Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and behavioural changes. Overlap of symptoms between AD and Post-Traumatic Stress Disorder (PTSD) includes anxiety, depression, sleeplessness, paranoia, spontaneous motor/startle movements and short-term memory loss. Alpha1-adrenergic receptors (₁AdRs) modulate fear response, sleep and startle behaviours and are preferentially distributed in prefrontal cortex, amygdala and hippocampus.Prazosin
(₁AdR antagonist) therapy alleviated PTSD symptoms in combat veterans and trauma sufferers (Raskind et al., 2002), thus may ameliorate similar symptoms in dementia. The aim of the study was to investigate
₁AdR status in frontal and temporal cortex of brains from people with dementia and to relate this to scores for aggressive behaviour, depression, overactivity and psychoses exhibited during life in patients with dementia (Minger et al., 2000), as well as specific behavioural abnormalities relevant to PTSD.

Membranes were prepared by three centrifugation and resuspension cycles (Minger et al., 2000) from f rontal cortex from 24 AD cases, 5 mixed dementia (AD and vascular dementia) and 25 controls and temporal cortex (28 AD, 9 mixed dementia, 31 controls) and were examined for density (B_max) and affinity (K_D) of [³H] prazosin binding (eight concentrations: 0.025-2.5 nM) to ₁AdR. Incubation with phentolamine (100 µM) determined non-specific binding (Shimohama et al., 1986) . Binding was terminated by rapid filtration. Data were expressed relative to total protein (Minger et al., 2000). Patients were matched for age and post-mortem delay.

Table 1. Specific binding of [³H] prazosin to ₁AdR in frontal and temporal cortices.

Values are mean ± SEM (n) after removal of outliers (boxplots).* Significantly different from control at p< 0.02, Kruskal-Wallis ANOVA followed Mann-Whitney U test.

Alterations in K_D for [³H] prazosin binding to ₁AdR in AD brains (Table 1) were unrelated to behavioural measures (stepwise multiple regression, p>0.05). While there were no significant changes in B _max  for [³H] prazosin binding ( Table 1), aggressive behaviour positively correlated with B_max in frontal cortex in AD (r=0.454, p=0.026) and negatively correlated in temporal cortex in mixed dementia (n=-0.741, p=0.035). These data suggest a rationale for treating aggressive behaviour in AD with prazosin. Scores for depression in the small number of mixed dementia cases negatively correlated with [³H] prazosin B_max in frontal cortex. Further studies are required in a larger cohort to confirm this observation.

Minger, SL, et al. (2000) Neurology. 55:1460-1467.
Raskind, MA, et al . ( 2002) Journal of Clinical Psychiatry. 63 : 565-568.
Shimohama, S, et al. (1986) Journal of Neurochem istry . 47 : 1294-1301.

This work was supported by local funds.