Classification of fundus autofluorescence patterns in early age-related macular disease

PURPOSE. To describe and classify patterns of abnormal fundus autofluorescence (FAF) in eyes with early nonexudative age-related macular disease (AMD). METHODS. FAF images were recorded in eyes with early AMD by confocal scanning laser ophthalmoscopy (cSLO) with excitation at 488 nm (argon or OPSL laser) and emission above 500 or 521 nm (barrier filter). A standardized protocol for image acquisition and generation of mean images after automated alignment was applied, and routine fundus photographs were obtained. FAF images were classified by two independent observers. The ? statistic was applied to assess intra- and interobserver variability. RESULTS. Alterations in FAF were classified into eight phenotypic patterns including normal, minimal change, focal increased, patchy, linear, lacelike, reticular, and speckled. Areas with abnormal increased or decreased FAF signals may or may not have corresponded to funduscopically visible alterations. For intraobserver variability, ? of observer I was 0.80 (95% confidence interval [CI]0.71-0.89) and of observer II, 0.74. (95% CI, 0.64-0.84). For interobserver variability, ? was 0.77 (95% CI, 0.67-0.87). CONCLUSIONS. Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. Distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast to a nonspecific aging process. The results indicate that the classification system yields a relatively high degree of intra- and interobserver agreement. It may be applicable for determination of novel prognostic determinants in longitudinal natural history studies, for identification of genetic risk factors, and for monitoring of future therapeutic interventions to slow the progression of early AMD. Copyright © Association for Research in Vision and Ophthalmology.

Quantitative evaluation of fundus autofluorescence imaged 'in vivo' in eyes with retinal disease

Aim - To describe a new method of evaluating the topographic distribution of fundus autofluorescence in eyes with retinal disease. Methods - Images of fundus autofluorescence were obtained in five patients and 34 normal volunteers using a confocal scanning laser ophthalmoscope (cSLO). To evaluate the topographic distribution of fundus autofluorescence throughout the posterior pole a rectangular box, 10 x 750 pixels, was used as the area of analysis. The box was placed, horizontally, across the macular region. The intensity of fundus autofluorescence of each pixel within the rectangular box was plotted against its degree of eccentricity. Profiles of fundus autofluorescence from patients were compared with those obtained from the age matched control group and with cSLO images. Results - Profiles of fundus autofluorescence appeared to represent the topographic distribution of fundus autofluorescence throughout the posterior pole appreciated in the cSLO images, and allowed rapid identification and quantification of areas of increased or decreased fundus autofluorescence. Conclusions - Fundus autofluorescence profiles appear to be useful to study the spatial distribution of fundus autofluorescence in eyes with retinal disease.

A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease

OBJECTIVES: The behavioral and psychological symptoms of Alzheimer's disease (AD) are associated with significant patient and caregiver distress and increased likelihood of institutionalization. We attempted to characterize in detail these symptoms and the distress they cause to caregivers. METHODS: Patients with probable AD were assessed with the Mini-Mental State Exam (MMSE), Functional Assessment Staging (FAST), and the Neuropsychiatric Inventory With Caregiver Distress (NPI-D). RESULTS: Four hundred and thirty-five patients were recruited. Neuropsychiatric symptoms of all types were highly prevalent. The most common and most persistent symptom was apathy (75%). Delusional symptoms were the least persistent. Depressive and apathetic symptoms were the earliest to appear, and hallucinations, elation/euphoria, and aberrant motor behavior were the latest symptoms to emerge. Hallucinations were significantly more common in severe dementia. Symptoms of irritability were most prevalent in early disease. Total Neuropsychiatric Symptom score was significantly correlated with MMSE and FAST score. Caregivers rated their own emotional distress levels as moderate or severe for 10 out of 12 symptom domains. The sum total of caregiver distress was strongly correlated with total NPI-D but not cognition or functional state. Distress levels did not vary when analyzed according to the patients' place of residence. CONCLUSIONS: Potentially treatable neuropsychiatric symptoms are common in AD and represent a major source of distress among caregivers. The extent of neuropsychiatric symptomatology is seen to correlate with the level of functional and cognitive disability although some symptoms are variably persistent and related to disease stage.

Association analysis of apolipoprotein E genotype and risk of depressive symptoms in Alzheimer's disease

OBJECTIVES: Behavioural and psychological symptoms of dementia (BPSD) are potent predictors of carer distress and admission to institutional care. In Alzheimer's disease (AD), depressive symptoms are one of the most common complaints affecting around 50% of all patients. There is speculation these symptoms result from known genetic risk factors for AD, therefore we investigated the role of apolipoprotein E epsilon4 in the aetiology of depression in AD. METHODS: In this well-characterised cohort (n = 404) from the relatively genetically homogeneous Northern Ireland population, we tested the hypothesis that genetic variants of apolipoprotein E influence the risk for depressive symptoms in AD patients using the Neuropsychiatric Inventory (NPI-D) to determine the presence of depressive symptoms during the dementing illness. RESULTS: A total of 55% of patients exhibited a history of depression/dysphoria during the course of the illness as gathered by the NPI-D questionnaire. Forty-six percent were suffering from depression/dysphoria when the analysis was restricted to the month prior to interview. No statistically significant association between genotypes or alleles of apolipoprotein E and depression/dysphoria in AD was observed, nor was any association noted between the presence of severe symptoms and genotypes/alleles of apolipoprotein E. CONCLUSIONS: These results suggest apolipoprotein E genotype creates no additional risk for depressive symptoms in AD.

Behavioural and psychological syndromes in Alzheimer's disease

The origins of behavioural and psychological symptoms of dementia are still poorly understood. By focusing on piecemeal behaviours as opposed to more robust syndrome change valid biological correlates may be overlooked. Our understanding of BPSD via the identification of neuropsychiatric syndromes.

Apolipoprotein E e4 allele influences aggressive behaviour in Alzheimer's disease

The rising number of people with cognitive impairment is placing health care budgets under significant strain. Dementia related behavioural change is a major independent risk factor for admission to expensive institutional care, and aggressive symptoms in particular are poorly tolerated by carers and frequently precipitate the collapse of home coping strategies. Aggressive change may result from known genetic risk factors for Alzheimer's disease (AD) and therefore accompany conventional markers such as apolipoprotein E (ApoE). We tested this hypothesis in 400 moderately to severely affected AD patients who were phenotyped for the presence of aggressive or agitated behaviour during the month prior to interview using the Neuropsychiatric Inventory with Caregiver Distress. The proportion of subjects with aggression/agitation in the month prior to interview was 51.8%. A significantly higher frequency of the e4 allele was found in individuals recording aggression/agitation in the month prior to interview (chi2 = 6.69, df = 2, p = 0.03). The additional risk for aggression/agitation conferred by e4 was also noted when e4 genotypes were compared against non-e4 genotypes (chi2 = 5.45, df = 1, p = 0.02, OR = 1.60, confidence interval (CI) 1.06 to 2.43). These results indicate that advanced Alzheimer's disease patients are at greater risk of aggressive symptoms because of a genetic weakness in apolipoprotein E.

Psychotic symptoms in Alzheimer's disease are not influenced by polymorphic variation at the dopamine receptor DRD3 gene

It has been suggested that genetic influences unmasked during neurodevelopment to produce schizophrenia may appear throughout neurodegeneration to produce AD plus psychosis. Risk of schizophrenia and psychosis in Alzheimer's disease (AD) has been linked to polymorphic variation at the dopamine receptor DRD3 gene implying similar causative mechanisms. We tested this association in a large cohort of Alzheimer's disease patients with a diagnosis of probable AD of 3 years or more duration from the relatively genetically homogenous Northern Irish population. We assessed relationships between genotypes/alleles of the DRD3 BalI polymorphism and the presence or absence of psychotic symptoms (delusions, hallucinations) in AD patients during the month prior to interview and at any stage during the dementia. No significant associations were found when delusions and hallucinations were cross-tabulated against S and G alleles and SS, SG and GG genotypes. Logistic regression failed to detect any influence of APOE, gender, family history or prior psychiatric history. In conclusion, we were unable to confirm previously reported associations between the DRD3 BalI polymorphism and psychotic symptoms in AD.