James Levy

The effect of apolipoprotein E (APOE) genotype on longitudinal cognitive decline in midlife was investigated with attentional scaling. Healthy individuals (mean age 59.6 years) genotyped for APOE were tested at 3 12-month intervals on a cued visual search task. A random effects model revealed significant interaction in effect of precue size on search speed between APOE-epsilon4 gene dose and assessment, with longitudinal increases in noncarriers and heterozygotes but longitudinal decreases in homozygotes. Association of APOE-epsilon4 with cognitive decline in midlife is consistent with an Alzheimer's disease (AD) prodrome, albeit a decade or more before average age of AD diagnosis. However, cognitive decline in midlife associated with a gene modulating neuronal response to insult argues that the concept of an AD prodrome includes factors that allow as well as cause AD.

To better define the influence of apolipoprotein E (ApoE) epsilon 4 genotype on the cognitive and biochemical features of Alzheimer's disease (AD), cross-sectional analysis of global cognitive measures and cerebrospinal fluid studies gathered on AD subjects at a tertiary care facility between 1986 and 1997 was carried out. The 112 AD patients examined included 62 women and 50 men with a mean (SD) age of 64.2 (9.2) years. Patient demographics; illness onset age and duration, education level and global cognitive measures were recorded systematically. Genetic analysis for ApoE allele type and biochemical characterization of CSF, including total tau concentration, was performed. Descriptive statistics of demographics, cognitive and CSF measures were performed by chi-square, ANOVA and Tukey's tests. Overrepresentation of the epsilon 4 allele was found, with 45.5% of AD patients heterozygous and 20.5% homozygous for ApoE epsilon 4. Overall, ApoE epsilon 4 status had no effect on mean onset age of AD (F = 1.56; p = 0.214), but an earlier mean onset age of AD (F = 4.10; p = 0.02) was seen in the late-onset subjects. No differences were found with regard to ApoE epsilon 4 status and measures of disease, duration of illness or global cognitive performance. Although CSF tau was elevated in our sample (575.4 +/- 290.3 pg/ml), ApoE epsilon 4 status did not influence total CSF tau or neurotransmitter metabolite levels. ApoE epsilon 4 genotype had no impact on a variety of illness severity, cognitive and CSF examinations in the largest cross-sectional analysis of AD subjects yet reported.

This book marks the first comprehensive history of Britain's naval bulwark, the Home Fleet. It illuminates the vital role that fleet played in preserving Britain as a base of operations against Hitler