Frontotemporal Dementia (FTD): Insights into Wisdom and Altruism
Bruce L. Miller, MD
Abstract
FTD attacks the frontoinsular brain circuits that mediate wisdom and altruism. By contrast,
Alzheimer’s disease (AD) attacks posterior brain regions that facilitate memory, navigation,
reading and writing. These circuits function in a reciprocal fashion – turning on the frontal circuit
turns off posterior brain regions, while turning on posterior circuits turns off frontal brain
regions. The symptoms associated with FTD include profound deficits in behavior, social
cognition, moral reasoning and empathy. Conversely, navigation, writing and drawing often
remain normal or become enhanced in these same patients. Visual creativity is seen in many
patients with left frontal or temporal degeneration. In AD, some individuals show enhanced
kindness and generosity in the early stages of the illness. The phenomenology of these changes is
described, and the aspects of brain aging that protect the future of humanity are noted.
Behavioral Variant Frontotemporal Dementia (bvFTD)
Patients with behavioral variant frontotemporal dementia (bvFTD) typically present with lateonset behavioral and personality changes that can be mistaken for psychiatric disorders.1 The
earliest behavioral changes include disinhibition, socially inappropriate behavior, poor impulse
control, hyperorality, diminishing empathy and increasing apathy.2 These behaviors create a
personality that is socially disconnected from other people, shows little concern for any
difficulties they cause others, has little insight to the situation and shows poor decision making
skills. Many of these patients first show up in a neurologist’s office after shoplifting, losing large
amounts of money, being swindled, or other behaviors resulting from diminished executive
functioning. Social wisdom has disappeared. The degeneration of these frontoinsular circuits has
stripped the patient of his social cognitive abilities.
By contrast, memory, language and visuospatial skills are initially spared, and cognitive
testing may look reasonably normal despite decreased functionality in daily life. Structurally, the
imaging shows focal anterior cingulate cortex (ACC) and orbital frontoinsula (FI) degeneration,
especially in the right hemisphere.3 Disinhibition is strongly linked to atrophy in the right orbitalfrontal region and apathy correlates with dysfunction in the right cingulate and medial frontal
lobes.4
Alzheimer’s Disease (AD)
Typical Alzheimer’s disease (AD) begins with memory problems, including impairment in the
learning and retrieving of recently learned information.5 Most AD patients maintain appropriate
social behavior maintain the expected eye contact with their loved one in an experimental
laboratory environment and can become gentler and sweeter at disease onset.6 These skills help
them maintain relationships that help and support them, even if specific identities and the details
of the relationship are lost. The personality of a typical AD patient presents as someone who is
able to maintain an emotional connection and relationship with someone, even if they cannot tell
you who the person is and why they know them. In AD, brain atrophy the posterior
hippocampal-cingulo-temporal-parietal network involved in the recall of episodic memory.7 8
Normal Aging
Healthy old age brings the growth of emotional control, social flexibility, creativity, wisdom,
optimism and resilience. Older adults become more adept at mitigating or avoiding negative
emotions by focusing on positive stimuli and a positive interpretation of situations and
suppressing reactions to the negative.9 10 Over a 30-day evaluation, older individuals were more
likely than younger participants to report never experiencing guilt, shame or hostility within the
time period.11 In essence, older adults create stable positive experiences and experience fewer
and more transient negative experiences.12 Older adults show a greater increase in prefrontal
cortex (PFC) activity than younger adults when viewing emotional stimuli and may recruit a
variety of PFC regions (ventromedial, dorsal and lateral) to compensate for any age-related loss
in the area when faced with negative stimuli.13
Socially, older adults improve at recognizing emotions when tested with dynamic,
naturalistic stimuli (i.e., emotionally laden, unrehearsed, interactions between real married
couples).14 This age-related increase in emotion recognition helps older people form stronger
social networks for support and enjoyment, which in turn can help promote cognitive and
physical wellbeing through lowered blood pressure, stress, and loneliness as well as mental
engagement and stimulation. Older adults are also tend for forgive more readily and quickly15,
which may further improve their relationships.
In support of the common sense that wisdom increases with age, a large, randomly
selected sample of older adults showed an increased composite score for wisdom in studies of
societal and interpersonal conflict, despite a concurrent age-related decline in Wechsler Adult
Intelligence Score IQ.16 These gains seem to occur mainly between 60 and 80 years old.
Reciprocal Networks
Human brain activity occurs within spatially distinct, functionally related groups of cortical and
subcortical regions.17 18 19 20 21 These functional and structural networks can be imaged on fMRI
and monitored for change due to activity or disease. Neurodegenerative diseases such as bvFTD
and AD disrupt specific, separate networks – leading to the distinct clinical syndromes. AD
affects the default mode network involved in episodic memory while FTD interrupts the
emotional salience processing network. 22 The AD and FTD circuits also function in a reciprocal
fashion. 23 Activity in the frontal circuit inhibits posterior brain regions, while turning on
posterior circuits turns off frontal brain regions. This reciprocity provides some insight into the
clinical strengths and deficits seen in patients with these diseases.
Discussion
Neurodegenerative diseases like bvFTD and AD offer insights into how the brain functions due
to the selective destruction of specific networks. We see skills diminished in isolation while
other skills thrive, based on the connectivity patterns between neurons. These changes raise
interesting questions about who we are and what is our capacity for self determination. They also
foster compassion, with increased understanding of the patient’s experience and perspective.
These networks may be able to serve as early markers of disease and disease progression.
Ultimately, these networks may be able to spread therapeutics along a vulnerable track and
protect or restore function.
Popular culture today tends to idolize youth and fear, even demonize aging. Aging is seen
as a process of steady destruction and demise. While yes, there are physical and cognitive
challenges associated with aging, this view misses the joys and strengths of aging: improved
emotional well-being, improved ability to resolve highly emotional problems like interpersonal
conflicts, the accumulation of wisdom and experience, increased resilience to bounce back from
difficulties, creativity, generosity and concerns for future generations. These skills are critical to
the survival and evolution of human society. Many of our great artists, leaders and humanitarians
barely got started until their golden years. Appreciating and finding the appropriate ways for
elderly citizens to contribute to a community is a winning strategy for any society.
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