOE4 copies confer an increased hazard towards DLB, as well. Again APOE2 and APOE3 appear unrelated to the risk of conversion. Of note, in individuals with DLB APOE4, carriage appears to be intermediately prevalent between AD and PDD-PD (AD > DLB > PDD > PD). Less consistency existed when it came to PD; APOE-PD associations tended to be markedly modified by ethnicity. Finally, we failed to establish an association between the APOE gene and MSA. Phenotypic associations (age of disease onset, survival, cognitive-neuropsychiatric- motor-, and sleep-related manifestations) between APOE alleles, and each of the aforementioned conditions were also outlined. Finally, a synopsis of literature gaps was provided followed by suggestions for future research.

Persistence of Kii amyotrophic lateral sclerosis after the 2000s and its characteristic aging-related tau astrogliopathy.

Kii amyotrophic lateral sclerosis (ALS) is a unique disease that occurs in the southern portion of the Kii Peninsula and exhibits a dual pathology of TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy and tauopathy. The incidence of ALS in this region was very high in the 1960s, briefly decreased through the 1980s, but began increasing again after 2000 with a change of high-concentration geographic foci. It is unclear, however, whether the unique pathological features have changed along with the incidence changes. This study analyzed postmortem specimens from neuropathologically confirmed Kii ALS cases from the 1970s (n = 4) and those after 1999 (n = 12) from the southern Kii Peninsula or outside of the area. Our results confirm the continued occurrence of Kii ALS after 2000 in the southern Kii Peninsula and the preservation of disease-specific neuronal tau pathology, including the widespread occurrence throughout the brain and spinal cord, sparse neuropil threads, and predominance in superficial layers. Furthermore, we assessed the glial tau pathology of Kii and non-Kii ALS in accordance with the aging-related tau astrogliopathy classification method for the first time and detected a unique brainstem predominant appearance of gray matter aging-related tau astrogliopathy in Kii ALS cases, which may provide clues to pathogenetic mechanisms.

GRN mutation spectrum and genotype-phenotype correlation in Chinese dementia patients: data from PUMCH dementia cohort.

BACKGROUND: METHODS: The GRN mutations, especially of the loss of function type, are causative of frontotemporal dementia (FTD). However, several GRN variants can be found in other neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease. So far, there have been over 300 GRN mutations reported globally. However, the genetic spectrum and phenotypic characteristics have not been fully elucidated in Chinese population.The participants were from the dementia cohort of Peking Union Medical College Hospital (n=1945). They received history inquiry, cognitive evaluation, brain imaging and exome sequencing. The dementia subjects carrying the rare variants of the GRN were included in this study. Those with the pathogenic or likely pathogenic variants of other dementia-related genes were excluded. RESULTS: 14 subjects carried the rare variants of GRN. They were clinically diagnosed with behavioural variant of FTD (n=2), non-fluent/agrammatic variant primary progressive aphasia (PPA, n=3), semantic variant PPA (n=1), AD (n=6) and mixed dementia (n=2). 13 rare variants of GRN were found, including 6 novel variants (W49X, S226G, M152I, A91E, G79E and A303S). The most prevalent symptom was amnesia (85.7%, 12/14), followed by psychiatric and behavioural disorder (78.6%, 11/14). In terms of lobar atrophy, temporal atrophy/hypometabolism was the most common (85.7%, 12/14), followed by parietal atrophy/hypometabolism (78.6%, 11/14). CONCLUSION: The novel GRN variants identified in this study contribute to enrich the GRN mutation repertoire. There is phenotypic similarity and diversity among Chinese patients with the GRN mutations.

Neuropathologic Burden and Dementia in Nonagenarians and Centenarians: Comparison of 2 Community-Based Cohorts

BACKGROUND AND OBJECTIVES: The aim of this study was to compare 2 large clinicopathologic cohorts of participants aged 90+ and to determine whether the association between neuropathologic burden and dementia in these older groups differs substantially from those seen in younger-old adults. METHODS: Autopsied participants from The 90+ Study and Adult Changes in Thought (ACT) Study community-based cohort studies were evaluated for dementia-associated neuropathologic changes. Associations between neuropathologic variables and dementia were assessed using logistic or linear regression, and the weighted population attributable fraction (PAF) per type of neuropathologic change was estimated. RESULTS: The 90+ Study participants (n = 414) were older (mean age at death = 97.7 years) and had higher amyloid/tau burden than ACT <90 (n = 418) (mean age at death = 83.5 years) and ACT 90+ (n = 401) (mean age at death = 94.2 years) participants. The ACT 90+ cohort had significantly higher rates of limbic-predominant age-related TDP-43 encephalopathy (LATE-NC), microvascular brain injury (µVBI), and total neuropathologic burden. Independent associations between individual neuropathologic lesions and odds of dementia were similar between all 3 groups, with the exception of µVBI, which was associated with increased dementia risk in the ACT <90 group only (odds ratio 1.5, 95% CI 1.2-1.8, p < 0.001). Weighted PAF scores indicated that eliminating µVBI, although more prevalent in ACT 90+ participants, would have little effect on dementia. Conversely, eliminating µVBI in ACT <90 could theoretically reduce dementia at a similar rate to that of AD neuropathologic change (weighted PAF = 6.1%, 95% CI 3.8-8.4, p = 0.001). Furthermore, reducing LATE-NC in The 90+ Study could potentially reduce dementia to a greater degree (weighted PAF = 5.1%, 95% CI 3.0-7.3, p = 0.001) than either ACT cohort (weighted PAFs = 1.69, 95% CI 0.4-2.7). DISCUSSION: Our results suggest that specific neuropathologic features may differ in their effect on dementia among nonagenarians and centenarians from cohorts with different selection criteria and study design. Furthermore, microvascular lesions seem to have a more significant effect on dementia in younger compared with older participants. The results from this study demonstrate that different populations may require distinct dementia interventions, underscoring the need for disease-specific biomarkers.

[Dementia with Lewy bodies and Parkinson disease dementia, their diagnoses and treatment strategies].

Parkinson's disease (PD), which has characteristic motor symptoms such as tremor, muscle rigidity, and akinesia, and as the disease progresses, Lewy bodies spread throughout the brain, eventually causing Parkinson disease dementia (PDD). The clinical picture of PDD is similar to Dementia with Lewy bodies (DLB) and their pathological features are indistinguishable from each other. More than 80% of PD cases will eventually develop dementia and their prognosis are generally 3 to 4 years from the onset of dementia, regardless of disease duration or age of onset. We found that patients with severe olfactory impairment had lower cognitive function scores, more frequent onset of dementia, brain atrophy, and prominent cerebral metabolic abnormalities in a 3-year longitudinal study (Brain 135:161-169, 2012). This study demonstrated for the first time in the world that olfaction tests are useful in predicting dementia in PD, and similar results have been followed up worldwide. Based on these results, a randomized, double-blind, multicenter comparative study of donepezil in PD with severe olfactory dysfunction (DASH-PD study) was conducted and completed a 4-year follow-up period. The results were recently published showing the efficacy and safety of cholinesterase inhibitors for PD without dementia (eClinicalMedicine 51: 101571, 2022).

Histogram-based features track Alzheimer's progression in brain MRI.

Alzheimer's disease is a form of general dementia marked by amyloid plaques, neurofibrillary tangles, and neuron degeneration. The disease has no cure, and early detection is critical in improving patient outcomes. Magnetic resonance imaging (MRI) is important in measuring neurodegeneration during the disease. Computer-aided image processing tools have been used to aid medical professionals in ascertaining a diagnosis of Alzheimer's in its early stages. As characteristics of non and very-mild dementia stages overlap, tracking the progression is challenging. Our work developed an adaptive multi-thresholding algorithm based on the morphology of the smoothed histogram to define features identifying neurodegeneration and track its progression as non, very mild, mild, and moderate. Gray and white matter volume, statistical moments, multi-thresholds, shrinkage, gray-to-white matter ratio, and three distance and angle values are mathematically derived. Decision tree, discriminant analysis, Naïve Bayes, SVM, KNN, ensemble, and neural network classifiers are designed to evaluate the proposed methodology with the performance metrics accuracy, recall, specificity, precision, F1 score, Matthew's correlation coefficient, and Kappa values. Experimental results showed that the proposed features successfully label the neurodegeneration stages.

The influence of limbic-predominant age-related TDP-43 encephalopathy on argyrophilic grain disease: A voxel-based morphometry analysis of pathologically confirmed cases.

BACKGROUND: The influence of limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathological change (LATE-NC) on structural alterations in argyrophilic grain disease (AGD) have not been documented. This study aimed to investigate the morphological impact of LATE-NC on AGD through voxel-based morphometry (VBM) technique. MATERIALS AND METHODS: Fifteen individuals with pathologically verified AGD, comprising 6 with LATE-NC (comorbid AGD [cAGD]) and 9 without LATE-NC (pure AGD [pAGD]), along with 10 healthy controls (HC) were enrolled. Whole-brain 3D-T1-weighted images were captured and preprocessed utilizing the Computational Anatomy Toolbox 12. VBM was employed to compare gray matter volume among (i) pAGD and HC, (ii) cAGD and HC, and (iii) pAGD and cAGD. RESULTS: In comparison to HC, the pAGD group exhibited slightly asymmetric gray matter volume loss, particularly in the ambient gyrus, amygdala, hippocampus, anterior cingulate gyrus, and insula. Alternatively, the cAGD group exhibited greater gray matter volume loss, with a predominant focus on the inferolateral regions encompassing the ambient gyrus, amygdala, hippocampus, and the inferior temporal area, including the anterior temporal pole. The atrophy of the bilateral anterior temporal pole and right inferior temporal gyrus persisted when contrasting the pAGD and cAGD groups. CONCLUSION: Comorbidity with LATE-NC is linked to different atrophic distribution, particularly affecting the inferolateral regions in AGD. Consequently, the consideration of comorbid LATE-NC is crucial in individuals with AGD exhibiting more widespread temporal atrophy.

Transition to healthier lifestyle associated with reduced risk of incident dementia and decreased hippocampal atrophy.

BACKGROUND: Research has estimated the associations of lifestyle at one-time point with the risk of dementia and hippocampal volume, but the impact of lifestyle transition on dementia and hippocampal volume remains unclear. This study aims to examine the associations of lifestyle transition with the risk of dementia and hippocampal volume. METHODS: Based on data from the UK Biobank, a weighted lifestyle score was constructed by incorporating six lifestyle factors. Within each baseline lifestyle group (i.e., healthy, intermediate, and unhealthy), lifestyle transition was classified into decline, maintenance, and improvement. Cox proportional hazard regression was used to estimate the association of lifestyle transition and incident dementia (N = 16,305). A multiple linear regression model was used to estimate the association between lifestyle transition and hippocampal volume (N = 5849). RESULTS: During a median follow-up period of 8.6 years, 120 (0.7 %) dementia events were documented. Among participants with healthy baseline lifestyles, the improvement group had a lower risk of incident dementia (HR: 0.18, 95 % CI: 0.04-0.81) and a larger hippocampal volume (ß = 111.69, P = 0.026) than the decline group. Similar results were observed among participants with intermediate baseline lifestyles regarding dementia risk but not hippocampal volume. No benefits were observed in the improvement group among those with unhealthy baseline lifestyles. LIMITATIONS: A lower incidence of dementia than other cohort study and this may have resulted in an underestimation of the risk of dementia. CONCLUSIONS: Earlier transitions to healthier lifestyle were associated with reduced risk of incident dementia and decreased hippocampal atrophy.

Radiotherapy-induced vascular cognitive impairment 20 years after childhood brain tumor.

BACKGROUND: Studies have established that radiotherapy for childhood brain tumors (BTs) increases the risk of cerebrovascular disease (CVD); however, it is unclear how this will affect cognitive function. This study aimed to investigate the associations between radiotherapy-induced CVD, white matter hyperintensities (WMHs), and neurocognitive outcomes in adult survivors of childhood BTs. METHODS: In a cross-sectional setting, we conducted a national cohort that included 68 radiotherapy-treated survivors of childhood BTs after a median follow-up of 20 years. Markers of CVD and WMHs were evaluated using brain MRI, and the sum of CVD-related findings was calculated. Additionally, the associations among CVD findings, WMHs, and neuropsychological test results were analyzed. RESULTS: Of the 68 childhood BT survivors, 54 (79%) were diagnosed with CVD and/or WMHs at a median age of 27 years. CVD and/or WMHs were associated with lower scores for verbal intelligence quotient, performance intelligence quotient (PIQ), executive function, memory, and visuospatial ability (P < .05). Additionally, survivors with microbleeds had greater impairments in the PIQ, processing speed, executive function, and visuospatial ability (P < .05). WMHs and CVD burden were associated with greater difficulties in memory function and visuospatial ability (P < .05). Small-vessel disease burden was associated with PIQ scores, processing speed, working memory, and visuospatial ability. CONCLUSIONS: The study results suggest that markers of radiotherapy-induced CVD, the additive effect of CVD markers, and risk factors of dementia are associated with cognitive impairment, which may suggest that the survivors are at a high risk of developing early-onset dementia.