Stroke recurrence in patients with atrial fibrillation: concomitant carotid artery stenosis doubles the risk.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) and significant carotid artery stenosis (CAS) often coexist in patients with acute stroke but whether CAS affects the stroke recurrence rate in anticoagulated AF patients is largely unknown. The effect of concomitant CAS on both short- and long-term prognosis after stroke in patients with AF was evaluated. METHODS: The multicentre, retrospective FibStroke registry included AF patients with an ischaemic stroke or transient ischaemic attack (TIA) during 2003-2012. In this sub-study, 165 AF patients with ischaemic stroke or TIA with significant (>50%) CAS (CAS group) and 734 AF patients without CAS (non-CAS group) were identified. The median follow-up time after an index event was 3.5 (interquartile range 3.9) years. Long-term stroke recurrence rate, 30-day mortality, CHA2 DS2 -VASc score, other risk factors and the use and intensity of anticoagulation were assessed. RESULTS: The recurrence rate of ischaemic stroke (21.2% vs. 12.7%, P = 0.005, 8.1 vs. 3.6 events per100 follow-up years) was significantly higher in CAS patients compared to the non-CAS group despite similar anticoagulation/antithrombotic therapy. CAS patients had higher mean CHA2 DS2 -VASc scores than non-CAS patients (4.3 vs. 3.3, P < 0.001). However, in a multivariate analysis CAS was shown to be an independent risk factor for stroke recurrence (hazard ratio 2.02, 95% confidence interval 1.37-3.01, P = 0.001). The 30-day all-cause mortality was significantly higher in CAS patients (7.9% vs. 1.9%, P < 0.001) and CAS was an independent risk factor also for 30-day mortality (odds ratio 3.34, 95% confidence interval 1.51-7.38, P = 0.003). CONCLUSIONS: In patients with AF, concomitant CAS was an independent risk factor for both long-term stroke recurrence and 30-day mortality.

Underuse of anticoagulation in stroke patients with atrial fibrillation--the FibStroke Study.

BACKGROUND AND PURPOSE: Current guidelines recommend oral anticoagulation (OAC) for patients with atrial fibrillation (AF) and increased risk of thromboembolic events. The reasons for not using OAC in AF patients suffering stroke or transient ischaemic attack (TIA) were assessed. METHODS: This retrospective registry included 3404 patients with previously diagnosed AF who suffered a total of 2955 ischaemic strokes and 895 TIAs during 2003-2012. RESULTS: A CHA2DS2-VASc score ≥2 and a CHADS2 score ≥2 was observed in 3590 (93.2%) and in 2784 (72.3%) of the events, respectively. Of the high-risk patients (CHADS2 ≥2) only 55.1% were on OAC before the onset of stroke or TIA. The most frequently documented reasons for withholding OAC were infrequent paroxysms of AF (14%), previous bleeding episodes (13%) and the patient's decline/independent discontinuation of treatment (9%). Moreover, patients with paroxysmal AF (40% using OAC), previous bleeding (26% using OAC) and alcohol abuse (30% using OAC) were using OAC significantly less often than patients without these characteristics. A significant increase in the proportion of high-risk patients using OAC from 49% in 2003 to 65% in 2012 was seen. CONCLUSIONS: Underuse of anticoagulation is a common contributor to ischaemic strokes and TIA episodes in patients with AF. Infrequent AF episodes, previous bleeds, patient preference and alcohol abuse were the most common reasons for not using OAC.

Abundant glial alpha-synuclein pathology in a case without overt clinical symptoms.

Screening of 1,800 brains with alpha-synuclein (alphaS) immunohistochemistry revealed five cases with abundant glial cytoplasmic inclusions (GCIs) within the white matter of the brainstem. Surprisingly, retrospective clinical assessment showed that one of these subjects did not fulfil the currently recommended clinical consensus criteria for the multiple system atrophy (MSA). One of the hallmark lesions of MSA, alphaS-positive GCIs, were widespread and abundant in this atypical case that nonetheless lacked any significant neuronal loss. If the patient had met the clinical criteria for MSA, the neuropathological phenotype would have undeniably confirmed the clinically suggested diagnosis. However, lacking overt clinical signs of MSA, the neuropathological phenotype in this subject is prone to be variably denoted or overlooked. We would therefore like to advise neuropathologists to acknowledge these cases with "occult" alpha-synucleinopathy and to inform the clinicians of such a finding. Whether these cases represent a preclinical stage of MSA or simply a biological coincidence, is yet unknown. The observation of abundant GCIs in an asymptomatic subject is, however, important, because even if these cases are rare in number, their occurrence challenge the current presumption, whereby simply the number of alphaS-positive GCIs mediates the neuronal dysfunction responsible for the clinical symptoms of MSA.

Patient satisfaction with switching to Stalevo: an open-label evaluation in PD patients experiencing wearing-off (Simcom Study).

OBJECTIVES AND METHODS: This study investigated the ease with which 52 Parkinson's disease patients already receiving adjunct entacapone to traditional levodopa were switched to Stalevo (levodopa/carbidopa/entacapone). RESULTS: The switch to Stalevo was straightforward for most patients taking standard-release levodopa with 86% of these patients being able to replace their entire regimen without having to change the amount of levodopa taken. The majority of patients (54%, P = 0.162) preferred Stalevo; 31% preferred their prior treatment regimen; 15% had no preference. Patients found Stalevo more simple to dose (94%), more convenient to use (84%), easier to handle (84%), easier to remember (67%) and easier to swallow (59%), compared with their previous medication. CONCLUSIONS: Stalevo was well tolerated, with a low incidence of adverse events. The study shows that Stalevo is an effective, preferred and well-tolerated means of delivering levodopa/carbidopa/entacapone in one easy-to-use tablet.

Molecular genetic analysis of the alpha-synuclein and the parkin gene in Parkinson's disease in Finland.

Two mutations in the alpha-synuclein gene and various mutations in the parkin gene are associated with familial Parkinson's disease (PD). The present study was performed to analyse if mutations in these genes could be detected in Finnish patients with familial PD. The subjects comprised 22 unrelated patients with familial PD. The molecular genetic analysis consisted of sequence analysis of the non-coding and coding exons of the alpha-synuclein gene and screening of eight point mutations in the parkin gene. In addition, a total of 67 controls and 45 patients with sporadic PD were included in the association analysis on polymorphism of the alpha-synuclein gene. Screened point mutations in the parkin gene were not detected. Sequencing of the coding exons 2-6 of the alpha-synuclein gene did not reveal any mutations or polymorphisms. However, three novel alterations in the T10A7 sequence at the 5' end of the non-coding exon 1' of the alpha-synuclein gene were found. The frequencies of the exon 1' polymorphic genotypes or alleles between familial PD patients and control subjects revealed no statistically significant differences. No association for sporadic PD was observed. The results do not support a role for the alpha-synuclein gene or point mutations of the parkin gene in familial PD in our sample.

Heterogeneity of cerebral blood flow: a fractal approach.

AIM: We demonstrate the heterogeneity of regional cerebral blood flow using a fractal approach and single-photon emission computed tomography (SPECT). METHOD: Tc-99m-labelled ethylcysteine dimer was injected intravenously in 10 healthy controls and in 10 patients with dementia of frontal lobe type. The head was imaged with a gamma camera and transaxial, sagittal and coronal slices were reconstructed. Two hundred fifty-six symmetrical regions of interest (ROIs) were drawn onto each hemisphere of functioning brain matter. Fractal analysis was used to examine the spatial heterogeneity of blood flow as a function of the number of ROIs. RESULTS: Relative dispersion (= coefficient of variation of the regional flows) was fractal-like in healthy subjects and could be characterized by a fractal dimension of 1.17 +/- 0.05 (mean +/- SD) for the left hemisphere and 1.15 +/- 0.04 for the right hemisphere, respectively. The fractal dimension of 1.0 reflects completely homogeneous blood flow and 1.5 indicates a random blood flow distribution. Patients with dementia of frontal lobe type had a significantly lower fractal dimension of 1.04 +/- 0.03 than in healthy controls. CONCLUSION: Within the limits of spatial resolution of SPECT, the heterogeneity of brain blood flow is well characterized by a fractal dimension. Fractal analysis may help brain scientists to assess age-, sex- and laterality-related anatomic and physiological changes of brain blood flow and possibly to improve precision of diagnostic information available for patient care.

A longitudinal quantitative EEG study of Alzheimer's disease: relation to apolipoprotein E polymorphism.

Apolipoprotein E (apoE) sigma4 allele is a risk factor for late-onset Alzheimer's disease (AD) and is proposed to have an impact on cholinergic function in AD. Slowing of the EEG is characteristic in AD and the cholinergic system has an important role in modulating EEG. QEEG was recorded from 31 AD patients at the early stage of the disease and after a 3-year follow-up. AD patients were divided into subgroups according to the apoE sigma4 allele (2sigma4, 1sigma4 and 0sigma4). AD subgroups did not differ in clinical severity or duration of dementia. The AD patients carrying the sigma4 allele had more pronounced slow-wave activity than AD patients without the sigma4 allele, although the progression rate did not change. The differences in EEG may suggest differences in the degree of the cholinergic deficit in these subgroups.

Rapidly progressive multifocal leukoencephalopathy with substantial cell-mediated inflammatory response and with cognitive decline of non-Alzheimer type in a 75-year-old female patient.

Autopsy findings of rapidly progressive and widespread multifocal leukoencephalopathy (PML) in a 75-year-old woman with no known predisposing disease are demonstrated. Originally she was given a clinical working diagnosis of syndrome of progressive supranuclear palsy (PSP). The neuropathological investigation revealed widespread white and gray matter changes consistent with PML, and the JC virus was verified by EM, in situ hybridization and immunohistochemistry. In contrast to the few chronic inflammatory cells generally seen in PML in this case there was a substantial cell-mediated inflammatory response reflected in numerous T-helper and T-killer cells. The uncommon, widespread distribution of lesions and substantial cell-mediated response reported might indicate that the rearrangement of viral genome, previously suggested of importance for viral growth in the central nervous system (CNS), is also important for viral spread within the CNS, infectivity of glial cells and for the activation of cell-mediated immunity.

Longitudinal SPECT study in Alzheimer's disease: relation to apolipoprotein E polymorphism.

OBJECTIVES: In mild Alzheimer's disease, SPECT imaging of regional cerebral blood flow has highlighted deficits in the posterior association cortex, and later in the disease process, the deficit spreads to involve the frontal cortex. The sigma4 allele of apolipoprotein E is a risk factor for Alzheimer's disease. The effect of apolipoprotein E polymorphism on cerebral perfusion was studied. The hypothesis was that those patients with Alzheimer's disease who carry the sigma4 allele would have more severe cerebral hypoperfusion. METHODS: Thirty one patients with Alzheimer's disease and eight age and sex matched control subjects were examined in a three year longitudinal study. Patients with Alzheimer's disease were divided into subgroups according to their number of sigma4 alleles. Regional cerebral blood flow ratios referred to the cerebellum were examined by 99mTc-HMPAO SPECT. Apolipoprotein E genotypes were determined by digestion of polymerase chain reaction products with the restriction enzyme Hha1. RESULTS: All patients with Alzheimer's disease had bilateral temporoparietal hypoperfusion compared with control subjects. The two sigma4 allele subgroups had the lowest ratios at the baseline assessment in the parietal and occipital cortices, and at the follow up in the temporal, parietal, and occipital cortices. They had the highest reduction in percentage terms in the temporal and occipital cortices compared with the other subgroups. However, the global clinical severity did not differ at the baseline or follow up examinations between the subgroups. CONCLUSION: Apolipoprotein E polymorphism is involved in the pathogenesis and heterogeneity of Alzheimer's disease as the most severe cerebral hypoperfusion was found in the sigma4 allele subgroups. This might have implications for therapeutic approaches in Alzheimer's disease.

Subclinical cerebral complications after coronary artery bypass grafting: prospective analysis with magnetic resonance imaging, quantitative electroencephalography, and neuropsychological assessment.

OBJECTIVE: To analyze the frequency and severity of subclinical cerebral complications associated with coronary artery bypass grafting (CABG). DESIGN: A prospective controlled study using preoperative and postoperative magnetic resonance imaging (MRI) of the brain, quantitative electroencephalography (QEEG), and detailed neuropsychological and neurologic examinations as potentially sensitive indicators of subclinical cerebral injury associated with CABG. SETTING: Multimodality evaluation in a tertiary care unit (Kuopio University Hospital, Kuopio, Finland). PATIENTS: Thirty-eight patients undergoing elective CABG and 20 control patients undergoing other major vascular surgery, mostly operations on the abdominal aorta. MAIN OUTCOME MEASURES: Coronary artery bypass grafting-associated cerebral complications assessed preoperatively and postoperatively by brain MRI, QEEG, detailed neurologic examination, and a neuropsychological test battery that evaluates cognitive functions in major areas known to be vulnerable to organic impairment (learning and memory, attention, flexible mental processing, and psychomotor speed). RESULTS: There were no major neurologic complications. A mild hemisyndrome developed in 1 patient who underwent CABG and in 1 control patient. Overall, there was no decline in mean cognitive performance 3 months after surgery. Electroencephalographic slowing of 0.5 Hz or more in at least 2 channels occurred in 11 patients who underwent CABG and in 1 control patient (P=.03). The postoperative brain MRI scan revealed new small ischemic lesions in 8 patients (21%) in the CABG group but in none of the control group (P=.03). These new cerebral MRI lesions did not explain deterioration in neuropsychological test performance or the QEEG slowing. CONCLUSIONS: Coronary artery bypass grafting causes more QEEG alterations and small ischemic cerebral lesions that are detectable by MRI than does other major vascular surgery. The effect is mainly subclinical, because no statistically significant deterioration in mean neuropsychological test performance was detected.

Slow-wave activity in the spectral analysis of the electroencephalogram and volumes of hippocampus in subgroups of Alzheimer's disease patients.

This study examined patients who fulfilled the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association Work Group criteria for probable Alzheimer's disease (AD; n = 35) and controls for magnetic resonance imaging and psychometric data (n = 16) and for quantitative electroencephalogram data (n = 34). A cluster analysis performed on neuropsychological variables identified 2 AD subgroups: The AD1 group (n = 12) had impaired memory and executive functions but preserved verbal and visuospatial functions. The AD2 group (n = 23) had global impairment. The AD2 group had higher theta amplitude in the temporo-occipital, centroparietal, and frontal derivation and lower peak and mean frequency than the AD1 group or controls. Both AD groups had more severe memory deficits and clearly smaller hippocampal volumes than controls. This may implicate that the degree of damage in ascending activating systems differs in these subgroups, although the damage in the hippocampus is equal.

Presymptomatic hippocampal atrophy in Alzheimer's disease. A longitudinal MRI study.

The hippocampal formation (HF) is known from pathological and MRI studies to be severely atrophied in established Alzheimer's disease. However, it is unclear when the earliest changes in the HF occur. We performed a longitudinal study of asymptomatic individuals at risk of autosomal dominant familial Alzheimer's disease in order to assess presymptomatic changes in the HF. Seven at risk members of a familial Alzheimer's disease pedigree associated with the amyloid precursor protein 717 valine to glycine mutation underwent serial MR scanning and neuropsychological assessments over 3 years. These assessments were compared with results from 38 normal controls. During the study three at risk subjects became clinically affected. Volumetric measurement of the HF showed that asymmetrical atrophy developed in these subjects before the appearance of symptoms. Verbal and visual memory measures declined in parallel with hippocampal loss. A loss of up to 8% per annum of the volume of the HF occurred in the 2 years over which symptoms first appeared. These findings may have implications for early diagnosis of Alzheimer's disease.

Spectral analysis of EEG in Alzheimer's disease: relation to apolipoprotein E polymorphism.

Apolipoprotein E (ApoE) epsilon 4 allele is a risk factor for late-onset Alzheimer's disease (AD) and proposed to have a direct impact on cholinergic function in AD. Slowing of the EEG is characteristic in AD and the cholinergic system has an important role in modulating EEG. Fifty-eight AD patients at the early stage of the disease and 34 age- and sex-matched controls were studied using the quantitative EEG recorded from T6-O2 derivation. AD patients were divided into two subgroups: a) according to the ApoE allele (2 epsilon, 1 epsilon 4, and 0 epsilon 4) and b) according to familial aggregation. AD subgroups did not differ in clinical severity or duration of dementia. The AD patients with the epsilon 4 allele had higher relative theta amplitude and lower relative beta amplitude than controls and patients without the epsilon 4 allele. The peak frequencies were lower in all AD subgroups compared to controls. In conclusion, we found a tendency towards more pronounced EEG slowing in AD patients carrying the epsilon 4 allele. The minor differences in EEG may suggest differences in the degree of the cholinergic deficit in these subgroups.

SPECT and MRI analysis in Alzheimer's disease: relation to apolipoprotein E epsilon 4 allele.

OBJECTIVES: The epsilon 4 allele of apolipoprotein E (ApoE) is a risk factor for late onset Alzheimer's disease. ApoE is present in senile plaques, neurofibrillary tangles, and cerebrovascular amyloid, and it is implicated in synaptogenesis. The effect of ApoE polymorphism on the volumes of hippocampus, amygdala, and frontal lobe was studied. The hypothesis was that the patients with Alzheimer's disease carrying the epsilon 4 allele have more pronounced atrophy. The relation of ApoE and cerebral blood flow on cortical areas was also assessed. METHODS: Fifty eight patients with Alzheimer's disease at the early stage of the disease and 34 control subjects were studied. Patients with Alzheimer's disease were divided into subgroups according to the number of the epsilon 4 alleles. Volumes were measured by MRI and regional cerebral blood flow ratios referred to the cerebellum were examined by 99mTc-HMPAO SPECT. ApoE genotypes were determined by digestion of ApoE polymerase chain reaction products with the restriction enzyme Hha1. RESULTS: patients with Alzheimer's disease had smaller volumes of hippocampi and amygdala compared with control subjects, and the patients with Alzheimer's disease homozygous for the epsilon 4 allele had the most prominent volume loss in the medial temporal lobe structures. The frontal lobe volumes did not differ significantly. All patients with Alzheimer's disease had bilateral temporoparietal hypoperfusion and the subgroups with one or no epsilon 4 alleles also had frontal hypoperfusion compared with control subjects. The occipital perfusion ratios tended to decrease with increasing number of epsilon 4 alleles. CONCLUSIONS: Patients with Alzheimer's disease homozygous for the epsilon 4 allele seem to have severe damage in the medial temporal lobe structures early in the disease process and differ from the patients with Alzheimer's disease with one or no epsilon 4 alleles.

Clinical and neuropsychological characteristics in familial and sporadic Alzheimer's disease: relation to apolipoprotein E polymorphism.

Alzheimer's disease (AD) is a heterogeneous entity presenting as sporadic and familial disease. In familial AD, there is evidence for genetic linkage to a yet undefined gene on chromosome 14 in early-onset pedigrees and on chromosome 19 in late-onset pedigrees. In a few early-onset kindreds, there were mutations in the amyloid precursor gene on chromosome 21. There is an increased frequency of apolipoprotein E (ApoE) epsilon4 allele in patients with late-onset AD. We studied the clinical presentation and profile of cognitive deficits in 58 AD patients at the early stage of the disease. We divided the AD patients into subgroups of sporadic late-onset (SLO) (> or = 65 years), familial late-onset (FLO) (> or = 65 years), sporadic early-onset (SEO) (<65 years), and familial early-onset (FEO) (<65 years) patients and into three subgroups according to their ApoE genotype zero epsilon4, one epsilon4, and two epsilon4 alleles. The AD subgroups did not differ in the global clinical severity of dementia or the duration of the disease. SLO, FLO, SEO, and FEO subgroups did not differ in clinical characteristics such as occurrence of rigidity, hypokinesia, tremor, myoclonus, hallucinations, delusions, or epileptic seizures nor in the profile of deficits on tests assessing memory, language, visuospatial, executive, and praxic functions. The epsilon4++ allele frequency was 0.43 for all AD patients and did not differ across subgroups divided according to the familial aggregation and age of onset. Patients with two epsilon4 alleles had earlier age at onset of dementia than those with no epsilon4 allele (63 +/- 9 versus 68 +/- 9 years), but otherwise the clinical symptoms and signs were not related to the ApoE genotype. However, the AD patients with two epsilon 4 alleles had lowest scores on memory tests and differed significantly from those with one or zero epsilon4 allele in the delayed list learning (p<0.05) and from those with zero epsilon4 allele in the immediate and delayed story recall. In contrast, verbal functions were better preserved in two epsilon4 patients than in those with other ApoE genotypes. This study failed to confirm the earlier reports of severe aphasia, agnosia, and apraxia in familial AD patients, but the clinical phenotype was similar irrespective to the familial aggregation. However, AD patients with two epsilon4 alleles are characterized by more severe memory loss and earlier age of onset than those without the epsilon4 allele.

Volumes of hippocampus, amygdala and frontal lobe in Alzheimer patients with different apolipoprotein E genotypes.

An increased frequency of apolipoprotein E E4 allele has been reported in patients with late onset Alzheimer's disease. Apolipoprotein E participates in the transport of cholesterol and other lipids and interferes with the growth and regeneration of both peripheral and central nervous system tissues during development and after injury. Apolipoprotein E is also implicated in synaptogenesis. Apolipoprotein E isoforms differ in binding to amyloid-beta-protein and tau protein in vitro. Here, we wanted to study the effect of apolipoprotein E genotype on the magnitude of damage in the hippocampus, where a marked synapse loss exists in Alzheimer's disease. We measured by magnetic resonance imaging the volumes of the hippocampus, amygdala, and frontal lobes in the three Alzheimer subgroups: patients with 2, 1 or 0 E4 alleles. We also investigated the profile of deficits on tests assessing memory, language, visuospatial, executive, and praxic functions of these Alzheimer subgroups. All Alzheimer patients were at early stage of the disease. We found that Alzheimer patients with E4/4 genotype (N = 5) had smaller volumes of the hippocampus and the amygdala than those with E3/4 (N = 9) and those with E3/3 or E2/3 (N = 12). The difference was significant for the right hippocampus (-54% of control) and the right amygdala (-37% of control). The volumes of the frontal lobes were similar across the Alzheimer subgroups. The patients with E4/4 also showed lowest scores on delayed memory tests and differed from E3/3, 3/2 patients in the list learning test (< 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Imaging of serotonin and dopamine transporters in the living human brain.

Alterations in brain serotonin (5-HT) and dopamine (DA) activity are associated with several neuropsychiatric disorders, but until now it has not been possible to simultaneously visualize or quantify the 5-HT and the DA transporter density in the living human brain. In this paper we report on the imaging of 5-HT and DA transporters in 28 healthy controls with single-photon emission tomography using iodine-123 labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([123I] beta-CIT) as the tracer. The [123I] beta-CIT distribution showed the most prominent 5-HT activity in the medial frontal cortex, hypothalamus, midbrain and occipital cortex and the greatest DA activity in the basal ganglia. The specific binding of the 5-HT transporters in the medial frontal cortex was 0.377 +/- 0.031 and that of the DA transporters in the basal ganglia, 0.916 +/- 0.007. Gjedde-Patlak plots indicated two separate components: the first was assumed to represent 5-HT transporters with a slope of 1.29 +/- 0.27 h-1 and the second, DA transporters with a slope of 0.30 +/- 0.04 h-1. This distinct kinetic pattern and the fact that 5-HT and DA transporters are situated in different parts of the brain provides an opportunity to study in vivo patients suffering from various neuropsychiatric disorders.

Regional cerebral blood flow measured by 99mTc-HMPAO SPECT differs in subgroups of Alzheimer's disease.

Alzheimer's disease (AD) is a heterogeneous entity. Identifying AD subtypes might have impact in patients' response to different treatment strategies. We designed a study to examine regional cerebral blood flow (rCBF) in AD subtypes. To identify AD subtypes, we performed a cluster analysis including performance on memory, language, visuospatial, praxic, and executive functions. The rCBF measured by 99mTc-HMPAO SPECT was referred to the cerebellum. We examined 35 patients fulfilling the NINCDS-ADRDA criteria of probable AD and 13 age and sex-matched healthy cognitively intact controls. AD patients were at the early stage of the disease, their mean Mini-Mental Status (MMS) score (S.D.) was 22.5 (3.6). The cluster analysis revealed two AD subgroups: AD1 (N = 12) and AD2 (N = 23). The subgroups did not differ in age, sex, or global clinical severity as assessed by MMS and Brief Cognitive Rating Scale (BCRS). Both subgroups had equally impaired memory. The AD2 group was inferior to the AD1 group on verbal, visuospatial, praxic, and executive functions. The AD1 group showed reduced rCBF ratios in the temporal and parietal cortices and the amygdala compared to controls. The AD2 group differed from controls in the rCBF ratios of frontal, temporal, parietal, occipital, basal ganglia, and amygdaloid regions bilateral and from AD1 in the rCBF ratios of frontal and temporal cortices. In AD patients, the rCBF ratios did not correlate with MMS or BCRS scores. In contrast, several significant correlations were found between decreases rCBF ratios and impairment of memory and other cognitive functions. In conclusion, a cluster analysis on neuropsychological test performance identified two AD subgroups that differed on the neuropsychological profile and on the rCBF in spite of similar global clinical severity.

Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer's disease: correlation with memory functions.

We studied the usefulness of measuring volumes of the hippocampus, amygdala and frontal lobes with coronal magnetic resonance imaging (MRI) scans in the diagnosis of early Alzheimer's disease (AD). We examined 32 patients diagnosed according to the NINCDS-ADRDA criteria of probable AD and 16 age-matched healthy cognitively normal controls. The AD patients had mild dementia with a mean score of 22.8 in the Mini-Mental Status Examination (MMSE). We used a 1.5 T magnetic resonance imager and normalized the volumes for brain area. The AD patients had significantly smaller volumes of the right and the left hippocampus (-38%) (ANOVA, p < 0.0001) and the left frontal lobe (-16%, p < 0.05) compared to controls. The reductions in volumes of the right frontal lobe (-13%), the right amygdala (-14%) or the left amygdala (-18%) were not statistically significant. In the discriminant function analysis which included the volumes of the hippocampus, amygdala, and the frontal lobes and age, the volumes of the left and right hippocampus, the left and right frontal lobe, and the right amygdala entered the model and we could correctly classify 92% of the subjects into AD and control groups (Chi-square 42.6, df 5, p < 0.001). By using the volumes of the hippocampus, the frontal lobes or the amygdala on their alone, the correct classification was achieved in 88%, 65% and 58% of the subjects, respectively. In addition, in AD patients the volumes of the left hippocampus correlated significantly with the MMSE score and with immediate and delayed verbal memory; the smaller the volume the more impaired was their performance. Our data indicate that measurements of volumes of the hippocampus might be useful in diagnosis of early AD.