Quantitative MRI biomarkers of cognitive morbidity in temporal lobe epilepsy

PURPOSE: To determine the relation between neuropsychological morbidity, quantitative magnetic resonance imaging (MRI) measures of whole brain structure, and clinical seizure factors reflecting epilepsy cause, course, and treatment. METHODS: Quantitative MRI measurements of total (whole brain) cerebrospinal fluid (CSF) and gray- and white-matter volumes and clinical seizure features were examined in relation to summary indices of cognitive morbidity in 96 patients with temporal lobe epilepsy. MRI volumes were adjusted for intracranial volume (ICV), and cognitive scores were adjusted for age, education, and gender, based on a sample of 82 healthy controls. RESULTS: Whole-brain volumes (gray, white, and CSF) were abnormal in chronic temporal lobe epilepsy patients compared with controls and were related significantly to neuropsychological morbidity, especially total CSF. Statistical modeling demonstrated that markers of total atrophy (CSF) was the primary mediator of the relation between clinical seizure variables and neuropsychological morbidity. CONCLUSIONS: Quantitative measurements of overall brain abnormality (atrophy) in temporal lobe epilepsy are clinically meaningful markers that are associated with increased cognitive morbidity. These biomarkers appear to mediate the adverse effects of some clinical seizure variables on cognition.     

MRI measures and progression of cognitive decline in nondemented elderly attending a memory clinic

OBJECTIVE: To investigate whether MRI-based volumes of whole brain, medial temporal lobe and white matter hyperintensities (WMH) predict progression of cognitive decline in a sample of nondemented elderly. METHODS: Thirty-seven nondemented elderly attending a memory clinic and 28 elderly controls participated in this follow-up study. The average follow-up period was 1.8 years. Cognitive function was measured at baseline and follow-up with the Cambridge Cognitive Examination (CAMCOG). Baseline Magnetic Resonance Imaging (MRI) provided quantitative measures of whole brain, medial temporal lobe and WMH. Linear mixed models controlled for age and sex were used to assess the independent associations between MRI measures, baseline cognition, and annual decline in cognition. RESULTS: Medial temporal lobe volume was independently associated with baseline CAMCOG score (p < 0.01), whereas whole brain volume (p < 0.01) and WMH (p < 0.05) were associated with annual decline in CAMCOG score. CONCLUSIONS: These data suggest that regional damage to the medial temporal lobes underlies initial mild cognitive impairment, whereas more global brain changes, such as whole brain atrophy and WMH, contribute to further progression of cognitive decline.     

脑小血管病总负荷与记忆力下降老年患者认知功能、脑萎缩及脑灌注的相关性

目的 探索脑小血管病（cerebral small vessel disease，CSVD）总负荷与记忆力下降老年患者认知功能、 脑萎缩及脑灌注的关系。 方法 回顾性纳入2015年12月-2017年12月同济医院神经内科门诊及记忆减退专病门诊主诉记忆力 下降患者，收集一般资料及影像学信息，进行认知评估、CSVD总负荷评分、全脑及各脑叶脑萎缩评分， 计算脑血流（cerebral blood flow，CBF）值。采用Spearman相关分析CSVD总负荷评分与认知功能、脑萎 缩及CBF的关系。 结果 共纳入200例，平均年龄69.16±9.44岁，男性99例（49.5%）。CSVD总负荷与MoCA评分呈负相 关（r =-0.202，P =0.004）；与全脑（r =-0.234，P =0.001）、额叶（r =-0.252，P <0.001）、顶叶（r =- 0.253，P <0.001）、枕叶（r =-0.224，P =0.001）CBF呈负相关；CSVD负荷与全脑（r =0.313，P <0.001）、 额叶（r =0.393，P＜0.001）及顶叶（r =0.237，P =0.001）的脑萎缩评分呈正相关。 结论 CSVD总负荷越高，认知功能越差、脑灌注越低、脑萎缩越严重。     

Elevated basal cortisol level predicts lower hippocampal volume and cognitive decline in Alzheimer’s disease

Elevated glucocorticoid concentrations, decreased hippocampal volume and frontal atrophy with poor cognitive function have been reported in the elderly but not extensively in Alzheimer’s disease (AD). We enrolled 172 patients with AD over a 2-year follow-up period. Basal cortisol levels, biochemistry tests and mini-mental state examination (MMSE) scores were obtained and hippocampal and frontal atrophy were measured by CT scan for correlation. Basal plasma cortisol levels increased with age. Further, basal plasma cortisol levels were correlated with the radial width of the temporal horn, and elevated levels of plasma cortisol predicted a worse general cognitive performance. Higher plasma cortisol levels also correlated with rapid declines in MMSE scores after 2 years. Bilateral frontal atrophy showed no correlation with the above parameters. The relationship between high cortisol levels and hippocampal atrophy might adversely affect AD patients disproportionately, either in anatomical or cognitive function.     

Pulmonary function, cognitive impairment and brain atrophy in a middle-aged community sample

OBJECTIVE: To determine the relationship of lung function to brain anatomical parameters and cognitive function and to examine the mediating factors for any relationships. METHODS: A random sub-sample of 469 persons (men = 252) aged 60-64 years from a larger community sample underwent brain magnetic resonance imaging scans and pulmonary function tests (forced vital capacity, FVC, forced expiratory volume in the first second, FEV(1)). Subjects were assessed for global cognitive function, episodic memory, working memory, information processing speed, fine motor dexterity and grip strength. The magnetic resonance imaging scans were analysed for overall brain atrophy, subcortical atrophy (ventricle-to-brain ratio, VBR), hippocampal volume, and white matter hyperintensity (WMH) volume. RESULTS: FEV(1) had a significant negative correlation with overall brain atrophy and VBR in men. The FEV(1)/FVC ratio had a significant correlation with WMHs in both men and women. In regression models that controlled for sex, age, height, level of activity, smoking, chronic respiratory disease and education, FEV(1) and FVC were significant predictors of VBR but no other structural brain measure. Pulmonary function was also significantly related to information processing speed and fine motor dexterity. Male subjects with chronic respiratory disease had more deep WMHs. Path analyses to examine if structural measures mediated between lung function and cognition, and whether markers of inflammation and oxidative stress or cortisol mediated between lung function and brain measures were negative. CONCLUSIONS: Decreased lung function is related to poorer cognitive function and increased subcortical atrophy in mid-adult life. Presence of chronic respiratory disease may be related to deep WMHs in men.     

The FAB: a Frontal Assessment Battery at bedside

OBJECTIVE: To devise a short bedside cognitive and behavioral battery to assess frontal lobe functions. METHODS: The designed battery consists of six subtests exploring the following: conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. It takes approximately 10 minutes to administer. The authors studied 42 normal subjects and 121 patients with various degrees of frontal lobe dysfunction (PD, n = 24; multiple system atrophy, n = 6; corticobasal degeneration, n = 21; progressive supranuclear palsy, n = 47; frontotemporal dementia, n = 23). RESULTS: The Frontal Assessment Battery scores correlated with the Mattis Dementia Rating Scale scores (rho = 0.82, p < 0.01) and with the number of criteria (rho = 0.77, p < 0.01) and perseverative errors (rho = 0.68, p < 0.01) of the Wisconsin Card Sorting Test. These variables accounted for 79% of the variance in a stepwise multiple regression, whereas age or Mini-Mental State Examination scores had no significant influence. There was good interrater reliability (kappa = 0.87, p < 0.001), internal consistency (Cronbach's coefficient alpha = 0.78), and discriminant validity (89.1% of cases correctly identified in a discriminant analysis of patients and controls). CONCLUSION: The Frontal Assessment Battery is easy to administer at bedside and is sensitive to frontal lobe dysfunction.     

颞叶癫(癎)后认知功能障碍与海马萎缩的相关性

目的 比较颞叶癫(癎)患者与健康者认知障碍、海马萎缩的差异,探讨颞叶癫(癎)患者认知障碍与海马萎缩的相关性.方法 随机选取颞叶癫(癎)患者49例和健康对照者20名,神经心理量表评价其认知状态并测量双侧海马体积.结果 与健康者相比,颞叶癫(癎)患者的记忆商(83.2±21.0)和智商(91.0±12.3)显著下降(t=-3.365,-4.291,P=0.001,0.000),双侧海马显著萎缩(P=0.000),不对称指数显著增高(t=3.975,P=0.000),差异有统计学意义.颞叶癫(癎)患者记忆力与癫(癎)病程显著负相关(r=-0.339,P=0-017),左右两侧海马萎缩程度与认知指数均显著负相关(左侧:r=-0.297,P=0.038;右侧:r=-0.305,P=0.033),不对称指数与认知指数显著负相关(r=-0.441,P=0.002).结论 颞叶癫(癎)患者双侧海马的萎缩程度越高、对称性越差,认知损伤也就越显著.海马体积测量可以作为颞叶癫(癎)患者智力下降的评价因子.     

Altered circadian cortisol secretion in Alzheimer's disease: clinical and neuroradiological aspects

We determined circadian salivary cortisol levels in 18 outpatients affected by probable Alzheimer's disease (AD) and looked for a possible correlation with both cognitive impairment and brain CT scan findings. The diagnosis of probable AD was made according to the NINCDS-ADRDA criteria. The severity of cognitive impairment was quantified using the Mini Mental State Examination (MMSE) and the Global Deterioration Scale (GDS). Cortisol levels were measured on saliva samples collected at 08:00 AM and 08:00 PM. For each sample, a duplicate cortisol measurement was performed on 50 microl of saliva by means of a modified commercial radioimmunoassay kit. At the same time, 11 of the 18 AD patients enrolled also underwent a brain CT scan to estimate cerebral atrophy by using linear indexes. The mean value of cortisol levels was significantly higher in AD patients than in controls at both the morning and the evening measurements, and the circadian fluctuation of cortisol was less marked in AD patients than in controls, although this difference did not reach statistical significance. Morning cortisol levels were significantly correlated to both the MMSE and the GDS scores. A significant correlation was also found between morning cortisol levels and all the cerebral atrophy indexes. By contrast, no correlation was observed between evening cortisol levels or cortisol circadian fluctuations and either cognitive impairment or cerebral atrophy. In conclusion, despite the potential biases deriving from the small sample and the limitations of the CT scan study, our results suggest that, in AD patients, hypercortisolemia is correlated with severity of the disease.     

脑小血管病总负荷与记忆力下降老年患者认知功能、脑萎缩及脑灌注的相关性

目的 探索脑小血管病（cerebral small vessel disease,CSVD）总负荷与记忆力下降老年患者认知功能、
脑萎缩及脑灌注的关系。
方法 回顾性纳入2015年12月-2017年12月同济医院神经内科门诊及记忆减退专病门诊主诉记忆力
下降患者,收集一般资料及影像学信息,进行认知评估、CSVD总负荷评分、全脑及各脑叶脑萎缩评分,
计算脑血流（cerebral blood flow,CBF）值。采用Spearman相关分析CSVD总负荷评分与认知功能、脑萎
缩及CBF的关系。
结果 共纳入200例,平均年龄69.16±9.44岁,男性99例（49.5%）。CSVD总负荷与MoCA评分呈负相
关（r =-0.202,P =0.004）;与全脑（r =-0.234,P =0.001）、额叶（r =-0.252,P <0.001）、顶叶（r =-
0.253,P <0.001）、枕叶（r =-0.224,P =0.001）CBF呈负相关;CSVD负荷与全脑（r =0.313,P <0.001）、
额叶（r =0.393,P＜0.001）及顶叶（r =0.237,P =0.001）的脑萎缩评分呈正相关。
结论 CSVD总负荷越高,认知功能越差、脑灌注越低、脑萎缩越严重。     

Elevation of serum copper levels in Alzheimer's disease

OBJECTIVE: To determine whether serum trace metals and oxidative species are related to abnormal cognition in AD. METHODS: The authors studied serum peroxides, copper, iron, transferrin, and antioxidant capacity in 79 patients with AD (mean age 74.3 years; 25 men, 54 women) and in 76 cognitively normal individuals (mean age 70.1 years; 33 men, 43 women). The relation of these oxidative and trace metals to APOE epsilon4 allele frequency, neuropsychological performance, and cerebrovascular or atrophic burden, as estimated by brain MRI and ultrasonography of cerebral vessels, was evaluated. RESULTS: Copper level was higher (p < 0.001) in subjects with AD than control subjects (specificity = 95%, sensitivity = 60%) with a cutoff serum level of 16 micro mol/L (1.02 mg/L). An increase of 1 micro mol/L in serum copper accounted for 80% of the risk of having AD and correlated with poor neuropsychological performance and medial temporal lobe atrophy (p < 0.03). Antioxidant capacity decreased and correlated with medial temporal lobe atrophy (p < 0.009) and with APOE epsilon4 allele (p = 0.004). CONCLUSIONS: Copper may play a role in neurodegenerative processes in AD, and serum copper measurement may prove to be a peripheral diagnostic marker for AD.     

Intracranial capacity and brain volumes are associated with cognition in healthy elderly men

BACKGROUND: Brain size and intracranial capacity are correlated with cognitive performance in young healthy adults, but data are lacking on these relationships in older healthy adults. OBJECTIVE: To test the hypotheses that intracranial capacity, volumes of specific brain regions, and a measure of the shared variance between brain regions are positively associated with cognitive function in a sample of healthy, unmedicated elderly men (n = 97; mean age 67.8, SD 1.3). METHODS: Individuals underwent MRI, with measurements of intracranial area and volumetric measurements of hippocampi, temporal lobes, and frontal lobes. Cognitive testing included measures of premorbid intelligence, fluid intelligence, verbal memory, visuospatial memory, verbal fluency, and attention and processing speed. RESULTS: Cognitive tests showed significant positive intercorrelations throughout, and regional brain volumes were also universally, significantly, and positively intercorrelated. Intracranial area and several regional brain volumes correlated with tests of premorbid and fluid intelligence and tests of visuospatial memory. Tests of verbal memory and verbal fluency did not correlate significantly with brain volumes. Structural equation modeling demonstrated that the relationships between specific cognitive tests and regional brain volumes could best be summarized by a significant positive relationship between a general brain size factor and a general cognitive factor, and not by associations between individual tests and particular brain regions. CONCLUSIONS: In healthy elderly men, there are significant relationships between multiple cognitive tests and both intracranial capacity and regional brain volumes. These relationships may be largely due to longstanding associations between general cognitive ability and overall brain size.     

Brain imaging evidence of preclinical Alzheimer's disease in normal aging

OBJECTIVE: This study was designed to test the hypothesis that baseline glucose metabolism and medial temporal lobe brain volumes are predictive of cognitive decline in normal older people. METHODS: We performed positron emission tomography using [18F]fluorodeoxyglucose and structural magnetic resonance imaging at baseline in 60 cognitively normal community-dwelling older subjects who were part of a longitudinal cohort study. Subjects were followed for a mean of 3.8 years, with approximately annual evaluation of global cognition (the Modified Mini-Mental State Examination) and episodic memory (delayed recall). Baseline brain volumes and glucose metabolism were evaluated in relation to the rate of change in cognitive test scores. RESULTS: Six subjects developed incident dementia or cognitive impairment (converters). Baseline positron emission tomography scans showed regions in left and right angular gyrus, left mid-temporal gyrus, and left middle frontal gyrus that predicted the rate of change on the Modified Mini-Mental State Examination (p < 0.001). The left hemisphere temporal and parietal regions remained significant when converters were excluded. Both hippocampal (p = 0.03) and entorhinal cortical volumes (p = 0.01) predicted decline on delayed recall over time, and entorhinal cortical volumes remained significant when converters were excluded (p = 0.02). These brain volumes did not predict Modified Mini-Mental State Examination decline. INTERPRETATION: These results indicate that temporal and parietal glucose metabolism predict decline in global cognitive function, and medial temporal brain volumes predict memory decline in normal older people. The anatomical location of these findings suggests detection of preclinical Alzheimer's disease pathology.     

Relation of plasma thyroid-stimulating hormone levels to vascular lesions and atrophy of the brain in the elderly

CONTEXT: Recent studies suggest that thyroid disease is associated with cardiovascular and peripheral vascular disease. However, little is known about the underlying pathophysiology and the relation with cerebrovascular disease or brain atrophy in the elderly. OBJECTIVE: To determine if plasma thyroid-stimulating hormone (TSH) levels are associated with vascular brain changes and cortical atrophy in the elderly. DESIGN: Community based, cross-sectional study. PARTICIPANTS AND SETTING: 268 participants of the Memory and Morbidity in Augsburg Elderly Study, 65-83 years of age and without contraindications for magnetic resonance imaging (MRI) of the brain. MAIN OUTCOME MEASURES: The presence of brain lesions and atrophy was determined using a standardized MRI protocol, an established rating scale and a single rater. Plasma TSH levels were assessed using standard laboratory methods. The association between plasma TSH levels and MRI findings was analyzed using logistic and linear regression models. RESULTS: Higher TSH levels within the normal clinical range were significantly associated with severer cortical atrophy (p = 0.04) and a higher proportion of infarct-like vascular lesions (p = 0.005) in men. These associations were independent of potential confounders, including thyroid hormone therapy, in multivariable regression analysis. No association between plasma TSH levels and both MRI outcomes were observed in women. In addition, neither in men nor in women was an association between TSH levels and white-matter lesions found. CONCLUSIONS: Increasing TSH levels even within the normal clinical range are associated with severer brain atrophy and infarct-like vascular lesions in elderly men.     

Visual rating of the hippocampus in non‐demented elders: Does it measure hippocampal atrophy or other indices of brain atrophy? The SMART‐MR study

Visual rating of hippocampal atrophy is often used to differentiate between normal aging and Alzheimer's disease. We investigated whether two visual rating scales of hippocampal atrophy were related to hippocampal volumes, and if visual rating was related to global, cortical and subcortical brain atrophy in persons without dementia. Within the SMART‐MR study, a prospective cohort study among patients with manifest arterial disease, medial temporal lobe atrophy was qualitatively rated in 95 participants without dementia (mean age 62 ± 10 years) using two visual rating scales: the medial temporal lobe (MTA) score was rated on coronal oriented images and the perihippocampal cerebrospinal fluid (HCSF) score was rated on axial oriented images. Hippocampal volume assessed by manual segmentation on a 3‐dimensional FFE T1‐weighted MR image. Automated segmentation was used to quantify volumes of brain tissue and cerebrospinal fluid. Total brain volume, gray matter volume, and ventricular volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF), gray matter fraction (GMF) and ventricular fraction (VF). Using ANOVA, crude hippocampal volumes were smaller with increasing MTA and HSCF scores as were hippocampal volumes normalized for intracranial volume (P < 0.05). However, hippocampal volumes normalized for total brain size were not smaller with increasing MTA or HSCF scores (P = 0.33 and P = 0.49). Also, with increasing visual rating scores, BPF was smaller and VF was larger (P < 0.001), and the GMF decreased with increasing HCSF score (P = 0.008). In this nondemented population, visual rating of the medial temporal lobe reflects hippocampal atrophy as well as global and subcortical atrophy. © 2009 Wiley‐Liss, Inc.     

Enlarged perivascular spaces are associated with cognitive function in healthy elderly men

OBJECTIVES: Increased white matter (WM) lesions on magnetic resonance imaging (MRI) are associated with worse cognitive function in older people. Enlarged perivascular spaces (EPVS) commonly coexist with and share some risk factors for WM lesions but are not quantified in published scales. It is not known whether the extent of EPVS is also associated with cognitive function. We tested the hypothesis that more EPVS would be associated with worse cognitive function. METHODS: Ninety seven healthy men (65-70 years), not on medications, underwent MRI scanning and comprehensive cognitive testing. EPVS were quantified in both the basal ganglia/centrum semiovale and the hippocampus, and WM lesions were measured. RESULTS: Scores on published WM lesion rating scales intercorrelated highly significantly and positively (rho = 0.61 to 0.91, p<0.0001). A summary (WML) factor derived from principal components analysis of the WM scales correlated with EPVS in the basal ganglia/centrum semiovale (rho = 0.48, p<0.0001) but not in the hippocampus. EPVS scores in the basal ganglia/centrum semiovale correlated significantly and negatively with non-verbal reasoning (rho = -0.21, p = 0.038) and general visuospatial ability (rho = -0.22, p = 0.032), adjusted for prior intelligence. The WML factor correlated significantly and negatively with visuospatial ability, as previously reported, and showed an unexpected positive correlation with one test of verbal memory (list-learning). CONCLUSIONS: These findings suggest that increased EPVS are correlated with worse cognitive function. Future studies examining changes in WM with ageing should consider incorporating measures of EPVS and examine the sequence of EPVS and WM lesion development over time. More work is needed to develop valid and reliable measures of EPVS.     

Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease.

BACKGROUND: Decreased hippocampal volume is observed in patients with Cushing's syndrome and other conditions associated with elevated cortisol levels, stress, or both. Reversibility of hippocampal neuronal atrophy resulting from stress occurs in animals. Our study investigated the potential for reversibility of human hippocampal atrophy. METHODS: The study included 22 patients with Cushing's disease. Magnetic resonance brain imaging was performed prior to transsphenoidal microadenomectomy and again after treatment. RESULTS: Following treatment, hippocampal formation volume (HFV) increased by up to 10%. The mean percent change (3.2 +/- 2.5) was significantly greater (p < .04) than that of the comparison structure, caudate head volume (1.5 +/- 3.4). Increase in HFV was significantly associated with magnitude of decrease in urinary free cortisol (r = -.61, p < .01). This relationship strengthened after adjustments for age, duration of disease, and months elapsed since surgery (r = -.70, p < .001). There was no significant correlation between caudate head volume change and magnitude of cortisol decrease. CONCLUSIONS: Changes in human HFV associated with sustained hypercortisolemia are reversible, at least in part, once cortisol levels decrease. While many brain regions are likely affected by hypercortisolemia, the human hippocampus exhibits increased sensitivity to cortisol, affecting both volume loss and recovery.     

Evidence for a gender-related effect of alcoholism on brain volumes

OBJECTIVE: The goal of this study was to compare brain volumes of alcoholic and nonalcoholic men and women and determine if the magnitudes of differences in brain volumes between alcoholic women and nonalcoholic women are greater than the magnitudes of the differences between alcoholic men and nonalcoholic men. METHOD: The study group included 118 subjects: 79 inpatients 30-60 years of age who were alcohol dependent but had no clinically apparent cognitive impairment or medical illness (43 men and 36 women) and 39 healthy comparison subjects of similar age who were not alcoholic (20 men and 19 women). The volume of intracranial contents was segmented into gray matter, white matter, sulcal CSF, and ventricular CSF from a T(1)-weighted magnetic resonance image obtained after the alcoholic subjects had attained 3 weeks of sobriety. RESULTS: Alcoholic women had significantly smaller volumes of gray and white matter as well as greater volumes of sulcal and ventricular CSF than nonalcoholic women. The differences in gray and white matter volumes between alcoholic and nonalcoholic men were significant, but the significance of these differences was of a smaller magnitude than the significance of the differences between alcoholic and nonalcoholic women. Direct comparisons of alcoholic men and women showed that the proportion of intracranial contents occupied by gray matter was smaller in alcoholic women than in alcoholic men. The magnitudes of differences in brain volumes adjusted for intracranial size between alcoholic women and nonalcoholic women were greater than the magnitudes of the adjusted differences between alcoholic men and nonalcoholic men. CONCLUSIONS: These results are consistent with greater sensitivity to alcohol neurotoxicity among women.     

Plasma melatonin--an index of brain aging in humans?

We investigated the age-related changes in the circadian rhythm of plasma melatonin as a potential index of brain aging in man. The subjects were 5 young men aged 19-25 years, 11 older men aged 51-65 years, 6 elderly men aged 66-89 years, 7 young women aged 19-25 years, 5 premenopausal women aged 45-50 years, 8 postmenopausal women aged 51-65 years, and 5 elderly women aged 66-75 years. They were all physically and psychiatrically normal. Serial blood samples were drawn from 8:00 AM until 8:00 AM on the next day, with the indoor illumination set at 300 Lux from 7:00 AM until 4:00 PM and at 50 Lux thereafter. Plasma melatonin was estimated by radioimmunoassay. The results show that there is a significant negative correlation between age and 24-hr secretion of plasma melatonin (r = -0.952, p less than 0.0001), between age and peak levels of plasma melatonin (r = -0.937, p less than 0.00001), and between age and the lag in time from sunset to the onset of significant elevation of plasma melatonin over daytime values (r = 0.916, p less than 0.0001). It is concluded that study of the circadian rhythm of plasma melatonin may prove to be a useful index of the aging process.     

Topographical patterns of lobar atrophy in frontotemporal dementia and Alzheimer's disease

BACKGROUND/AIMS: Fronto-temporal dementia (FTD) designates a group of relatively common neurodegenerative disorders. The aim of this study was to characterize the patterns of brain atrophy in FTD compared to Alzheimer's disease (AD). METHODS: A novel semiautomatic volumetric MRI analysis method was applied to measure regional brain volumes in FTD (n = 15; behavioural variant n = 9, language variant n = 6) in contrast with AD patients (n = 15) and age-matched controls (NC) (n = 15). FTD and AD patients were matched on demographic measures and Mini Mental State Examination scores. RESULTS: Significant atrophy was present in the frontal and anterior temporal lobes of subjects with FTD compared to AD (p = 0.02; effect size = 1.11) and compared to NC (p < 0.001; effect size = 1.86). Severe atrophy of the left anterior temporal region distinguished the language variant. AD patients, by contrast, did not differ from NC for frontal lobe volume but had smaller anterior temporal lobes (p = 0.03). Both dementia groups had medial temporal lobe atrophy of similar magnitude. A logistic regression model including 4 regional measures correctly classified 100% of subjects. CONCLUSION: FTD can be reliably differentiated from AD by virtue of a topographical pattern of atrophy involving the frontal lobes and anterior temporal regions. Medial temporal lobe volumes do not distinguish FTD from AD.     

Ambulatory blood pressure and brain atrophy in the healthy elderly

BACKGROUND: Brain lesions and atrophy increase with age and hypertension. OBJECTIVE: To evaluate the relationship of age and ambulatory blood pressure (BP) to brain atrophy in healthy elderly individuals. METHODS: MRI volume measurements (normalized to intracranial volume) were taken of total brain and lateral and third ventricles in 155 healthy men and women who went through extensive medical examinations. Younger (56 to 66 years old) and older (67 to 80 years old) subgroups were compared on casual and 24-hour ambulatory BP values and MRI volume measurements. RESULTS: Older subjects had smaller brain volumes and larger lateral and third ventricles. Compared with women, men had larger lateral and third ventricles. With age controlled for, greater sleep systolic BP (SBP) variability was associated with smaller brain volumes; greater waking and sleep SBP variability were associated with larger lateral and third ventricles. Subjects with higher casual and waking SBP and waking diastolic BP had larger lateral ventricles. Among older subjects, only those with elevated SBP had smaller brain volumes and larger lateral ventricles. CONCLUSIONS: These results indicate that if BP levels are within the upper normal range, even healthy individuals with no prior diagnosis of hypertension are more likely to have brain atrophy than those with lower BP. Moreover, not only do BP level and variability relate to brain atrophy, but the combination of high level and greater variability shows an even stronger relationship to brain atrophy than either one of these variables alone.