There is increasing evidence for the role of activated microglia in the neurotoxic pathways of Alzheimer's disease (AD). Amyloid-β1-42 is a potent activator of microglia (Benveniste et al., 2001), causing them to release pro-inflammatory cytokines including IL-6, IL-1β, TNF-α among others. A peripheral blood marker reflecting CNS inflammatory processes would be useful for treatment development, but the search for such an in vivo marker has been elusive. Peripheral blood and CSF levels of pro-inflammatory cytokines do not consistently differ in AD and controls (reviewed in Rosenberg, 2005). Both microglia and peripheral blood mononuclear cells (PBMCs) release pro-inflammatory cytokines when exposed to immunologic stimuli including lipopolysaccharide (LPS) and phytohemagglutinin (PHA). There are recent data suggesting that PBMCs from AD patients release more cytokines in this paradigm than normal controls (Reale et al., 2004).

We recently reported age-associated suicide rates and trends over time for elderly suicide rates for the whole of the U.K. and its three constituent countries (England and Wales, Scotland and Northern Ireland) (Shah and Coupe, 2009). That study, in part, was conducted to examine the impact of the suicide prevention policies for each of the three constituent countries as the governmental suicide reduction targets for 2010, 2011 and 2013 move closer for England, Northern Ireland and Scotland respectively.

Two paradoxical hypotheses – (i) that countries with low population growth rates or a decline in population growth rate will have high elderly dependency ratios leading to high elderly suicide rates, and (ii) that countries with high population growth rates will have high elderly suicide rates because of Durkheim's hypothesis that the overall cohort size may influence suicide rates due to competition for scarce resources – were supported by a recent study (Shah, 2008). The relationship between average annual population growth rates and elderly suicide rates was shown to be curvilinear (U-shaped curve) fitting the quadratic equation y = a + bx + cx2 (where y is the elderly suicide rate, x is the average annual population growth rate and a, b and c are constants) using an ecological study design.

Marin et al. (2003) have suggested that apathy may be independent of executive functions in older-aged patients with major depression, although the correlation between apathy and the “controlled oral word association test,” a test of executive measures, approached significance. However, Feil et al. (2003), using the same definition and measure of apathy, observed a strong correlation between apathy and both verbal and non-verbal executive cognitive measures. The question thus arises as to whether apathy contributes to executive cognitive dysfunction in non-demented patients with late-life depression. We therefore re-examined this issue, looking particularly at whether apathy distinctly affects executive control functions. Our hypothesis was that apathy would contribute to cognitive impairment in depressed elderly patients independently of the severity of depression.

Alcohol-use disorders have been reported to be associated with the risk of suicide in the general population (Schneider et al., 2009) and in the elderly (Shah and Ganesvaran, 1997). This allows identification of individuals potentially at increased risk for suicide and target preventative interventions at an individual level. Moreover, alcohol is often taken during the process of committing suicide (Conwell et al., 1990). Identification of the relationship between the national consumption of alcohol and suicide rates would support generation of public health measures to reduce the national consumption of alcohol to facilitate reduction in suicide rates. Thus, a cross-national ecological study examining the relationship between national per capita consumption of alcohol and suicide rates was undertaken.

The patient–doctor relationship is central to medicine. This relationship has two fundamental components (Calman and McLean, 1984). The first is the doctor's care, skill and knowledge; the second is information-giving to help the individual make decisions. Hence, communication and trust are essential in this relationship.

Suicide rates increase with aging in many countries (Shah and De, 1998). In a recent study of 62 developed and developing countries, suicide rates increased with age for males and females in 25 and 27 countries respectively, and in both sexes in 17 countries (Shah, 2007). Suicide rates increased with age in 47 of the 49 medium- and high-income countries (Kiemo, 2004). Comprehensive understanding of the substantial worldwide variation in population patterns of suicide may be critical for developing prevention programs (Knox et al., 2004). Much is known about individual level proximal risk factors (Shah and De, 1998) and preventative strategies can target identified high-risk groups (Shah and De, 1998). Also, proximal risk factors for elderly suicide victims are generally different from those for younger suicide victims (Shah and De, 1998). However, distal risk factors may be similar for older and younger suicide victims. Such factors include societal socio-economic status (Kennedy et al., 1999; Shah et al., 2008), societal income inequality (Kowalski et al., 1987; Shah et al., 2008), education (Kowalski et al., 1987; Shah and Chaterjee, 2008), degree of urbanization (Stack, 1993; Shah, 2008a), degree of social integration (Durkheim, 1992; Shah, 2008b) and provision of health and mental health service provision (Shah and Bhat, 2008). In general, preventative measures targeting distal risk factors require development of public health strategies at a societal level.

Although not approved by the Food and Drug Administration (FDA) for behavioral disturbances, the largest number of antipsychotic prescriptions in older adults is for this indication associated with dementia (Sultzer et al., 2008). In 2005, the FDA determined that atypical antipsychotic medications were associated with a 1.6 to 1.7 greater risk of mortality compared with placebo when administered to older patients with dementia (De-Deyn et al., 2005). Psychosis and agitation symptoms in patients with dementia are common, disruptive, and costly but there are no well-established, evidenced-based effective treatment alternatives (Jeste et al., (2008). A limited amount of mostly anecdotal scientific data suggests that anticonvulsant medications, including some of the newer agents like lamotrigine, may be helpful for agitation and psychosis in older patients with dementia (DeLeon, 2004). Lamotrigine is an anti-epileptic drug whose mechanism of action is thought to be linked to voltage-sensitive sodium channel blockade in the neuronal membrane and inhibition of presynaptic glutamate and aspartate release (Baumann et al., 2007). Lamotrigine has a safe profile and has documented efficacy in delaying recurrence of mood episodes in patients with bipolar disorder in trials conducted for up to 18 months.

Psychostimulants (including dexamphetamine, methylphenidate and modafinil) are a broad class of drugs that reduce fatigue, promote alertness and wakefulness and possess possible mood enhancing properties. A recent Cochrane Review of randomized controlled trials (RCTs) up to June 2006 systematically investigated the effectiveness of psychostimulants in depression (Candy et al., 2008). Most of the 24 RCTs included in the review were of poor quality and did not exclusively involve geriatric patients. In a meta-analysis involving three trials (none having geriatric patients), the authors concluded that oral psychostimulants may have a possible antidepressant effect in the short term (up to four weeks) and appeared to be well tolerated. However, the clinical significance of this effect was unclear and the potential medium or long-term benefits and side effects were virtually unknown (Candy et al., 2008).

I enjoyed the recent editorial by Förstl (2008) on time. Here he presents a different way of thinking about what might be happening to people with neurodegenerative diseases and the consequent difficulties for their carers. I was not so sure, however, how the neuropathology was meant to contribute to philosophical discussions about the nature of time.

On 30 May 2009, shortly after completing this book review, Dr Johann Claassen died suddenly while out running. He was 47 years old. His colleagues and students acknowledged him as a first-rate psychiatrist and an outstanding teacher, especially of medical students, which is why he was asked to undertake this review. To all his former colleagues in Western Australia, New Zealand and South Africa, and to his surviving family, especially his wife and two young boys, I and the entire International Psychogeriatrics team extend our sincere condolences.