Polygenic Risk Scoring is an Effective Approach to Predict Those Individuals Most Likely to Decline Cognitively Due to Alzheimer's Disease.

BACKGROUND: There is a clear need for simple and effective tests to identify individuals who are most likely to develop Alzheimer's Disease (AD) both for the purposes of clinical trial recruitment but also for improved management of patients who may be experiencing early pre-clinical symptoms or who have clinical concerns. OBJECTIVES: To predict individuals at greatest risk of progression of cognitive impairment due to Alzheimer's Disease in individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) using a polygenic risk scoring algorithm. To compare the performance of a PRS algorithm in predicting cognitive decline against that of using the pTau/Aß1-42 ratio CSF biomarker profile. DESIGN: A longitudinal analysis of data from the Alzheimer's Disease Neuroimaging Initiative study conducted across over 50 sites in the US and Canada. SETTING: Multi-center genetics study. PARTICPANTS: 515 subjects who upon entry to the study were diagnosed as cognitively normal or with mild cognitive impairment. MEASUREMENTS: Use of genotyping and/or whole genome sequencing data to calculate polygenic risk scores and assess ability to predict subsequent cognitive decline as measured by CDR-SB and ADAS-Cog13 over 4 years. RESULTS: The overall performance for predicting those individuals who would decline by at least 15 ADAS-Cog13 points from a baseline mild cognitive impairment in 4 years was 72.8% (CI:67.9-77.7) AUC increasing to 79.1% (CI: 75.6-82.6) when also including cognitively normal participants. Assessing mild cognitive impaired subjects only and using a threshold of greater than 0.6, the high genetic risk participant group declined, on average, by 1.4 points (CDR-SB) more than the low risk group over 4 years. The performance of the PRS algorithm tested was similar to that of the pTau/Aß1-42 ratio CSF biomarker profile in predicting cognitive decline. CONCLUSION: Calculating polygenic risk scores offers a simple and effective way, using DNA extracted from a simple mouth swab, to select mild cognitively impaired patients who are most likely to decline cognitively over the next four years.

Increased neural progenitors in individuals with cerebral small vessel disease.

AIMS: Recent work has highlighted a significant increase of neural stem/progenitor cells after stroke in humans. In this study, we examined neurogenesis in small vessel disease, a key concurrent pathology in Alzheimer's disease. METHODS: We assayed autopsy tissue from 13 vascular dementia patients with small vessel disease and 12 age-matched subjects without cerebrovascular pathology, undertaking immunohistochemistry in the affected brain area and the subventricular zone with a well-characterized battery of antibodies to detect neural stem cells/progenitors and immature neurones, as well as choline acetyltransferase immunoreactivity. RESULTS: We showed significant increases ranging from 33% to 92% (P < 0.05) in neural progenitor cells around the areas of microvascular pathology and in the subventricular zone in patients with small vessel disease compared to individuals without cerebrovascular changes, even in patients with severe cerebrovascular disease, as defined by neuropathological assessment. Some of the progenitor cells give rise to immature neurones in the affected areas. These alterations were associated with vascular changes, but were unrelated to the cholinergic deficit observed in the cortex and subventricular zone in these patients, in contrast to other dementias examined such as dementia with Lewy bodies. CONCLUSIONS: This study provides evidence for neurogenesis in small vessel disease and may have important implications for the development of new therapies for neurodegenerative diseases.

Vesicular glutamate transporter and cognition in stroke: a case-control autopsy study.

OBJECTIVES: Vascular dementia (VaD) accounts for approximately 15%-20% of all dementias, but the relationship of progressive cognitive impairment to neurochemical changes is poorly understood. We have therefore investigated glutamatergic synaptic markers in VaD. METHODS: We used homogenates prepared from gray matter from 2 neocortical regions (Brodmann area [BA] 9 and BA 20) and Western blotting to determine the concentrations of key components of the glutamatergic neurotransmitter system, vesicular glutamate transporter 1 (VGLUT1) and excitatory amino acid transporter EAAT2 (GLT-1), and the ubiquitous synaptic protein, synaptophysin, in 73 individuals-48 patients with cerebrovascular disease with and without dementia, 10 patients with AD, and 15 controls-in a case-control design. RESULTS: VGLUT1 concentrations in BA 20 and BA 9 were correlated with CAMCOG total (Rs 0.525, p = 0.018, n = 20; Rs 0.560, p = 0.002, n = 27) and CAMCOG memory scores (Rs 0.616, p = 0.004, n = 20; Rs 0.675, p = 0.000, n = 27). VGLUT1 concentration in BA 9 differed between the different dementia groups and the stroke no dementia group (1-way analysis of variance F = 6.69, p = 0.001 and Bonferroni p < 0.01 in each case), with subjects with stroke who did not develop dementia exhibiting the highest mean value for VGLUT1. CONCLUSIONS: These data suggest that loss of glutamatergic synapses is a feature of VaD and Alzheimer disease but the preservation of synapses, in particular glutamatergic synapses, in the frontal cortex against the temporal cortex plays a role in sustaining cognition and protecting against dementia following a stroke.

The period of hypotension following orthostatic challenge is prolonged in dementia with Lewy bodies.

OBJECTIVES: To determine whether orthostatic hypotension (OH) is more common in patients with dementia than in older people without cognitive impairment and to identify key differences in the profile of the orthostatic response and the pulse drive during orthostatic challenge between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). METHODS: The orthostatic response was evaluated in 235 patients with AD, 52 patients with DLB and 62 elderly controls. The blood pressure and pulse rate were measured in supine position, immediately after standing up and after 1, 3, 5 and 10 min of standing. OH was defined as a reduction of systolic blood pressure (SBP) of at least 20 mm Hg or a reduction of diastolic blood pressure (DBP) of at least 10 mm Hg. RESULTS: OH occurred in 69% of the DLB patients and in 42% of the AD patients, but only in 13% of the controls (p<0.001 controls vs AD and controls vs DLB, p=0.001 AD vs DLB) The DLB patients had a greater drop in SBP than the other study groups during orthostatic challenge and had a more prolonged period of orthostasis. The pulse drive on orthostatic challenge was similar in between groups. However, in the DLB group it was not adequate to restore the blood pressure to supine values. CONCLUSIONS: Patients with DLB react different to orthostatic challenge than patients with AD or controls, with important clinical implications for key disease symptoms and treatment.

Cholinesterase inhibitors reduce cortical Abeta in dementia with Lewy bodies.

Cholinesterase inhibitors (ChEIs) are effective symptomatic treatments in dementia with Lewy bodies (DLB), although effects on pathologic mechanisms are unknown. In the first human autopsy study examining the impact of ChEI treatment on brain pathology, we compared treated patients with DLB with matched untreated patients for cortical beta-amyloid (Abeta) and tau pathologies. Treated patients with DLB had significantly less parenchymal Abeta deposition, which is relevant to disease management and treatment of dementia patients using ChEI.

Autonomic dysfunction in dementia.

BACKGROUND: There are no studies of autonomic function comparing Alzheimer's disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). AIMS: To assess cardiovascular autonomic function in 39 patients with AD, 30 with VAD, 30 with DLB, 40 with PDD and 38 elderly controls by Ewing's battery of autonomic function tests and power spectral analysis of heart rate variability. To determine the prevalence of orthostatic hypotension and autonomic neuropathies by Ewing's classification. RESULTS: There were significant differences in severity of cardiovascular autonomic dysfunction between the four types of dementia. PDD and DLB had considerable dysfunction. VAD showed limited evidence of autonomic dysfunction and in AD, apart from orthostatic hypotension, autonomic functions were relatively unimpaired. PDD showed consistent impairment of both parasympathetic and sympathetic function tests in comparison with controls (all p<0.001) and AD (all p<0.03). DLB showed impairment of parasympathetic function (all p<0.05) and one of the sympathetic tests in comparison with controls (orthostasis; p = 0.02). PDD had significantly more impairment than DLB in some autonomic parameters (Valsalva ratio: p = 0.024; response to isometric exercise: p = 0.002). Patients with VAD showed impairment in two parasympathetic tests (orthostasis: p = 0.02; Valsalva ratio: p = 0.08) and one sympathetic test (orthostasis: p = 0.04). These results were in contrast with AD patients who only showed impairment in one sympathetic response (orthostasis: p = 0.004). The prevalence of orthostatic hypotension and autonomic neuropathies was higher in all dementias than in controls (all p<0.05). CONCLUSION: Autonomic dysfunction occurs in all common dementias but is especially prominent in PDD with important treatment implications.

Quantification of Alzheimer pathology in ageing and dementia: age-related accumulation of amyloid-beta(42) peptide in vascular dementia.

Clinicopathological observations suggest there is considerable overlap between vascular dementia (VaD) and Alzheimer's disease (AD). We used immunochemical methods to compare quantities of amyloid-beta (Abeta) peptides in post mortem brain samples from VaD, AD subjects and nondemented ageing controls. Total Abeta peptides extracted from temporal and frontal cortices were quantified using a previously characterized sensitive homogenous time-resolved fluorescence (HTRF) assay. The HTRF assays and immunocapture mass spectrometric analyses revealed that the Abeta(42) species were by far the predominant form of extractable peptide compared with Abeta(40) peptide in VaD brains. The strong signal intensity for the peak representing Abeta(4-42) peptide confirmed that these N-terminally truncated species are relatively abundant. Absolute quantification by HTRF assay showed that the mean amount of total Abeta(42) recovered from VaD samples was approximately 50% of that in AD, and twice that in the age-matched controls. Linear correlation analysis further revealed an increased accumulation with age of both Abeta peptides in brains of VaD subjects and controls. Interestingly, VaD patients surviving beyond 80 years of age exhibited comparable Abeta(42) concentrations with those in AD in the temporal cortex. Our findings suggest that brain Abeta accumulates increasingly with age in VaD subjects more so than in elderly without cerebrovascular disease and support the notion that they acquire Alzheimer-like pathology in older age.

Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.

The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Neuroleptics are associated with more severe tangle pathology in dementia with Lewy bodies.

BACKGROUND: Neuroleptics are only modestly effective in dementia and associated with a range of adverse effects including cognitive decline. Effects of the drugs on molecular pathology in brain tissue from people with dementia have not been investigated. OBJECTIVES: To compare the severity of Alzheimer type pathology in matched groups of people with dementia with Lewy bodies (DLB), treated and not treated with neuroleptics. METHODS: The relationship between neuroleptics and Alzheimer-type pathology was determined in 40 (17 neuroleptic treated, 23 neuroleptic free, matched for age, disease duration and psychosis) clinically prospectively studied, autopsy diagnosed DLB patients. RESULTS: In regression analyses, taking neuroleptics was significantly associated with increased neurofibrillary tangles but not amyloid plaques in cortical areas examined. The patient characteristics and the frequencies of key psychiatric symptoms were similar in the patients taking and not taking neuroleptics. CONCLUSION: Although patients were not randomized and the results which are observed need to be interpreted cautiously, if substantiated, this is an important finding with major implications for the pharmacological management of DLB patients and highlights the need to determine the impact of neuroleptics upon tangle pathology in AD.

Positive modulation of mood and cognitive performance following administration of acute doses of Salvia lavandulaefolia essential oil to healthy young volunteers.

Members of the Sage family, such as Salvia officinalis and Salvia lavandulaefolia, have a long history of use as memory-enhancing agents coupled with cholinergic properties that may potentially be relevant to the amelioration of the cognitive deficits associated with Alzheimer's disease. The current study utilised a placebo-controlled, double-blind, balanced, crossover design in order to comprehensively assess any mood and cognition modulation by S. lavandulaefolia. Twenty-four participants received single doses of placebo, 25 microl and 50 microl of a standardised essential oil of S. lavandulaefolia in an order dictated by a Latin square. Doses were separated by a 7-day washout period. Cognitive performance was assessed prior to the day's treatment and at 1, 2.5, 4 and 6 h thereafter using the Cognitive Drug Research (CDR) computerised test battery. Subjective mood ratings were measured using Bond-Lader visual analogue scales. The primary outcome measures were scores on the five cognitive factors that can be derived by factor analysis of the task outcomes from the CDR battery. The results showed that administration of S. lavandulaefolia resulted in a consistent improvement for both the 25- and 50-microl dose on the 'Speed of Memory' factor. There was also an improvement on the 'Secondary Memory' factor for the 25-microl dose. Mood was consistently enhanced, with increases in self-rated 'alertness', 'calmness' and 'contentedness' following the 50-microl dose and elevated 'calmness' following 25 microl. These results represent further evidence that Salvia is capable of acute modulation of mood and cognition in healthy young adults. The data also suggest that previous reports of memory enhancement by Salvia may be due to more efficient retrieval of target material.

Autonomic function assessed by heart rate variability is normal in Alzheimer's disease and vascular dementia.

Heart rate variability (HRV) is a sensitive method for the assessment of autonomic function and requires little cooperation from the subject, making it suitable for use in dementia. Preliminary studies have suggested that HRV may be impaired in Alzheimer's disease (AD). HRV has not been studied in vascular dementia (VAD). We investigate autonomic function in AD and VAD, using power spectral analysis of HRV. One hundred and fourteen participants were evaluated (14 AD, 20 VAD and 80 controls). The resting ECG was recorded for 5 min with participants in the supine position. Power spectral analysis used to obtain spectral bands in the very-low-frequency (<0.04 Hz), low-frequency (0.04-0.15 Hz) and high-frequency (0.15-0.40 Hz) bands and total spectral power (<0.40 Hz) according to international HRV guidelines. There were no differences in HRV in patients with AD or VAD when compared with controls.

APOE epsilon4 and cognitive decline in older stroke patients with early cognitive impairment.

BACKGROUND: Dementia is common post stroke, but the potential role of early cognitive impairment and APOE epsilon4 as risk factors is unclear. METHOD: Stroke survivors older than 75 years without dementia at 3 months post stroke received a detailed neuropsychological evaluation at 3 and 15 months post stroke, which included the Cambridge Assessment of Mental Disorders in the Elderly (CAMCOG). Early cognitive impairment was diagnosed using the criteria for cognitive impairment/no dementia (vascular CIND). APOE genotype was determined using a standardized method. RESULTS: One hundred thirty-seven older stroke patients without dementia (mean age 80.6 +/- 4.3, mean CAMCOG score 83.5 +/- 10.4, 68 women) participated in the study, of whom 40 met the criteria for CIND. Stroke patients with one or more APOE epsilon4 alleles were significantly more likely to have CIND (14/40 vs 17/97, odds ratio = 2.5, 95% CI 1.1 to 5.8). Over the 1 year of follow-up, CIND patients with one or more APOE epsilon4 alleles had a mean decline on the total CAMCOG of 2.7 points compared with an improvement of >4 points among patients without APOE epsilon4 (T = 2.9 p = 0.006). CIND patients with an APOE epsilon4 allele also experienced greater decline in memory (T = 2.5, p = 0.015). CONCLUSION: In older stroke patients with early cognitive impairment, the presence of an APOE epsilon4 allele is associated with greater progression of cognitive decline. This has implications for interventions aimed at the secondary prevention of dementia in stroke patients.

Neuropsychological characteristics of mild vascular cognitive impairment and dementia after stroke.

BACKGROUND: Post-stroke cognitive impairment is frequent, with characteristic impairments of attentional and executive performance. OBJECTIVE: The study aims to determine whether the profile and severity of impairment in vascular Cognitive Impairment No Dementia (vascular CIND) is intermediate between that seen in stroke patients without significant cognitive impairment and patients with post-stroke dementia and thus to establish if the potential value of vascular CIND is a useful concept for predicting further cognitive decline and dementia in stroke patients. METHODS: Stroke patients (n=381) > 75 were recruited from representative hospital-based stroke registers in Tyneside and Wearside, UK. Sixty six age matched controls were also recruited. A detailed battery of neuropsychological assessments was completed 3 months post stroke. RESULTS: Deficits of attention (z=5.7; p <0.0001) and executive function (z=5.9; p <0.0001) were seen even in stroke patients without vascular CIND, compared to controls. However, stroke patients with CIND were significantly more impaired again on tests of executive function (z=10.3; p <0.0001) compared to those not meeting CIND criteria; and also had greater impairments of memory (z=10.4; p <0.0001) and language expression (z=10.1; p <0.0001). A similar overall profile of deficits was evident in the CIND and the dementia group, but specific deficits were significantly more pronounced in those with dementia, particularly in orientation (z=7.2; p <0.0001) and memory (z=5.8; p <0.0001). CONCLUSIONS: The current study indicates that attentional and executive impairments are frequent in stroke patients, but deficits of memory, orientation and language are more indicative of CIND and dementia. Further longitudinal studies are required to clarify the relationship between specific lesions and the progression of specific cognitive deficits in post-stroke patients.

NINDS AIREN neuroimaging criteria do not distinguish stroke patients with and without dementia.

OBJECTIVE: To determine the utility of the neuroimaging component within the National Institute of Neurological Disorders and Stroke (NINDS) Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria for vascular dementia for distinguishing between patients with and without dementia in the context of cerebrovascular disease. METHOD: One hundred twenty-five poststroke patients age > or =75 (27 with and 98 without poststroke dementia) from representative hospital-based stroke registers in the North East of England were evaluated using a 1.5 T MR scanner. The proportion of patients with and without poststroke dementia meeting the imaging component of the NINDS AIREN criteria was determined, and hippocampal atrophy (measured using the Schelten scale) was compared between the two groups. RESULTS: There were no significant differences between the patients with and without poststroke dementia on any criteria of the imaging parameters within the NINDS AIREN criteria. In addition, there were no significant differences in the number or size of cortical or subcortical infarcts between the two groups, with 13 patients without dementia having cortical infarcts >50 mm. Patients with dementia had greater hippocampal atrophy (right: Mann-Whitney U test, Z = 2.5, p = 0.01; left: Mann-Whitney U test, Z = 2.5, p = 0.01). CONCLUSION: The neuroimaging component of the NINDS AIREN criteria does not distinguish between older patients with and without poststroke dementia.

Are Parkinson's disease with dementia and dementia with Lewy bodies the same entity?

The diagnosis of Parkinson's disease with dementia (PDD) or dementia with Lewy bodies (DLB) is based on an arbitary distinction between the time of onset of motor and cognitive symptoms. These syndromes share many neurobiological similarities, but there are also differences. Deposition of beta-amyloid protein is more marked and more closely related to cognitive impairment in DLB than PDD, possibly contributing to dementia at onset. The relatively more severe executive impairment in DLB than PDD may relate to the loss of frontohippocampal projections in DLB. Visual hallucinations and delusions associate with more abundant Lewy body pathology in temporal cortex in DLB. The differential involvement of pathology in the striatum may account for the differences in parkinsonism. Longitudinal studies with neuropathological and neurochemical evaluations will be essential to enable more robust comparisons and determine pathological substrates contributing to the differences in cognitive, motor, and psychiatric symptoms.

Influence of the amyloid precursor protein locus on dementia in Down syndrome.

BACKGROUND: The amyloid precursor protein (APP) locus on chromosome 21 influences the development of Alzheimer disease. METHOD: The authors investigated the relationship between a tetranucleotide repeat on intron 7 of the APP gene and the age at onset of dementia in Down syndrome (DS). RESULTS: There was a 13-year difference in the age at onset of dementia in DS associated with the number of tetranucleotide repeat alleles in APP. CONCLUSION: APP is an important locus predicting the age at onset of dementia in people with Down syndrome.

Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers.

Sage (Salvia) has a longstanding reputation in British herbal encyclopaedias as an agent that enhances memory, although there is little evidence regarding the efficacy of sage from systematized trials. Based on known pharmacokinetic and binding properties, it was hypothesised that acute administration of sage would enhance memory in young adult volunteers. Two experiments utilised a placebo-controlled, double-blind, balanced, crossover methodology. In Trial 1, 20 participants received 50, 100 and 150 microl of a standardised essential oil extract of Salvia lavandulaefolia and placebo. In Trial 2, 24 participants received 25 and 50 microl of a standardised essential oil extract of S. lavandulaefolia and placebo. Doses were separated by a 7-day washout period with treatment order determined by Latin squares. Assessment was undertaken using the Cognitive Drug Research computerised test battery prior to treatment and 1, 2.5, 4 and 6 h thereafter. The primary outcome measures were immediate and delayed word recall. The 50 microl dose of Salvia essential oil significantly improved immediate word recall in both studies. These results represent the first systematic evidence that Salvia is capable of acute modulation of cognition in healthy young adults.

Cardiovascular effects of donepezil in patients with dementia.

Heart rate variability is used to assess cardiovascular autonomic function. The cholinesterase inhibitor donepezil potentially affects parasympathetic activity. Twenty participants with Alzheimer's disease or dementia with Lewy bodies were treated with donepezil in a pilot study. Power spectral analysis was used to analyse 5 min of beat-to-beat RR interval data in 15 cases. Heart rate variability was significantly reduced following treatment with donepezil; mainly for high frequency (median changed from 581 to 78 ms2; p = 0.001) but also for total power (median changed from 1,563 to 844 ms2; p = 0.047). Donepezil may adversely influence cardiovascular autonomic control. These results indicate the need for larger controlled trials to further investigate the cardiovascular effects of donepezil.

Fluctuations in attention: PD dementia vs DLB with parkinsonism.

BACKGROUND: Marked impairments in and fluctuation of attention are characteristic of dementia with Lewy bodies (DLB). The comparative impairment of these cognitive domains in PD and PD dementia (PD dementia) has not been studied, and is important to the conceptual understanding of parkinsonian dementias. METHOD: Detailed evaluations of attention and fluctuating attention (Cognitive Drug Research computerized battery) were undertaken in 278 subjects (50 DLB, 48 PD dementia, 50 PD, 80 AD, 50 elderly controls) from the Newcastle dementia register and the Stavanger PD register (controls, PD, and PD dementia patients were recruited from both centers). DLB, AD, PD, and PD dementia were diagnosed using operationalized criteria. RESULTS: Impairments in reaction time, vigilance, and fluctuating attention were comparable in patients with DLB and PD dementia, but were less substantially impaired in patients with DLB without parkinsonism. Patients with PD had significantly greater impairment of cognitive reaction time than elderly controls, and comparable impairments of cognitive reaction time to patients with AD. Patients with PD, however, did not exhibit fluctuation of attention. CONCLUSION: The profile of attentional impairments and fluctuating attention is similar in PD dementia and DLB with parkinsonism. The current findings do not support the current arbitrary distinctions between these patient groups. Importantly, patients with PD do not experience fluctuating attention.

Patterns of cerebral atrophy in dementia with Lewy bodies using voxel-based morphometry.

Previous cross-sectional MRI studies based on region-of-interest analyses have shown that increased cerebral atrophy is a feature of both Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Relative preservation of the hippocampus and temporal lobe structures in DLB compared to AD has been reported in region-of-interest-based studies. Recently, image processing techniques such as voxel-based morphometry (VBM) have been developed to provide an unbiased, visually informative, and comprehensive means of studying patterns of cerebral atrophy. We report the first study to use the voxel-based approach to assess patterns of cerebral atrophy in DLB compared to control subjects and AD. Regional gray matter volume loss was observed bilaterally in the temporal and frontal lobes and insular cortex of patients with DLB compared to control subjects. Comparison of dementia groups showed preservation of the medial temporal lobe, hippocampus, and amygdala in DLB relative to AD. Significant gray matter loss was also observed in the thalamus of AD patients compared to DLB.