The concept of early detection

There has been a recent shift to thinking about Alzheimer’s disease in pre-dementia terms (Ganguli, 2006; Petersen et al., 2007; Winblad et al., 2004). This is evident in the literature where patients presenting with cognitive impairment have been depicted by a variety of terms, such as mild cognitive impairment (MCI: Ganguli et al., 2004; Gauthier et al., 2006), subjective memory complaints/impairment (or subjective cognitive impairment) (SMC: Abdulrab and Heun, 2008; Geerlings et al., 1999;

Jungwirth et al., 2004; Reisberg et al., 2008; Schofield et al., 1997), age-associated cognitive decline (Schonknecht et al., 2005), as well as cognitive impairment no dementia (CIND: Palmer et al., 2002; 2003), questionable dementia (Lam et al., 2005a; 2005b) and isolated memory impairment (Bowen et al., 1997; Tierney et al., 1996). Each of these terms has been used to identify a pre-dementia stage of cognitive impairment (e.g., aMCI), with variable prognosis.

The use of the term ‘preclinical’ denotes a clinical condition with high progression to Alzheimer’s disease, whilst the use of the word ‘predementia’

denotes a stage of cognitive impairment with variable prognosis. It is important to emphasize that some persons might have a clinical presentation of cognitive impairment in the predementia state.

The MCI criteria have undergone significant change over the last 10 years. In 1958 Kral introduced the term “benign senescent forgetfulness” or (mild memory loss) to describe a mild memory disorder in the elderly that accompanied old age but was not considered to be abnormal or become pathological. Since this initial report, MCI has undergone a significant evolution over the past 10 years with a number of related concepts having emerged to describe memory impairment in old age. Some of these include:

‘Cognitive Impairment no Dementia’ (Jacova et al., 2008), ‘Age Associated Memory Impairment’ (Goldman and Morris, 2001). All of these terms have different criteria to identify a type of memory impairment that inevitably leads to dementia and Alzheimer’s disease. Hence MCI research findings that are often disparate are likely to be partly due to this.

However, AD development is associated with objective cognitive decline prior to clinical diagnosis, it is vital to improve the diagnostic tools, such as brief screening tests able to detect the disease (Oksengard et al., 2004). This will facilitate the early detection. Recently, there has been increased awareness that persons who complain about their memory should be taken seriously and be assessed for dementia (Dufoil et al., 2005; Coley et al., 2008). In this setting, general practitioners are a critical point of early intervention (Brodaty et al., 2006; Ganguli et al., 2004)

In primary care, several brief screening tests have been proposed by Brodaty et al. (2006), including the GP Assessment of Cognition; the Mini-Cog and the Memory Impairment Screen. However none have been as universally accepted as the Mini-Mental State Examination (MMSE: Folstein et al., 1975) which continues to be used widely in clinical practice (Lavery et al., 2007). The question is whether brief screening tests, such as the MMSE or Mini-Cog are able to detect early signs of Alzheimer’s disease, especially in high functioning individuals. The next section provides a more detailed discussion of the limitations of brief screening tests and the need for formal assessment.

3.2.1 Screening for early dementia

It has been suggested that neuropsychological assessment will play a pivotal role in the new diagnostic challenges faced by all clinicians (Bondi et al., 2008; Cummings et al., 2007). However, identifying subjects who are in the earliest phases and are likely to progress to Alzheimer’s disease is not straightforward.

There are current concerns regarding the ability of brief screening tools such as the MMSE to identify impairment in cognitive domains other than memory. With new evidence identifying impairments in semantic memory and executive function (Ahmed et al., 2008; Hodges et al., 2006;

Rouch et al., 2008), the sole reliance on brief screening tools seems inappropriate.

The MMSE is thought to be an insensitive screening tool for identifying both MCI and dementia (Tariq et al., 2006), especially in pre-morbidly high-functioning individuals with memory complaints (Geerlings et al., 1999; van Oijen et al., 2007). This has been attributed to its ceiling effect and lack of delayed recall condition (Chen et al., 2000). Also, impairments in those with MCI are mild and subtle (Gallassi et al., 2008) and not easily detected by simple global screening tasks.

In addition, the cut-off score to define impairment in those with MCI may not be appropriate. Solomon et al. (2002) reported that in a research clinic, an MMSE cut-off score of 24 and above, accurately identified Alzheimer’s disease in 98 of 110 (89%) patients (mean age= 71.6, SD=7.5) with very mild impairment (mean MMSE score on initial assessment = 25.7 + 1.4). This suggests that the MMSE is useful in identifying individuals in the later phases of the disease.

There are alternative screening tests highly relevant in the study of dementia, such as the Seven Minute Screen (7MS). The 7MS has been shown to reliably distinguish Alzheimer’s disease from normal ageing and other dementias (e.g., Meulen et al., 2004; Solomon et al., 1998). However, it has not been examined in the study of subjective memory complaints (SMC). The 7MS is highly sensitive and specific in the identification of Alzheimer’s disease (92.9%; 93.5%, respectively) and performance is not affected by age, sex or education (Solomon et al., 1998). It includes several tests, selected because they examine areas typically compromised in early Alzheimer’s disease (orientation, memory, clock drawing and animal fluency).

Similarly, the Dementia Rating Scale (DRS: Mattis et al., 1976) is highly sensitive in identifying cognitive impairment that is associated with dementia. It also consists of several domains of cognitive functioning in addition to memory. The sensitivity and specificity of the DRS is 74% and 93%, respectively (Vangel and Lichenberg, 1995). Unlike the MMSE, age, education and IQ do not affect performance on the DRS (Chan et al., 2001).

The process of intervention begins with being able to identify deficits related to SMC by examining a wide range of cognitive functions.

Neuropsychological assessment and more sensitive screening tests may help identify those with suspected cognitive compromise. As mentioned in Chapter 1 (Section 1.7), the early identification of Alzheimer’s disease provides therapeutic opportunities for intervention at an earlier stage rather than waiting for significant decline to occur.