Degree Of Hippocampal Atrophy Research Articles

APOE ε4-associated downregulation of the IL-7/IL-7R pathway in effector memory T cells: Implications for Alzheimer's disease.

The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.

Role of T2 relaxometry in localization of mesial temporal sclerosis and the degree of hippocampal atrophy in patients with intractable temporal lobe epilepsy: A cross sectional study.

Mesial temporal lobe epilepsy is one of the most common causes of refractory epilepsy worldwide. A good percentage of patients do not have detectable hippocampal atrophy on magnetic resonance imaging (MRI). The objective of this study is to evaluate whether T2 relaxometry can identify hippocampal pathology and lateralize the epileptic focus in patients with intractable temporal lobe epilepsy (TLE). T2 relaxometry can also be used to correlate the clinical severity of the disease with the relaxometry readings in those who have hippocampal atrophy as well as those who do not. Thirty two patients having clinical and electrophysiological features of TLE were enrolled and a MRI brain with T2 relaxometry was done. Hippocampal T2 relaxometry values were calculated in the head, body, and tail of the hippocampus and average T2 relaxometry values were calculated, and a comparison was done with the controls. For patients with unilateral involvement, the contralateral side was taken as control and in cases of bilateral involvement, controls were identified from normal subjects. T2 relaxometry is found to be superior to MR visual analysis in the early detection of cases of hippocampal sclerosis where there is no atrophy on visual analysis. Nine out of 32 patients (28%) were normal on MR visual analysis; however, showed increased values on T2 relaxometry, correlating with clinical and electrophysiological diagnosis. The rest of the patients with hippocampal atrophy showed a correlation of T2 relaxometry values with the degree of atrophy. The hippocampal T2 measurement is thus more sensitive and specific. The study was clinically significant (p < .0001). There was a mild female predilection of the disease and there was no significant correlation with comorbidities. There was a strong positive correlation with patients having a history of febrile seizures in childhood. T2 relaxometry may accurately lateralize the majority of patients with persistent TLE and offers evidence of hippocampus injury in those patients who do not show evidence of atrophy on MRI and also the T2 relaxometry values correlated with the degree of atrophy. Early identification of hippocampal sclerosis is crucial for prompt management which offers better outcomes.

Relationship between neuropsychological test scores and hippocampal atrophy in non-demented Japanese older adults

BackgroundIt is essential to detect morphological changes in the brain prior to the onset of cognitive decline. Although hippocampal volumes have been reported to be correlated with scores on neuropsychological tests, this relationship is still unclear among Japanese non-demented older adults. Thus, this exploratory retrospective study aimed to identify neuropsychological tests that correlate with the degree of hippocampal atrophy in Japanese non-demented older adults. MethodsThirteen non-demented Japanese older adults aged 71.2 ± 5.2 years were included. Hippocampal atrophy was evaluated by assessing the participants’ MRI scans using the voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) software. Spearman’s partial correlation analyses were conducted to reveal relationships between VSRAD scores and neuropsychological test scores, including Raven’s Colored Progressive Matrices test (RCPM), the Standard Verbal Paired Associate Learning test (SP-A), and the Trail Making Test (TMT) scores by controlling for age, sex, and years of education. ResultsThe Spearman’s partial correlation analysis results revealed that there were significant correlations between the degree of hippocampal atrophy and RCPM (rho = -0.691, p = 0.027), TMT part B (rho = 0.823, p = 0.003), and the related SP-A test scores (rho = -0.663, p = 0.027). ConclusionsOur results indicate that neuropsychological tests, particularly the TMT part B, might be used in assessing the degree of hippocampal atrophy in non-demented Japanese elderly individuals and should be studied further in the future to develop screening methods to detect brain atrophy.

MO392: Mildly Impaired Kidney Function May Be Associated With the Risk of Hippocampal Atrophy in Young and Midlife Adults

Abstract BACKGROUND AND AIMS To date, associations between kidney function and brain structural abnormalities have been described in several studies [1]. Reports of renal function in relation to hippocampal atrophy have been scarce and the majority of studies have been focussed on older end-stage renal disease populations [2]. Particularly, with the ageing process, the hippocampus has a greater propensity to atrophy than other cerebral structures.The purpose of this study was to evaluate the relationship between kidney function assessed by estimated glomerular filtration rate (eGFR) and the degrees of hippocampal atrophy among young and midlife adults. METHOD In this cross-sectional study, the risk factors for hippocampal atrophy were evaluated in a cohort of 219 non-diabetic chronic kidney disease (CKD) patients, age ≤ 55 years, who had undergone magnetic resonance imaging (MRI) of the brain. The eGFR was calculated using the CKD-EPI formula. Hippocampal volume (HV) was assessed in brain MRIs with the Scheltens’ Medial Temporal Atrophy score, including a 5-stage escalation—0: no atrophy, 1: only widening of choroid fissure, 2: also widening of the temporal horn of lateral ventricle, 3: moderate loss of HV (decrease in height) and 4: severe loss of HV [3]. RESULTS In our group, the median and interquartile ranges (IQR) of age was 45 (14) years, 57.53% (126 patients) being males. The median eGFR was 100.6 (34.7) mL/min/1.73m2 and 46.75% (102 patients) presented with mild reduction in eGFR (eGFR between 60 to 89 mL/min/1.73m2). In univariable regression analysis, eGFR (R2 = 0.207, P &amp;lt; 0.001), arterial hypertension (R2 = 0.018, P = 0.045), dyslipidaemia (R2 = 0.044, P = 0.002), haematocrit (R2 = 0.021, P = 0.032), natrium levels (R2 = 0.018, P = 0.047), and potassium levels ( R2 = 0.019, P = 0.042) were associated with smaller HV. In multivariable regression analysis, eGFR [odds ratio (OR), 0.95; 95% confidence interval (CI), 0.94–0.97; P &amp;lt; 0.001) and serum natrium (OR, 0.91; 95% CI, 0.83–0.98; P = 0.027) were significantly associated with hippocampal atrophy. CONCLUSION This cross-sectional study shows that mild decrease in eGFR is independently associated with hippocampal atrophy. Our results suggest that brain imaging tests should be routinely performed in patients with mild reduction of eGFR, as the hippocampal atrophy process appears to be due, in part, to the mild renal dysfunction itself.

Post-Mortem 7.0-Tesla Magnetic Resonance Imaging of the Hippocampus in Progressive Supranuclear Palsy with and without Cerebral Amyloid Angiopathy

Introduction and Purpose: Cerebral amyloid angiopathy (CAA) can be observed in patients with progressive supranuclear palsy (PSP), though to a lesser degree than in Alzheimer’s disease. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) evaluates whether CAA has an influence on the degree of hippocampal atrophy (HA) and on the incidence of associated micro-infarcts (HMIs) and cortical micro-bleeds (HMBs). Material and Methods: Eight brains with PSP-CAA were compared to 20 PSP brains without CAA. In addition to the neuropathological examination, the hippocampus was evaluated on the most representative coronal section with T2 and T2*-weighted MRI sequences. The average degree of HA was determined in both groups. The incidence of HMIs and HMBs was also compared as well as the frequency of cortical micro-infarcts (CoMIs) and cortical micro-bleeds (CoMBs) in the hemispheric neocortex. Results: The neuropathological examination showed a higher incidence of lacunar infarcts in the PSP-CAA brains compared to the PSP ones. With magnetic resonance imaging (MRI), the severity of HA and the incidence of HMIs and HMBs was similar between both groups. Additionally, the frequency of CoMIs and CoMBs in the neocortex was comparable. Conclusions: The association of CAA in PSP brains has no influence on the degree of HA and on the incidence of the small cerebrovascular lesions in the hippocampus as well as in the neocortex.

Post-mortem 7.0-Tesla Magnetic Resonance Imaging of the Hippocampus in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is reported to be probably linked to frontotemporal lobar degeneration (FTLD). Since FTLD is characterized by severe frontotemporal degeneration along with hippocampal atrophy (HA), the present study used post-mortem 7.0-tesla magnetic resonance imaging to investigate whether a certain degree of HA occurs in the ALS brains as well. The examined post-mortem brain samples comprised 9 from the ALS cases and 17 from the age-matched controls. The hippocampus samples were examined on the most representative coronal section using T2 and T2* MRI sequences, and the average degree of HA was determined for both groups. The occurrence of hippocampal micro-infarcts (HMIs) and hippocampal micro-bleeds (HMBs), as well as the frequency of cortical micro-infarcts (CoMIs) and cortical micro-bleeds (CoMBs) in the neocortex, were compared between the groups. Considerable HA was observed in the ALS group compared to the control group. The incidence of HMIs and HMBs was low and comparable in the ALS and control groups. Moreover, the frequency of CoMIs and CoMBs in the neocortex was relatively comparable in the two groups. This post-mortem observation of HA is an additional argument in favor of the link between ALS and FTLD. Furthermore, both ALS and FTLD share a low vascular risk profile.

Comparison of Post-mortem 7.0-Tesla Magnetic Resonance Imaging of the Brains of Alzheimer Patients with and without Cerebral Amyloid Angiopathy

Purpose: The influence of cerebral amyloid angiopathy (CAA) in Alzheimer’s disease (AD) remains unexplored. The present post-mortem study investigated possible differences in the degree of hippocampal atrophy (HA) between AD patients with and without CAA using 7.0-tesla magnetic resonance imaging (MRI). Also, the incidence of the hippocampal cortical micro-infarcts (HCoMIs) and hippocampal cortical micro-bleeds (HCoMBs) is compared to those in the neocortex. Methods: The examined post-mortem brains included 30 AD-CAA cases and 20 AD without CAA cases. The samples of the hippocampus were evaluated on the most representative coronal section with T2 and T2* MRI sequences. The average degree of HA was determined in both groups. The incidences of HCoMIs and HCoMBs, along with the frequency of CoMIs and CoMBs in the neocortex were compared in both groups: AD-with CAA and AD without CAA cases. Results: No significant differences were observed in the degree of HA and the incidence of hippocampal micro-infarcts (HMIs) and hippocampal micro-bleeds (HMBs) between the AD-CAA and the AD brains in contrast to the higher incidence of these cerebrovascular lesions in the neocortex of AD-CAA brains. The incidence of CoMIs and CoMBs in the neocortex showed similarity to that in the hippocampus of AD patients without CAA. Conclusions: CAA does not influence the degree of HA and the incidence of micro-infarcts (MIs) and micro-bleeds (MBs) in the hippocampus, in contrast to the high contribution of the latter with CAA in the neocortex. The hippocampus seems to be more spared from cerebrovascular involvement than the other parts of the brain.

Plasma Biomarkers Ascertained With Immunomagnetic Reduction Diagnosing Early-Stage Alzheimer's Disease: A Systematic Review

ABSTRACT Introduction Alzheimer's disease (AD) will become a prominent public health issue in the future given its cognitively debilitating nature. As the advent of global ageing society is expected, AD may bring tremendous socioeconomical costs if current diagnosis methods stay put. In this article, we performed a systematic review of a recent (less than 10 years) ultrasensitive technology, the immunomagnetic reduction (IMR), which shows promising potential of early diagnosis of AD. Methods We searched the Pubmed and Embase databases for studies that included keywords “early-stage Alzheimer's disease” and “immunomagnetic signal reduction.” Results After full-text review, a total of 7 studies were included for final analysis. Most included studies have reported on Aβ40, Aβ42, t-tau, and levels of these biomarkers in the plasma of early AD patients comparing those in the healthy population. The ranges of the mean Aβ40 levels are as follows: 59.2 to 60.9 for control groups and 36.9 to 39.5 pg/mL for AD. Aβ42 and t-tau concentrations are both markedly lower than Aβ40, Aβ42 at 15.5 to 16.1 for control groups and 17.9 to 19 pg/mL for AD; t-tau levels were 13.5 to 14.3 for control groups and 39.4 to 46.7 pg/mL for AD. There is a significant increasing level of plasma Aβ42 by IMR assays in early AD patients across nearly all the included studies. There is a possible relationship between plasma levels of IMR AD biomarkers and (1) degree of hippocampal atrophy using magnetic resonance imaging, and (2) amount of brain amyloid accumulation using positron emission tomography. Conclusion IMR assay is an ultrasensitivity technique that is useful for detection of early AD, which can provide benefits on understanding the disease progression of AD and encourage early medical invention for AD patients.

Utility of Plasma Neurofilament Light in the 1Florida Alzheimer's Disease Research Center (ADRC).

Background:Plasma NfL (pNfL) levels are elevated in many neurological disorders. However, the utility of pNfL in a clinical setting has not been established.Objective:In a cohort of diverse older participants, we examined: 1) the association of pNfL to age, sex, Hispanic ethnicity, diagnosis, and structural and amyloid imaging biomarkers; and 2) its association to baseline and longitudinal cognitive and functional performance.Methods:309 subjects were classified at baseline as cognitively normal (CN) or with cognitive impairment. Most subjects had structural MRI and amyloid PET scans. The most frequent etiological diagnosis was Alzheimer’s disease (AD), but other neurological and neuropsychiatric disorders were also represented. We assessed the relationship of pNfL to cognitive and functional status, primary etiology, imaging biomarkers, and to cognitive and functional decline.Results:pNfL increased with age, degree of hippocampal atrophy, and amyloid load, and was higher in females among CN subjects, but was not associated with Hispanic ethnicity. Compared to CN subjects, pNfL was elevated among those with AD or FTLD, but not those with neuropsychiatric or other disorders. Hippocampal atrophy, amyloid positivity and higher pNfL levels each added unique variance in predicting greater functional impairment on the CDR-SB at baseline. Higher baseline pNfL levels also predicted greater cognitive and functional decline after accounting for hippocampal atrophy and memory scores at baseline.Conclusion:pNfL may have a complementary and supportive role to brain imaging and cognitive testing in a memory disorder evaluation, although its diagnostic sensitivity and specificity as a stand-alone measure is modest. In the absence of expensive neuroimaging tests, pNfL could be used for differentiating neurodegenerative disease from neuropsychiatric disorders.

Influences of Folate Supplementation on Homocysteine and Cognition in Patients with Folate Deficiency and Cognitive Impairment.

Although folate deficiency was reported to be associated with hyperhomocysteinemia, influence of folate supplementation on cognition remains controversial. Therefore, we explored the effects of folate supplementation on the cognition and Homocysteine (Hcy) level in relatively short periods in patients with folate deficiency and cognitive impairment. Enrolled 45 patients (mean age of 79.7 ± 7.9 years old) with folate deficiency (<3.6 ng/mL) with cognitive impairment underwent Mini-Mental State Examination (MMSE), and laboratory examinations, including folate, vitamin B12, and Hcy. The degree of hippocampal atrophy in MRI was estimated using a voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD). Patients were administrated folate (5 mg/day), then Hcy, and MMSE score were re-examined after 28 to 63 days. Mean Hcy significantly decreased from 25.0 ± 18.0 to 11.0 ± 4.3 nmol/mL (p < 0.001). Average MMSE scores also significantly changed from 20.1 ± 4.7 to 22.2 ± 4.3 (p < 0.001). The degree of change in the MMSE score and basic Hcy or Hcy change was significantly positively correlated, while degree of hippocampal atrophy in MRI did not. Although several factors should be taken into account, folate supplementation ameliorated cognitive impairment, at least for a short period, in patients with folate deficiency.

Hippocampal magnetic resonance imaging morphometry and neuropsychological parameters in patients with Alzheimer's disease

Alzheimer's disease (AD) is the leading cause of dementia in the population. Difficulties in diagnosing AD have served as an incentive for actively studying different current methods that increase the accuracy of diagnosis of the current neurodegenerative process in this disease. One of these areas is the post-processing of magnetic resonance imaging (MRI) data, by exactly calculating the volume of various anatomical formations, namely MRI morphometry.Objective:to determine the possible relationship between the results of evaluating the higher brain functions and the reduction in the hippocampal volume calculated by MRI morphometry in AD patients with mild and moderate dementia and in healthy controls.Patients and methods.Examinations were made in 41 AD patients aged 70.63±8.38 years with mild and moderate dementia and in healthy individuals. All study participants underwent neuropsychological testing that included the Mini-Mental State Examination (MMSE), the frontal lobe dysfunction battery (FLDB); immediate and delayed 12-word recall trials (12-word test); Benton's revised visual retention test; test of literal and categorical associations; clock drawing test; and series number test, Part A. MRI was performed on a Siemens Magnetom Skyra 3T MRI scanner. Statistical Parametric Mapping software was used to convert images and the volume of the hippocampus was estimated by FMRIB Software Library.Results and discussion.A statistically significant decrease in hippocampal volumes was established in patients with AD compared with healthy individuals. No statistically significant differences in hippocampal volumes were found in patients with varying degrees of dementia. Patients with mild and moderate dementia differed in all indicators of neuropsychological tests, with exception for the 12-word test and Benton's test. There was a statistically significant correlation of the total volume of the hippocampi with the indicators of MMSE, FLDB, 12- word test, clock drawing test, and test of categorical associations.Conclusion.Hippocampal MRI morphometry in combination with neuropsychological tests is an informative technique in the diagnosis of AD. There is a relationship between the degree of hippocampal atrophy and the neuropsychological characteristics of patients.

EEG Patterns in Patients With Calcified Neurocysticercosis With or Without Hippocampal Atrophy

To assess whether hippocampal atrophy develops in conjunction with clinical or subclinical epileptiform or encephalopathic activity in subjects with neurocysticercosis (NCC). Using a population-based and nested case-control study design, scalp EEGs and brain MRIs were performed in Atahualpa residents aged ≥40 years, who have imaging-confirmed NCC (case patients), as well as in age- and sex-matched NCC-free control subjects. Sixty-two case patients and 62 control subjects were included. Encephalopathic EEG patterns were more common in five NCC subjects with epilepsy than in those without a history of seizures. Epileptiform EEG activity was noted in one patient with NCC but in none of the control subjects. This subject's focal epileptiform discharges correlated with the location of calcified cysticerci in the brain parenchyma, and the hippocampus ipsilateral to the epileptiform discharges was more atrophic than the contralateral hippocampus. The degree of hippocampal atrophy in patients with NCC without a history of seizures was significantly greater than in control subjects (P < 0.01) and tended to be even greater in patients with NCC with a history of seizures. Hippocampal atrophy may not be exclusively related to seizure activity in patients with NCC. Other mechanisms, such as recurrent bouts of inflammation around calcified cysticerci, might explain the association between NCC and hippocampal atrophy.

Effects of amyloid pathology and neurodegeneration on cognitive change in cognitively normal adults.

Understanding short-term cognitive decline in relation to Alzheimer's neuroimaging biomarkers in early stages of the development of neuropathology and neurodegeneration will inform participant recruitment and monitoring strategies in clinical trials aimed at prevention of cognitive impairment and dementia. We assessed associations among neuroimaging measures of cerebral amyloid pathology, a hallmark Alzheimer's neuropathology, hippocampal atrophy, and prospective cognition among 171 cognitively normal Baltimore Longitudinal Study of Aging participants (baseline age 56-95 years, 48% female, 562 cognitive assessments, 3.7 years follow-up). We categorized each individual based on dichotomous amyloid pathology (A) and hippocampal neurodegeneration (N) status at baseline: A-N-, A+N-, A-N+, A+N+. We conducted linear mixed effects analyses to assess cross-sectional and longitudinal trends in cognitive test z-scores by amyloid and neurodegeneration group. To investigate the effects of amyloid dose and degree of hippocampal atrophy, we assessed the associations of continuous mean cortical amyloid level and hippocampal volume with cognitive performance among individuals with detectable amyloid pathology at baseline. Individuals with amyloidosis or hippocampal atrophy had steeper longitudinal declines in verbal episodic memory and learning compared to those with neither condition (A+N- versus A-N-: β = - 0.069, P = 0.017; A-N+ versus A-N-: β = - 0.081, P = 0.025). Among individuals with hippocampal atrophy, amyloid positivity was associated with steeper declines in verbal memory (β = - 0.123, P = 0.015), visual memory (β = - 0.121, P = 0.036), language (β = - 0.144, P = 0.0004), and mental status (β = - 0.242, P = 0.002). Similarly, among individuals with amyloidosis, hippocampal atrophy was associated with steeper declines in verbal memory (β = - 0.135, P = 0.004), visual memory (β = - 0.141, P = 0.010), language (β = - 0.108, P = 0.006), and mental status (β = - 0.165, P = 0.022). Presence of both amyloidosis and hippocampal atrophy was associated with greater declines than would be expected by their additive contributions in visual memory (β = - 0.139, P = 0.036), language (β = - 0.132, P = 0.005), and mental status (β = - 0.170, P = 0.049). Neither amyloidosis nor hippocampal atrophy was predictive of declines in executive function, processing speed, or visuospatial ability. Among individuals with amyloidosis, higher baseline amyloid level was associated with lower concurrent visual memory, steeper declines in language, visuospatial ability, and mental status, whereas greater hippocampal atrophy was associated with steeper declines in category fluency. Our results suggest that both amyloid pathology and neurodegeneration have disadvantageous, in part synergistic, effects on prospective cognition. These cognitive effects are detectable early among cognitively normal individuals with amyloidosis, who are in preclinical stages of Alzheimer's disease according to research criteria. Our findings highlight the importance of early intervention to target both amyloidosis and atrophy to preserve cognitive function before further damage occurs.

DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy in Alzheimer’s disease and amnesic mild cognitive impairment patients

Several studies have noted an effect of DNA methylation on the pathogenesis of Alzheimer’s disease (AD). We have already reported that DNA methylation levels in the NCAPH2/LMF2 promoter region can be a useful biomarker for the diagnosis of AD and amnesic mild cognitive impairment (aMCI). However, there is still uncertainty about the mechanism by which NCAPH2/LMF2 methylation affects the pathogenesis of AD and aMCI. In this study, we investigated relationships between NCAPH2/LMF2 methylation and other factors. AD (n=30) and aMCI (n=28) subjects were included in this study. NCAPH2/LMF2 methylation levels were measured by pyrosequencing. Correlations between methylation levels and other factors including age at onset, sex, duration of disease, education, mini-mental state examination (MMSE) and frontal assessment battery (FAB) scores, APOE genotype, degree of hippocampal atrophy, and total brain atrophy were measured. Degrees of hippocampal atrophy and total brain atrophy were measured by VSRAD (Voxel-Based Specific Regional Analysis System for Alzheimer’s Disease). Regression analysis revealed that only hippocampal atrophy according to VSRAD is a significant dependent variable correlated with NCAPH2/LMF2 methylation levels. Our results suggest that DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy through apoptosis.

Abstract TP453: Physical Inactivity Associated With Vascular Depression or Apathy Leads to Hippocampal Atrophy and Memory Dysfunction in Community-dwelling Elderly Subjects: The Sefuri Study

Background and Purpose: Vascular depression has negative effects on physical activity, which is a robust preventive factor against Alzheimer's disease or hippocampal atrophy. Therefore, we investigated the relationship among vascular depression (i.e., apathy associated with deep white matter lesions [DWMLs]), physical activity, hippocampal atrophy, and memory function using structural equation modeling (SEM). Subjects and Methods: We examined 213 non-demented elderly subjects without clinically apparent depression. All participants underwent Mini-Mental State Examination, Rivermead Behavioral Memory Test [RBMT] for episodic long-term memory, and a visual analogue version of the Starkstein’s apathy scale (Yao et al., Hypertens Res 2009;32:586). Physical activities were assessed with a questionnaire consisted of 3 components: leisure-time, work, and sport activities (Baecke et al., Am J Clin Nutr 1982;36:936). We evaluated the degree of hippocampal atrophy, using a software program the voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD advance) based on SPM8 plus DARTEL (Diffeomorphic Anatomical Registration Through an Exponentiated Lie algebra). Results: When possible confounders were entered into the logistic regression model, the independent predictors of hippocampal atrophy (the highest quintile of VSRAD z-score) were age (OR per 10 years 3.257, 95%CI 1.988-5.338), and leisure-time physical activity (OR per 1-point 0.810, 95%CI 0.707-0.928). Path analysis based on SEM indicated that the direct paths from DWMLs to apathy (β= -0.18, p&lt;0.01) and from apathy to leisure-time activity (β= 0.23, p&lt;0.001) were significant. Furthermore, the direct paths from leisure-time activity to hippocampal atrophy (β= -0.18, p&lt;0.01) and from hippocampal atrophy to memory dysfunction (RBMT) (β= -0.26, p&lt;0.001) were significant. The presented model reasonably fit the data: goodness of fit index = 0.97, adjusted goodness of fit index = 0.93, comparative fit index = 0.97, and root mean square error of approximation = 0.04. Conclusions: Based on the present SEM analysis, we propose a hypothesis that physical inactivity associated with vascular depression would lead to hippocampal atrophy or Alzheimer’s disease.

Memory impairment is not necessarily related to seizure frequency in mesial temporal lobe epilepsy with hippocampal sclerosis.

To investigate the effect of seizure frequency on memory, we performed a cross sectional study comparing mesial temporal lobe epilepsy (MTLE) patients with frequent and infrequent seizures. We performed magnetic resonance imaging (MRI) hippocampal volume (HV) measurements and neuropsychological assessment in 22 patients with frequent seizures (at least one dyscognitive seizure [DS] per month) that were refractory to antiepileptic drugs and 20 patients with infrequent seizures (three or less DS per year and no event evolving to a bilateral convulsive seizure), all with MRI signs of hippocampal sclerosis (HS) on visual analysis. We also included 29 controls for comparison of volumetric data. There was no difference in memory performance between patients with frequent seizures and infrequent seizures. We observed a significant bilateral reduction of HV in patients with MTLE when compared to controls (p < 0.001). The degree of hippocampal atrophy (HA) between patients with frequent and infrequent seizures was not different. There was a negative correlation between seizure frequency and HV, with r = -0.3 for the HV ipsilateral to the HS and r = -0.55 for the contralateral side, thus, explaining only 9% and 30% of the HV loss. There was a positive correlation between age of onset and degree of HA (r = 0.37). Our data suggest that seizure frequency does not explain most of the HV loss or memory impairment in MTLE. Memory impairment appears to be more influenced by hippocampal damage than by seizure frequency. Further studies are necessary to identify the factors that influence memory decline in patients with MTLE.

Intrinsic Connectivity Identifies the Hippocampus as a Main Crossroad between Alzheimer’s and Semantic Dementia-Targeted Networks

Alzheimer's disease (AD) and semantic dementia (SD) are both characterized by severe atrophy in the hippocampus, a brain region underlying episodic memory; paradoxically, episodic memory is relatively preserved in SD. Here, we used intrinsic connectivity analyses and showed that the brain networks differentially vulnerable to each disease converge to the hippocampus in the healthy brain. As neurodegeneration is thought to spread within preexisting networks, the common hippocampal atrophy in both diseases is likely due to its location at the crossroad between both vulnerable networks. Yet, we showed that in the normal brain, these networks harbor different functions, with episodic memory relying on the AD-vulnerable network only. Overall, disease-associated cognitive deficits seem to reflect the disruption of targeted networks more than atrophy in specific brain regions: in AD, over hippocampal atrophy, episodic memory deficits are likely due to disconnection within a memory-related network.

Behavioral and psychological symptoms and hippocampal atrophy in subcortical ischaemic vascular disease.

BackgroundNeuropsychiatric symptoms are common in patients with cognitive impairments, mediated by both neurodegenerative processes and cerebrovascular disease. Previous studies have reported that Behavioral and Psychological Symptoms of Dementia (BPSD) might correlate with severity of cognitive decline. Thus far, the impact of the association between white-matter hyperintensities (WHM) and hippocampal atrophy (HA) on the incidence of these symptoms has been less studied.ObjectiveThis cross-sectional study aimed to describe the clinical profile of a sample with large extensions of WMH, examining the association between different degrees of HA and cognitive, functional, and behavioral status.MethodsFifty outpatients (mean age: 76.86±8.70 years; 58% female; mean schooling: 7.44±4.69 years) with large extensions of WMH (modified-Fazekas scale=3) on MRI and different degrees of hippocampal atrophy (according to de Leon Score) underwent cognitive, functional, and behavioral assessments.ResultsPatients with mild-moderate to severe HA had worse performance on the Mini-Mental State Examination, Cambridge Cognitive Examination, Clinical Dementia Rating and Pfeffer's Functional Activities Questionnaire, compared to the group with none or questionable HA. Appetite/Eating Behavior was the only cluster of neuropsychiatric symptoms associated with presence of HA in Vascular Cognitive Impairment patients.DiscussionAlthough HA may exhibit distinct impact on cognitive performance and functional status, it appears to have little effect on behavioral symptoms in patients with high severity WMH.

Michael Foundation Forum 2010

Michael Foundation Forum 2010

Association between executive dysfunction and hippocampal volume in Alzheimer's disease

Some previous research has hypothesized that executive dysfunction in patients with early Alzheimer's disease (AD) occurs as a result of a disconnection between different cerebral areas. The aim of the present study was to evaluate how the hippocampal volume influences executive function as a non-memory cognitive function. From 157 consecutive patients with AD or amnestic mild cognitive impairment (A-MCI), we recruited 107 subjects who had a global Clinical Dementia Rating (CDR) of 0.5 or 1.0 and whose degree of hippocampal atrophy had been measured using magnetic resonance imaging (MRI); the severity of atrophy was assessed using the voxel-based specific regional analysis for Alzheimer's disease (VSRAD) system. We divided the subjects into three groups: mild atrophy, 0 < Z-score < 1.0 (N = 21); moderate atrophy, 1.0 ≤ Z-score < 2.0 (N = 46); or severe atrophy, 2.0 ≤ Z-score < 4.0 (N = 40) according to the Z-score and compared the Frontal Assessment Battery (FAB) and its subtest scores between each atrophy group. The results demonstrated that age, sex ratio, duration of illness, education years, MMSE score, Behave-AD score, and proportion of atrophy area in total brain (%) were not significantly different among the three groups. Only the go/no-go score among the six subtests was significantly lower for increasing atrophy severity (P < 0.05). Furthermore, hippocampal atrophy significantly influenced the go/no-go score independently of interactions from whether the diagnosis was early AD or A-MCI (P < 0.05). These results support a significant association between hippocampal atrophy and executive dysfunction as a non-memory cognitive impairment in patients with early AD and A-MCI.