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Primary degenerative dementia syndromes are an increasingly relevant problem worldwide because of the progressive aging of the population. Their diagnosis is often a challenge for clinicians and, even in the best cases, only a possible or probable diagnosis can be reached. Molecular neuroimaging techniques can be very useful in dementia patients, especially for obtaining a diagnosis in the early stage of disease. The most diffuse and widely available nuclear medicine method for neurological studies is F-fluoro-deoxy-glucose (F-FDG)-PET, which allows the quantification of glucose gray matter metabolism and helps visualize typical, adequately specific, patterns for many kinds of degenerative dementia, not only for the well-known and well-studied Alzheimer's disease. This paper aims to describe the clinical and F-FDG-PET profiles of the principal non-Alzheimer type of degenerative dementias.

The authors implemented a group in a state psychiatric institution for women with primary degeneration dementia. The group provided scheduled opportunity in a nonrestrictive environment for structured movement and sensory stimulation. Over a period of nine sessions, small but significant changes were noted in the members' behavior. This type of therapy can benefit such limited clients by enhancing the quality of their life in the institution.

Wide variations in frequency of depression in primary degenerative dementia (PDD) and in vascular dementia (VD) have been reported. This may perhaps be due to inadequacy of common diagnostic tools in detecting depression in the face of cognitive decline. We evaluated here the Hamilton Depression Rating Scale (HDRS) in demented patients with PDD and VD.We examined 50 consecutive patients with PDD and 50 consecutive patients with VD. All patients underwent neurological examination and their depression was evaluated using DSM-III-R criteria and the HDRS. The data obtained were analysed for distribution of depression and pattern of responses obtained in the HDRS. Sensitivity, specificity and Youden's J-indices for different cut-off scores of the HDRS in its ability to detect depression in this population were calculated.Dementia was associated with depression in 38% of the patients (DSM-III-R criteria). HDRS scores were higher in depressed patients (z= -5.7, P0.0001) with an HDRS cut-off score of 10 being indicative of depression in demented patients. Symptoms related to 'affective' components of the HDRS (such as depressive mood and anxiety) were strongly associated with the diagnosis of depression (Mann-Whitney tests, P0.0001).Depression is frequent in demented patients. The HDRS has good criterion validity in the evaluation of depression in demented patients. (Int J Psych Clin Pract 2002; 6: 91-94).

Among the psychiatric illnesses associated with old age primary degenerative dementia of the Alzheimer type (DAT) has gained increasing importance in recent years. Even though a curative treatment of the disease is currently impossible, various drugs can be used to slow down its progression. In the present study the influence of oral treatment with 240 mg/day of Ginkgo bilabo special extract EGb 761 (Tebonin forte, manufactured by Dr Willmar Schwabe, Karlsruhe) on the clinical course of DAT was investigated in a double-blind, randomized, placebo-controlled parallel-group design in 20 outpatients. The duration of treatment was 3 months. The primary outcome variable was the sum score in the SKT-test for the determination of attention and memory. Other psychometric tests (trailmaking test, ADAS, CGI) and electrophysiological investigations (EEG topography) were evaluated descriptively. Although the active-treatment group, with a mean sum score of 19.67 points in the, S.K.T., had a poorer baseline level than the placebo group (18.11 points), it experienced an improvement to 16.78 points under treatment with EGb 761 whereas the placebo group deteriorated to 18.89 points. The differences between the baseline and final values formed the basis for a statistical group comparison, which gave a result favourable to EGb 761, at a significance level of p < .013. In addition to this psychometric confirmation of efficacy, certain descriptive trends were found at the psychopathological (Clinical Global Impression) and dynamic functional (EEG findings) levels, which can be interpreted as evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system. Inter-group differences in the ADAS cognitive and non-cognitive subscales did not reach statistical significance, probably because of the small sample size.

The efficacy of the Ginkgo biloba special extract EGb 761 in outpatients with presenile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) according to DSM-III-R was investigated in a prospective, randomized, double-blind, placebo-controlled, multi-center study. After a 4-week run-in period, 216 patients were included in the randomized 24-week treatment period. These received either a daily oral dose of 240 mg EGb 761 or placebo. In accordance with the recommended multi-dimensional evaluation approach, three primary variables were chosen: the Clinical Global Impressions (CGI Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT)(1) for the assessment of the patient's attention and memory, and the Nürnberger Alters-Beobachtungsskala (NAB)(2) for behavioral assessment of activities of daily life. Clinical efficacy was assessed by means of a responder analysis, with therapy response being defined as response in at least two of the three primary variables. The data from the 156 patients who completed the study in accordance with the study protocol were taken into account in the confirmatory analysis of valid cases. The frequency of therapy responded in the two treatment groups differed significantly in favor of EGb 761, with p0.005 in Fisher's Exact Test. The intent-to-treat analysis of 205 patients led to similar efficacy results. Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated.

A longitudinal study was undertaken assessing the efficacy of the Hierarchic Dementia Scale (HDS) as a measure of cognitive function over time, for individuals with dementia who were residing in the community. The participants were administered the HDS and the Mini Mental State Examination (MMSE). One hundred eighty-six people with a diagnosis of primary degenerative dementia were assessed. Two years later, 78 of the original sample were reassessed using the same measures. The HDS revealed a significant decline in cognitivefunctions with initial scores significantly predicting patient institutionalization or death. The study also reported additional psychometric data for the HDS.

1. Flash visual evoked responses of 31 patients meeting DSM-III-R criteria for primary degenerative dementia of the Alzheimer type were compared with 31 healthy controls. 2. P1 latency was normal (75 +/- 6 msec Alzheimer's; 75 +/- 6 msec controls). 3. P2 was significantly delayed (162 +/- 32 msec, 147 +/- 20 msec, p0.03) among patients. 4. P1-P2 interpeak latency was significantly increased (87 +/- 32 msec, 71 +/- 21 msec, p0.03) among patients.

Thirty spousal caregivers and their partners (who had been diagnosed as having primary degenerative dementia) jointly performed four cognitive tasks: Block Design (from the WAIS-R), the Token Test, and two memory tasks. Two of the tasks were unstructured, and two were structured. Caregivers served as the instructor on all tasks. Interactions were videotaped. Results showed that caregivers provided appropriate verbal instructions to a greater extent on the unstructured nonverbal task (Block Design) than on the unstructured memory task. Results are discussed in terms of implications for dyadic cognition research and intervention in dementia.

The authors compared the 2-year survival rates of patients with 1) mixed clinical presentations (n=58), 2) major depression without cognitive impairment (n = 51), and 3) primary degenerative dementia without depression (n = 34). Two-year survival rates were 100% in healthy controls, 91% in patients with major depression, and 76.1% and 78.3%, respectively, in patients with primary degenerative dementia and mixed symptoms. Patients with cognitive impairment (either primary degenerative dementia or mixed symptoms) were 2.55 times more likely to die within the 2-year follow-up than patients with major depression. These data are consistent with previous observations that survival rates of elderly patients with organic mental syndromes are lower than those of elderly patients with "functional" or "psychogenic" disorders.

Parkinson's and Alzheimer's diseases are age-related degenerative disorders that share common clinical, pathological and biochemical features. Epidemiological studies demonstrate a similar distribution of the disease in place and time. Causes of death and populations at higher risk are similar. These findings suggest that these diseases must have common determinants.

In detailed published accounts to date of 40 twin pairs one or both of whom were said to have Alzheimer's disease (AD), 16 of 35 monozygotic (MZ) pairs were described as concordant for the disease and the remaining 19 pairs as discordant, while of the five pairs of dizygotic (DZ) twins two pairs were designated as concordant. However, these data have emerged almost exclusively from selective case reports and volunteer samples, resulting in an over-representation of MZ twins that complicates the overall interpretation of the data. In an effort to reduce such ascertainment bias, we screened for diagnoses consistent with AD in the Maudsley Hospital Twin Register, which consists of twins registered at the Bethlem Royal and the Maudsley Hospitals (London, UK) since 1948. Seven twins were identified who met criteria for primary degenerative dementia of the Alzheimer type. Available details of their affected status as well as of the status of their co-twins are presented and discussed.

Summary Primary brain tumour may present in the elderly purely as a dementing illness before the onset or detection of sensorimotor neurological symptoms or signs. Although neurological examination may indicate no definite signs, close attention to accepted DSM-IIIR and NINCDS-ADRDA diagnostic criteria for primary degenerative dementia and 'probable' Alzheimer's disease respectively will suggest a process other than a degenerative one. This was the case in two patients with primary brain tumour presenting clinically with dementing illness similar to but distinct from Alzheimer's disease.

Primary degenerative dementia (PDD) and multi-infarct dementia (MID) are the two most common categories of cognitive decline in old age. The definitions of these two clinical entities are currently based on clinical evaluation and on the exclusion of other underlying causes, and still lack a consensus. The DSM-III-R criteria are widely used for the diagnosis of dementia. However, their role in the differentiation between PDD and MID has not been thoroughly examined. A consecutive series of 98 demented patients who met the DSM-III-R criteria for dementia were admitted to a clinical study. Upon evaluating their type of dementia according to these criteria, 53 patients could not be diagnosed either as having PDD or MID. The DSM-III-R criteria for these two types of dementia are critically reviewed. Proposed modifications, aimed at refining their differential diagnostic role, are presented, enabling better allocation of demented patients into PDD, MID, or intermediate groups.

The test-retest and split-half reliability of flicker threshold measurement was determined in 23 female and three male patients with primary degenerative dementia of the Alzheimer's type (PDDAT). Patients had a mean age of 81.7 ± 6.05 years (range 67–89). Diagnosis of PDDAT was based on DSM-IIIR criteria. The psychophysical method of limits was used to determine the flicker threshold and was the average of four separate measurements. The split-half reliability was found to be 0.97 and the test-retest reliability 0.941 (both p < 0.0001). The measurement of flicker thresholds is a quick, easy and reliable technique in patients with PDDAT. Future work will also need to examine the validity and pharmacosensitivity of the measure if it is to be used to assess potentially therapeutic agents for the management of the underlying disease process.

Serum and cerebrospinal fluid (CSF) from 118 patients with primary degenerative dementia (PDD; Alzheimer''s disease) and 50 healthy controls were examined in order to investigate intrathecal synthesis of immunoglobulin G (IgG), defined as an elevated IgG index (≧ 0.7) and/or the presence of oligoclonal IgG bands in CSF but not in serum. In the PDD group, 7 patients (6%) showed an intrathecal IgG synthesis. Eight patients (7%) showed oligoclonal IgG bands in serum and CSF, interpreted as a diffusion of IgG across the blood-brain barrier. In the early-onset PDD group, the mean IgG index was higher than in age-matched controls. The PDD patients with intrathecal IgG synthesis were less demented than those with normal CSF, but the intrathecal synthesis was not related to age, sex, or blood-brain barrier function. The findings suggest that immunological dysfunction could be related to PDD.

Finger tapping parameters were investigated in a group of 21 patients suffering from early (mild) stage of a tentative presenile dementia of the Alzheimer type (DAT), in a group of 14 patients with a questionable beginning dementia on the background of cardiovascular disease (CVD), in an age-matched (elder) control group (n = 10) and in a younger control group (n = 16). DAT patients responded significantly more slowly and less accurately in tapping with maximal frequency, with a self-chosen preferred frequency and in tasks to follow rhythmic acoustic clicks. CVD patients responded slightly more slowly but more accurately than DAT patients. The data confirm the hypothesis that decrease of brain operational speed and of focussed attention are early symptoms of dementia, especially of DAT and develop prior to memory decline.

Critical Flicker Fusion Threshold (CFFT) and the difference between fusion and flicker thresholds were examined in 23 female and three male patients with Primary Degenerative Dementia of the Alzheimer’s type (PDDAT). The control group consisted of age, sex, and occupational class-matched, normal volunteers. Patients had a mean age of 81.7 years ±6.05 (range 67–89); diagnosis was based on DSM-IIIR criteria. The psychophysical method of limits was used to measure three ascending (fusion) and three descending (flicker) means the average being the CFFT. Both the CFFT and the flicker thresholds were able to distinguish between patients and volunteers at a high level of statistical significance (t=2.054, df=50, p

The diagnostic utility of determinations of insidious or stepwise progression of illness was examined in 124 geriatric inpatients with primary dementia. Such determinations failed to distinguish patients with primary degenerative dementia of the Alzheimer type from those with multi-infarct dementia. Episodic behavioral complications, especially depression and delusions, in the patients with primary degenerative dementia were associated with stepwise progression. Determinations of stepwise progression were made in only six (15%) of the 40 demented patients with at least two cerebral infarctions, a finding inconsistent with current diagnostic criteria for multi-infarct dementia.

Patients suffering from Alzheimer type dementia have demonstrated an increase in MAO-B activity. Treatment of these patients with an inhibitor of the monoamine oxidase activity, such as L-Deprenyl (LD), might therefore provide a valid therapeutic intervention. The efficacy of LD was examined in a double-blind, drug versus placebo (PL) study on 20 patients diagnosed between stages 3 and 5 of primary degenerative dementia. Treatment duration was 90 days (5 mg twice a day). All patients underwent clinical, behavioral, and memory evaluations every 30 days. Subjects in the LD group demonstrated an improvement on both attention and memory measures; some of the changes were apparent after only 30 days of treatment. PL patients showed no such improvement and also evidenced a decrease in behavior efficiency during the experimental period. Two patients dropped out of the study, 1 from each treatment group. No differences were found in either the type and number of concomitant treatments or side effects between groups.

B12 analogues, homocysteine, methylmalonic acid (MMA), and unsaturated transcobalamins, all potential markers of vitamin B12 status, were analyzed in blood and cerebrospinal fluid (CSF) from 22 patients with primary degenerative dementia of Alzheimer type. The level of active vitamin B12 in serum correlated significantly with serum homocysteine, serum MMA, and CSF homocysteine. CSF B12 correlated significantly with serum homocysteine and serum MMA. The ratio of analogues and active vitamin B12 concentrations in serum (analogue/active B12 ratio) correlated significantly with serum homocysteine, serum MMA and CSF B12. This study had no control group. However, based on available reference values, high concentrations of homocysteine and MMA in serum and unsaturated transcobalamin II in plasma were interpreted as evidence of vitamin B12 depletion or deficiency. Such high concentrations were found in a significant number of patients. In 9 patients, vitamin B12 injections were administered. After treatment, serum homocysteine levels fell significantly. We conclude that vitamin B12 analogues, homocysteine, MMA, and transcobalamins may be useful as markers in studies aimed at clarifying the role of vitamin B12 deficiency in dementia disorders.

Dementia disorders are syndromes of cognito-emotional impairment which are disabling and longstanding. Subgroups of dementia are idiopathic dementias or primary degenerative dementias, vascular dementias and secondary dementias. Neurochemical investigations of postmortem human brain material have shown multiple changes in the neurotransmitter metabolism in patients with Alzheimer''s disease (AD) and senile dementia of the Alzheimer type (SDAT). The cholinergic system is severely disturbed, but also the serotonin system and the catecholamines are disturbed. Reduced concentrations of neuropeptides have also been reported in AD/SDAT. It is obvious, however, that in brains from Alzheimer-afflicted patients, there are also disturbances in gangliosides and white matter components. At present, it is not possible to single out one of these changes as of special importance for the dementia disorder. The recorded neurochemical changes in brains from patients with AD/SDAT must, at present, be assumed to be secondary phenomena to a more fundamental disturbance, the nature of which we still do not know. Another explanation may be that the group AD/SDAT is a heterogeneous group, including several from an etiopathological point of view different disorders. In vascular dementia, there seem to be subgroups, and the multi-infarct dementia (MID) is only one of these. In a non-MID vascular group, there are general neurochemical disturbances in the form of reduced activity of cholineacetyl transferase and concentrations of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Although the neurochemical changes in dementia disorders are looked upon as secondary phenomena, they are of pathogenetic importance. Significant correlations have also been shown between neurotransmitter disturbances and behavioral symptoms. Thus, the neurochemical changes form a basis for formulating treatment strategies.

21 patients (54 +/- 7 years old) with early cognitive deficit (ECD) during the presenile stage of presumptive primary degenerative dementia (mild stage) and 14 patients (54 +/- 4 years old) with early cognitive deficit with a background of cardiovascular disease (CVD) were examined in a labyrinth learning test of Milner (modified by Roth). 15 patients in the ECD group made 3 times more errors to negative fields (p less than 0.01), about 10 times more errors to positive fields (p less than 0.01) and needed treble the amount of time for passing through the labyrinth (p less than 0.01) compared with a healthy control group (51 +/- 4 years). A further 6 patients of the ECD group had no success in performing the labyrinth test. The CVD group was not different from the control group in making errors, but slower (p less than 0.05). The labyrinth test is found suitable for a more precise diagnosis of early cognitive deficit in the early stage of a primary degenerative dementia of the Alzheimer type.

Electroencephalography (EEG) can be a valuable technique to assess electrophysiological changes related to dementia. In patients suspected of having dementia, the EEG is often quite informative. The sensitivity of the EEG to detect correlates of psychiatric disorders has been enhanced by means of quantitative methods of analysis (quantitative EEG). Quantitative features are extracted from, at least, 2 minutes of artifact-free, eyes closed, resting EEG, log-transformed to obtain Gaussianity, age-regressed, and Z-transformed relative to population norms (Neurometrics database). Using a subset of quantitative EEG (qEEG) features, forward stepwise discriminant analyses are used to construct classifier functions. Along this vein, the main objective of this experiment is to distinguish profiles of qEEG, which differentiate depressive from demented patients (n = 125). The results showed that demented patients present deviations above the control group in variables associated to slow rhythms: Normed Monopolar Relative Power Theta for Cz and Normed Bipolar Relative Power Theta for Head. On the other hand, the deviation below the control group occurs with the variable associated to alpha rhythm: Normed Monopolar Relative Power Alpha for P3, in dementia. Using this method, the present investigation demonstrated high discriminant accuracy in separating Primary Degenerative Dementia from Major Depressive Disorder (Depression). A Eletroencefalografia (EEG) pode ser utilizada como uma técnica valiosa na avaliação de mudanças eletrofisiológicas relacionadas à demência. Em pacientes com suspeita de demência, o EEG é em geral bastante informativo. A sensibilidade do EEG em detectar correlatos de desordens psiquiátricas pode ser incrementada através de métodos de análise quantitativa (EEG quantitativo). Padrões quantitativos são extraídos de pelo menos 2 minutos de dados livres de artefatos, em que os sujeitos estão com olhos fechados e em estado de repouso. São aplicados métodos quantitativos, tais como: transformação logarítmica para obtenção de uma distribuição Gaussiana, regressão por faixa etária e o escore Z relativo a normas populacionais preestabelecidas (Neurometrics). Utilizando uma amostra de padrões de EEG quantitativo (EEGq), será implementada uma análise discriminante (forward stepwise) a fim de estabelecer funções classificatórias. Neste contexto, o objetivo principal deste estudo é distinguir perfis de EEGq que diferenciem pacientes com depressão de pacientes com demência (n = 125). Os resultados demonstraram que pacientes acometidos por demência apresentam desvios acima do grupo controle em variáveis associadas a ritmos lentos: Potência Monopolar Relativa Normalizada em Teta para Cz e Potência Bipolar Relativa Normalizada em Teta para Cabeça. Por outro lado, desvios abaixo do grupo controle ocorrem em variáveis associadas ao ritmo alfa: Potência Monopolar Relativa Normalizada em Alfa para P3. Através deste método, a presente investigação demonstrou uma alta acurácia em discriminar pacientes com Demência Degenerativa Primária de pacientes com Transtorno Depressivo Maior.

Quantitative magnetic resonance imaging (MRI) was used to investigate volumes of different brain structures in 19 patients with late-onset major depression (DSM-III-R), 27 patients with Alzheimer's disease (NINCDS-ADRDA criteria) and 13 age matched controls. 3-D MRI sequences were acquired using a Siemens 1.5 T scanner. Whole brain volume, CSF volume, volume of the frontal and temporal lobes and the volume of the amygdala-hippocampus complex were assessed using the software NMR Win. Compared to the controls, depressed patients showed a significantly lower whole brain volume and a significantly higher CSF volume, whereas volumes of the frontal and temporal lobes as well as the amygdala-hippocampus complex volumes were not significantly decreased. In addition, depressed patients exhibited a higher ventricle-brain ratio suggesting a higher degree of central atrophy compared to healthy individuals. In contrast, Alzheimer patients showed significantly lower volumes than depressed patients and controls with respect to all volumetric parameters. Although the findings indicate the presence of brain atrophy in patients with late-onset depression, the pattern of volumetric changes in these patients differs markedly from that observed in patients with primary degenerative dementia.

Summary Eight subjects, 60–75 years of age, with at least 5 years of education and mild memory impairments were recruited for a rehabilitation program. Other 8 subjects, not exposed to the rehabilitative training and with the same neuropsychological profile, represented a control group. In the first day of this program an evaluation of cognitive/behavioral functions was performed. Our program consisted of a neuropsychological rehabilitative intervention along 12 weeks, with a 5-day-period of domiciliary training with a set of home exercises and a 1-day training in our Center with rehabilitative exercises administered with the aid of a personal computer, each week. Rehabilitative training administered in our Center was aimed at stimulating visuo-verbal, verbal and spatial memory and the utilization of “memory strategies”. After 4, 8 and 12 weeks of therapeutic program, other evaluations of the cognitive functions with the same battery tests were performed to evaluate possible improvements: the results indicated an improvement of memory test scores that demonstrated the positive effect of neuropsychological training on memory performances. There was no improvement in the control group.

To test the hypothesis that primary degenerative dementia of the Alzheimer type (PDD-AT) may increase the likelihood of expression of a lifetime vulnerability to the development of depression, the authors compared the premorbid rates of major depression in psychiatric inpatients with dementia, with or without a concurrent syndrome of depression. A premorbid history of major depression was four times more common in patients with the depressive syndrome of PDD-AT than in PDD-AT patients without depression. The authors discuss the significance of these findings for pathophysiologic models and estimates of comorbidity of depression in PDD-AT.

In 1907 Alois Alzheimer reported the case of a 51 year old woman who died after a brief illness characterized by dementia, aphasia and psychosis (Alzheimer, 1907). Postmortem examination of the brain revealed the presence of abundant plaques and tangles in the cerebral cortex, the latter being demonstrated for the first time by means of a newly developed silver-staining technique. The case was noteworthy because of its close resemblance, clinically and histologically, to senile dementia which was well known at the time, but in persons of greater age. Some 50 years later, it was usual practice to recognize ‘senile dementia’ and ‘presenile dementia’ as two closely related, but distinct, clinical entities. The latter had become synonymous with Alzheimer’s disease (AD), terminology more likely to be heard, at the time, in neurological than in psychiatric circles. As knowledge of the two disorders grew, it became customary for investigators to refer to them as ‘senile and presenile dementia of the Alzheimer type’. Clinical psychiatrists preferred the terminology of DSM-III, ‘Primary degenerative dementia, senile onset’ and ‘Primary degenerative dementia, presenile onset’. Currently, because histological and clinical findings are virtually identical in the senile and presenile types of AD, it is customary to refer to both as Alzheimer’s disease.

Brain computed tomography (CT) scans were performed in hospitalized geriatric patients with major depression (n = 45) or primary degenerative dementia (n = 21). Depressed patients with onset of illness at age 60 years or older (n = 32) had greater ventricular size than geriatric depressives with earlier age of illness onset (n = 3). CT parameters of late-onset depressives were comparable to those of patients with primary degenerative dementia. However, early-onset geriatric depressives had significantly smaller ventricles and less sulcal widening than demented patients. The findings suggest that late-onset depression may have a stronger association with neurological dementing disorders than early-onset depression.

Ten patients diagnosed as affected by primary degenerative dementia of the Alzheimer type, with a mild to moderate cognitive and behavioral impairment, were studied in a double blind design when taking for 60 days 5 mg twice a day of L -deprenyl or placebp. Cognitive functions and cerebral blood flow were assessed at the beginning and at the end of treatment by a wide array of memory, attention, and language efficiency measures and by SPECT- 99 TcHMPAO procedure. Reduced CBF on the parietal lobes was demonstrated in the patients at baseline together with a reduction of memory and cognitive efficiency. At the end of the treatment patients who received L -deprenyl showed an improvement in cognitive efficiency and no changes in CBF, while patients treated with placebo showed a worsening of cognitive efficiency and further reduction of parietal lobe CBF.