Tracer‐specific reference tissues selection improves detection of 18F‐FDG, 18F‐florbetapir,and 18F‐flortaucipir PET SUVR changes in Alzheimer's disease

This study sought to identify a reference tissue‐based quantification approach for improving the statistical power in detecting changes in brain glucose metabolism, amyloid, and tau deposition in Alzheimer''s disease studies. A total of 794, 906, and 903 scans were included for ¹⁸F‐FDG, ¹⁸F‐florbetapir, and ¹⁸F‐flortaucipir, respectively. Positron emission tomography (PET) and T1‐weighted images of participants were collected from the Alzheimer''s disease Neuroimaging Initiative database, followed by partial volume correction. The standardized uptake value ratios (SUVRs) calculated from the cerebellum gray matter, centrum semiovale, and pons were evaluated at both region of interest (ROI) and voxelwise levels. The statistical power of reference tissues in detecting longitudinal SUVR changes was assessed via paired t‐test. In cross‐sectional analysis, the impact of reference tissue‐based SUVR differences between cognitively normal and cognitively impaired groups was evaluated by effect sizes Cohen''s d and two sample t‐test adjusted by age, sex, and education levels. The average ROI t values of pons were 86.62 and 38.40% higher than that of centrum semiovale and cerebellum gray matter in detecting glucose metabolism decreases, while the centrum semiovale reference tissue‐based SUVR provided higher t values for the detection of amyloid and tau deposition increases. The three reference tissues generated comparable d images for ¹⁸F‐FDG, ¹⁸F‐florbetapir, and ¹⁸F‐flortaucipir and comparable t maps for ¹⁸F‐florbetapir and ¹⁸F‐flortaucipir, but pons‐based t map showed superior performance in ¹⁸F‐FDG. In conclusion, the tracer‐specific reference tissue improved the detection of ¹⁸F‐FDG, ¹⁸F‐florbetapir, and ¹⁸F‐flortaucipir PET SUVR changes, which helps the early diagnosis, monitoring of disease progression, and therapeutic response in Alzheimer''s disease.     

18F-FDG PET,the early phases and the delivery rate of 18F-AV45 PET as proxies of cerebral blood flow in Alzheimer's disease: Validation against 15O-H2O PET

IntroductionDual-biomarker positron emission tomography (PET), providing complementary information on cerebral blood flow and amyloid-β deposition, is of clinical interest for Alzheimer's disease (AD). The purpose of this study was to validate the perfusion components of early-phase ¹⁸F-florbetapir (eAV45), the ¹⁸F-AV45 delivery rate (R1), and ¹⁸F-FDG against ¹⁵O-H₂O PET and assess how they change with disease severity.MethodsThis study included ten controls, 19 amnestic mild cognitive impairment, and 10 AD dementia subjects. Within-subject regional correlations between modalities, between-group regional and voxel-wise analyses of covariance per modality, and receiver operating characteristic analyses for discrimination between groups were performed.ResultsFDG standardized uptake value ratio, eAV45 (0–2 min) standardized uptake value ratio, and AV45-R1 were significantly associated with H₂O PET (regional Pearson r = 0.54–0.82, 0.70–0.94, and 0.65–0.92, respectively; P < .001). All modalities confirmed reduced cerebral blood flow in the posterior cingulate of patients with amnestic mild cognitive impairment and AD dementia, which was associated with lower cognition (r = 0.36–0.65, P < .025) and could discriminate between patient and control groups (area under the curve > 0.80). However, eAV45 was less sensitive to reflect the disease severity than AV45-R1 or FDG.DiscussionR1 is preferable over eAV45 for accurate representation of brain perfusion in dual-biomarker PET for AD.     

Peripheral glucose metabolism and insulin sensitivity in Alzheimer's disease

Twenty-four patients with Alzheimer's disease and matched controls were examined with reference to metabolic parameters such as peripheral insulin and glucose metabolism, serum lipid concentrations and blood pressure levels. Blood glucose levels and insulin response were measured during an intravenous glucose tolerance test and peripheral insulin sensitivity was estimated with the hyperinsulinemic euglycemic clamp technique. There were no differences recorded between the two groups in glucose metabolism, triglyceride, cholesterol or HDL-cholesterol levels. The patients with Alzheimer's disease had significantly lower blood pressure levels, which partly could be explained by ongoing treatment with neuroleptics and antidepressives. Previous findings of higher insulin levels in Alzheimer's disease could not be verified.     

Comparison of velocity- and acceleration-selective arterial spin labeling with [15O]H2O positron emission tomography

In the last decade spatially nonselective arterial spin labeling (SNS-ASL) methods such as velocity-selective ASL (VS-ASL) and acceleration-selective ASL have been introduced, which label spins based on their flow velocity or acceleration rather than spatial localization. Since labeling also occurs within the imaging plane, these methods suffer less from transit delay effects than traditional ASL methods. However, there is a need for validation of these techniques. In this study, a comparison was made between these SNS-ASL techniques with [¹⁵O]H₂O positron emission tomography (PET), which is regarded as gold standard to measure quantitatively cerebral blood flow (CBF) in humans. In addition, the question of whether these techniques suffered from sensitivity to arterial cerebral blood volume (aCBV), as opposed to producing pure CBF contrast, was investigated. The results show high voxelwise intracranial correlation (0.72 to 0.89) between the spatial distribution of the perfusion signal from the SNS-ASL methods and the PET CBF maps. A similar gray matter (GM) CBF was measured by dual VS-ASL compared with PET (46.7±4.1 versus 47.1±6.5 mL/100 g/min, respectively). Finally, only minor contribution of aCBV patterns in GM to all SNS-ASL methods was found compared with pseudo-continuous ASL. In conclusion, VS-ASL provides a similar quantitative CBF, and all SNS-ASL methods provide qualitatively similar CBF maps as [¹⁵O]H₂O PET.     

Increased cortical atrophy in patients with Alzheimer's disease and type 2 diabetes mellitus

BACKGROUND: The risk of Alzheimer's disease (AD) is increased in type 2 diabetes (DM2). This increased risk has been attributed to vascular comorbidity, but other mechanisms, such as accelerated ageing of the brain, have also been implicated. OBJECTIVE: To determine whether AD in patients with DM2 is associated with an increased occurrence of vascular lesions in the brain, by increased cerebral atrophy, or a combination of both. METHODS: In total, 29 patients with AD and DM2 and 58 patients with AD and without DM2 were included in the study. Clinical characteristics were recorded, and a neuropsychological examination and magnetic resonance imaging (MRI) scan were performed. MRI scans were rated for cortical and subcortical atrophy, medial temporal lobe atrophy, white matter lesions, and infarcts. RESULTS: The neuropsychological profiles of the two groups were identical. Patients with AD and DM2 had increased cortical atrophy on MRI (p<0.05) compared with the non-DM2 group. In addition, infarcts were more common (odds ratio 2.4; 95% CI 0.8 to 7.8), but this effect did not account for the increased atrophy. The other MR measures did not differ between the groups. CONCLUSION: The results suggest that non-vascular mechanisms, leading to increased cortical atrophy, are also involved in the increased risk of AD in DM2.     

Quantification of [18F]DPA-714 binding in the human brain: initial studies in healthy controls and Alzheimer's disease patients

Fluorine-18 labelled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide ([¹⁸F]DPA-714) binds to the 18-kDa translocator protein (TSPO) with high affinity. The aim of this initial methodological study was to develop a plasma input tracer kinetic model for quantification of [¹⁸F]DPA-714 binding in healthy subjects and Alzheimer''s disease (AD) patients, and to provide a preliminary assessment whether there is a disease-related signal. Ten AD patients and six healthy subjects underwent a dynamic positron emission tomography (PET) study along with arterial sampling and a scan protocol of 150 minutes after administration of 250±10 MBq [¹⁸F]DPA-714. The model that provided the best fits to tissue time activity curves (TACs) was selected based on Akaike Information Criterion and F-test. The reversible two tissue compartment plasma input model with blood volume parameter was the preferred model for quantification of [¹⁸F]DPA-714 kinetics, irrespective of scan duration, volume of interest, and underlying volume of distribution (V_T). Simplified reference tissue model (SRTM)-derived binding potential (BP_ND) using cerebellar gray matter as reference tissue correlated well with plasma input-based distribution volume ratio (DVR). These data suggest that [¹⁸F]DPA-714 cannot be used for separating individual AD patients from heathy subjects, but further studies including TSPO binding status are needed to substantiate these findings.     

维生素与阿尔茨海默病

阿尔茨海默病（AD）是多种病因导致的神经退行性疾病之一。维生素是人体不可或缺的微量元素。近年来,越来越多的证据表明,维生素与AD之间有一定的关联。维生素在AD的发生和发展过程中起着重要作用。该文对维生素B₁₂、维生素D、维生素E与AD的关系进行了综述。     

Reversal of metabolic deficits by lipoic acid in a triple transgenic mouse model of Alzheimer's disease: a 13C NMR study

Alzheimer''s disease is an age-related neurodegenerative disease characterized by deterioration of cognition and loss of memory. Several clinical studies have shown Alzheimer''s disease to be associated with disturbances in glucose metabolism and the subsequent tricarboxylic acid (TCA) cycle-related metabolites like glutamate (Glu), glutamine (Gln), and N-acetylaspartate (NAA). These metabolites have been viewed as biomarkers by (a) assisting early diagnosis of Alzheimer''s disease and (b) evaluating the efficacy of a treatment regimen. In this study, 13-month-old triple transgenic mice (a mouse model of Alzheimer''s disease (3xTg-AD)) were given intravenous infusion of [1-¹³C]glucose followed by an ex vivo ¹³C NMR to determine the concentrations of ¹³C-labeled isotopomers of Glu, Gln, aspartate (Asp), GABA, myo-inositol, and NAA. Total (¹²C+¹³C) Glu, Gln, and Asp were quantified by high-performance liquid chromatography to calculate enrichment. Furthermore, we examined the effects of lipoic acid in modulating these metabolites, based on its previously established insulin mimetic effects. Total ¹³C labeling and percent enrichment decreased by ∼50% in the 3xTg-AD mice. This hypometabolism was partially or completely restored by lipoic acid feeding. The ability of lipoic acid to restore glucose metabolism and subsequent TCA cycle-related metabolites further substantiates its role in overcoming the hypometabolic state inherent in early stages of Alzheimer''s disease.     

Hypermetabolic state in the 7-month-old triple transgenic mouse model of Alzheimer's disease and the effect of lipoic acid: a 13C-NMR study

Alzheimer''s disease (AD) is characterized by age-dependent biochemical, metabolic, and physiologic changes. These age-dependent changes ultimately converge to impair cognitive functions. This study was carried out to examine the metabolic changes by probing glucose and tricarboxylic acid cycle metabolism in a 7-month-old triple transgenic mouse model of AD (3xTg-AD). The effect of lipoic acid, an insulin-mimetic agent, was also investigated to examine its ability in modulating age-dependent metabolic changes. Seven-month-old 3xTg-AD mice were given intravenous infusion of [1-¹³C]glucose followed by an ex vivo ¹³C nuclear magnetic resonance to determine the concentrations of ¹³C-labeled isotopomers of glutamate, glutamine, aspartate, gamma aminobutyric acid, and N-acetylaspartate. An intravenous infusion of [1-¹³C]glucose+[1,2-¹³C]acetate was given for different periods of time to distinguish neuronal and astrocytic metabolism. Enrichments of glutamate, glutamine, and aspartate were calculated after quantifying the total (¹²C+¹³C) concentrations by high-performance liquid chromatography. A hypermetabolic state was clearly evident in 7-month-old 3xTg-AD mice in contrast to the hypometabolic state reported earlier in 13-month-old mice. Hypermetabolism was evidenced by prominent increase of ¹³C labeling and enrichment in the 3xTg-AD mice. Lipoic acid feeding to the hypermetabolic 3xTg-AD mice brought the metabolic parameters to the levels of nonTg mice.     

Levels of CSF prostaglandin E2, cognitive decline, and survival in Alzheimer's disease

BACKGROUND: Although epidemiological, clinical, and experimental evidence indicates that the inducible isoform of cyclo-oxygenase (COX-2) may be involved in the pathogenesis of several neurodegenerative disorders, the mechanisms whereby COX-2 contributes to Alzheimer's disease are largely unknown. OBJECTIVE: To undertake a longitudinal study of CSF levels of a major product of COX activity, prostaglandin E2 (PGE2), in relation to cognitive decline and survival in patients with Alzheimer's disease. METHODS: CSF PGE2 was measured on at least three annual visits in 35 controls and 33 Alzheimer patients (26 necropsy confirmed) who completed the Cambridge cognitive assessment (CAMCOG). RESULTS: Compared with controls, CSF PGE2 was higher in patients with mild memory impairment, but lower in those with more advanced Alzheimer's disease. The median survival time of patients with higher initial PGE2 levels was five years longer than those with lower levels. CONCLUSIONS: COX activity in Alzheimer's disease varies with stage of the disease. PGE2 levels correlate positively with patient survival. These findings suggest that inhibition of COX activity does not represent a major target for the pharmacological treatment of Alzheimer's disease.     

Comparing cerebral perfusion in Alzheimer's disease and Parkinson's disease dementia: an ASL-MRI study

Emerging evidence suggests that Alzheimer''s disease (AD) and Parkinson''s disease dementia (PDD) share neurodegenerative mechanisms. We sought to directly compare cerebral perfusion in these two conditions using arterial spin labeling magnetic resonance imaging (ASL-MRI). In total, 17 AD, 20 PDD, and 37 matched healthy controls completed ASL and structural MRI, and comprehensive neuropsychological testing. Alzheimer''s disease and PDD perfusion was analyzed by whole-brain voxel-based analysis (to assess absolute blood flow), a priori specified region of interest analysis, and principal component analysis (to generate a network differentiating the two groups). Corrections were made for cerebral atrophy, age, sex, education, and MRI scanner software version. Analysis of absolute blood flow showed no significant differences between AD and PDD. Comparing each group with controls revealed an overlapping, posterior pattern of hypoperfusion, including posterior cingulate gyrus, precuneus, and occipital regions. The perfusion network that differentiated AD and PDD groups identified relative differences in medial temporal lobes (AD<PDD) and right frontal cortex (PDD<AD). In conclusion, the pattern of cerebral hypoperfusion is very similar in AD and PDD. This suggests closely linked mechanisms of neurodegeneration mediating the evolution of dementia in both conditions.     

De novo development of artistic creativity in Alzheimer's disease

The case of an 82-year-old female with probable Alzheimer''s disease (AD), who developed unusual artistic creativity after development of her disease, is described. The possible pathogenetic mechanism is discussed. The patient showed no inclination toward visual arts during her premorbid years. However, 4 years after development of AD suggestive symptoms she started painting beautiful pictures rather impulsively. Some such paintings have been appreciated even by a qualified art expert. Such de novo development of artistic creativity had been described earlier in subjects with the semantic form of fronto-temporal dementia (FTD), but not in AD. The prevailing concept of lateralized compromise and paradoxical functional facilitation, proposed in connection with FTD subjects, may not be applicable in AD subjects where the affection is more diffuse and more posterior in the brain. Hence, the likely pathogenetic mechanism involved in the case described may remain uncertain. Possibilities are discussed.     

Construction of a novel Chinese normal brain database using 18F-FDG PET images and MIMneuro software,the initial application in epilepsy

Purpose: To create a standard Western Chinese normal functional brain database for quantitative analysis using 2-deoxy-2-[18F] fluoro-d-glucose (¹⁸F-FDG) positron emission tomography (PET) images and MIMneuro software.

Methods: 78 healthy right-handed Chinese volunteers from Tangdu Hospital were scanned using ¹⁸F-FDG PET to evaluate brain metabolism between March and October 2016. All PET images were processed using MIMneuro software to create a normal database platform. The platform included anatomical optimization to facilitate spatial localization of abnormalities and a statistical comparison with normal cases utilizing the Z-scores, which represent the number of standard deviations from the mean of the normal controls in the database.

Results: The novel Chinese brain metabolism database platform including 78 healthy volunteers (male: female 40:38; age 3–78 years, mean age, 45 years) was constructed based on the MIMneuro software, which increased the diagnostic confidence in the test patient by quantifying and emphasizing the abnormality. The BrainAlign^TM deformation algorithm of MIMneuro matched the size, shape, and orientation of the patient's brain scan to a template brain for comparison against a database of normal controls. The quantitative analysis performed on a voxel and regional level was useful in assessing the areas of abnormalities.

Conclusions: A novel Chinese ¹⁸F-FDG PET-based normal brain function database was created to highlight the local regions of abnormal metabolic activity through quantitative comparisons against the normal database. The Z-scores obtained by MIMneuro potentially aid in visualizing and quantifying the subtle lesions on ¹⁸FDG-PET scan images as observed in a patient diagnosed with epilepsy.     

Visuo-cognitive skill deficits in Alzheimer's disease and Lewy body disease: A comparative analysis

Dementia is a chronic neurodegenerative disorder characterized by progressive cognitive loss. Alzheimer''s disease (AD) and the Lewy body disease are the two most common causes of age-related degenerative dementia. Visuo-cognitive skills are a combination of very different cognitive functions being performed by the visual system. These skills are impaired in both AD and dementia with Lewy bodies (DLB). The aim of this review is to evaluate various studies for these visuo-cognitive skills. An exhaustive internet search of all relevant medical databases was carried out using a series of key-word applications, including The Cochrane Library, MEDLINE, PSYCHINFO, EMBASE, CINAHL, AMED, SportDiscus, Science Citation Index, Index to Theses, ZETOC, PEDro and occupational therapy (OT) seeker and OT search. We reviewed all the articles until March 2013 with key words of: Visual skills visual cognition dementia AD, but the direct neurobiological etiology is difficult to establish., Dementia of Lewy body disease. Although most studies have used different tests for studying these abilities, in general, these tests evaluated the individual''s ability of (1) visual recognition, (2) visual discrimination, (3) visual attention and (4) visuo-perceptive integration. Performance on various tests has been evaluated for assessing these skills. Most studies assessing such skills show that these skills are impaired in DLB as compared with AD. Visuo-cognitive skills are impaired more in DLB as compared with AD. These impairments have evident neuropathological correlations, but the direct neurobiological etiology is difficult to establish.     

Protective Effects of Physical Exercise in Alzheimer's Disease and Parkinson's Disease: A Narrative Review

Alzheimer''s disease (AD) and Parkinson''s disease (PD) are devastating, frequent, and still incurable neurodegenerative diseases that manifest as cognitive and motor disorders. Epidemiological data support an inverse relationship between the amount of physical activity (PA) undertaken and the risk of developing these two diseases. Beyond this preventive role, exercise may also slow down their progression. Several mechanisms have been suggested for explaining the benefits of PA in the prevention of AD. Aerobic physical exercise (PE) activates the release of neurotrophic factors and promotes angiogenesis, thereby facilitating neurogenesis and synaptogenesis, which in turn improve memory and cognitive functions. Research has shown that the neuroprotective mechanisms induced by PE are linked to an increased production of superoxide dismutase, endothelial nitric oxide synthase, brain-derived neurotrophic factor, nerve growth factor, insulin-like growth factor, and vascular endothelial growth factor, and a reduction in the production of free radicals in brain areas such as the hippocampus, which is particularly involved in memory. Other mechanisms have also been reported in the prevention of PD. Exercise limits the alteration in dopaminergic neurons in the substantia nigra and contributes to optimal functioning of the basal ganglia involved in motor commands and control by adaptive mechanisms involving dopamine and glutamate neurotransmission. AD and PD are expansive throughout our ageing society, and so even a small impact of nonpharmacological interventions, such as PA and exercise, may have a major impact on public health.     

A prospective longitudinal study of apathy in Alzheimer's disease

BACKGROUND: Apathy and depression are the most frequent behavioural and psychiatric disorders in Alzheimer's disease, and may both have a negative impact on the progression of the illness. OBJECTIVES: To examine the clinical correlates of apathy in Alzheimer's disease (AD), and to determine whether apathy is a significant predictor of more rapid cognitive, functional and emotional decline. METHODS: Using a structured psychiatric evaluation, we examined a consecutive series of 354 subjects meeting clinical criteria for AD. Apathy was assessed by the Apathy Scale, and diagnosed using standardised criteria. Additional measurements included scales for depression, functional impairment, and global cognitive functions. A follow up evaluation was carried out in 247 patients (70% of the total sample) between 1 and 4 years after the baseline evaluation. RESULTS: Apathy was significantly associated with older age (p = 0.009), and a higher frequency of minor and major depression (p < 0.0001). Apathy at baseline was a significant predictor of depression at follow up (p = 0.01), and was associated with a faster cognitive (p = 0.0007) and functional decline (p = 0.006). CONCLUSIONS: Apathy in AD is a behavioural marker of a more aggressive dementia, characterised by a faster progression of cognitive, functional, and emotional impairment.     

Comparison of brain MRI and 18F-FDG PET in the differential diagnosis of multiple system atrophy from Parkinson's disease.

To investigate the diagnostic value of brain magnetic resonance image (MRI) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in the differentiation of multiple system atrophy (MSA) from Parkinson's disease (PD). Thirty-five patients with MSA (23 MSA-P and 12 MSA-C) and 17 patients with PD were included in this study. Overall correct diagnosis rates between clinical and imaging diagnosis among MSA-P, MSA-C, and PD patients were 80% for visual MRI analysis, 88.5% for visual (18)F-FDG PET analysis, and 84.3% for SPM-supported analysis of (18)F-FDG PET. The sensitivity of brain MRI, and visual and SPM analysis of (18)F-FDG PET in differentiating MSA from PD was 72.7%, 90.9%, and 95.5%, respectively, the specificity was 100% for each imaging analysis, the positive predictive value was 100% for each imaging analysis, and the negative predictive value was 60%, 81.8%, and 90%, respectively. Our results suggest that brain MRI and (18)F-FDG PET are diagnostically useful in differentiating MSA (MSA-P and MSA-C) from PD, and indicate that (18)F-FDG PET has a tendency toward higher sensitivity compared to brain MRI, but a larger longitudinal study including pathological data will be required to confirm our findings.     

Latrepirdine: molecular mechanisms underlying potential therapeutic roles in Alzheimer's and other neurodegenerative diseases

Latrepirdine (Dimebon^TM) was originally marketed as a non-selective antihistamine in Russia. It was repurposed as an effective treatment for patients suffering from Alzheimer''s disease (AD) and Huntington''s disease (HD) following preliminary reports showing its neuroprotective functions and ability to enhance cognition in AD and HD models. However, latrepirdine failed to show efficacy in phase III trials in AD and HD patients following encouraging phase II trials. The failure of latrepirdine in the clinical trials has highlighted the importance of understanding the precise mechanism underlying its cognitive benefits in neurodegenerative diseases before clinical evaluation. Latrepirdine has shown to affect a number of cellular functions including multireceptor activity, mitochondrial function, calcium influx and intracellular catabolic pathways; however, it is unclear how these properties contribute to its clinical benefits. Here, we review the studies investigating latrepirdine in cellular and animal models to provide a complete evaluation of its mechanisms of action in the central nervous system. In addition, we review recent studies that demonstrate neuroprotective functions for latrepirdine-related class of molecules including the β-carbolines and aminopropyl carbazoles in AD, Parkinson''s disease and amyotrophic lateral sclerosis models. Assessment of their neuroprotective effects and underlying biological functions presents obvious value for developing structural analogues of latrepirdine for dementia treatment.     

Hippocampal atrophy on MRI in frontotemporal lobar degeneration and Alzheimer's disease

BACKGROUND: Hippocampal atrophy on magnetic resonance imaging (MRI) is an early characteristic of Alzheimer's disease. However, hippocampal atrophy may also occur in other dementias, such as frontotemporal lobar degeneration (FTLD). OBJECTIVE: To investigate hippocampal atrophy on MRI in FTLD and its three clinical subtypes, in comparison with Alzheimer's disease, using volumetry and a visual rating scale. METHODS: 42 patients with FTLD (17 frontotemporal dementia, 13 semantic dementia, and 12 progressive non-fluent aphasia), 103 patients with Alzheimer's disease, and 73 controls were included. Hippocampal volumetry and the easily applicable medial temporal lobe atrophy (MTA) rating scale were applied to assess hippocampal atrophy. RESULTS: Multivariate analysis of variance for repeated measures showed an effect of diagnostic group on hippocampal volume. There was a significant diagnosis by side (left v right) interaction. Both FTLD and Alzheimer's disease showed hippocampal atrophy compared with controls. Results of the visual MTA rating scale confirmed these findings. Within the FTLD subtypes there were marked differences in hippocampal atrophy. Frontotemporal dementia and semantic dementia showed bilateral hippocampal atrophy, and in semantic dementia the left hippocampus was smaller than in Alzheimer's disease. No significant hippocampal atrophy was detected in non-fluent progressive aphasia. CONCLUSIONS: Hippocampal atrophy is not only a characteristic of Alzheimer's disease but also occurs in FTLD. The three clinical subtypes of FTLD show different patterns of hippocampal atrophy.     

Impact of White Matter Lesions on Depression in the Patients with Alzheimer's Disease

Objective

Comorbid depression is common in patients with Alzheimer''s disease (AD). An increase in white matter lesions (WMLs) has been associated with depression in both elderly individuals with normal cognition and patients with Alzheimer''s disease. We investigated whether the severity and location of WMLs influence the association between WMLs and comorbid depression in AD.

Methods

We enrolled 93 AD patients from Seoul National University Bundang Hospital. We administered both the Mini International Neuropsychiatric Inventory (MINI) and the Korean version of the Consortium to Establish a Registry for Alzheimer''s Disease Assessment Packet (CERAD-K) clinical and neuropsychological battery. Subjects also underwent brain magnetic resonance imaging (MRI). We diagnosed AD according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer''s Disease and Related Disorders Association. We diagnosed depressive disorders according to the DSM-IV diagnostic criteria, and evaluated the severity of depressive symptoms using the Korean version of the Geriatric Depression Scale (GDS-K). We quantified the WML volumes from the brain MRI using a fully automated segmentation algorithm.

Results

The log of the WML volume in the frontal lobe was significantly associated with depressive disorders (odds ratio=1.905, 95% CI=1.027-3.533, p=0.041), but not with the severity of depressive symptoms as measured by the GDS-K.

Conclusion

The WML volume in the frontal lobe conferred a risk of comorbid depressive disorders in AD, which implies that comorbid depression in AD may be attributed to vascular causes.