Differences In Alzheimer Research Articles

Sex and gender differences in Alzheimer's disease: current challenges and implications for clinical practice: Position paper of the Dementia and Cognitive Disorders Panel of the European Academy of Neurology.

Alzheimer's disease (AD) is characterized by high heterogeneity in disease manifestation, progression and risk factors. High phenotypic variability is currently regarded as one of the largest hurdles in early diagnosis and in the design of clinical trials; there is therefore great interest in identifying factors driving variability that can be used for patient stratification. In addition to genetic and lifestyle factors, the individual's sex and gender are emerging as crucial drivers of phenotypic variability. Evidence exists on sex and gender differences in the rate of cognitive deterioration and brain atrophy, and in the effect of risk factors as well as in the patterns of diagnostic biomarkers. Such evidence might be of high relevance and requires attention in clinical practice and clinical trials. However, sex and gender differences are currently seldom appreciated; importantly, consideration of sex and gender differences is not currently a focus in the design and analysis of clinical trials for AD. The objective of this position paper is (i) to provide an overview of known sex and gender differences that might have implications for clinical practice, (ii) to identify the most important knowledge gaps in the field (with a special regard to clinical trials) and (iii) to provide conclusions for future studies. This scientific statement is endorsed by the European Academy of Neurology.

The heterogeneous functional architecture of the posteromedial cortex is associated with selective functional connectivity differences in Alzheimer's disease.

The posteromedial cortex (PMC) is a key region involved in the development and progression of Alzheimer's disease (AD). Previous studies have demonstrated a heterogenous functional architecture of the region that is composed of discrete functional modules reflecting a complex pattern of functional connectivity. However, little is understood about the mechanisms underpinning this complex network architecture in neurodegenerative disease, and the differential vulnerability of connectivity‐based subdivisions in the PMC to AD pathogenesis. Using a data‐driven approach, we applied a constrained independent component analysis (ICA) on healthy adults from the Human Connectome Project to characterise the local functional connectivity patterns within the PMC, and its unique whole‐brain functional connectivity. These distinct connectivity profiles were subsequently quantified in the Alzheimer's Disease Neuroimaging Initiative study, to examine functional connectivity differences in AD patients and cognitively normal (CN) participants, as well as the entire AD pathological spectrum. Our findings revealed decreased functional connectivity in the anterior precuneus, dorsal posterior cingulate cortex (PCC), and the central precuneus in AD patients compared to CN participants. Functional abnormalities in the dorsal PCC and central precuneus were also related to amyloid burden and volumetric hippocampal loss. Across the entire AD spectrum, functional connectivity of the central precuneus was associated with disease severity and specific deficits in memory and executive function. These findings provide new evidence showing that the PMC is selectively impacted in AD, with prominent network failures of the dorsal PCC and central precuneus underpinning the neurodegenerative and cognitive dysfunctions associated with the disease.

Regional differences in Alzheimer's disease pathology confound behavioural rescue after amyloid-β attenuation.

Failure of Alzheimer's disease clinical trials to improve or stabilize cognition has led to the need for a better understanding of the driving forces behind cognitive decline in the presence of active disease processes. To dissect contributions of individual pathologies to cognitive function, we used the TgF344-AD rat model, which recapitulates the salient hallmarks of Alzheimer's disease pathology observed in patient populations (amyloid, tau inclusions, frank neuronal loss, and cognitive deficits). scyllo-Inositol treatment attenuated amyloid-β peptide in disease-bearing TgF344-AD rats, which rescued pattern separation in the novel object recognition task and executive function in the reversal learning phase of the Barnes maze. Interestingly, neither activities of daily living in the burrowing task nor spatial memory in the Barnes maze were rescued by attenuating amyloid-β peptide. To understand the pathological correlates leading to behavioural rescue, we examined the neuropathology and in vivo electrophysiological signature of the hippocampus. Amyloid-β peptide attenuation reduced hippocampal tau pathology and rescued adult hippocampal neurogenesis and neuronal function, via improvements in cross-frequency coupling between theta and gamma bands. To investigate mechanisms underlying the persistence of spatial memory deficits, we next examined neuropathology in the entorhinal cortex, a region whose input to the hippocampus is required for spatial memory. Reduction of amyloid-β peptide in the entorhinal cortex had no effect on entorhinal tau pathology or entorhinal-hippocampal neuronal network dysfunction, as measured by an impairment in hippocampal response to entorhinal stimulation. Thus, rescue or not of cognitive function is dependent on regional differences of amyloid-β, tau and neuronal network dysfunction, demonstrating the importance of staging disease in patients prior to enrolment in clinical trials. These results further emphasize the need for combination therapeutic approaches across disease progression.

C-11 Neurocognitive Differences in Alzheimer’s Dementia Compared to Healthy Controls on the WAIS-IV

Abstract Objective The present study seeks to identify neurocognitive patterns of those diagnosed with Alzheimer’s dementia (AD) compared to those with no diagnosis (ND), potentially aiding in the diagnostic process. Previous research found visuospatial differences, but on previous versions of the WAIS. Method Participants (n = 580) were referred to a large assessment outpatient clinic with a variety of presenting problems, such as neurological diagnosis, personality functioning, and ADHD assessment. To measure cognitive functioning, participants were administered the WAIS-IV. Participants included individuals diagnosed with AD (n = 43) and those with ND (n = 40). Results Subtest scores for those diagnosed with AD were lower than participants with ND. We adjusted the mean level difference using vocabulary (VC). Using regression, variance associated with VC was pulled out, as it is not susceptible to cognitive decline. Both Matrix Reasoning (MR) (r-square = .04; p =.001) and Digit Span (DS) (r-square = .04; p = .001) were significantly different for the two groups even after controlling for VC. Block Design (BD) was not significantly different (p = 0.07). Conclusions While previous research indicates patterns of visuospatial difficulties in neurocognitive functioning among those with AD, the current findings suggest impairments in perceptual reasoning and working memory. Previous research also suggests that BD predicts AD. However, the current study indicates MR and DS predicts AD, whereas BD does not. While these results may be due to small sample size, this study did control for intellectual functioning. Additional research involving an extensive test battery is needed to further examine these findings.

Sex differences in the genetic predictors of Alzheimer's pathology.

Autopsy measures of Alzheimer's disease neuropathology have been leveraged as endophenotypes in previous genome-wide association studies (GWAS). However, despite evidence of sex differences in Alzheimer's disease risk, sex-stratified models have not been incorporated into previous GWAS analyses. We looked for sex-specific genetic associations with Alzheimer's disease endophenotypes from six brain bank data repositories. The pooled dataset included 2701 males and 3275 females, the majority of whom were diagnosed with Alzheimer's disease at autopsy (70%). Sex-stratified GWAS were performed within each dataset and then meta-analysed. Loci that reached genome-wide significance (P < 5 × 10-8) in stratified models were further assessed for sex interactions. Additional analyses were performed in independent datasets leveraging cognitive, neuroimaging and CSF endophenotypes, along with age-at-onset data. Outside of the APOE region, one locus on chromosome 7 (rs34331204) showed a sex-specific association with neurofibrillary tangles among males (P = 2.5 × 10-8) but not females (P = 0.85, sex-interaction P = 2.9 × 10-4). In follow-up analyses, rs34331204 was also associated with hippocampal volume, executive function, and age-at-onset only among males. These results implicate a novel locus that confers male-specific protection from tau pathology and highlight the value of assessing genetic associations in a sex-specific manner.

Alzheimer Disease-associated Cortical Atrophy Does not Differ Between Chinese and Whites.

To assess whether there are differences in Alzheimer disease (AD)-associated atrophy regions in Chinese and white patients with AD versus cognitively normal older adults, and to test whether associations between clinical severity and gray matter volume are similar or different across these ethnic groups in a cross-sectional analysis. Chinese and white patients with AD, individuals with mild cognitive impairment, and cognitively normal controls (46 white and 48 Chinese) were clinically evaluated at an academic center within 1 year of magnetic resonance imaging acquisition. Clinical severity was assessed using the Clinical Dementia Rating Sum of Boxes and cortical atrophy was measured using voxel-based morphometry as well as Freesurfer. Chinese and white cohorts were demographically matched for age, sex, and education. Clinical severity by diagnosis was similar across ethnicities. Chinese and white patient groups showed similar amounts of atrophy in the regions most affected in AD after accounting for demographic variables and head size. There was no significant difference between ethnic groups when compared by atrophy and clinical severity. Our study suggests that Chinese and white patients with AD, when matched demographically, are clinically and neuroanatomically similar on normalized measures of cortical atrophy and clinical severity.

Racial and Ethnic Differences in Alzheimer's Disease Knowledge Among Community-Dwelling Middle-Aged and Older Adults in Florida.

Objective: To compare Alzheimer's disease (AD) knowledge by race and ethnicity in a community sample of middle-aged and older adults aged 50 and over in Florida. Method: Data from HealthStreet, a University of Florida community engagement program, which uses community health workers to assess the health conditions, concerns, and knowledge of community members, was used (n = 842). A multivariate regression model was used to quantify differences in AD knowledge by race and ethnicity. Results: Older age and recruitment from Miami were associated with higher AD knowledge while being non-Hispanic Black, reporting male sex, having less than high school diploma, and reporting food insecurity were associated with lower AD knowledge. Discussion: Hispanics had comparable AD knowledge to non-Hispanic Whites and more knowledge than non-Hispanic Blacks after adjusting for other factors that could differentiate these groups. Almost half of the participants did not know hypertension is a risk factor for AD, highlighting a point of intervention.

Ethnoracial differences in Alzheimer's disease from the FLorida Autopsied Multi-Ethnic (FLAME) cohort

IntroductionOur primary goal was to examine demographic and clinicopathologic differences across an ethnoracially diverse autopsy-confirmed cohort of Alzheimer's disease cases. MethodsA retrospective study was conducted in the Florida Autopsied Multi-Ethnic cohort on 1625 Alzheimer's disease cases, including decedents who self-reported as Hispanic/Latino (n = 67), black/African American (n = 19), and white/European American (n = 1539). ResultsHispanic decedents had a higher frequency of family history of cognitive impairment (58%), an earlier age at onset (median age of 70 years), longer disease duration (median of 12 years), and lower MMSE proximal to death (median of 4 points) compared with the other ethnoracial groups. Black decedents had a lower Braak tangle stage (stage V) and higher frequency of coexisting hippocampal sclerosis (21%); however, only hippocampal sclerosis differences survived adjustment for sex, age at onset, and disease duration. Neither Thal amyloid phase nor coexisting Lewy body disease differed across ethnoracial groups. DiscussionDespite a smaller sample size, Hispanics demonstrated longer disease duration with Alzheimer's disease, but not greater lifespan. Neuropathologic differences across ethnoracial groups supported differences in tau pathology distribution and coexisting hippocampal sclerosis, which may impact biomarker studies.

Integrated DNA methylation and gene expression profiling across multiple brain regions implicate novel genes in Alzheimer's disease.

Late-onset Alzheimer's disease (AD) is a complex age-related neurodegenerative disorder that likely involves epigenetic factors. To better understand the epigenetic state associated with AD, we surveyed 420,852 DNA methylation (DNAm) sites from neurotypical controls (N = 49) and late-onset AD patients (N = 24) across four brain regions (hippocampus, entorhinal cortex, dorsolateral prefrontal cortex and cerebellum). We identified 858 sites with robust differential methylation collectively annotated to 772 possible genes (FDR < 5%, within 10kb). These sites were overrepresented in AD genetic risk loci (p = 0.00655) and were enriched for changes during normal aging (p < 2.2 × 10-16), and nearby genes were enriched for processes related to cell-adhesion, immunity, and calcium homeostasis (FDR < 5%). To functionally validate these associations, we generated and analyzed corresponding transcriptome data to prioritize 130 genes within 10kb of the differentially methylated sites. These 130 genes were differentially expressed between AD cases and controls and their expression was associated with nearby DNAm (p < 0.05). This integrated analysis implicates novel genes in Alzheimer's disease, such as ANKRD30B. These results highlight DNAm differences in Alzheimer's disease that have gene expression correlates, further implicating DNAm as an epigenetic mechanism underlying pathological molecular changes associated with AD. Furthermore, our framework illustrates the value of integrating epigenetic and transcriptomic data for understanding complex disease.

Molecular differences in Alzheimer's disease between male and female patients determined by integrative network analysis.

Alzheimer's disease (AD) is a complex neurodegenerative disease and the most common cause of dementia among the elderly. There has been increasing recognition of sex differences in AD prevalence, clinical manifestation, disease course and prognosis. However, there have been few studies on the molecular mechanism underlying these differences. To address this issue, we carried out global gene expression and integrative network analyses based on expression profiles (GSE84422) across 17 cortical regions of 125 individuals with AD. There were few genes that were differentially expressed across the 17 regions between the two sexes, with only four (encoding glutamate metabotropic receptor 2, oestrogen‐related receptor beta, kinesin family member 26B, and aspartoacylase) that were differentially expressed in three regions. A pan‐cortical brain region co‐expression network analysis identified pathways and genes (eg, glycogen synthase kinase 3β) that were significantly associated with clinical characteristics of AD (such as neurofibrillary score) in males only. Similarity analyses between region‐specific networks indicated that male patients exhibited greater variability, especially in the superior parietal lobule, dorsolateral prefrontal cortex and occipital visual cortex. A network module analysis revealed an association between clinical traits and crosstalk of sex‐specific modules. An examination of temporal and spatial patterns of sex differences in AD showed that molecular networks were more conserved in females than in males in different cortical regions and at different AD stages. These findings provide insight into critical molecular pathways governing sex differences in AD pathology.

Sex differences in Alzheimer's disease and common neuropathologies of aging.

Alzheimer's dementia is significantly more common in women than in men. However, few pathological studies have addressed sex difference in Alzheimer's disease (AD) and other brain pathologies. We leveraged postmortem data from 1453 persons who participated in one of two longitudinal community-based studies of older adults, the Religious Orders Study and the Rush Memory and Aging Project. Postmortem examination identified AD pathologies, neocortical Lewy bodies, DNA-binding protein 43 (TDP-43), hippocampal sclerosis, gross and micro infarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy. Linear and logistic regressions examined the association of sex with each of the pathologic measures. Two-thirds of subjects were women (n = 971; 67%), with a mean age at death of 89.8 (SD = 6.6) years in women and 87.3 (SD = 6.6) in men. Adjusted for age and education, women had higher levels on a global measure of AD pathology (estimate = 0.102, SE = 0.022, p < 0.001), and tau tangle density in particular (estimate = 0.334, SE = 0.074, p < 0.001), and there was a borderline difference between women and men in amyloid-β load (estimate = 0.124, SE = 0.065, p = 0.056). In addition, compared to men, women were more likely to have more severe arteriolosclerosis (OR = 1.28, 95% CI:1.04-1.58, p = 0.018), and less likely to have gross infarcts (OR = 0.78, 95% CI:0.61-0.98, p = 0.037), although the association with gross infarct was attenuated after controlling for vascular risk factors. These data help elucidate the neuropathologic footprint of sex difference in AD and other common brain pathologies of aging.

Sex and age interact to determine clinicopathologic differences in Alzheimer\u2019s disease

Women reportedly make up two-thirds of Alzheimer’s disease (AD) dementia sufferers. Many estimates regarding AD, however, are based on clinical series lacking autopsy confirmation. The Florida Autopsied Multi-Ethnic (FLAME) cohort was queried for AD cases with a total of 1625 identified ranging in age from 53 to 102 years at death. Standard neuropathologic procedures were employed and clinical information was retrospectively collected. Clinicopathologic and genetic data (MAPT and APOE) were stratified by sex. Within the neuropathologically diagnosed AD cohort, the overall number of women and men did not differ. Men were younger at onset of cognitive symptoms, had a shorter disease duration, and more often had atypical (non-amnestic) clinical presentations. The frequency of autopsy-confirmed AD among women and men stratified by age at death revealed an inverse U-shaped curve in men and a U-shaped curve in women, with both curves having inflections at approximately 70 years of age. Regional counts of neurofibrillary tangles differed in women and men, especially when examined by age intervals. Women had overall greater severity of neurofibrillary tangle counts compared to men, especially in the hippocampus. Men were more often classified as hippocampal sparing AD, whereas limbic predominant AD was more common in women. Men and women did not differ in frequency of MAPT haplotype or APOE genotype. Atypical clinical presentations, younger age at onset and shorter disease duration were more frequent in men, suggesting that the lower reported frequency of AD in men may be due to more frequent atypical clinical presentations not recognized as AD. Our data suggest that neuropathologically diagnosed AD cases have the same frequency of women and men, but their clinical presentations and ages at onset tend to differ.

Variation among intact tissue samples reveals the core transcriptional features of human CNS cell classes.

It is widely assumed that cells must be physically isolated to study their molecular profiles. However, intact tissue samples naturally exhibit variation in cellular composition, which drives covariation of cell-class-specific molecular features. By analyzing transcriptional covariation in 7221 intact CNS samples from 840 neurotypical individuals representing billions of cells, we reveal the core transcriptional identities of major CNS cell classes in humans. By modeling intact CNS transcriptomes as a function of variation in cellular composition, we identify cell-class-specific transcriptional differences in Alzheimer’s disease, among brain regions, and between species. Among these, we show that PMP2 is expressed by human but not mouse astrocytes and significantly increases mouse astrocyte size upon ectopic expression in vivo, causing them to more closely resemble their human counterparts. Our work is available as an online resource (http://oldhamlab.ctec.ucsf.edu/) and provides a generalizable strategy for determining the core molecular features of cellular identity in intact biological systems.

Sex differences in Alzheimer disease - the gateway to precision medicine.

Alzheimer disease (AD) is characterized by wide heterogeneity in cognitive and behavioural syndromes, risk factors and pathophysiological mechanisms. Addressing this phenotypic variation will be crucial for the development of precise and effective therapeutics in AD. Sex-related differences in neural anatomy and function are starting to emerge, and sex might constitute an important factor for AD patient stratification and personalized treatment. Although the effects of sex on AD epidemiology are currently the subject of intense investigation, the notion of sex-specific clinicopathological AD phenotypes is largely unexplored. In this Review, we critically discuss the evidence for sex-related differences in AD symptomatology, progression, biomarkers, risk factor profiles and treatment. The cumulative evidence reviewed indicates sex-specific patterns of disease manifestation as well as sex differences in the rates of cognitive decline and brain atrophy, suggesting that sex is a crucial variable in disease heterogeneity. We discuss critical challenges and knowledge gaps in our current understanding. Elucidating sex differences in disease phenotypes will be instrumental in the development of a 'precision medicine' approach in AD, encompassing individual, multimodal, biomarker-driven and sex-sensitive strategies for prevention, detection, drug development and treatment.

Sex Differences in Cognitive Decline in Subjects with High Likelihood of Mild Cognitive Impairment due to Alzheimer\u2019s disease

Sex differences in Alzheimer’s disease (AD) biology and progression are not yet fully characterized. The goal of this study is to examine the effect of sex on cognitive progression in subjects with high likelihood of mild cognitive impairment (MCI) due to Alzheimer’s and followed up to 10 years in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cerebrospinal fluid total-tau and amyloid-beta (Aβ42) ratio values were used to sub-classify 559 MCI subjects (216 females, 343 males) as having “high” or “low” likelihood for MCI due to Alzheimer’s. Data were analyzed using mixed-effects models incorporating all follow-ups. The worsening from baseline in Alzheimer’s Disease Assessment Scale-Cognitive score (mean, SD) (9 ± 12) in subjects with high likelihood of MCI due to Alzheimer’s was markedly greater than that in subjects with low likelihood (1 ± 6, p < 0.0001). Among MCI due to AD subjects, the mean worsening in cognitive score was significantly greater in females (11.58 ± 14) than in males (6.87 ± 11, p = 0.006). Our findings highlight the need to further investigate these findings in other populations and develop sex specific timelines for Alzheimer’s disease progression.

Simulation study on differences in Alzheimer Disease (AD) Cooperative Study–Preclinical Alzheimer Cognitive Composite (ADCS-PACC) Based on Long-term Clinical Outcomes (P5.193)

Simulation study on differences in Alzheimer Disease (AD) Cooperative Study–Preclinical Alzheimer Cognitive Composite (ADCS-PACC) Based on Long-term Clinical Outcomes (P5.193)

Sex differences in Alzheimer's disease.

Women are more impacted by Alzheimer's disease than men - they are at significantly greater risk of developing Alzheimer's disease, and recent research shows that they also appear to suffer a greater cognitive deterioration than men at the same disease stage. The purpose of this article is to review recent studies on examining sex differences in cognitive function in Alzheimer's disease. We searched electronically for articles, reviews and meta-analyses published between 1/2016 and 12/2017 and identified 298 articles on sex differences in cognition in Alzheimer's disease. The key themes to emerge were sex differences in cognitive function, risk factors, resilience, and cognitive reserve. Evidence is steadily and increasingly accumulating to confirm the poorer cognitive outcome for women than men with Alzheimer's disease. Although small in size, the effects occur across a broad range of cognitive domains including visuospatial, verbal, episodic memory, and semantic memory - some of which typically reveal a sex-related processing advantage for healthy women. Explanations have been linked to a variety of factors including differences in cognitive reserve, resilience, as well as genetics (apolipoprotein ε4) and functional and structural brain changes. Sex-related differences in risk factors, resilience, cognitive reserve, and rates of deterioration have implications for clinical practice.

Sex differences in obesity and cognitive function in a cognitively normal aging Chinese Han population.

BackgroundSex differences in Alzheimer’s disease and mild cognitive impairment have been well recognized. However, sex differences in cognitive function and obesity in cognitively normal aging Chinese Han population have not attracted much attention.ObjectiveThe aim of this study was to investigate the relationship between sex, obesity, and cognitive function in an elderly Chinese population with normal cognitive function.Subjects and methodsA total of 228 cognitively normal aging participants (males/females =93/135) entered this study. Their general demographic information (sex, age, and education) was collected by standardized questionnaire. Apolipoprotein E (APOE) genotype and serum lipid levels were measured. The Montreal Cognitive Assessment (MoCA) was used to assess participants’ cognitive function.ResultsThe prevalence of obesity in elderly women (18/133, 13.5%) was significantly higher than that in men (5/92, 5.4%, P=0.009). Regression analyses showed that obesity was associated with drinking alcohol (OR =13.695, P=0.045) and triglyceride (OR =1.436, P=0.048) in women and limited to low-density lipoprotein (OR =11.829, P=0.023) in men. Women performed worse on the naming score for MoCA than men (P<0.01). Stepwise linear regression analysis showed that education (t=3.689, P<0.001) and smoking (t=2.031, P=0.045) were related to the score of naming in female, while high-density lipoprotein (t=−2.077, P=0.041) was related to the score of naming in male; however, no correlation was found between body mass index and cognitive function in both male and female (P>0.05).ConclusionOur finding suggests that there are significant sex differences in obesity and specific cognitive domains in aging Chinese Han population with normal cognitive function.

INDIVIDUAL CLASSIFICATION OF ALZHEIMER’S DISEASE WITH DIFFUSION MAGNETIC RESONANCE IMAGING

Diffusion magnetic resonance imaging (MRI) is a powerful non-invasive method to study white matter integrity, and is sensitive to detect differences in Alzheimer's disease (AD) patients. Diffusion MRI may be able to contribute towards reliable diagnosis of AD. We used diffusion MRI to classify AD patients (N=77), and controls (N=173). We use different methods to extract information from the diffusion MRI data. First, we use the voxel-wise diffusion tensor measures that have been skeletonised using tract based spatial statistics. Second, we clustered the voxel-wise diffusion measures with independent component analysis (ICA), and extracted the mixing weights. Third, we determined structural connectivity between Harvard Oxford atlas regions with probabilistic tractography, as well as graph measures based on these structural connectivity graphs. Classification performance for voxel-wise measures ranged between an AUC of 0.888, and 0.902. The ICA-clustered measures ranged between an AUC of 0.893, and 0.920. The AUC for the structural connectivity graph was 0.900, while graph measures based upon this graph ranged between an AUC of 0.531, and 0.840. All measures combined with a sparse group lasso resulted in an AUC of 0.896. Overall, fractional anisotropy clustered into ICA components was the best performing measure. These findings may be useful for future incorporation of diffusion MRI into protocols for AD classification, or as a starting point for early detection of AD using diffusion MRI.

Individual classification of Alzheimer's disease with diffusion magnetic resonance imaging

Diffusion magnetic resonance imaging (MRI) is a powerful non-invasive method to study white matter integrity, and is sensitive to detect differences in Alzheimer's disease (AD) patients. Diffusion MRI may be able to contribute towards reliable diagnosis of AD. We used diffusion MRI to classify AD patients (N=77), and controls (N=173). We use different methods to extract information from the diffusion MRI data. First, we use the voxel-wise diffusion tensor measures that have been skeletonised using tract based spatial statistics. Second, we clustered the voxel-wise diffusion measures with independent component analysis (ICA), and extracted the mixing weights. Third, we determined structural connectivity between Harvard Oxford atlas regions with probabilistic tractography, as well as graph measures based on these structural connectivity graphs. Classification performance for voxel-wise measures ranged between an AUC of 0.888, and 0.902. The ICA-clustered measures ranged between an AUC of 0.893, and 0.920. The AUC for the structural connectivity graph was 0.900, while graph measures based upon this graph ranged between an AUC of 0.531, and 0.840. All measures combined with a sparse group lasso resulted in an AUC of 0.896. Overall, fractional anisotropy clustered into ICA components was the best performing measure. These findings may be useful for future incorporation of diffusion MRI into protocols for AD classification, or as a starting point for early detection of AD using diffusion MRI.