When do we diagnose severe Alzheimer's disease?

by Sergio Salmerón, MD PhD on 2 December 2016

Among patients diagnosed with Alzheimer's disease (AD), the percentage in the severe stage ranges from 28% [1] to 33% [2] to a maximum of 50% [3]. In institutionalized patients, prevalence is higher, with an estimated 75% of patients with severe AD [4]. Cognitive impairment is well defined when it is considered "mild" and "moderate", however, there is a lack of precision and consensus when cognitive impairment is considered "severe", “profound”, or "advanced". The reference manual DSM (Diagnostic and Statistical Manual of Mental Disorders) contains too simple a definition: DSM-IV-TR [5] describes advanced dementia as a "final period, during which there is personal disorientation and a complete loss of self-care. In more advanced stages of dementia, memory impairment is so severe that the person forgets his occupation, studies, date of birth, family composition, and sometimes even his name. In these stages, subjects may suffer mutism or have a speech pattern characterized by echolalia, and unable to recognize his family or even his own image in the mirror". DSM-V [6] is shorter, describing patients with AD at an advanced stage as "become mute and bedridden”. The ICD-10 [7] defines the degree of memory loss in this phase as "characterized by the complete inability to retain new information, and only remaining fragments of previously learned information. The subject cannot recognize even close relatives, and there is a decline in all cognitive functions characterized by an absence, or virtual absence, of intelligible thought”. If we had to put cut off points in cognitive assessment scales, we would find that some authors have defined severe AD as a score less than or equal to 95 points in the Dementia Rating Scale [8]. In other studies, it was considered to be severe AD when a Mini-Mental State Examination (MMSE) [9] under 10 [10] or 12 points [11] was obtained. On many occasions, the patient's functional status was used as an indicator to classify the stage of dementia. This is because, usually, at this stage the patient requires constant supervision, has lost all Instrumental Activities of Daily Living and most or all of the Basic Activities of Daily Living. This functional situation corresponds to the values of the Global Deterioration Scale [12] and the Functional Assessment Staging [13] greater than or equal to 6, and the Clinical Dementia Rating Scale [14] with level 3 [15]. One of the advantages of functional scales regarding cognitive scales is that the level of education, age, sex, country of origin, and educational level have less influence when applying these scales. So it seems more appropriate to use functional scales to determine the AD as severe, but a number of factors must be taken into account which preclude the exclusive use of functional scales [10]:

  • They can be affected by other diseases, primarily psychiatric, such as depression or anxiety.
  • They can be influenced by the overprotection of the caregiver.
  • They can be influenced by the quality of the relationship between the informant and patient.
  • It is difficult to accommodate variability in the progression of dementia in different cognitive and behavioral domains.

They do not provide enough information about the cognitive status of the patient to facilitate an adequate intervention plan with the means to improve the problems caused by this deterioration. It has been shown that there is a correlation between global measures of functional status in patients with severe AD, as measured by the Alzheimer's Disease Cooperative Study Activities of Daily Living [16], and the measured cognitive status with the Severe Impairment Battery [17] and the MMSE [9], indicating that the execution of these general indices of cognitive functioning predict functional capacities. Therefore, it is advisable to use both types of scales, functional and cognitive, if we want to assess whether a patient has progressed to the severe stage of the disease.

  • What criteria or cut off point do you use in your clinical practice to define severe AD?
  • For the diagnosis of severe AD: Do you think we should use more cognitive or functional scales?

References
[1] De Pedro-Cuesta J, Virués-Ortega J, Vega S (2009) Prevalence of dementia and major dementia subtypes in Spanish populations: a reanalysis of dementia prevalence surveys, 1990-2008. BMC Neurol 19, 9-55.
[2] Dartigues JF, Helmer C, Dubois B, Duyckaerts C, Laurent B, Pasquier F, Touchon J (2002) Alzheimer's disease: a public health problem: yes, but a priority? Rev Neurol (Paris) 158, 311-315.
[3] Canadian Study of Health and Ageing (1994) Study methods and prevalence of dementia. CMAJ 150, 899-913.
[4] Boller F, Verny M, Hugonot-Diener L, Saxton J (2002) Clinical features and assessment of severe dementia: a review. Eur J Neurol 9, 125-136.
[5] American Psychiatric Association (2000) DSM-IV-TR: Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association, Washington, DC.
[6] American Psychiatric Association (2013) DSM-V: Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association, Arlington, VA.
[7] World Health Organization (2010) International statistical classification of diseases and related health problems, 10th revision. Geneva.
[8] Mattis S (1988) DRS: Dementia Rating Scale professional manual. Psychological Assessment Resources, Odessa, FL.
[9] Folstein MF, Folstein SE, McHugh PR (1975) "Mini-Mental State": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12, 189-198.
[10] Martín-Sánchez FJ, Gil-Gregorio P (2006) Valoración funcional en la demencia grave. Rev Esp Geriatr Gerontol 41, S43-S49.
[11] Doody RS, Strehlow SL, Massman PJ, Feher EP, Clark C, Roy JR (1999) Baylor profound mental status examination: a brief staging measure for profoundly demented Alzheimer disease patients. Alzheimer Dis Assoc Disord 13, 53-59.
[12] Reisberg B, Ferris SH, de Leon MJ, Crook T (1982) Modified from Global Deterioration Scale. Am J Psychiatry 139, 1136-1139.
[13] Reisberg B (1988) Functional assessment staging (FAST). Psychopharmacol Bull 24, 653-659.
[14] Morris JC (1993) The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43, 2412-2414.
[15] García FJ, Manubens JM (2004) Enfermedad de Alzheimer evolucionada. Concepto y epidemiología. Med Clin Monogr (Barc) 5, 3-8.
[16] Galasko DR, Schmitt FA, Jin S, Saxton J, Bennett D, Sano M, Ferris SH (2000) Detailed assessment of cognition and activities of daily living in moderate to severe Alzheimer's disease. Neurobiol Aging 21, S168.
[17] Saxton J, McGonigle-Gibson K, Swihart A, Miller V, Boller F (1990) Assessment of the severely impaired patient: Description and validation of a new neuropsychological test battery. Psychol Assess 2, 298-303.

Last comment on 2 December 2016 by Maheen Adamson, PhD

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In the severe stage of Alzheimer's disease (AD), the cognitive and functional degeneration becomes accelerated. The common symptoms are the followings: 1) weight maintenance issues, 2) difficulty with eating and swallowing, 3) no bladder or bowel control, 4) considerable loss of memory, 5) gradual loss of speech and inability to say anything coherently, 6) inability to recognize once familiar surroundings and objects, 7) hallucinations, and 8) wander aimlessly [1].

As AD enters the severe stage, independence is gradually lost and caregivers must provide consistent direct care with most if not all Basic Activities of Daily Living and Instrumental Activities of Daily Living. Safety issues and wandering require constant monitoring [2] and there is the need to create a safe environment [3, 4].

In addition to DSM 5 and ICD-10, National Institute on Aging-Alzheimer's Association (NIAAA) criteria [5] are widely used to define severe AD. Moreover, another scale should be performed to define and manage AD patients in the severe stage. This scale is Neuropsychiatric Inventory (NPI) [6], based on a structured interview with a caregiver and/or patient’s relative. This scale is useful to assess the presence of neuropsychiatric symptoms in AD patients, and their impact on caregiver burden level. The NPI has shown stage-specific trends in neuropsychiatric symptoms in AD patients and has been demonstrated to be sensitive to drug treatment effects [7]. J. L. Cummings had written that the following neuropsychiatric abnormalities increase with dementia severity: delusions, agitation, dysphoria, anxiety, apathy, and aberrant motor behavior [8]. Disinhibition, indeed, seems to decrease with dementia severity [8].

References
[1] Alzheimerott (2015) Stages of Alzheimer’s disease. Available from: http://www.alzheimerott.org/stages-of-alzheimers-disease.php. Accessed November 24, 2016.
[2] Futrell M, Melillo KD, Remington R, Schoenfelder DP (2010) Evidence-based guideline. Wandering. J Gerontol Nurs 36, 6–16.
[3] Eshkoor SA, Hamid TA, Nudin SS, Mun CY (2014) A research on functional status, environmental conditions, and risk of falls in dementia. Int J Alzheimers Dis 2014, 769062.
[4] Volicer L, van der Steen JT (2014) Outcome measures for dementia in the advanced stage and at the end of life. Adv Geriatr 2014, 346485. 
[5] McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7, 263–269.
[6] Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J (1994) The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 44, 2308–2314.
[7] Mega MS, Cummings JL, Fiorello T, Gornbein J (1996) The spectrum of behavior changes in Alzheimer's disease. Neurology 46, 130–135.
[8] Cummings JL (1997) The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology 48, S10-S16.

Dr. Salmeron provides an excellent commentary regarding how best to diagnose patients with advanced AD. He correctly points out that most cognitive tests have floor effects that would preclude them from being useful while functional tests, which are generally administered less frequently, are probably more helpful. However, in advanced dementia, even functional scales may have limited utility given most patients with advanced dementia have no or very limited functional ability. Nevertheless, they are more sensitive than cognitive scales to subtle changes, particularly in patients with more advanced disease. Interestingly, behavioural symptoms often improve with progression from moderate to advanced dementia so may have limited utility. I myself find that certain cognitive scales, such as the severe impairment battery, which are sensitive to changes in social awareness, may be useful in helping to differentiate moderate from advanced dementia. The lack of valid and reliable tools highlights the need for future research in this area.

Dr. Salmeron's blog post above highlights some very important aspects of Alzheimer's Disease in a stage that devastates the lives of the patient and the caregivers and for a long time, was the stage where family members knew for certain that their loved one had dementia/Alzheimer's. For the past few decades’ awareness about AD has increased substantially and stages of cognitive impairment have been somewhat clearly delineated for mild and moderate AD. However, there is less clarity available for the designation of cognitive impairment as 'severe' or "advanced". This is the stage which requires the patient’s family to plan accordingly and timely assessment of function can provide accurate insight to the patient’s management team. There are two ways to characterize this change from moderate to severe: on a cognitive scale (such as MMSE or DRS) and on functional status (such as the Global Deterioration Scale or the Functional Assessment Staging). Dr. Salmeron's blog explains the advantages for these functional scales as this is the time when supervision and other changes are required to be made for the patient. It is important to understand the limitations of these functional scales as well. His short explanation does conclude that we should use both cognitive and functional scales to evaluate the patient in this late stage. The lack of tools to assess and manage this disease at this stage makes it very difficult for caregivers and providers. More research, suggested above, needs to focus on development of better care and management as well as awareness for severe AD.