MRI-based axis-referenced morphometric model corresponding to lamellar organization for assessing hippocampal atrophy in dementia.

Research on the local hippocampal atrophy for early detection of dementia has gained considerable attention. However, accurately quantifying subtle atrophy remains challenging in existing morphological methods due to the lack of consistent biological correspondence with the complex curving regions like the hippocampal head. Thereby, this article presents an innovative axis-referenced morphometric model (ARMM) that follows the anatomical lamellar organization of the hippocampus, which capture its precise and consistent longitudinal curving trajectory. Specifically, we establish an "axis-referenced coordinate system" based on a 7 T ex vivo hippocampal atlas following its entire curving longitudinal axis and orthogonal distributed lamellae. We then align individual hippocampi by deforming this template coordinate system to target spaces using boundary-guided diffeomorphic transformation, while ensuring that the lamellar vectors adhere to the constraint of medial-axis geometry. Finally, we measure local thickness and curvatures based on the coordinate system and boundary surface reconstructed from vector tips. The morphometric accuracy is evaluated by comparing reconstructed surfaces with those directly extracted from 7 T and 3 T MRI hippocampi. The results demonstrate that ARMM achieves the best performance, particularly in the curving head, surpassing the state-of-the-art morphological models. Additionally, morphological measurements from ARMM exhibit higher discriminatory power in distinguishing early Alzheimer's disease from mild cognitive impairment compared to volume-based measurements. Overall, the ARMM offers a precise morphometric assessment of hippocampal morphology on MR images, and sheds light on discovering potential image markers for neurodegeneration associated with hippocampal impairment.

Predicting progression from subjective cognitive decline to mild cognitive impairment or dementia based on brain atrophy patterns.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder where pathophysiological changes begin decades before the onset of clinical symptoms. Analysis of brain atrophy patterns using structural MRI and multivariate data analysis are an effective tool in identifying patients with subjective cognitive decline (SCD) at higher risk of progression to AD dementia. Atrophy patterns obtained from models trained to classify advanced AD versus normal subjects, may not be optimal for subjects at an early stage, like SCD. In this study, we compared the accuracy of the SCD progression prediction using the 'severity index' generated using a standard classification model trained on patients with AD dementia versus a new model trained on ß-amyloid (Aß) positive patients with amnestic mild cognitive impairment (aMCI). METHODS: We used structural MRI data of 504 patients from the Swedish BioFINDER-1 study cohort (cognitively normal (CN), Aß-negative = 220; SCD, Aß positive and negative = 139; aMCI, Aß-positive = 106; AD dementia = 39). We applied multivariate data analysis to create two predictive models trained to discriminate CN individuals from either individuals with Aß positive aMCI or AD dementia. Models were applied to individuals with SCD to classify their atrophy patterns as either high-risk "disease-like" or low-risk "CN-like". Clinical trajectory and model accuracy were evaluated using 8 years of longitudinal data. RESULTS: In predicting progression from SCD to MCI or dementia, the standard, dementia-based model, reached 100% specificity but only 10.6% sensitivity, while the new, aMCI-based model, reached 72.3% sensitivity and 60.9% specificity. The aMCI-based model was superior in predicting progression from SCD to MCI or dementia, reaching a higher receiver operating characteristic area under curve (AUC = 0.72; P = 0.037) in comparison with the dementia-based model (AUC = 0.57). CONCLUSION: When predicting conversion from SCD to MCI or dementia using structural MRI data, prediction models based on individuals with milder levels of atrophy (i.e. aMCI) may offer superior clinical value compared to standard dementia-based models.

"Back to Braak": Role of Nucleus Reuniens and Subcortical Pathways in Alzheimer's Disease Progression.

BACKGROUND: Patients with Alzheimer's Disease (AD) exhibit structural alterations of the thalamus that correlate with clinical symptoms. However, given the anatomical complexity of this brain structure, it is still unclear whether atrophy affects specific thalamic nuclei and modulates the clinical progression from a prodromal stage, known as Mild Cognitive Impairment (MCI), to full-fledged AD. OBJECTIVES: To characterize the structural integrity of distinct thalamic nuclei across the AD spectrum, testing whether MCI patients who convert to AD (c-MCI) show a distinctive pattern of thalamic structural alterations compared to patients who remain stable (s-MCI). DESIGN: Investigating between-group differences in the volumetric features of distinct thalamic nuclei across the AD spectrum. SETTING: Prodromal and clinical stages of AD. PARTICIPANTS: We analyzed data from 84 healthy control subjects (HC), 58 individuals with MCI, and 102 AD patients. The dataset was obtained from the AD Neuroimaging Initiative (ADNI-3) database. The MCI group was further divided into two subgroups depending on whether patients remained stable (s-MCI, n=22) or progressed to AD (s-MCI, n=36) in the 48 months following the diagnosis. MEASUREMENTS: A multivariate analysis of variance (MANOVA) assessed group differences in the volumetric features of distinct thalamic nuclei obtained from magnetic resonance (MR) images. A stepwise discriminant function analysis identified which feature most effectively predicted the conversion to AD. The corresponding predictive performance was evaluated through a Receiver Operating Characteristic approach. RESULTS: AD and c-MCI patients showed generalized atrophy of thalamic nuclei compared to HC. In contrast, no significant structural differences were observed between s-MCI and HC subjects. Compared to s-MCI, c-MCI individuals displayed significant atrophy of the nucleus reuniens and a trend toward significant atrophy in the anteroventral and laterodorsal nuclei. The discriminant function analysis confirmed the nucleus reuniens as a significant predictor of AD conversion, with a sensitivity of 0.73 and a specificity of 0.69. CONCLUSIONS: In line with the pathophysiological relevance of the nucleus reuniens proposed by seminal post-mortem studies on patients with AD, we confirm the pivotal role of this nucleus as a critical hub in the clinical progression to AD. We also propose a theoretical model to explain the evolving dysfunction of subcortical brain networks in the disease process.

Graded Multidimensional Clinical and Radiologic Variation in Patients With Alzheimer Disease and Posterior Cortical Atrophy.

BACKGROUND AND OBJECTIVES: Alzheimer disease (AD) spans heterogeneous typical and atypical phenotypes. Posterior cortical atrophy (PCA) is a striking example, characterized by prominent impairment in visual and other posterior functions in contrast to typical, amnestic AD. The primary study objective was to establish how the similarities and differences of cognition and brain volumes within AD and PCA (and by extension other AD variants) can be conceptualized as systematic variations across a transdiagnostic, graded multidimensional space. METHODS: This was a cross-sectional, single-center, observational, cohort study performed at the National Hospital for Neurology & Neurosurgery, London, United Kingdom. Data were collected from a cohort of patients with PCA and AD, matched for age, disease duration, and Mini-Mental State Examination (MMSE) scores. There were 2 sets of outcome measures: (1) scores on a neuropsychological battery containing 22 tests spanning visuoperceptual and visuospatial processing, episodic memory, language, executive functions, calculation, and visuospatial processing and (2) measures extracted from high-resolution T1-weighted volumetric MRI scans. Principal component analysis was used to extract the transdiagnostic dimensions of phenotypical variation from the detailed neuropsychological data. Voxel-based morphometry was used to examine associations between the PCA-derived clinical phenotypes and the structural measures. RESULTS: We enrolled 93 participants with PCA (mean: age = 59.9 years, MMSE = 21.2; 59/93 female) and 58 AD participants (mean: age = 57.1 years, MMSE = 19.7; 22/58 female). The principal component analysis for PCA (sample adequacy confirmed: Kaiser-Meyer-Olkin = 0.865) extracted 3 dimensions accounting for 61.0% of variance in patients' performance, reflecting general cognitive impairment, visuoperceptual deficits, and visuospatial impairments. Plotting AD cases into the PCA-derived multidimensional space, and vice versa, revealed graded, overlapping variations between cases along these dimensions, with no evidence for categorical-like patient clustering. Similarly, the relationship between brain volumes and scores on the extracted dimensions was overlapping for PCA and AD cases. DISCUSSION: These results provide evidence supporting a reconceptualization of clinical and radiologic variation in these heterogenous AD phenotypes as being along shared phenotypic continua spanning PCA and AD, arising from systematic graded variations within a transdiagnostic, multidimensional neurocognitive geometry.

Rate of abnormalities in quantitative MR neuroimaging of persons with chronic traumatic brain injury.

BACKGROUND: Mild traumatic brain injury (mTBI) can result in lasting brain damage that is often too subtle to detect by qualitative visual inspection on conventional MR imaging. Although a number of FDA-cleared MR neuroimaging tools have demonstrated changes associated with mTBI, they are still under-utilized in clinical practice. METHODS: We investigated a group of 65 individuals with predominantly mTBI (60 mTBI, 48 due to motor-vehicle collision, mean age 47 ± 13 years, 27 men and 38 women) with MR neuroimaging performed in a median of 37 months post-injury. We evaluated abnormalities in brain volumetry including analysis of left-right asymmetry by quantitative volumetric analysis, cerebral perfusion by pseudo-continuous arterial spin labeling (PCASL), white matter microstructure by diffusion tensor imaging (DTI), and neurometabolites via magnetic resonance spectroscopy (MRS). RESULTS: All participants demonstrated atrophy in at least one lobar structure or increased lateral ventricular volume. The globus pallidi and cerebellar grey matter were most likely to demonstrate atrophy and asymmetry. Perfusion imaging revealed significant reductions of cerebral blood flow in both occipital and right frontoparietal regions. Diffusion abnormalities were relatively less common though a subset analysis of participants with higher resolution DTI demonstrated additional abnormalities. All participants showed abnormal levels on at least one brain metabolite, most commonly in choline and N-acetylaspartate. CONCLUSION: We demonstrate the presence of coup-contrecoup perfusion injury patterns, widespread atrophy, regional brain volume asymmetry, and metabolic aberrations as sensitive markers of chronic mTBI sequelae. Our findings expand the historic focus on quantitative imaging of mTBI with DTI by highlighting the complementary importance of volumetry, arterial spin labeling perfusion and magnetic resonance spectroscopy neurometabolite analyses in the evaluation of chronic mTBI.

Assessment of local sensitivity in incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) lesions in intermediate age-related macular degeneration (iAMD).

Lesions of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) are associated with disease progression in age-related macular degeneration. However, the corresponding functional impact of these precursor lesions is unknown.We present a cross-sectional study of four patients employing clinical-grade MAIA (stimulus size: 0.43°, ~125 µm) and adaptive optics scanning light ophthalmoscope (AOSLO, stimulus size 0.07°, ~20 µm) based microperimetry (MP) to assess the specific impact of iRORA lesions on retinal sensitivity.AOSLO imaging showed overall reduced photoreceptor reflectivity and patches of hyporeflective regions at drusen with interspersed hyper-reflective foci in iRORA regions. MAIA-MP yielded an average retinal sensitivity loss of -7.3±3.1 dB at iRORA lesions compared with the in-eye control. With AOSLO-MP, the corresponding sensitivity loss was 20.1±4.8 dB.We demonstrated that iRORA lesions are associated with a severe impairment in retinal sensitivity. Larger cohort studies will be necessary to validate our findings.

Retinal peri-arteriolar versus peri-venular amyloidosis, hippocampal atrophy, and cognitive impairment: exploratory trial.

The relationship between amyloidosis and vasculature in cognitive impairment and Alzheimer's disease (AD) pathogenesis is increasingly acknowledged. We conducted a quantitative and topographic assessment of retinal perivascular amyloid plaque (AP) distribution in individuals with both normal and impaired cognition. Using a retrospective dataset of scanning laser ophthalmoscopy fluorescence images from twenty-eight subjects with varying cognitive states, we developed a novel image processing method to examine retinal peri-arteriolar and peri-venular curcumin-positive AP burden. We further correlated retinal perivascular amyloidosis with neuroimaging measures and neurocognitive scores. Our study unveiled that peri-arteriolar AP counts surpassed peri-venular counts throughout the entire cohort (P < 0.0001), irrespective of the primary, secondary, or tertiary vascular branch location, with a notable increase among cognitively impaired individuals. Moreover, secondary branch peri-venular AP count was elevated in the cognitively impaired (P < 0.01). Significantly, peri-venular AP count, particularly in secondary and tertiary venules, exhibited a strong correlation with clinical dementia rating, Montreal cognitive assessment score, hippocampal volume, and white matter hyperintensity count. In conclusion, our exploratory analysis detected greater peri-arteriolar versus peri-venular amyloidosis and a marked elevation of amyloid deposition in secondary branch peri-venular regions among cognitively impaired subjects. These findings underscore the potential feasibility of retinal perivascular amyloid imaging in predicting cognitive decline and AD progression. Larger longitudinal studies encompassing diverse populations and AD-biomarker confirmation are warranted to delineate the temporal-spatial dynamics of retinal perivascular amyloid deposition in cognitive impairment and the AD continuum.

Quantifying chronic lesion expansion in multiple sclerosis: Exploring imaging markers for longitudinal assessment.

OBJECTIVES: Gradual expansion of multiple sclerosis lesions over time is known to have a significant impact on disease progression. However, accurately quantifying the volume changes in chronic lesions presents challenges due to their slow rate of progression and the need for longitudinal segmentation. Our study addresses this by estimating the expansion of chronic lesions using data collected over a 1-2 year period and exploring imaging markers that do not require longitudinal lesion segmentation. METHODS: Pre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 42 patients with MS. Lesion expansion, stratified by the severity of tissue damage as measured by mean diffusivity change, was analysed between baseline and 48 months (Progressive Volume/Severity Index, PVSI). Central brain atrophy (CBA) and the degree of tissue loss inside chronic lesions (measured by the change of T1 intensity and mean diffusivity (MD)) were used as surrogate markers. RESULTS: CBA measured after 2 years of follow-up estimated lesion expansion at 4 years with a high degree of accuracy (r = 0.82, p < 0.001, ROC area under the curve 0.92, sensitivity of 94 %, specificity of 85 %). Increased MD within chronic lesions measured over 2 years was strongly associated with future expansion (r = 0.77, p < 0.001, ROC area under the curve 0.87, sensitivity of 81 % and specificity of 81 %). In contrast, change in lesion T1 hypointensity poorly explained future PVSI (best sensitivity and specificity 60 % and 59 % respectively). INTERPRETATION: CBA and, to a lesser extent, the change in MD within chronic MS lesions, measured over a period of 2 years, can provide a reliable and sensitive estimate of the extent and severity of chronic lesion expansion.

Evaluation of the correlation between trigeminal nerve atrophy and trigeminal neuralgia using multimodal image fusion: A single-center retrospective study.

BACKGROUND: 3D-Slicer is an open-source medical image processing and visualization software. In the surgical treatment of trigeminal neuralgia, it is commonly used to predict the responsible vessels. However, there are few reports on the use of 3D-Slicer software to quantitatively measure the bilateral trigeminal nerve volume in patients with primary trigeminal neuralgia (PTN) based on the three-dimensional images. Therefore, this study aims to explore the role of three-dimensional fused images processed by 3D-Slicer in the evaluation of trigeminal nerve atrophy, providing an objective basis for the diagnosis of PTN. METHODS: 57 PTN patients who underwent microvascular decompression (MVD) or percutaneous balloon compression (PBC) surgery in Hebei general hospital between January 2020 and April 2023 were included. Additionally, 30 patients with facial spasms(HFS) were included as a control group. All patients underwent 3D-TOF-MRA and 3D-FIESTA sequence examinations. Comparisons of bilateral trigeminal nerve volumes within and between groups were conducted by performing image fusion using 3D-slicer. RESULTS: The volume of the affected trigeminal nerve in the MVD group (33.96 mm³±12.61 mm³) and PBC group (23.05 mm³±7.71 mm³) was smaller than that of the unaffected trigeminal nerve in the MVD group (39.61 mm³±12.83 mm³) and PBC group (26.14 mm³±6.42 mm³), as well as the average volume of the trigeminal nerve in the control group (40.27 mm³±10.25 mm³) (P<0.05). The differences in bilateral trigeminal ganglion volume (∆V) was significant between the MVD group (∆V=23.59 %±14.32 %) and the control group (∆V=14.64 %±10.00 %) (P<0.05). There was no statistical difference in the trigeminal nerve volume difference between the MVD group (∆V=23.59 %±14.32 %) and the PBC group (∆V=26.52 %±15.00 %) (P>0.05). CONCLUSION: Trigeminal nerve atrophy is correlated with primary trigeminal neuralgia. 3D-slicer software can quantitatively measure trigeminal nerve volume and assist in the diagnosis of primary trigeminal neuralgia based on the difference in bilateral trigeminal nerve volumes. However, trigeminal nerve atrophy is not associated with postoperative pain recurrence in patients.

Cortex-to-caudate volume ratio as a predictor of cognitive decline in Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Brain and cortical atrophy play crucial roles in supporting the clinical diagnosis of Alzheimer's disease (AD). This study hypothesized that the ratios of brain or cortical volume to subcortical gray matter structure volumes are potential imaging markers for cognitive alterations in AD dementia and amnestic mild cognitive impairment (aMCI). METHODS: Seventy-seven subjects diagnosed with AD dementia or aMCI underwent baseline neuropsychological testing, 2-year follow-up cognitive assessments, and high-resolution T1-weighted MRI scans. Total brain/cortical volume and subcortical gray matter structure volumes were automatically segmented and measured. Univariate and multiple linear regression analyses were conducted to determine the associations between volumetric ratios and interval changes in cognitive scores. RESULTS: The ratio of cortical volume to caudate volume showed the most significant association with changes in MoCA (B = 0.132, SE = 0.042, p = 0.002), MMSE (B = 0.140, SE = 0.040, p = 0.001), and CDR-SOB (B = -0.013, SE = 0.005, p = 0.007) scores over the 2-year follow-up period. These associations remained significant after adjusting for various covariates. Similar associations were observed for the ratios of cortical volume to putamen and globus pallidum volumes. CONCLUSIONS: The cortex-to-caudate volume ratio is significantly associated with cognitive decline in AD dementia and aMCI. This ratio may serve as a useful biomarker for monitoring disease progression and predicting cognitive outcomes. Our findings highlight the importance of considering the relative atrophy of cortical and subcortical structures in understanding AD pathology.

Association of Levels of CSF Osteopontin With Cortical Atrophy and Disability in Early Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: To evaluate CSF inflammatory markers with accumulation of cortical damage as well as disease activity in patients with early relapsing-remitting MS (RRMS). METHODS: CSF levels of osteopontin (OPN) and 66 inflammatory markers were assessed using an immune-assay multiplex technique in 107 patients with RRMS (82 F/25 M, mean age 35.7 ± 11.8 years). All patients underwent regular clinical assessment and yearly 3T MRI scans for 2 years while 39 patients had a 4-year follow-up. White matter lesion number and volume, cortical lesions (CLs) and volume, and global cortical thickness (CTh) were evaluated together with the 'no evidence of disease activity' (NEDA-3) status, defined by no relapses, no disability worsening, and no MRI activity, including CLs. RESULTS: The random forest algorithm selected OPN, CXCL13, TWEAK, TNF, IL19, sCD30, sTNFR1, IL35, IL16, and sCD163 as significantly associated with changes in global CTh. OPN and CXCL13 were most related to accumulation of atrophy after 2 and 4 years. In a multivariate linear regression model on CSF markers, OPN (p < 0.001), CXCL13 (p = 0.001), and sTNFR1 (p = 0.024) were increased in those patients with accumulating atrophy (adjusted R-squared 0.615). The 10 markers were added in a model that included all clinical, demographic, and MRI variables: OPN (p = 0.002) and IL19 (p = 0.022) levels were confirmed to be significantly increased in patients developing more CTh change over the follow-up (adjusted R-squared 0.619). CXCL13 and OPN also revealed the best association with NEDA-3 after 2 years, with OPN significantly linked to disability accumulation (OR 2.468 [1.46-5.034], p = 0.004) at the multivariate logistic regression model. DISCUSSION: These data confirm and expand our knowledge on the prognostic role of the CSF inflammatory profile in predicting changes in cortical pathology and disease activity in early MS. The data emphasize a crucial role of OPN.

Gray Matter Atrophy in a 6-OHDA-induced Model of Parkinson's Disease.

INTRODUCTION: Magnetic resonance imaging (MRI) based brain morphometric changes in unilateral 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) model can be elucidated using voxel-based morphometry (VBM), study of alterations in gray matter volume and Machine Learning (ML) based analyses. METHODS: We investigated gray matter atrophy in 6-OHDA induced PD model as compared to sham control using statistical and ML based analysis. VBM and atlas-based volumetric analysis was carried out at regional level. Support vector machine (SVM)-based algorithms wherein features (volume) extracted from (a) each of the 150 brain regions (b) statistically significant features (only) and (c) volumes of each cluster identified after application of VBM (VBM_Vol) were used for training the decision model. The lesion of the 6-OHDA model was validated by estimating the net contralateral rotational behaviour by the injection of apomorphine drug and motor impairment was assessed by rotarod and open field test. RESULTS AND DISCUSSION: In PD, gray matter volume (GMV) atrophy was noted in bilateral cortical and subcortical brain regions, especially in the internal capsule, substantia nigra, midbrain, primary motor cortex and basal ganglia-thalamocortical circuits in comparison with sham control. Behavioural results revealed an impairment in motor performance. SVM analysis showed 100% classification accuracy, sensitivity and specificity at both 3 and 7 weeks using VBM_Vol. CONCLUSION: Unilateral 6-OHDA induced GMV changes in both hemispheres at 7th week may be associated with progression of the disease in the PD model. SVM based approaches provide an increased classification accuracy to elucidate GMV atrophy.

Cerebellar gray matter and white matter damage among older adults with prediabetes.

AIMS: To investigate alterations in cerebrum and cerebellum in prediabetes. Cerebellar injury in diabetes is traceable, but it has not been systematically studied, and whether cerebellar injury occurs and the degree of damage in prediabetes are not known. METHODS: The current study investigated cerebral and cerebellar gray matter volume, white matter volume, white matter microstructure and white matter hyperintensity on T1-weighted, T2-weighted fluid-attenuated inversion recovery and diffusion tensor imaging scans in 78 individuals with normal glucose metabolism, 92 with prediabetes, and 108 with type 2 diabetes. RESULTS: Participants with prediabetes showed significant gray matter and white matter atrophy, microstructural damage in the cerebellar and cerebral regions. Additionally, widespread structural alterations were observed in the diabetic stage. The function of the damaged brain area was further decoded in Neurosynth, and the damaged cerebellar area with prediabetic lesions was closely related to motor function, while the area affected by diabetes was related to complex cognitive function in addition to motor function. CONCLUSIONS: Cerebellar injury had already appeared in the prediabetic stage, and cerebellar injury was aggravated in the diabetic stage; therefore, the cerebellum is a key area that is damaged early in the development of diabetes.

Neurofilaments and progranulin are related to atrophy in frontotemporal lobar degeneration - A transdiagnostic study cross-validating atrophy and fluid biomarkers.

INTRODUCTION: Frontotemporal lobar degeneration (FTLD) encompasses behavioral variant frontotemporal dementia (bvFTD), progressive supranuclear palsy, corticobasal syndrome/degeneration, and primary progressive aphasias (PPAs). We cross-validated fluid biomarkers and neuroimaging. METHODS: Seven fluid biomarkers from cerebrospinal fluid and serum were related to atrophy in 428 participants including these FTLD subtypes, logopenic variant PPA (lvPPA), Alzheimer's disease (AD), and healthy subjects. Atrophy was assessed by structural magnetic resonance imaging and atlas-based volumetry. RESULTS: FTLD subtypes, lvPPA, and AD showed specific profiles for neurofilament light chain, phosphorylated heavy chain, tau, phospho-tau, amyloid beta1-42 from serum/cerebrospinal fluid, and brain atrophy. Neurofilaments related to regional atrophy in bvFTD, whereas progranulin was associated with atrophy in semantic variant PPA. Ubiquitin showed no effects. DISCUSSION: Results specify biomarker and atrophy patterns in FTLD and AD supporting differential diagnosis. They identify neurofilaments and progranulin in interaction with structural imaging as promising candidates for monitoring disease progression and therapy. HIGHLIGHTS: Study cross-validated neuroimaging and fluid biomarkers in dementia. Five kinds of frontotemporal lobar degeneration and two variants of Alzheimer's disease. Study identifies disease-specific fluid biomarker and atrophy profiles. Fluid biomarkers and atrophy interact in a disease-specific way. Neurofilaments and progranulin are proposed as biomarkers for diagnosis and therapy.

Effects of sleep deprivation on brain atrophy in individuals with mild cognitive impairment and Alzheimer's disease.

Dementia, a prevalent condition in the United States, affecting millions of individuals and their families, underscores the importance of healthy cognitive ageing, which involves maintaining cognitive function and mental wellness as individuals grow older, promoting overall well-being and quality of life. Our original research study investigates the correlation between lifestyle factors and brain atrophy in individuals with mild cognitive impairment (MCI) or Alzheimer's disease (AD), as well as healthy older adults. Conducted over six months in West Texas, the research involved 20 participants aged 62-87. Findings reveal that sleep deprivation in MCI subjects and AD patients correlate with posterior cingulate cortex, hippocampal atrophy and total brain volume, while both groups exhibit age-related hippocampal volume reduction. Notably, fruit/vegetable intake negatively correlates with certain brain regions' volume, emphasizing the importance of diet. Lack of exercise is associated with reduced brain volume and hippocampal atrophy, underlining the cognitive benefits of physical activity. The study underscores lifestyle's significant impact on cognitive health, advocating interventions to promote brain health and disease prevention, particularly in MCI/AD cases. While blood profile data showed no significant results regarding cognitive decline, the study underscores the importance of lifestyle modifications in preserving cognitive function.

Poly­d,l­lactic acid­enhanced atrophic scar treatment via transdermal microjet drug delivery in Asians.

BACKGROUND: Acne vulgaris often results in permanent scars, with atrophic scars being the most common type and posing a significant therapeutic challenge due to their prevalence and impact on patients' quality of life. Various treatment options exist, including the use of poly-d,l-lactic acid delivered via different methods. OBJECTIVE: This study aimed to assess the efficacy and safety of poly-d,l-lactic acid delivered via laser-assisted needle-free microjet injection for treating atrophic scars. METHODS: Five Korean participants with atrophic facial scars were recruited. Poly-d,l-lactic acid solution was administered via the Mirajet system in five sessions, with clinical assessments conducted at baseline, before each session, and at 12-week and 22-week follow-ups. Outcome measures included the Global Aesthetic Improvement Scale and patient satisfaction scores. RESULTS: Positive results were observed at the 12-week and 22-week follow-ups, with high patient satisfaction and improvements in atrophic scars and skin texture. Mild discomfort and transient side effects were reported, with no adverse events observed during the follow-up period. CONCLUSION: Poly-d,l-lactic acid delivered by a laser-assisted needle-free microjet injector was judged to be effective for improving atrophic the facial area. Further research, particularly through randomized controlled trials, is needed to validate these findings and assess the longer-term safety and sustainability of outcomes.

Diabetes accelerates Alzheimer's disease progression in the first year post mild cognitive impairment diagnosis.

BACKGROUND: Mild cognitive impairment (MCI) heightens Alzheimer's disease (AD) risk, with diabetes mellitus (DM) potentially exacerbating this vulnerability. This study identifies the optimal intervention period and neurobiological targets in MCI to AD progression using the Alzheimer's Disease Neuroimaging Initiative dataset. METHODS: Analysis of 980 MCI patients, categorized by DM status, used propensity score matching and inverse probability treatment weighting to assess rate of conversion from MCI to AD, neuroimaging, and cognitive changes. RESULTS: DM significantly correlates with cognitive decline and an increased risk of progressing to AD, especially within the first year of MCI follow-up. It adversely affects specific brain structures, notably accelerating nucleus accumbens atrophy, decreasing gray matter volume and sulcal depth. DISCUSSION: Findings suggest the first year after MCI diagnosis as the critical window for intervention. DM accelerates MCI-to-AD progression, targeting specific brain areas, underscoring the need for early therapeutic intervention. HIGHLIGHTS: Diabetes mellitus (DM) accelerates mild cognitive impairment (MCI)-to-Alzheimer's disease (AD) progression within the first year after MCI diagnosis. DM leads to sharper cognitive decline within 12 months of follow-up. There is notable nucleus accumbens atrophy observed in MCI patients with DM. DM causes significant reductions in gray matter volume and sulcal depth. There are stronger correlations between cognitive decline and brain changes due to DM.

Genetic evidence for the causal relationships between migraine, dementia, and longitudinal brain atrophy.

BACKGROUND: Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR). METHODS: We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer's disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis. RESULTS: The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10- 4). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10- 4) and thalamic volume (-9.507 cm3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10- 3). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10- 9) and accelerated annual atrophy of the total cortical surface area (-31.401 cm2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10- 6). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect. DISCUSSION: This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients.

Potential role of blood pressure variability and plasma neurofilament light in the mechanism of comorbidity between Alzheimer's disease and cerebral small vessel disease.

INTRODUCTION: Long-term blood pressure variability (BPV) and plasma neurofilament light (pNfL) have been identified as potential biomarkers for Alzheimer's disease (AD) and cerebral small vessel disease (CSVD). However, the relationship between BPV, pNfL, and their association with the comorbidity of AD and CSVD remains unknown. METHODS: Participants with normal cognition and mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study were included in the data analysis. Linear mixed-effects regression models and causal mediation analyses were conducted to investigate the relationship among BPV, pNfL, comorbidity-related brain structural changes (hippocampal atrophy and white matter hyperintensities [WMH]), and cognitive function. RESULTS: BPV was associated with pNfL, volumes of hippocampus and WMH, and cognition. pNfL mediated the effects of BPV on brain structural changes and cognition. DISCUSSION: Our findings suggest a potential role of BPV and pNfL in the mechanism of comorbidity between AD and CSVD, underscoring the importance of BPV intervention in the general population. HIGHLIGHTS: Individuals with both Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) pathologies had elevated blood pressure variability (BPV) and plasma neurofilament light (pNfL). The association between different components of BPV and brain structural changes may vary. BPV was associated with pNfL levels independent of average blood pressure. pNfL mediated the effects of BPV on comorbidity-related brain structural changes and cognitive performance.

Association of Basal Forebrain Atrophy With Cognitive Decline in Early Alzheimer Disease.

BACKGROUND AND OBJECTIVES: In early Alzheimer disease (AD), ß-amyloid (Aß) deposition is associated with volume loss in the basal forebrain (BF) and cognitive decline. However, the extent to which Aß-related BF atrophy manifests as cognitive decline is not understood. This study sought to characterize the relationship between BF atrophy and the decline in memory and attention in patients with early AD. METHODS: Participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who completed Aß-PET imaging and repeated MRI and cognitive assessments were included. At baseline, participants were classified based on their clinical dementia stage and Aß status, yielding groups that were cognitively unimpaired (CU) Aß-, CU Aß+, and mild cognitive impairment (MCI) Aß+. Linear mixed-effects models were used to assess changes in volumetric measures of BF subregions and the hippocampus and changes in AIBL memory and attention composite scores for each group compared with CU Aß- participants. Associations between Aß burden, brain atrophy, and cognitive decline were evaluated and explored further using mediation analyses. RESULTS: The cohort included 476 participants (72.6 ± 5.9 years, 55.0% female) with longitudinal data from a median follow-up period of 6.1 years. Compared with the CU Aß- group (n = 308), both CU Aß+ (n = 107) and MCI Aß+ (n = 61) adults showed faster decline in BF and hippocampal volumes and in memory and attention (Cohen d = 0.73-1.74). Rates of atrophy in BF subregions and the hippocampus correlated with cognitive decline, and each individually mediated the impact of Aß burden on memory and attention decline. When all mediators were considered simultaneously, hippocampal atrophy primarily influenced the effect of Aß burden on memory decline (ß [SE] = -0.139 [0.032], proportion mediated [PM] = 28.0%) while the atrophy of the posterior nucleus basalis of Meynert in the BF (ß [SE] = -0.068 [0.029], PM = 13.1%) and hippocampus (ß [SE] = -0.121 [0.033], PM = 23.4%) distinctively influenced Aß-related attention decline. DISCUSSION: These findings highlight the significant role of BF atrophy in the complex pathway linking Aß to cognitive impairment in early stages of AD. Volumetric assessment of BF subregions could be essential in elucidating the relationships between the brain structure and behavior in AD.