Most people with dementia undergo behavioral changes during the course of the disease. They may become anxious or repeat the same question or activity over and over. The unpredictability of these changes can be stressful for caregivers. As the disease progresses, your loved one's behavior may seem inappropriate, childlike or impulsive. Anticipating behavioral changes and understanding the causes can help you deal with them more effectively.

1. Dr. Ennapadam.S. Krishnamoorthy
MD., DCN, PhD (Lond), FRCP (Lond, Glas, Edin), MAMS (India)
TS Srinivasan Chair in Clinical Neuroscience
&
Founder Director
TRIMED I NEUROKRISH
www.trimedtherapy.com I www.neurokrish.com
Behavioral changes that predict early
dementia

2. Neurobiology of Aging
 Prefrontal, entorhinal, and
temporal cortices are the most
severely affected, whereas
primary visual and
somatosensory cortices might
be more resistant to the
influence of aging
 All these affected areas are
polymodal and association
cortices of the limbic system
which is involved in cognitive
processes that include
attention, working memory,
and the control of behavior

3. Multimodal Neurobiological
Mechanisms in the Aging Brain
 Age-related changes in regional cerebral blood flow and glucose
metabolism, including insular decline, have been demonstrated- role
in processing sensory information
 Imaging studies have documented a substantial decline in D1 and
D2 receptors and dopamine transporters- associated with changes
in motor as well as cognitive/ behavioral functions
 Hippocampal volumes are strong predictors of memory performance
in normal aging- Left hippocampal measurements especially delayed
retention of verbal material are predictive of memory performance
and as has been recently demonstrated, depression
 Alterations in the white matter might represent the predominant
neuroanatomic change in normal aging

4. ORBITOFRONTAL SYNDROME
DISINHIBITION
INAPPROPRIATE AFFECT
IMPAIRED JUDGEMENT
DISTRACTIBILITY

5. DORSOLATERAL SYNDROME
EXECUTIVE FUNCTION
DEFECTS
PERSEVERATION
STIMULUS-BOUND
BEHAVIOUR
DIMINISHED VERBAL
FLUENCY

6. MEDIAL FRONTAL SYNDROME
• APATHY
• MUTISM
• TRANSCORTICAL
APHASIA
• LOWER EXTREMITY
PARESIS
• INCONTINENCE

7. The limbic system & its connections

8. Geschwind’s Temporal Lobe
Personality
A behavioural syndrome described in temporal lobe
epilepsy characterised by
 intensified and labile emotionality
 viscosity (orderliness, excessive attention to detail
and persistence)
 Hypo-sexuality
 Hyper-religiosity
 Hyper-graphia

9. GESCHWIND & KLUVER-BUCY
HYPERCONNECTION
 EMOTIONAL
INTENSITY
 VISCOSITY
 HYPOSEXUALITY
DISCONNECTION
 PLACIDITY
 HYPERMETAMOR-
PHOSIS
 HYPERSEXUALITY

10. Disinhibition Syndrome
related terms:
“emotional incontinence”
“pathological emotionalism”
“pseudobulbar affect”
postulated cause
 disconnection of frontal lobe control from limbic
(emotional) brain regions

11. IEED- involuntary emotional
expression disorder

12. Behavioral and Psychological Disturbances
 Behavioral and psychological symptoms of dementia
(BPSD) include non-cognitive symptoms and behaviors
that commonly occur in patients with dementia.
Lawlor B. Br J Psychiatry. 2002
 They include psychotic symptoms, mood symptoms,
aberrant motor behaviors, and inappropriate behaviors.
 BPSD occurs due to both anatomical and biochemical
changes within the brain. Psychological factors such as
premorbid neuroticism and low frustration tolerance
appear to predispose individuals to develop BPSD.
McIlroy S, Craig D. Curr Alzheimer Res. 2004

13. Mild Behavioral Dysfunction

14. The advantages of early
detection
 Early detection of BPSD:
- enables the clinician to identify and treat problem
behaviors earlier
- reducing patient suffering and prevent caregiver
burnout
- protect the patient’s social support structure
- anticipate dementia?
 There are several behavioral markers for earlier detection
of Dementia and these are not limited to Alzheimer’s
Disease
 Behavioral markers have also been shown to be accurate
in predicting the conversion from MCI to AD

15.  Patients diagnosed with mild cognitive impairment (MCI)
present with a higher rate of NPS than healthy people
 Moreover, in the MCI population, the risk of developing
dementia is high when NPS are present
 Patients with a diagnosis of mild behavioral impairment
(MBI), even those with normal cognition, show a notably
increased risk of progression to degenerative dementia

16. Depression as a predictor of MCI
conversion to AD. Collins, 2013
c-
ia
al
on
ia
r-
ot
al
m-
or
re
ng
dementia during follow-up was 2.6 times greater if depression
was present in MCI subjects at baseline.6
Another longitudi-
nal study showed an increased presence of depression, from
baseline status, in patients who developed cognitive impair-
ment and dementia versus the control population with stable
cognition and healthy patients,32
concluding that depressive
symptoms are associated with cognitive decline. However,
the importance of depression as a risk factor for developing
dementia could not be demonstrated in other studies. 5,33
Butters et al34
propose that depression alters an indi-
vidual’s risk of cognitive dysfunction, shortening the latent
period between the development of AD neuropathology and
the onset of clinical dementia, thus increasing the incidence
and prevalence of AD among older adults with depression.
Apathy (lack of motivation, diminished goal-directed
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Dovepress
1446
NPSin MCI
Various empirical studies have been developed to investigate
NPS in MCI. Table 2 summarizes data from the last 3 years.
Depression is the most studied symptom in MCI and
dementia.The most frequent depressive symptoms observed
in these patients are irritability, impairment of attention
and concentration, paranoid and obsessive thoughts, lack
of insight, psychomotor retardation, and weight loss. The
prevalence of depressive symptoms may be as high as 45%.31
In a large prospective study, the possibility of converting to
to
an
an
D
v
fo
o
th
1

17. Sleep as a predictor?
 REM Behavior Disorder (RBD) can be early marker
for development of neurodegenerative diseases.
 RBD is characterized by the acting out of dreams that
are vivid, intense, and violent. Dream-enacting
behaviors include talking, yelling, punching, kicking,
sitting, jumping from bed, arm flailing, and grabbing.
 More than half of those with RBD will eventually
exhibit signs and symptoms of a neurodegenerative
neurological disorder gradually over months or years.
Vyas U, BJMP 2012

18. Apathy as a predictor
 Apathy (lack of motivation, diminished goal directed
behavior, decreased emotional engagement) is seen is
as many as one-third of all patients with MCI.
Apostolova LG & Cummings JL. Dement. Geriatr Cogn Disord
2008; 25(2):115-126
 Persons with mild cognitive impairment were more likely
to convert to AD a year later if they also had apathy.
Robert, Clin Neurol Neurosurg. 2006
 One European study showed a 7 fold risk of conversion from
Amnestic MCI to AD when Apathy was a core symptom.
Palmer K. J Alzheimers Dis
2010;20(1); 175-183

19. Anxiety as a predictor
 Anxiety, defined as excessive apprehension and
a feeling of foreboding is the third most common
BPS
 Demey found that 37% of all patients with MCI
had anxiety when compared with 5% of the
control group (Vertex 2007; 18(74): 252-57)
 People with MCI & anxiety were found in a 3 year
study to have a higher risk predictor of
progression to AD (Palmer K. Neurology 2007;
68(19): 1596-1602

20. Other BPS in MCI
 Irritability has been reported to be as common as
20% of all patients with MCI in a large community
based study (Geda et al. Arch Gen Psych 2008;
65(10): 1193-98
 Other symptoms like agitation, delusions &
psychotic symptoms may be markers of rapid
cognitive decline and represent major risk of
developing dementia

21. Behavioral correlates of FTD
 Executive dysfunction with prominent behavioral
symptoms
 Early:
 Set aside personal and professional responsibilities
 Lose empathy for others
 Unaware of goings on in their environment
 Cannot perceive complex social emotions: shame, guilt,
pride, embarassment
 Late
 Disinhibition
 Apathy
 Dramatic changes in personal care: personal hygiene &
dressing
 Hyper-orality, Hyper-metamorphosis, altered eating
behavior, hypersexuality (Kluver-Bucy syndrome)
 Affective disorder, visual and auditory agnosia,
anosognosia

22. Hypersexual Behavior
 Hypersexual behavior may be a particular feature of
behavioral variant frontotemporal dementia (bvFTD),
which affects ventromedial frontal and adjacent anterior
temporal regions specialized in interpersonal behavior.
 On comparing the behavior with AD, it has been found
that it is uniquely associated bvFTD. Mendez &
Shapira. Arch Sex Behav. 2013

23. Are there sensitive time periods for dementia caregivers? The
occurrence of behavioral and psychological symptoms in the
early stages of dementia
K. A. Ornstein1,2, J. E. Gaugler3, D. P. Devanand4,5, N. Scarmeas5, C. W. Zhu1, and Y. Stern5
1Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount
Sinai, New York, New York, USA
2Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York,
New York, USA
3School of Nursing, University of Minnesota, Minneapolis, Minnesota, USA
4Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and
Surgeons, Columbia University, New York, New York, USA
5Taub Institute and the Department of Neurology, Columbia University Medical Center, New York,
New York, USA
Abstract
Background—The behavioral and psychological symptoms associated with dementia (BPSD)
Published in final edited form as:
Int Psychogeriatr. 2013 September ; 25(9): 1453–1462. doi:10.1017/S1041610213000768.
that occur during early stage dementia with subsequent caregiver depressive symptoms.
Methods—Patients were followed from the early stages of dementia every six months for up to
12 years or until death (n = 160). Caregiver symptoms were assessed on average 4.5 years
following patient’s early dementia behaviors. A generalized estimating equation (GEE) extension
of the logistic regression model was used to determine the association between informal caregiver
depressive symptoms and BPSD symptoms that occurred at the earliest stages dementia, including
those persistent during the first year of dementia diagnosis.
Results—BPSD were common in early dementia. None of the individual symptoms observed
during the first year of early stage dementia significantly impacted subsequent caregiver
depressive symptoms. Only patient agitation/aggression was associated with subsequent caregiver
depressive symptoms (OR = 1.76; 95% CI = 1.04–2.97) after controlling for concurrent BPSD,
although not in fully adjusted models.
© International Psychogeriatric Association 2013
Correspondence should be addressed to: K. A. Ornstein, Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of
Medicine at Mount Sinai, New York, NY 10029, USA. Phone: 212-659-5555; Fax: 212-849-2566. katherine.ornstein@mssm.edu.
Conflict of interest
None.
Conclusions—Persistent agitation/aggression early in dementia diagnosis may be associated
with subsequent depressive symptoms in caregivers. Future longitudinal analyses of the dementia
caregiving relationship should continue to examine the negative impact of persistent agitation/
aggression in the diagnosis of early stage dementia on caregivers.
eywords
in et al.

24. Table 2 Neuropsychiatric symptoms in mild cognitive impairment. Datareviewed from 2010 to 2012
Study Patients Objective Conclusions
Somme et al87
132 To identify NPSthat predict the progression
from a-MCI to dementiausingan
easy-to-administer screeningtool for NPS
Faster progression to dementiawas observed in
patients with either night-time behavioral disturbance,
apathy, or anxiety as well as in those with ahigher
number of items affected
Peters et al88
230 To examine the association of NPSseverity
with risk of transition to all-cause dementia,
AD and VaD
The presence of at least one NPSwas arisk factor
for all-cause dementia, as was the presence of NPS
with mild severity. Night-time behaviors were arisk
factor for all-cause dementiaand of AD, whereas
hallucinations were arisk factor for VaD
Shahnawaz et al89
767 To study the prevalence and characteristics
of depressive symptoms in MCI
Individuals with MCI symptoms, when compared
especially with a-MCI, express more depressive
symptoms than cognitively intact individuals.
These fin
d
i ngs hi ghl ight the imp or tance of assessi ng
and treatingdepressive symptoms in MCI
Richard et al90
397 To investigate if apathy predicts the
progression from MCI to AD
Symptoms of apathy, but not of depressive affect,
increase the risk of progression from MCI to AD.
Apathy in the context of symptoms of depressive affect
does not increase this risk. Symptoms of apathy and
depression have differential effects on cognitive decline
Lee et al91
243 To examine the neuroanatomical changes
associated with depressive symptoms in MCI
Depressive symptoms were associated with greater
atrophy in AD-affected regions, increased cognitive
decline, and higher rates of conversion to AD.
Depression in individuals with MCI may be associated
with underlyingneuropathological changes, including
prodromal AD, and may be apotentially useful clinical
marker in identifyingMCI patients who are most likely
to progress to AD
Gallagher et al92
161 To determine whether NPStrack existing
measures of decliningcognitive and functional
status or may be considered distinct and
sensitive biomarkers of evolvingAlzheimer’s
NPSand, in particular, anxiety symptoms are common
in patients with MCI. In this sample, anxiety for
upcomingevents and purposeless activity frequently
co-occurred and were signific
a
nt cl ini cal pr edi ct or sd

25. to progress to AD
Gallagher et al92
161 To determine whether NPStrack existing
measures of decliningcognitive and functional
status or may be considered distinct and
sensitive biomarkers of evolvingAlzheimer’s
pathology
NPSand, in particular, anxiety symptoms are common
in patients with MCI. In this sample, anxiety for
upcomingevents and purposeless activity frequently
co-occurred and were signific
a
nt cl ini cal pr edi ct or s
of earlier conversion to AD. However, these fin
d
i ngs
were not independent of cognitive status at baseline
and therefore may be markers of severity rather than
independent predictors of disease progression
Chan et al93
321 To explore the association between NPSand
risk of cognitive decline in Chinese older
persons residingin the community
Depression in non-demented older patients may
represent an independent dimension refle
c
t ing earl y
neuronal degeneration. Further studies should be
conducted to assess whether effective management
of NPSexerts benefic
i
al ef fect s on cogni tive funct ion
Ryu et al94
220 To determine the persistence of NPSover 6
months in participants with MCI
NPSwere highly persistent overall in older people
with MCI. Persistence was predicted by havingmore
severe symptoms at baseline. Clinically signific
a
nt
levels of NPSwere associated with decreased quality
of life. We conclude that clinicians should be aware
that NPSsymptoms in MCI usually persist
Palmer et al5
131 To evaluate whether depression or apathy
in patients with a-MCI increases the risk of
progressingto AD
Apathy, but not depression, predicts which patients
with a-MCI will progress to AD. Thus, apathy has an
important impact on a-MCI and should be considered
amixed cognitive/psychiatric disturbance related to
ongoingAD neurodegeneration
Ramarkers et al95
263 To investigate the predictive accuracy of
affective symptoms for AD duringafollow-up
study in subjects with MCI, and whether the
predictive accuracy was modifie
d
by age, the
presence of a-MCI or the length of follow-up
Affective symptoms are associated with adecreased
risk for AD. The risk may be dependent on MC I
subtype or length of follow-up, but it does not
depend on age
Abbreviations: AD, Alzheimer’sdisease; a-MC I, amnestic mild cognitive impairment; NPS, neuropsychiatric symptoms; VaD, vascular dementia.

26. Take home messages
 A range of neuropsychiatric symptoms (NPS) also
called behavioral & psychological symptoms (BPS)
underlie MCI and dementia
 Depression, apathy and anxiety have specific
importance in predicting the conversion of amnestic
MCI to AD
 Irritability is seen in about 20% of patients and may be
more prevalent in multi-domain MCI
 NPS/BPS can be correlated with various
neurobiological changes seen in imaging and are
reflective of the ongoing neurodegenerative process
 NPS/ BPS (like cognitive decline) are core symptoms
of dementia and need to be better researched.

27. Thank You for your attention