Diagnosing neuropsychiatric symptoms in Alzheimer’s disease

Neuropsychiatric symptoms occur commonly in patients with neurodegenerative disorders. Such symptoms are important. Often they are associated with increased mortality and progression. To be able to discuss symptoms meaningfully, it is essential that they are clearly defined to facilitate their diagnosis. At AAIC 2021, diagnostic criteria for apathy, psychosis, agitation and depression were discussed.

Apathy in Alzheimer’s disease

Apathy is probably the most frequent neuropsychiatric symptom (NS) noted in Alzheimer’s disease. Yet, despite its presence in many neuropsychiatric pathologies and consequences for patient functioning and quality of life, it is, paradoxically, difficult to define. Philippe Robert, University Côte d’Azure, Nice, France, explained that operational diagnostic criteria have been developed, with apathy defined as a clinical syndrome characterized by a reduction in self-initiated, goal-directed activity.1

These new diagnostic criteria are easier to use in clinical and research practices than previous iterations. Professor Robert hopes they will allow the development of new and tailor-made therapies to aid in the management of patients.

New apathy diagnostic criteria - easy to use in clinical and research practices



As with apathy, so too are psychotic symptoms common in patients with neurodegenerative symptoms.2,3 Due to advancements in the field when guidelines were last agreed in 2020, two new sets of criteria have been devised:

  • Clinical and research criteria – developed by the International Psychogeriatric Association (IPA) working group3
  • Research-based criteria – developed by the International Society to Advance Alzheimer’s Research Treatment (ISAART) Neuropsychiatric Syndromes (NPS) Professional Interest Area (PIA) psychosis group4.

Corinne Fischer, University of Toronto, ON, Canada, told how new diagnostic criteria have been incorporated into the updated guidelines including use of biomarkers and markers of prodromal psychoses. She anticipates that the new guidelines will advance the etiopathogenesis of psychotic symptoms in neurodegenerative disease. 

New diagnostic criteria including use of biomarkers and markers of prodromal psychoses in updated psychosis guideline



Mary Sano, Mount Sinai School of Medicine, New York, NY, USA, explained the processes underlying the amendment of the provisional IPA 2015 criteria for agitation to formally accepted criteria.5

A survey of IPA members gathered 90% agreement for the work ‘provisional’ to be removed and for the criteria to be formally adopted. However, 10% of members had reservation and made a variety of suggestions for further improvements. For example, provision of additional supporting data, clearer differentiation from clinical delirium, recognition of distress caused by sub-optimal care and distinguishing agitation from aggression. These suggestions have been taken on board; work on finalizing agitation criteria is under way.



Depression is prevalent in Alzheimer’s disease. However, the constellation of symptoms seen in major depressive disorder (MDD) differs from those commonly seen in dementia. For example, in those with late life depression (LLD), memory improves with cuing – it does not improve in those with depression; in LLD, IALD is minimally affected while it is usually markedly affected in those with dementia.

Paul Rosenberg, John’s Hopkins Medical School, Baltimore, MD, USA, suggested that LLD may be considered a prodromal symptom of dementia as depression is associated with an increased risk of cognitive impairment in Alzheimer’s disease – even where he severity of the depression is low.6

That the onset of dementia and depression may share a common vascular mechanism has been suggested. 7-8. So, too, has hearing loss – which is associated with cognitive decline and LLD. Both theorems offer obvious potential therapeutic targets.


 AAIC : Alzheimer's Association International Conference 
NS : neuropsychiatric symptoms 
ISAART : International Society to Advance Alzheimer's Research Treatment  
NPS : Neuropsychiatric Syndromes 
PIA : Professional Interest Area
NY : New York
USA : United States of America 
ON: Ontario
IPA : International Psychogeriatric Association
MDD : Major depressive disorder 
LLD : late life depression
IALD : indole-3-carboxaldehyde 

BE-NOTPR-0133, approval date : 09.2022



Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

  1. Chong TT. Definition: Apathy. Cortex 2020;128:326-327.
  2. Ropacki SA et al. Epidemiology of and risk factors for psychosis in Alzheimer’s disease: a review of 55 studies published from 1990 to 2003. Am Journal Psychiatry 2005;162:2022-2030.
  3. Cummings J et al. Criteria for psychosis in major and mild neurocognitive disorders: IPA consensus clinical and research definitions. Am J Geriatr Psychiatry2020;28:1256-1269.
  4. Fischer CE et al. Revisiting criteria for psychosis in Alzheimer’ disease and related dementias: Towards better phenotypic classification and biomarker research. J Alzheimer’s Disease 2020;73:1143-1156.
  5. Cummings J et al. Agitation in cognitive disorders: IPA provisional consensus clinical and research definition. Int Psychogeriatrics 2015;27:7-17.
  6. Rosenberg P et al. Depressive symptoms predict incident cognitive impairment in cognitive healthy older women. Am J Geriatr Psychiatry 2010;18:204-211.
  7. Alexopoulos GS et al. ‘Vascular depression’ hypothesis. Arch Gen Psychiatry 1997;54:915-22.
  8. Taylor WD et al. The vascular depression hypothesis: mechanisms linking vascular disease with depression. Mol Psychiatry 2013;18:963-974.


Further reading

  1. Leyhe et al. 2017
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