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