Understanding Advanced Dementia – Back to Basics

Dementia is characterized by a decline in cognition involving one or more cognitive domains (learning and memory, language, executive function, complex attention, perceptual-motor, social cognition).1 Managing patients with dementia requires proper identification of the stage of dementia and the associated care issues to prevent complications, manage symptoms and support caregivers.2

Recent Enclara Palliative Pearls cases have focused on deprescribing dementia medications, identifying contributors to troublesome symptoms and reconsidering pharmacological interventions. This month’s education goes back to basics, to reorient our audience to the fundamentals of dementia care.


The Global Deterioration Scale (GDS) and the Functional Assessment Stage Test (FAST) are two clinical tools commonly used. Higher scores on these scales represent worsening function and/or cognition. The GDS uses a 7-stage scale of cognitive deterioration while the FAST scale tracks functional status, such as Instrumental Activities of Daily Living (IADLs) (e.g., managing finances or driving) and Activities of Daily Living (ADLs) (e.g., personal hygiene, dressing, and feeding).2

Stage Mild/Early Moderate/Middle Severe/Late (i.e., Advanced)
Clinical Scale Staging2 GDS 4; FAST 3-4 GDS 5-6; FAST 5-6 GDS 7; FAST 6-7
Features2,3 Mainly independent

Begin to make mistakes in IADLs

Trouble managing finances

Forgetting recent events/names

Difficulty remembering to take medications

Difficulty recognizing acquaintances

May withdraw from social situations and deny issues

Often retain decision-making capacity

IADL and ADL issues emerge

Needing help with complex chores and hobbies

Getting lost in familiar places

Periods of irritability, agitation, sundowning

Difficulty recognizing family members

Surrogate takes on more health-care decision-making

Requires help for most, if not all, ADLs

Swallowing and eating problems

Inability to walk, bathe, dress, and toilet independently

Minimal verbal communication

Recurrent infections

Lacks decision-making capacity

Medications indicated for dementia in the early to moderate stages include donepezil (Aricept®) and memantine (Namenda®). They are generally indicated for patients who are functional enough to derive possible benefit. These medications have limited effect on improving or maintaining cognitive function, cannot stop or delay disease progression and become less beneficial over time. Adverse effects such as nausea, vomiting, diarrhea, loss of appetite, weight loss, drowsiness, and dizziness are common. It’s important to balance risk of harm compared to benefit and consider high cost and lack of benefit when making prescribing decisions. See Enclara’s Palliative Pearls case focused on deprescribing dementia medications for additional guidance.


Eating problems

In advanced dementia, most develop eating and swallowing problems, including: 3

  • Refusal to eat due to lack of hunger or early satiety
  • Difficulty with manipulating food to the mouth
  • Pharyngeal dysphagia – Difficulty manipulating food and liquids in and through the mouth due to neurodegeneration
  • Oral dysphagia – Foods and liquids do not move through the pharynx well and may be left behind after the swallow.
  • Consequences of eating and swallowing difficulties include:
    • Malnutrition
    • Weight loss
    • Dehydration
    • Increased risk of aspiration pneumonia

Considerations to manage eating problems: 3

  • Evidence does not support the use of percutaneous feeding tubes in patients with advanced dementia. Instead, offer careful handfeeding. Careful handfeeding both improves comfort and may prolong life, while feeding tubes reduce comfort and have not been shown to improve survival.
  • There is evidence that good oral care for individuals with dementia, including dental hygiene, can decrease risk of complications of aspiration (including pneumonia).
  • Modifying food texture may help with acceptance of food and maintaining safe swallowing for longer periods of time. Diet consistencies range from soft-to-chew to ground to pureed.
  • Liquids can be thickened to facilitate swallowing however, there is no evidence that this prevents aspiration pneumonias.
  • Cater to the past food preferences, including consideration of their cultural backgrounds. Other strategies include:
    • Adequate time for meals
    • Feeding assistance
    • Attending to the smell of food and the environment
    • Making mealtime a social experience
    • Providing more frequent, smaller meals; providing more finger foods, incorporating spicy, sweet, and sour foods to stimulate impaired taste.
    • Main goal: provide food and drink to the extent that it is enjoyable for the patient.
  • Although high-calorie supplements may increase weight in older adults, there is no evidence that they improve other outcomes, including quality of life, functional or cognitive status, or survival.
  • Avoid appetite stimulants in older adults. There is insufficient evidence that they improve clinically- important outcomes such as quality of life and survival.


Almost half of patients with advanced dementia will experience infections, mainly pneumonia and urinary tract infection (UTI). Distressing signs and symptoms, including dyspnea, pain, and aspiration, are common for individuals with advanced dementia, and occur more frequently as death approaches.3

  • Pneumonia 3-5
    • CASCADE (Choices, Attitudes, and Strategies for Care of Advanced Dementia at the End-of Life) is a study published in 2006 evaluating 323 nursing home residents over an 18-month period. Findings included infections and eating problems as common complications – 41% had pneumonia, 53% had a febrile episode and 86% developed an eating problem over the course of the study. Investigators found that infections and eating problems were associated with high mortality. 4
    • Aggressive management approaches (e.g., IV medication or hospitalization) were speculated as the source of greatest discomfort for patients receiving antimicrobial therapy in the CASCADE study. 4
    • Antibiotic risks: 6
      • Antibiotic associated diarrhea such as Clostridioides difficile (C. diff) infection
      • Polypharmacy and drug interactions
      • Medication side effects
      • Developing antibiotic-resistant bacterial infections
    • Patients not treated with antibiotics can receive treatments that relieve discomfort from the pneumonia: 6
      • Low doses of opioids reduce the sensation of shortness of breath
      • Oxygen and a bedside fan pointed at the face can be considered for shortness of breath
      • Antipyretics, such as acetaminophen, may help with fevers
    • Urinary Tract Infection 3,6,7
      • Most UTIs in nursing home patients reflect asymptomatic bacteriuria, a condition for which no antibiotic treatment is indicated.
      • A diagnosis of urinary tract infection requires that the patient has signs and symptoms of an infection (e.g., fever, pain on urination/dysuria) and has a positive urine culture. Neither a positive urinalysis nor a positive urine culture indicates a requirement for antibiotics. Antibiotics should not be started for cloudy or foul-smelling urine.
      • If comfort is a primary goal, it would be reasonable to avoid both a work-up and antibiotics. Instead, focus on relieving symptoms with antipyretics, bladder analgesics (e.g., phenazopyridine), and analgesics.


Pain should be considered as a possible underlying cause for all challenging behaviors (agitation, striking out, refusal to eat, altered mental status, and changes in usual behavior) associated with dementia.3

Pain assessment in those with more advanced dementia, or those unable to verbally communicate, should include caregiver reports, observation of signs and symptoms of distress or withdrawal, and pain assessment tools.3

When observed, the following behaviors should trigger assessment for pain:

  • Facial grimacing, knitted brow
  • Verbalizations/vocalizations, moaning, screaming, calling out
  • Body movements reflecting restlessness, agitation or withdrawal, or resistance to care
  • Changes in interpersonal interactions
  • Changes in activity patterns/routines
  • Mental status changes

A variety of tools are available to assess pain in older adults with advanced dementia. A common, validated scale is the Pain Assessment in Advanced Dementia (PAINAD) instrument. 3

Items 0 1 2 Score
Breathing independent of vocalization Normal Occasional labored breathing. Short period of hyperventilation Noisy, labored breathing. Long period of hyperventilation. Cheyne-stokes respirations.
Negative vocalization None Occasional moan or groan. Low-level of speech with a negative or disapproving quality. Repeated, troubled calling out. Load moaning or groaning. Crying.
Facial expression Smiling or inexpressive Sad, frightened, frown Facial grimacing
Body language Relaxed Tense. Distressed pacing. Fidgeting Rigid. Fists clenched. Knees pulled up. Pulling or pushing away. Striking out.
Consolability No need to console Distracted or reassured by voice or touch. Unable to console, distract or reassure.
Total scores range from 0 to 10 (based on a scale of 0 to 2 for five items), Obtained scores are not to be used to inter absolute pain intensity. For example, a score of 10 on the PAINAD is not necessarily equal to a Numerical Pain Scale rate of 10 (severe pain). Instead, compare the total score to the previous score received. An increased score suggests an increase in pain, while a lower score suggests pain is decreased.

Instructions: Observe the older person for 3-5 minutes during activity/with movement (such as bathing, turning, transferring).  For each of the items included in the PAINAD, select the score (0, 1, or 2) that reflects the current state of the person’s behavior.  Add the score for each item to achieve a total score. Monitor changes in the total score over time and in response to treatment to determine changes in pain. An increased score suggests an increase in pain, while a lower score suggests pain is decreased.

Nonpharmacologic management includes exercise, massage, acupuncture, hot or cold packs and/or mind-body interventions (e.g., music therapy)

Considerations for prescribing analgesics in dementia include:

  • Around-the-clock dosing and the use of a long-acting formulation as opposed to PRN should be considered, as individuals with dementia are usually unable to request pain medications
  • Use a stepped-care approach to analgesics, starting with medications such as acetaminophen
  • An opioid may be appropriate for any patient with moderate or severe pain, or pain that does not respond to non-opioid therapy
  • Start with low doses and titrate up slowly
  • Behavior is communication: Monitor for improvements in behavior, mood, and function that indicate better pain control
Medication Considerations
Acetaminophen Often helpful for mild to moderate pain caused by musculoskeletal issues

Evidence for scheduled empiric use for behavioral issues in dementia

NSAIDs Use cautiously, if at all, given high risk of adverse effects in older adults, including renal failure, GI bleeding, fluid retention, and exacerbation of heart failure
Anticonvulsants (e.g., gabapentin, pregabalin) Often used in neuropathic pain or fibromyalgia

Exercise caution in dementia care due to the potential to worsen sedation and cognition, and other side effects such as dizziness, falls, dry mouth

Antidepressants Often used for neuropathic pain and chronic low back pain

SNRIs (e.g., duloxetine and venlafaxine) are better tolerated than tricyclic antidepressants (TCAs) (e.g., nortriptyline, amitriptyline) in dementia due to the anticholinergic side effects of TCAs

Opioids Typically, effective for multiple types of pain, but cognitive side effects may be more pronounced in dementia until tolerance develops to any sedation

Use very low starting doses

Avoid codeine and tramadol due to variability in metabolism and increased side effect profile

Constipation is an expected and serious side effect of opioid therapy; patients on opioid medications should be proactively prescribed laxatives with bowel stimulants (e.g. sennosides or bisacodyl) as a first-line therapy (avoid stool softeners, e.g., docusate sodium, in chronic constipation due to the lack of evidence to support its use)



  • Psychosis (hallucinations, delusions)
  • Confusion
  • Aggression, verbal and physical (associated with avoiding discomfort, communication of needs or a demand for personal space)
  • Agitation, restlessness, pacing or wandering (associated with boredom and the need for activity and stimulation)
  • Verbal/vocal behaviors (e.g., calling out, screaming, refusal to cooperate with care, repeated questioning) (often associated with pain, loneliness, or depression)

Behavior equals (=) Patient Communication3

  • Dementia can prevent a person from expressing the cause of their distress in words
  • Agitated or restless behavior is due to pain or discomfort until proven otherwise
  • Treating physical symptoms and providing an environment that meets the patient’s needs and preferences are the most effective ways to address behaviors

Common Contributing Factors3


  • Undiagnosed medical illness (e.g., urinary tract infection)
  • Unmet needs (hunger, thirst, boredom, poor sleep)
  • Untreated symptoms (e.g., pain, constipation)
  • Depression, anxiety, or feeling out of control
  • Adverse medication effects
  • Being overwhelmed or asked to do more than able
  • Hearing or vision loss, or limitations in functional abilities
  • Routines from the past (e.g., never fell asleep before midnight)


  • Poor understanding of the illness leading to over- or underestimation of the patient’s abilities
  • Lack of education about how to interpret and respond to dementia-related behaviors
  • Lack of education about effective communication strategies (i.e., avoiding arguing, complex instructions, or frequent corrections)
  • Caregiver stress, burden, and emotional health
  • Difficult prior relationship between the person with dementia and their caregiver


  • Over- or under- stimulating environment
  • Unsafe or challenging environment to navigate (i.e., clutter)
  • Daily routines that are not aligned with patient preferences
  • Lack of pleasurable activities
  • New or changing environment
  • New or changing caregivers

Key Initial Behavioral Management Strategies 10-13

  • Take a holistic approach as symptoms may be expressed differently
  • Treat underlying causes of symptoms first
  • Avoid overly aggressive, burdensome, or futile treatment; consider non-pharmacological treatment
  • Distinguish between sources of discomfort, considering environmental factors such as noise, temperature and uncomfortable chairs or bedding
  • Utilize tools specific for dementia to screen and monitor
  • Provide psychosocial and spiritual support and promote family care and involvement when possible
  • Acknowledge patient requests and respond; redirect person’s attention
  • Provide sources of comfort such as security objects and music

Pharmacotherapy Evidence for Managing Behavioral Symptoms in Dementia14-41

Medication/Class Symptoms Considerations
SSRIs16 Depression; mild-moderate anxiety; mild-moderate agitation Sertraline (Zoloft®) has the most data for managing depression in patients with Alzheimer’s 18
Citalopram (Celexa®)17
SNRIs Depression; mild-moderate anxiety e.g., Venlafaxine (Effexor®), duloxetine (Cymbalta®)
Trazodone (Desyrel®) Depression; mild-moderate anxiety; irritability; mild-moderate agitation Useful for concomitant insomnia
Carbamazepine (Tegretol®) Mild-moderate agitation; aggression Low dose seems effective but limited evidence 19,20
Divalproex sod. (Depakote®) No evidence to support efficacy in dementia 21-23
Lamotrigine (Lamictal®) Case report data supports efficacy.24 Many side effects.
Valproic acid (Depakene®) No evidence to support efficacy in dementia 21-23
Buspirone (BuSpar®) Mild-moderate anxiety; irritability; mild-moderate agitation Reserve for chronic anxiety; Limited data on efficacy in dementia. May take 2 to 4 weeks for effect.22, 25
Benzodiazepines Severe anxiety or alcohol withdrawal; Severe agitation or psychoses Reserve for acute crisis. Benzodiazepine side effects include worsening gait, potential paradoxical agitation, and possible physical dependence. 26

Lorazepam is preferred for short duration and low accumulation in elderly.

Dextromethorphan-quinidine (DM/Q) (Nuedexta®) Mild-moderate agitation Ongoing trials of off-label use in Alzheimer’s dementia. One in 6 patients will see improvement over 10 weeks.27

Limited evidence suggests it may provide some benefit for severe agitation in patients with dementia. When cost is not a concern and other strategies have failed, a trial may be reasonable.28-37

Brexpiprazole (Rexulti®) Severe agitation or psychoses Atypical antipsychotic that gained the first and only FDA-approval for the treatment of agitation associated with dementia due to Alzheimer’s disease in May 2023.

Given the increased risk of death of antipsychotics in elderly patients with dementia related psychosis, the risks versus benefits should be considered.

Antipsychotics should be reserved for specific indications such as delirium, mania, or psychosis or when a patient is a danger to themselves or others. 26,38-41

Currently cost prohibitive compared to other commonly used, generically available antipsychotics (haloperidol, risperidone, quetiapine) in the general hospice population.


Most persons living with dementia are cared for in their homes and depend upon care from family, friends, neighbors, and other unpaid help for complex care needs over the long course of the disease. The economic value of this unpaid caregiving dramatically surpasses spending for formal home health care and nursing home care.

Caring for individuals with dementia has a physical, psychological, social, and financial impact on caregivers, the combination of which places the patient at risk for negative consequences. Caregiving requires many tasks, all of which must be done while juggling other responsibilities such as childcare, daily errands, or working full- or part-time jobs. Tasks include:

  • Household tasks (e.g., laundry, meals, shopping, transportation)
  • Activities of daily living, safety, and behaviors
    • Assisting with personal activities of daily living (ADLs) (e.g., bathing, dressing, mobility)
    • Supervising personal safety of the individual living with dementia
    • Managing behavioral symptoms of the disease (e.g., wandering, agitation)
  • Emotional and social support
  • Health and medical care
  • Advocacy and care coordination
  • Surrogate decision-making

Caregivers often receive inadequate support from health professionals and frequently feel abandoned and unrecognized by health care systems. Caregivers often state that they want more information about their loved one’s illness and symptoms, referral to support services, and emotional support. Only a quarter of caregivers have ever been asked about their own self-care needs.

Three Steps for Clinicians Supporting Caregivers

  1. Include the caregiver as a member of the care team
  2. Ask about the caregiver’s health and well-being, not just about the patient’s
  3. Address Caregiver’s Needs

Patient and Caregiver Support Resources



Click here to download a copy of this month’s article to share with your colleagues or to keep for personal reference.


  1. Larson EB. Evaluation of cognitive impairment and dementia. In: UpToDate, DeKosky ST, Wilterdink JL, et al, eds. Updated Nov. 2, 2023. Literature current through Mar 2024.
  2. Omlor R, Cleveland J, Brooten J, et al. Anticipatory Guidance in Dementia Across the Stages. PCNOW Fast Facts #455. Dec. 28, 2022. Article link
  3. Center to Advance Palliative Care (CAPC). Best Practice in Dementia Care and Caregiver Support. 2018. capc.org
  4. Mitchell SL, Kiely DK, Jones RN, et al. The CASCADE study. Alzheimer Dis Assoc Disord. 2006; 20(3): 166-175.
  5. Givens JL, et al. Arch Intern Med. 2010 July 12; 170(13): 1102–1107.
  6. Dufour AB, Shaffer ML, D’Agata EM, et al. J Am Geriatr Soc. 2015 Dec; 63(12): 2472-2477.
  7. Jablonski L, Pruskowski J. Antimicrobial Therapy at the End-of-Life. PCNOW Fast Facts #351. Mar. 6, 2019. Article link
  8. Burling S. ‘Mom, I didn’t steal your dentures’: Coping when dementia turns to delusion. The Inquirer. 2017 Jul 6. Article link
  9. Fairman N, Hirst JM, Irwin SA. Clinical manual of palliative care psychiatry.1st ed. Arlington: American Psychiatric Association; 2016.
  10. van der Steen JT, et al. White paper defining optimal palliative care in older people with dementia: A Delphi study and recommendations from the European Association for Palliative Care. Palliative Medicine. 2014;28(3):197-209.
  11. Salzman C, et al. Elderly patients with dementia-related symptoms of severe agitation and aggression: Consensus statement on treatment options, clinical trials methodology, and policy. J Clin Psychiatry. 2008 June; 69(6):889-898.
  12. Vernooij-Dassen M, et al. Psychosocial interventions for dementia patients in long-term care. Internat’l Psychogeriatrics. 2010;22(7):1121-1128.
  13. Ecumen Awakenings. 2020. Accessed 2024 Apr. Site link
  14. Clinical Resource, Pharmacotherapy of Dementia Behaviors. Pharmacist’s Letter/Prescriber’s Letter. June 2022.
  15. Clinical Pharmacology [database online]. Elsevier/Gold Standard. 2024.
  16. Seitz DP, et al. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. 2011
  17. Porsteinsson AP, Drye LT, Pollock BG, et al. Effect of citalopram on agitation in Alzheimer disease: The CitAD randomized controlled trial. JAMA 2014;311:682-91.
  18. Lyketsos CG, DelCampo L, Steinberg M, et al. Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: The DIADS. Arch Gen Psychiatry 2003;60:737-46.
  19. Olin JT, Fox LS, Pawluczyk S, et al. A pilot randomized trial of carbamazepine for behavioral symptoms in treatment-resistant outpatients with Alzheimer disease. Am J Geriatr Psychiatry 2001;9:400-5.
  20. Tariot PN, Erb R, Podgorski CA, et al. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Am J Psychiatry 1998;155:54-61.
  21. Lonergan E, et al. Valproate preparations for agitation in dementia. Cochrane Database Syst Rev 2009 Jul 8;3.
  22. Sadowsky CH, Galvin JE. Guidelines for the management of cognitive and behavioral problems in dementia. J Am Board Fam Med 2012;25;350-66.
  23. Tariot PN, Schneider LS, Cummings J, et al. Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Arch Gen Psychiatry 2011;68:853-61.
  24. Suzuki H, Gen K. Clinical efficacy of lamotrigine and changes in the dosages of concomitantly used psychotropic drugs in Alzheimer’s disease with behavioral and psychological symptoms of dementia: A preliminary open-label trial. Psychogeriatrics 2015;15:32-7.
  25. American Geriatrics Society. A guide to the management of psychotic disorders and neuropsychiatric symptoms of dementia in older adults. April 2021. PDF link
  26. Press D. Management of neuropsychiatric symptoms of dementia. In UpToDate, DeKosky ST, Schmader KE, Mendez MF, Wilterdink JL, eds. Waltham, MA: UpToDate, Inc. Updated Apr. 7, 2022; Literature current through Mar 2024.
  27. Cummings JL, Lyketsos CG, Peskind ER, et al. Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial. JAMA 2015;314:1242-54.
  28. Cummings JL, et al. Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial. JAMA 2015;314:1242-54.
  29. Ballard C, Sharp S, Corbett A. Dextromethorphan and Quinidine for Treating Agitation in Patients with Alzheimer Disease Dementia. JAMA 2015; 314:1233.
  30. Shi J, et al. Nuedexta for treating pseudobulbar affect in Alzheimer’s disease. ClinicalTrials.gov ID:NCT01832350. [cited 2017 Nov 21].
  31. Efficacy, Safety and Tolerability of AVP-786 for the Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type. ClinicalTrials.gov ID: NCT 02442765.
  32. Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type. ClinicalTrials.gov ID: NCT02442778.
  33. Long Term, Extension Study of the Safety and Efficacy of AVP-786 for the Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type. ClinicalTrials.gov ID: NCT02446132.
  34. Garay RP, Grossberg GT. AVP-786 for the treatment of agitation in dementia of the Alzheimer’s type. Expert Opinion Invest Drugs. 2017;26(1):121-132.
  35. Chen Q, et al. Effectiveness of Dextromethorphan/Quinidine in Frontotemporal Dementia. Am J Geriatr Psychiatry. 2018 Apr;26(4):506. doi: 10.1016/j.jagp.2017.10.008.
  36. Kongpakwattana K, et al. Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis. Br J Clin Pharmacol. 2018 Jul;84(7):1445-1456. doi: 10.1111/bcp.13604.
  37. Watt JA, et al. Safety of pharmacologic interventions for neuropsychiatric symptoms in dementia: a systematic review and network meta-analysis. BMC Geriatr. 2020 Jun 16;20(1):212. doi: 10.1186/s12877-020-01607-7
  38. Maust, DT, et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia. Number needed to harm. JAMA Psychiatry. 2015 Mar 18. Published online. doi:10.1001/jamapsychiatry.2014.3018
  39. Reus VI, et al. The American Association Practice Guidelines on the use of antipsychotics to treat agitation or psychosis in patients with dementia. 1st ed. Arlington: American Psychiatric Association; 2016. Article link
  40. Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ 2015 Mar 2;350.