Correct differential diagnosis is critical in any clinical presentation, but particularly when the prognosis, treatment and future prospects of the conditions under consideration vary significantly (Dierckx, Engelborghs, De Raedt, De Deyn, & Ponjaert-Kristoffersen, 2007; Dubois et al., 2007; Gray, Rattan & Dean, 1986; Murray, 2002). This is true for the case scenario of a 60-year-old farmer referred for neuropsychological assessment following his wife’s concerns about problems with his memory, reduced motivation and disorientation, where the neuropsychologist needs to determine whether this man is suffering from depression or Alzheimer’s disease (AD). In such scenario misdiagnosis can interfere with the provision of timely interventions (e.g. administration of antidepressants or symptomatic treatment for AD), lead to false expectations regarding prognosis and the consequent failure to prepare for disease progression (Murray, 2002). However, significant overlap in the presenting cognitive, behavioural and affective impairments in depression and AD makes discrimination between these two conditions particularly difficult (Christensen, Griffiths, Makinnon & Jacomb, 1997; Dierckx et al., 2007; Dudas et al., 2005; Gainotti & Marra, 1994; Rotomskis et al., 2015; Swainson et al., 2001).
In making a differential diagnosis, the neuropsychologist must firstly evaluate demographic information, clinical history and presenting problems during the clinical interview (Evans, 2010). In the presenting case the age at which symptoms appear to have started would suggest that a distinction between early-onset AD (EOAD) and late-onset depression would need to be made. This may be of particular relevance given that in an EOAD profile executive and visuo-constructional functions are more strongly affected than in later-onset AD (Joubert et al., 2016), and loss of interest is more prominent in late-onset depression (Bieliauskas & Drag, 2013). Occupation and level of education, on the other hand, might provide an indication of pre-morbid functioning.
Clinical history, including family history of dementia or depression, previous affective symptoms, any medications being taken, as well as onset and changes in symptoms over time can also inform diagnosis. In depression, the onset of symptoms tends to be well-defined with fluctuations in perceived impairment that correspond closely to mood changes, while AD is characterised by more gradual and progressive changes (Dubois et al., 2007; Geldmacher & Whitehouse, 1997; Vannorsdall & Schretlen, 2011). Information relating to possible precipitating factors (such as the death of the patient’s daughter in this case), and changes in activities of daily living are also significant. Additionally, the patient’s level of insight regarding the problem also needs to be assessed. Olin, Katz, Meyer, Schneider and Lebowitz (2002) suggest that whereas depression patients tend to emphasize their cognitive impairments, AD patients will tend to have less insight and ascribe less importance to their impairments (Geldmacher & Whitehouse, 1997). The clinical interview also allows assessment of impact of symptoms on daily living Rotomskis difficulties
While symptom presentation can provide valuable insight into the existing problem, the assessment of cognitive and psychological functioning is necessary for differential diagnosis (Bieliauskas & Drag, 2013; Dudas, Berrios & Hodges, 2005). Levels of cognitive functions can be assessed using tests such as the Addenbrooke’s Cognitive Examination-Revised (ACE-R) (Rotomskis et al., 2015). Screening for depression can be done through the use of instruments such as the Beck Depression Inventory-II (Bieliauskas & Drag, 2013), however if dementia is present this would be unsuitable, and the Cornell Scale for Depression in Dementia (Alexopoulos, Abrams, Young & Shamoian, 1988) can be used, as it been shown to have better metric properties (Morris & Brookes, 2013). As expressed above, however, depression and AD can present with similar cognitive and affective deficits. Thus, while diagnostic tools might be sensitive to impairments present, they might not be able to specifically discriminate whether these arise as a result of depression or AD (Beck, Smith, Berres & Monsh, 2014 ; Rotomskis et al., 2015). For example, while poor performance in free delayed recall allows accurate discrimination of AD patients from healthy controls, it can’t specify whether memory problems arise from depression or AD (O’Carroll, Conway, Ryman & Prentice, 1997).
The absence of reliable biological markers to distinguish between these conditions (Korczyn & Halperin, 2009) and the comparable white matter and hippocampal changes reported in neuroimaging of both AD and depression (Dubois et al., 2007; Korczyn & Halperin, 2009; Raskind, 1997) exacerbate this difficulty in making a differential diagnosis. It is thus imperative for the neuropsychologist to carry out a comprehensive range of assessments and analyse performance across different cognitive domains, since AD and depressed patients have distinct neuropsychological profiles (Beck et al., 2014; Dudas, Berrios & Hodges, 2005; Rotomskis et al., 2015). For example, cued recall, in which cues are encoded with test material during the learning phase, was found to allow discrimination since depressed patients will show an improvement with cued recall as opposed to free recall while AD patients do not (Dierckx et al., 2007). The external cue is thought to counteract for motivational problems and subsequent attentional deficits in depression that hinders the generation of internal cues in free recall, and thus poor performance. Cued recall does not improve performance in AD patients as memory deficits in AD occur at the level of encoding (Dierckx et al., 2007; Dubois et al., 2007; Fahlander, Berger, Wahlin & Backmän, 1999). These results, however, need to be considered with caution because of the presence of use of antidepressants among depressed participants that can have affected performance (Kaschel, Logie, Kazén, & Della Sala, 2009).
Rotomskis et al. (2015) found that while depression patients are significantly more likely to be identified as having dementia than healthy patients from their global ACE-R score, accuracy of differential diagnosis can be improved by looking at the performance across all five subtests. AD patients present severe impairments in memory, language and attention and orientation subtests, and moderate impairments in verbal fluency, with category fluency being more impaired than letter fluency indicating impairments in semantic memory. Depressed patients will have milder deficits in overall score, and low scores in subtests involving memory and verbal fluency, characterised by more severe letter fluency deficits that represent impairment in executive functioning (Lockwood, Alexopoulos & van Gorp, 2002; Rotomskis et al., 2015). This is in line with findings that patients with late-onset depression tend to manifest significant deficits in executive functioning (Lockwood et al., 2002) and research that highlights that depressed patients will tend to exhibit psychomotor slowing, show less effort in participating in tests, less uniform performance across tests of similar difficulty, and also improved performance with fewer false-positive errors in recognition vs recall memory tests (Geldmacher & Whitehouse, 1997; Houston & Bondi, 2006).
References:
McTiernan, K., Jackman, L., Robinson, L., & Thomas, M. (2020). A Thematic Analysis of the Multidisciplinary Team Understanding of the 5P Team Formulation Model and Its Evaluation on a Psychosis Rehabilitation Unit. Community Mental Health Journal, 57, 579-588. https://doi.org/10.1007/s10597-020-00684-7.
Thompson, D., Rutter, L., Bell, L., Townson, D., & Lewis, C. (2024). Creative ways of embedding 5P formulation in community treatment teams: The role of the assistant psychologist. Clinical Psychology Forum. https://doi.org/10.53841/bpscpf.2024.1.378.55.
Johnstone, L. (2018). Psychological Formulation as an Alternative to Psychiatric Diagnosis. Journal of Humanistic Psychology, 58, 30 – 46. https://doi.org/10.1177/0022167817722230.
Kontunen, J., Weiste, E., Liukkonen, T., Timonen, M., & Aaltonen, J. (2019). Predicting response to interpersonal counselling (IPC) from case formulation: a systematic comparison between recovered and unchanged depressive cases. Counselling Psychology Quarterly, 33, 465 – 489. https://doi.org/10.1080/09515070.2019.1588101.
UKEssays. (November 2018). The 5Ps of Counselling. Retrieved from https://www.ukessays.com/guides/the-5ps-of-counselling.php?vref=1