Professional Documents
Culture Documents
Psychiatric Aspects
Address correspondence to
Dr Chiadi U. Onyike, Johns
Hopkins University, 600 N
Wolfe St, Meyer 279, Baltimore,
MD 21287, conyike1@jhmi.edu.
Relationship Disclosure:
Dr Onyike has received
of Dementia
personal compensation as Chiadi U. Onyike, MD, MHS
special issue editor for the
International Review of
Psychiatry and the Psychiatric
Clinics of North America and ABSTRACT
has given expert legal
testimony for the Paley Rothman Purpose of Review: The psychiatric aspects of dementia are increasingly recognized
law firm on disabilities related as significant contributors to distress, disability, and care burden, and, thus, are of
to frontotemporal dementia. increasing interest to practicing neurologists. This article examines how psychiatric
Dr Onyike receives research
funding from the Jane Tanger disorders are entwined with dementia and describes the predictive, diagnostic, and
Black Fund for Young-Onset therapeutic implications of the psychiatric symptoms of dementia.
Dementia Research, the Recent Findings: Psychiatric disorders, particularly depression and schizophrenia,
National Institute of Neurological
Disorders and Stroke, the are associated with higher risk for late-life dementia. Psychiatric phenomena also
National Institute on Aging, the define phenotypes such as frontotemporal dementia and dementia with Lewy bodies,
National Institutes of Health, cause distress, and amplify dementia-related disabilities. Management requires a
the Robert and Nancy Hall
family, and Tau Therapeutics. multidisciplinary team, a problem-solving stance, programs of care, and pharmacologic
Unlabeled Use of management. Recent innovations include model programs that provide structured
Products/Investigational problem-solving interventions and tailored in-home care.
Use Disclosure:
Dr Onyike discusses the
Summary: There is new appreciation of the complexity of the relationship between
unlabeled/investigational psychiatric disorders and dementia as well as the significance of this relationship for
indications and evidence for treatment, community services, and research.
efficacy and risks of
prescribing antidepressants,
antipsychotics, and other Continuum (Minneap Minn) 2016;22(2):600–614.
psychotropic agents for
treating psychiatric aspects of
dementia, as well as the
alternatives to making these INTRODUCTION and their predictive, diagnostic, and
prescriptions, which include
behavioral interventions, The coincidence of primary (ie, neuro- treatment implications.
care programs, caregiver
support and training, degenerative) dementia and psychiatric LINKS BETWEEN PSYCHIATRIC
environment modulation, and disorders is increasingly seen as a com- DISORDERS AND DEMENTIA
structured recreation.
mon occurrence and as a significant con- The earliest descriptions of the primary
* 2016 American Academy
of Neurology. tributor to distress, handicap, care needs, dementias included psychiatric distur-
and health costs. Psychiatric disorders bances alongside the cognitive and
have long been viewed as epiphenom- functional symptoms. Alois Alzheimer
ena that complicate dementias that are identified anxiety, hallucinations, delu-
‘‘essentially’’ cognitive disorders, but sions, and agitation amid confusion and
contemporary views suggest: (1) some dense impairments of memory, orienta-
psychiatric disorders are integral to the tion, and knowledge that would define
dementia phenotype, (2) dementia the illness named for him.1 His con-
may be foreshadowed by syndromes temporaries, Arnold Pick, Paul Sérieux,
such as major depression and schizo- and Joseph Dejerine, described mid-
phrenia and states such as apathy and life deterioration of conduct and lan-
irritability, and (3) many psychiatric guage, which are the first descriptions
disorders complicate the course of the of frontotemporal dementia (FTD).2Y4
dementia by amplifying or adding to From these beginnings, primary de-
distress and disability. This article mentias came to be viewed narrowly
examines the overlap between psychi- as cognitive disorders, but in the past
atric disorders and primary dementias 35 years, observations of the ubiquity
KEY POINT
h Depressive symptoms and dementia, compared to those who polar disorder.30,31 Whether the risk
have been associated had schizophrenia and no dementia.23 for dementia is greater for young-onset
with cognitive decline A more recent analysis showed that versus late-onset depression is still un-
and transitions to neuritic plaques and neurofibrillary settled as studies have yielded mixed
dementia in individuals tangles that did not meet the threshold results.30,32 Recent data from a Swedish
with mild cognitive for a formal AD diagnosis showed a cohort of military conscripts suggests
impairment and other positive correlation with dementia se- that depression in youth is associated
mild cognitive disorders. verity.24 Thus, dementia in schizophre- with a nearly twofold higher risk for
nia appears to be related primarily to young-onset dementia, 33 although
insidious brain atrophy and, for some, this finding has not been replicated.
a consequent lowering of the thresh- Whereas a causal relationship between
old for coincident neurodegeneration major depression and dementia has
to cause dementia. not been established, depressive symp-
It may be that some cases of schizo- toms may appear in the dementia
phrenia, a schizophreniform state, or prodrome (Case 11-1). Furthermore,
other psychotic presentations, are pro- depressive symptoms have been as-
dromes of a dementia. One study of sociated with cognitive decline and
progranulin (GRN) mutation carriers transitions to dementia in individuals
describes a family in which two sib- with MCI and other mild cognitive
lings manifested a classic schizophre- disorders (ie, states of cognitive dys-
nia phenotype and a third sibling had function that do not reach a thresh-
a typical FTD.25 It is also now increas- old for dementia, or match formal
ingly recognized that up to 20% of definitions for MCI). Psychiatric dis-
carriers of the C9ORF72 mutation orders are more frequently observed
associated with FTD and amyotrophic in elderly patients with MCI and other
lateral sclerosis experience psycho- mild cognitive disorders than in their
sis,26Y28 although it is still uncertain age-matched peers with normal cog-
what proportion present with primary nition, and these associations have
psychosis. Earlier clinicopathologic been linked to worse cognition and
analysis of a brain bank cohort has functional disabilities.16,34,35 Studies
suggested that schizophreniform and of community-based elderly indi-
other psychiatric presentations are viduals have shown associations
more likely in patients with FTD who between depression, apathy, and
are younger than 45 years of age, irritability/agitation, and transitions
whereas later-life presentations are from normal cognition to MCI, and
more likely to feature impairments of from MCI to dementia.36Y40 A recent
cognition and social conduct.29 meta-analysis reached the same con-
Cognitive dysfunction has been ob- clusions, showing that transitions
served in cases of remitted major from mild cognitive disorders to
depression and bipolar disorder, par- dementia are predicted by depres-
ticularly affecting attention, executive sion (in community samples) and
function, and memory, and depression apathy (in the clinic).41
appears to be associated with increased
risk for late-life dementia.30 The risk for PSYCHIATRIC PHENOMENA
dementia appears to be higher in in- AS DEFINING FEATURES
dividuals with more severe depressive OF DEMENTIA
symptoms and appears to be associated Although dementia syndromes are
with the frequency of admission to psy- widely viewed essentially as cognitive
chiatric wards for depression and bi- disorders, many of these are defined by
602 www.ContinuumJournal.com April 2016
KEY POINTS
h Cognitive deficits and syndrome or dementia syndrome by ered a rarity in FTD, was common in a
behavioral symptoms many years. Huntington disease fea- recently described neuropathology
are present in patients tures a triad of cognitive, affective, and cohort and may distinguish a subtype
with Huntington motor phenomena. The motor fea- of FTD caused by mutations in the
disease beginning tures, typically chorea, athetosis, tics, C9ORF72 gene, although the diagnos-
approximately 15 years bradykinesia, incoordination, and tic utility of this association has not
prior to motor diagnosis. ideomotor apraxias, are preceded by been examined. Visual illusions and
h The behavioral variant executive dysfunction, apathy, irri- hallucinations develop early in DLB
of frontotemporal tability, depression, and anxiety.43 and become florid, persistent, and,
dementia typically Such cognitive deficits and behavioral in many cases, associated with mis-
presents as a combination symptoms are present beginning identification, paranoia, delusions,
of socially offensive about 15 years prior to motor diag- and anxiety.26Y28,49 PDD manifests
behaviors, such as nosis.44 In asymptomatic Huntington illusions, hallucinations, paranoia,
indifference, impatience, disease mutation carriers, the earliest and delusions very late in the illness,
carelessness, insensitivity,
cognitive deficits are found in atten- usually many years after the de-
jocularity, intrusiveness,
tion, working memory, verbal learn- velopment of parkinsonism, subclini-
distractibility,
impulsiveness,
ing, verbal long-term memory, and cal cognitive dysfunction, anxiety, and
stereotyped behaviors, learning of random associations.45 depression. In PDD, visual hallucina-
compulsions, food Still, clinical diagnosis in Huntington tions, paranoia, and anxiety often
craving and gluttony, disease emphasizes the motor phe- arise as complications of dopaminer-
and slovenliness, and nomena and genetic testing; the gic therapy. REM sleep behavior dis-
many of these patients cognitive deficits and psychiatric order is a characteristic of DLB and
do not have noticeable phenomena lack the specificity for Parkinson disease that, when present
cognitive deficits until differential diagnosis but may facil- in advance of cognitive and motor
illness is established. itate early recognition in individu- dysfunction, facilitates the clinical
h Visual illusions and als who are known carriers of the diagnosis.42,50,51
hallucinations develop Huntington mutation or have a posi-
early in dementia with tive family history.46 IMPACTS OF PSYCHIATRIC
Lewy bodies and For some dementia syndromes, psy- DISORDERS ON DEMENTIA
become florid, persistent chiatric states are defining elements of Psychiatric disorders are frequently the
and, in many cases,
the illness and its diagnosis. Psychiatric main clinical focus because they bring
are associated
phenomena that define the dementia about distress directly and can exacer-
with misidentification,
paranoia, delusions,
syndrome are integrated into the diag- bate other morbidity. These states in-
and anxiety. nostic criteria for FTD and DLB, for crease the demands placed on relatives
example.47,48 To illustrate further, FTD and other caregivers and, thus, the
h Psychiatric symptoms in
is characterized by gross decline in levels of caregiver stress, and they also
dementia have been
linked to more severe
conduct (ie, the behavioral variant) or result in higher rates of resource utili-
cognitive and functional speech and language (the language zation.52 Psychiatric symptoms in de-
disabilities and faster variant). The behavioral variant of FTD mentia have also been linked to more
progression to severe typically presents as a combination of severe cognitive and functional disabil-
dementia and death. socially offensive behaviors, such as ities and faster progression to severe
indifference, impatience, carelessness, dementia and death.53,54 It has been
insensitivity, jocularity, intrusiveness, estimated, for example, that nearly
distractibility, impulsiveness, stereo- one-third of all dementia treatment
typed behaviors, compulsions, food costs are accounted for by psychiatric
craving and gluttony, and slovenliness, symptoms.55,56 These symptoms also
and many of these patients do not have shape the quality of life for many in-
noticeable cognitive deficits until illness dividuals with dementia. They are also
is established. Psychosis, once consid- major drivers of transfers to residential
KEY POINT
h A multidisciplinary team on self-reports, caregiver interviews, shadow the cognitive impairments; and
model involving or direct observations, and may be (3) syndromes defined by motor dys-
physicians, nursing, structured or semistructured. Since functions that usually overshadow
physical therapy, and self-reports are bedeviled by the loss cognitive and psychiatric phenomena,
other rehabilitative of self-monitoring and decisional ca- such as progressive supranuclear
services, as well as pacities in people with dementia, palsy and corticobasal degeneration.68
social work and measurements are usually sourced The alternative approach is to take
caregiver/family from caregiver interviews or direct a problem-solving stance, based on the
advocacy is often observations. Two classes of instru- understanding that some of the psy-
required for the optimal ments are used: standard psychiatric chiatric disturbances seen in demen-
management of
instruments adapted to dementia tia may be maladaptive reactions or
patients with psychiatric
practice and research objectives as patient-caregiver conflicts, rather than
disorders and dementia.
well as specially designed scales and symptoms of neurophysiologic distur-
questionnaires. The Neuropsychiatric bance. In this perspective, the psychiat-
Inventory (NPI),62 the most widely ric state is understood as arising from
used tool for measuring psychiat- the interplay of personal and environ-
ric phenomena in dementia, is a mental factors, implying that they can
semistructured screen-and-probe in- be extinguished or reshaped by behav-
terview of the patient’s spouse, care- ioral and environmental manipulations.
giver, or other source. It covers a
swarth of psychiatric states, and ver- PERSPECTIVES ON
sions have been developed for as- CLINICAL MANAGEMENT
sisted living and nursing home A multidisciplinary team model involv-
settings. The Neuropsychiatric Inven- ing physicians, nursing, physical ther-
tory Questionnaire (NPI-Q),63 a short apy, and other rehabilitative services,
version of the NPI, has found wide as well as social work and caregiver/
application in clinical practice and family advocacy is often required for
research. Numerous other tools for the optimal management of patients
measuring specific psychiatric phe- with psychiatric disorders and demen-
nomena in elderly individuals with tia. At the author’s institution, behavioral
dementia exist, such as the Geriatric care, case management, pharmacologic
Depression Scale and the Frontal Be- prescriptions, and physical, speech/
havioral Inventory for use in FTD.64Y67 language, and occupational therapy
At Johns Hopkins Hospital, we have are melded into an individualized treat-
described an algorithmic approach,68 in ment plan to relieve distress, provide
which the temporal clustering of cog- direction, promote adaptation, and
nitive, neuropsychiatric, and motor optimize quality of life.69 A healthy
symptoms and signs is used to define partnership with the patient and the
syndrome categories that facilitate dif- caregiver, and their education about
ferential diagnosis (Figure 11-1). The psychiatric symptoms, dementia, and
method classifies syndromes into: the interventions are vital for success.
(1) primarily cognitive syndromes, such The clinical formulation is the frame-
as the canonical (amnestic) AD phe- work for managing the psychiatric
notype and the primary progressive aspects of dementia. Where the for-
aphasias, in which the cognitive defi- mulation emphasizes specific disorders,
cits are the signal features; (2) predo- pharmacologic intervention specific to
minantly psychiatric syndromes such the underlying neurodegenerative dis-
as the behavioral variant of FTD and ease or psychiatric disorder may be in-
DLB, where psychiatric disorders over- dicated (ie, cholinesterase inhibitors for
606 www.ContinuumJournal.com April 2016
AD or selective serotonin reuptake in- terventions directed at the environment, KEY POINT
hibitors [SSRIs] for depression). When their comfort, or the patient-caregiver h Where the clinical
problem solving is emphasized, psycho- relationship.70 The choice of approach formulation for
social approaches such as environment derives from careful analysis of the managing the psychiatric
aspects of dementia
remodeling, structured recreation, care- context of the psychiatric state. An-
emphasizes problem
giver education and training, and psy- other model views psychiatric states as
solving, psychosocial
chotherapy are more pertinent. One catastrophic reactions to frustration, approaches such as
commonly used psychosocial approach failure, or being thwarted, in which case, environment remodeling,
calls for formal analysis of the context simplifying tasks and providing direc- structured recreation,
and antecedents of the psychiatric state, tion and assistance can go a long way. caregiver education
so as to identify and remove (or man- Yet another approach is to examine the and training, and
age) precipitating factors. A patient patient-caregiver dyad for dysfunctional psychotherapy
who has exhibited agitated resistance interactions that will be corrected are pertinent.
of morning hygiene routines might through caregiver counseling and skill-
do much better when allowed to wake building training sessions. The efficacy
naturally or to eat first. The patient of structured skill-building programs
might also respond to nonspecific in- and tailored problem-solving methods
KEY POINT
h Typical and atypical for dementia care has been demon- (Figure 11-2), which requires that the
antipsychotic agents strated in formal trials that examined problem be specified (describe) along
are associated with a effects on psychiatric disorders and with the contexts, triggers, and modi-
high risk for mortality caregiver coping.71Y74 fiers (investigate), that a collaboration is
in patients who Pharmacologic interventions for psy- undertaken with the caregiver to devise
have dementia. chiatric symptoms in dementia mirror a program of care (create), and that the
standard psychiatric practice, albeit implementation and results are moni-
with more cautious dosing, and they tored (evaluate).52 The DICE approach
remain in need of the validation of is now part of the Centers for Medicare
formal clinical trials.70,75,76 The na- and Medicaid Services toolkit of non-
tionwide Clinical Antipsychotic Trials pharmacologic programs for dementia
of Intervention Effectiveness did not care, which hopefully will stimulate
demonstrate efficacy for treatment of broad implementation, dissemination,
dementia-related psychosis, agitation, and evaluation. Another innovation is
and aggression, although a secondary the Maximizing Independence (MIND)
analysis suggested the atypical agents at Home study, which has used multi-
may have value, but that any bene- disciplinary teams for home-based case
fits might be offset by worsening of management that consists of individu-
cognitive disabilities, somnolence, par- alized care planning with monitoring,
kinsonism, weight gain, metabolic de- links to local services, dementia-related
rangements, and death.77,78 In DLB and education, and caregiver skills building,
PDD, quetiapine and clozapine are the which resulted in far fewer transfers
only antipsychotics recommended from home to residential care and
given the higher risk of extrapyramidal higher quality-of-life ratings than usual
side effects with other antipsychotic care in the pilot study.91 A larger
medications. Other antipsychotic drugs follow-up study, now underway, is aimed
must be avoided in these patients as at demonstrating the efficacy and scal-
they may precipitate life-threatening ability of this program.
rigidity and autonomic dysfunction. Pharmacologic interventions are still
The atypical antipsychotics are associ- indicated in some cases, owing to the
ated with mortality from cardiovascular biological grounding of some of the
and cerebrovascular events (and other psychiatric symptoms of dementia; vi-
causes of mortality, including infectious sual hallucinations in DLB, for example,
causes) in patients who have demen- cannot be formulated as arising from a
tia.79,80 The risk is higher still with the caregiver’s mishandling of a situation, a
conventional agents.81Y85 Where these patient’s misunderstanding, misinter-
agents are prescribed, risk can be pretation, or overreaction, or other so-
mitigated by routine use of planned cial mishap. Psychiatric states such as
discontinuation trials, in line with evi- these warrant pharmacologic interven-
dence that most psychiatric states in tion when they cause distress, are offen-
dementia do not persist longer than sive, or bring about significant morbidity
3 to 6 months and results from discon- (such as when depression causes an-
tinuation trials that show benefit.14,86Y90 orexia, weight loss, and malnutrition).
The development of structured be- Thus, present-day research continues
havioral programs that can be readily the search for physiologic indices of
disseminated are now underway, which psychiatric states in dementia, with the
will facilitate intervention in the home. hope that biomarkers will lead to more
One innovation is the Describe, Inves- effective case recognition and physio-
tigate, Create, Evaluate (DICE) method logic targets for drug development.
608 www.ContinuumJournal.com April 2016
Tanger Black Fund for Young-Onset 12. Lyketsos CG, Lopez O, Jones B, et al. Prevalence
of neuropsychiatric symptoms in dementia and
Dementia Research; the National In-
mild cognitive impairment: results from the
stitutes of Health (NIH)/National In- cardiovascular health study. JAMA 2002;288(12):
stitute on Aging grants (P50AG05146 1475Y1483. doi:10.1001/jama.288.12.1475.
and U19AG033655); NIH/National 13. Ikeda M, Fukuhara R, Shigenobu K, et al.
Institute of Neurological Disorders Dementia associated mental and behavioural
and Stroke grants (R01NS056307 and disturbances in elderly people in the community:
findings from the first Nakayama study. J Neurol
1U54NS092089-01); the Robert and Neurosurg Psychiatry 2004;75(1):146Y148.
Nancy Hall family; and TRx 237-007
14. Aalten P, de Vugt M, Jaspers N, et al. The
from Tau Therapeutics. course of neuropsychiatric symptoms in
dementia. Part I: findings from the two-year
REFERENCES longitudinal Maasbed study. Int J Geriatr
1. Alzheimer A. Über eigenartige Psychiatry 2005;20(6):523Y530. doi:10.1002/
Krankheitsfälle des späteren Alters. Z Ges gps.1316.
25. Momeni P, DeTucci K, Straub RE, et al. 36. Banks SJ, Raman R, He F, et al. The Alzheimer’s
Progranulin (GRN) in two siblings of a disease cooperative study prevention
Latino family and in other patients with instrument project: longitudinal outcome of
schizophrenia. Neurocase 2010;16(3):273Y279. behavioral measures as predictors of cognitive
doi:10.1080/13554790903456209. decline. Dement Geriatr Cogn Dis Extra
2014;4(3):509Y516. doi:10.1159/000357775.
26. Snowden JS, Rollinson S, Thompson JC, et al.
Distinct clinical and pathological characteristics 37. Donovan NJ, Amariglio RE, Zoller AS, et al.
of frontotemporal dementia associated with Subjective cognitive concerns and
neuropsychiatric predictors of progression
C9ORF72 mutations. Brain 2012;
to the early clinical stages of Alzheimer
135(pt 3):693Y708. doi:10.1093/brain/awr355.
disease. Am J Geriatr Psychiatry
27. Sha SJ, Takada LT, Rankin KP, et al. 2014;22(12):1642Y1651. doi:10.1016/
Frontotemporal dementia due to C9ORF72 j.jagp.2014.02.007.
38. Geda YE, Roberts RO, Mielke MM, et al. 49. Landqvist Waldö M, Gustafson L, Passant U,
Baseline neuropsychiatric symptoms and the Englund E. Psychotic symptoms in
risk of incident mild cognitive impairment: a frontotemporal dementia: a diagnostic
population-based study. Am J Psychiatry dilemma? Int Psychogeriatr 2015;27(4):
2014;171(5):572Y581. doi:10.1176/ 531Y539. doi:10.1017/S1041610214002580.
appi.ajp.2014.13060821.
50. Ferman TJ, Boeve BF, Smith GE, et al.
39. Masters MC, Morris JC, Roe CM. Inclusion of RBD improves the diagnostic
‘‘Noncognitive’’ symptoms of early classification of dementia with Lewy bodies.
Alzheimer disease: a longitudinal analysis. Neurology 2011;77(9):875Y882. doi:10.1212/
Neurology 2015;84(6):617Y622. doi:10.1212/ WNL.0b013e31822c9148.
WNL.0000000000001238. 51. Boeve BF, Silber MH, Ferman TJ, et al.
40. Copeland MP, Daly E, Hines V, et al. Clinicopathologic correlations in 172 cases of
Psychiatric symptomatology and prodromal rapid eye movement sleep behavior disorder
Alzheimer’s disease. Alzheimer Dis Assoc with or without a coexisting neurologic
Disord 2003;17(1):1Y8. disorder. Sleep Med 2013;14(8):754Y762.
doi:10.1016/j.sleep.2012.10.015.
41. Cooper C, Sommerlad A, Lyketsos CG,
Livingston G. Modifiable predictors of 52. Kales HC, Gitlin LN, Lyketsos CG; Detroit
dementia in mild cognitive impairment: a Expert Panel on Assessment and Management
systematic review and meta-analysis. Am J of Neuropsychiatric Symptoms of Dementia.
Psychiatry 2015;172(4):323Y334. doi:10.1176/ Management of neuropsychiatric
appi.ajp.2014.14070878. symptoms of dementia in clinical settings:
recommendations from a multidisciplinary
42. Boeve BF. REM sleep behavior disorder: expert panel. J Am Geriatr Soc 2014;62(4):
updated review of the core features, the REM 762Y769. doi:10.1111/jgs.12730.
sleep behavior disorder-neurodegenerative
53. Stern Y, Tang MX, Albert MS, et al. Predicting
disease association, evolving concepts,
time to nursing home care and death in
controversies, and future directions. Ann N Y
individuals with Alzheimer disease.
Acad Sci 2010;1184:15Y54. doi:10.1111/
JAMA 1997;277(10):806Y812. doi:10.1001/
j.1749<6632.2009.05115.x.
jama.1997.03540340040030.
43. Ross CA, Pantelyat A, Kogan J, Brandt J.
Determinants of functional disability in 54. Rabins PV, Schwartz S, Black BS, et al.
Huntington’s disease: role of cognitive and Predictors of progression to severe Alzheimer’s
motor dysfunction. Mov Disord 2014;29(11): disease in an incidence sample. Alzheimers
1351Y1358. doi:10.1002/mds.26012. Dement 2013;9(2):204Y207. doi:10.1016/
j.jalz.2012.01.003.
44. Paulsen JS. Cognitive impairment in
Huntington disease: diagnosis and treatment. 55. Beeri MS, Werner P, Davidson M, Noy S.
Curr Neurol Neurosci Rep 2011;11(5):474Y483. The cost of behavioral and psychological
doi:10.1007/s11910<011<0215-x. symptoms of dementia (BPSD) in community
dwelling Alzheimer’s disease patients. Int J
45. Lemiere J, Decruyenaere M, Evers-Kiebooms G, Geriatr Psychiatry 2002;17(5):403Y408.
et al. Cognitive changes in patients with doi:10.1002/gps.490.
Huntington’s disease (HD) and asymptomatic
carriers of the HD mutationVa longitudinal 56. Herrmann N, Lanctôt KL, Sambrook R, et al.
follow-up study. J Neurol 2004;251(8): The contribution of neuropsychiatric
935Y942. doi:10.1007/s00415-004-0461-9. symptoms to the cost of dementia care. Int J
Geriatr Psychiatry 2006;21(10):972Y976.
46. Reilmann R, Leavitt BR, Ross CA. Diagnostic doi:10.1002/gps.1594.
criteria for Huntington’s disease based on
57. Rosenblatt A, Samus QM, Steele CD, et al.
natural history. Mov Disord 2014;29(11):
The Maryland Assisted Living Study:
1335Y1341. doi:10.1002/mds.26011.
prevalence, recognition, and treatment of
47. Rascovsky K, Hodges JR, Knopman D, et al. dementia and other psychiatric disorders in
Sensitivity of revised diagnostic criteria the assisted living population of central
for the behavioural variant of frontotemporal Maryland. J Am Geriatr Soc 2004;52(10):
dementia. Brain 2011;134(pt 9):2456Y2477. 1618Y1625. doi:10.1111/j.1532-5415.
doi:10.1093/brain/awr179. 2004.52452.x.
48. McKeith IG, Dickson DW, Lowe J, et al. 58. Kverno KS, Rabins PV, Blass DM, et al.
Diagnosis and management of dementia Prevalence and treatment of neuropsychiatric
with Lewy bodies: third report of the DLB symptoms in advanced dementia. J Gerontol
Consortium. Neurology 2005;65(12):1863Y1872. Nurs 2008;34(12):8Y15. doi:10.3928/
doi:10.1212/01.wnl.0000187889.17253.b1. 00989134-20081201-03.
81. Schneider LS, Dagerman KS, Insel P. Risk of institutionalized dementia patients: results
death with atypical antipsychotic drug of a double-blind, baseline-treatment-controlled
treatment for dementia: meta-analysis of pilot study. J Geriatr Psychiatry Neurol
randomized placebo-controlled trials. JAMA 1997;10(3):119Y126. doi:10.1177/
2005;294(15):1934Y1943. doi:10.1001/ 089198879701000306.
jama.294.15.1934.
88. Cohen-Mansfield J, Lipson S, Werner P, et al.
82. Wang PS, Schneeweiss S, Avorn J, et al. Risk Withdrawal of haloperidol, thioridazine,
of death in elderly users of conventional vs. and lorazepam in the nursing home: a
atypical antipsychotic medications. N Engl J controlled, double-blind study. Arch Intern
Med 2005;353(22):2335Y2341. doi:10.1056/ Med 1999;159(15):1733Y1740. doi:10.1001/
NEJMoa052827. archinte.159.15.1733.
83. Kales HC, Valenstein M, Kim HM, et al. 89. Ballard C, Lana MM, Theodoulou M, et al. A
Mortality risk in patients with dementia randomised, blinded, placebo-controlled
treated with antipsychotics versus other trial in dementia patients continuing or
psychiatric medications. Am J Psychiatry stopping neuroleptics (the DART-AD trial).
2007;164(10):1568Y1576. doi:10.1176/ PLoS Med 2008;5(4):e76. doi:10.1371/
appi.ajp.2007.06101710. journal.pmed.0050076.
84. Schneeweiss S, Setoguchi S, Brookhart A, 90. Ballard C, Hanney ML, Theodoulou M, et al.
et al. Risk of death associated with the The dementia antipsychotic withdrawal
use of conventional versus atypical trial (DART-AD): long-term follow-up of a
antipsychotic drugs among elderly patients. randomised placebo-controlled trial. Lancet
CMAJ 2007;176(5):627Y632. doi:10.1503/ Neurol 2009;8(2):151Y157. doi:10.1016/
cmaj.061250. S1474-4422(08)70295-3.
85. Kales HC, Kim HM, Zivin K, et al. Risk of 91. Samus QM, Johnston D, Black BS, et al.
mortality among individual antipsychotics in A multidimensional home-based
patients with dementia. Am J Psychiatry care coordination intervention for
2012;169(1):71Y79. doi:10.1176/ elders with memory disorders: the
appi.ajp.2011.11030347. maximizing independence at home
(MIND) pilot randomized trial.
86. Onyike CU. Neuroleptic discontinuation Am J Geriatr Psychiatry 2014;
during dementia care: a recent trial and its 22(4):398Y414. doi:10.1016/j.jagp.
implications for practice. Nat Clin Pract 2013.12.175.
Neurol 2008;4(10):528Y529. doi:10.1038/
ncpneuro0884. 92. Onyike CU, Huey ED. Frontotemporal
dementia and psychiatry. Int Rev Psychiatry
87. Bridges-Parlet S, Knopman D, Steffes S. 2013;25(2):127Y129. doi:10.3109/
Withdrawal of neuroleptic medications from 09540261.2013.785169.