Measures are needed that identify persons that will develop Alzheimer's disease in order to target them for preventative interventions. There is evidence from animal, pathological and imaging studies that disruption of white matter occurs in the course of Alzheimer's disease and may be an early event. Prior studies have suggested that late-myelinating regions or white matter connecting limbic structures are particularly susceptible to degradation. Persons destined to develop the disease by virtue of fully penetrant genetic alterations (familial Alzheimer's disease or FAD) provide a model in which early and even presymptomatic changes of the disease may be identified. In this study we performed diffusion tensor imaging (DTI) on 2 demented and 21 subjects at-risk for inheriting an FAD mutation. We compared global and localized fractional anisotropy (FA) measures in white matter between FAD mutation carriers and non-carriers in the preclinical (clinical dementia rating <1, n = 20) and presymptomatic (clinical dementia rating = 0, n = 15) stages of the disease. There were no significant differences between mutation carriers and non-carriers with regard to absolute age, age relative to the typical age of disease diagnosis in their family, gender or Mini-Mental Status Examination Score. Among preclinical FAD mutation carriers (n = 12), mean whole brain white-matter FA (P = 0.045), FA of the columns of the fornix (P = 0.012), area of the perforant pathways bilaterally (right side: P = 0.028, left side: P = 0.027) and left orbitofrontal lobe (P = 0.024) were decreased relative to that of non-carriers (n = 8). We also found that FA in the columns of the fornix (P = 0.008) and left orbitofrontal lobe white matter (P = 0.045) were decreased in the eight presymptomatic mutation carriers compared to seven non-carriers. Logistic regression demonstrated that FA of the columns of the fornix was a better predictor of mutation status than was cross-sectional area of the fornix, global mean white-matter FA and left frontal lobe white-matter FA. In a linear regression analysis, white-matter volume (P = 0.002), hippocampal volume (P = 0.023) and mutation status (P = 0.032) significantly predicted fornix FA. We conclude that FA is decreased in the white matter in preclinical and even presymptomatic FAD mutation carriers, particularly in the late-myelinating tracts connecting limbic structures. Decreased FA in of the columns of the fornix is particularly robust in early FAD and may provide a biomarker for early disease in sporadic Alzheimer's disease.

Mild cognitive impairment (MCI) has emerged as an identifiable condition and in many cases is a transitional state preceding diagnosable Alzheimer disease (AD). Neurobiological and neuroimaging characteristics of amnestic-type MCI have been investigated, but few comprehensive neuropsychiatric studies have been reported. The aim of this preliminary study was to define the neuropsychiatric features of the amnestic-type MCI and compare them with those of mild AD and normal controls. The Neuropsychiatric Inventory (NPI) was used to assess the neuropsychiatric symptoms in three age and education comparable groups, i.e., 28 MCI, 124 mild AD, and 50 normal subjects. Individual subscores of the 10 NPI symptoms and total NPI scores were compared between the MCI patients and the other 2 groups. The results of this preliminary investigation showed that MCI patients frequently manifested neuropsychiatric symptoms. The most common symptoms in the MCI group were dysphoria (39%), apathy (39%), irritability (29%), and anxiety (25%). There were significant differences in apathy, dysphoria, irritability, anxiety, agitation, and aberrant motor behavior between the MCI and control groups; in contrast, only delusions were significantly less common in MCI compared with mild AD. There was a significant difference between the MCI and control groups on total NPI scores (p = 0.001), but not between the MCI and mild AD groups (p = 0.304). Amnestic MCI is associated with significant neuropsychiatric symptoms, especially mood disturbances and apathy. Psychotic symptoms are significantly more common in the early stage of AD than in MCI. These results are derived from a limited clinical sample and require confirmation in longitudinal community-based investigations.

Neuropsychological assessment of monolingual Spanish-speaking people in the United States is both a common practice and an ethical dilemma. Lack of appropriate tests, the absence of norms, use of interpreters, and the multiplicity of in-house translations of commonly used measures add to the problem of accurate assessment. This paper helps address the lack of appropriate measures for the neuropsychological assessment of Latinos in the United States by providing a standardization of the Neuropsychological Screening Battery for Hispanics (NeSBHIS). Normative data on a sample of 300 Hispanic subjects stratified by gender, age, and education are provided. Current results reveal that not one measure of cognitive functioning is free from education effects. Both nonverbal measures and psychomotor speed measures were highly related to education. Age effects were noted on measures of psychomotor speed, visuospatial reasoning, and visuoconstructive skills. Gender effects were found on measures of psychomotor speed and language, with males achieving higher scores than females. The limitations of the current findings are considered. Further research for the validation of the NeSBHIS with clinical populations, as well as further normative data collection at the national and international levels, is needed. (JINS, 1996, 2, 96–104.)

In comparison with data from predominantly white populations, our proportion of AD cases was lower and that of VascD cases was considerably higher than anticipated. The percentage of clinically depressed older individuals was also high. These findings could have implications for differential cultural and genetic risk factors for dementia among diverse ethnic/racial groups. Further studies are needed to obtain accurate prevalence estimates of dementing disorders among the different U.S. Hispanic populations.