behaviour as predictor of dementia
TRANSCRIPT
Dr. Ennapadam.S. KrishnamoorthyMD., 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
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
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
ORBITOFRONTAL SYNDROME
DISINHIBITION
INAPPROPRIATE AFFECT
IMPAIRED JUDGEMENT
DISTRACTIBILITY
DORSOLATERAL SYNDROME
EXECUTIVE FUNCTION DEFECTS
PERSEVERATION
STIMULUS-BOUND BEHAVIOUR
DIMINISHED VERBAL FLUENCY
MEDIAL FRONTAL SYNDROME
• APATHY• MUTISM• TRANSCORTICAL
APHASIA• LOWER EXTREMITY
PARESIS• INCONTINENCE
The limbic system & its connections
Geschwind’s Temporal Lobe PersonalityA behavioural syndrome described in temporal lobe epilepsy characterised by
intensified and labile emotionalityviscosity (orderliness, excessive attention to
detail and persistence)Hypo-sexuality Hyper-religiosityHyper-graphia
GESCHWIND & KLUVER-BUCY
HYPERCONNECTIONEMOTIONAL
INTENSITYVISCOSITYHYPOSEXUALITY
DISCONNECTIONPLACIDITYHYPERMETAMOR-
PHOSISHYPERSEXUALITY
Disinhibition Syndrome
related terms:
“emotional incontinence”
“pathological emotionalism”
“pseudobulbar affect”
postulated cause disconnection of frontal lobe control from limbic
(emotional) brain regions
IEED- involuntary emotional expression disorder
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
Mild Behavioral Dysfunction
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
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
Depression as a predictor of MCI conversion to AD. Collins, 2013
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
Apathy as a predictorApathy (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
Anxiety as a predictorAnxiety, 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
Other BPS in MCIIrritability 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
Behavioral correlates of FTDExecutive dysfunction with prominent behavioral symptomsEarly:
Set aside personal and professional responsibilitiesLose empathy for othersUnaware of goings on in their environment Cannot perceive complex social emotions: shame, guilt, pride,
embarassmentLate
DisinhibitionApathyDramatic changes in personal care: personal hygiene &
dressingHyper-orality, Hyper-metamorphosis, altered eating behavior,
hypersexuality (Kluver-Bucy syndrome)Affective disorder, visual and auditory agnosia, anosognosia
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
Take home messagesA 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.
Thank You for your attention