ADHD, Alzheimer’s, and the “Paisa Mutation”

ADHD Alzheimer's Paisa

Could studying a genetically linked population shed light on a link between ADHD and Alzheimer’s Disease? That is just one of the questions researchers are pondering in studying the Paisa people of Colombia.

For generations, a disease called the “foolishness” has suddenly struck middle-age members of an extended family in Colombia’s Antioquia region.  It starts with mild forgetfulness. Soon, however, it reduces its victims to infantile incapacitation.

People here have long attributed La Bobera to a host of superstitions: a mythic priest’s revenge or touching a mysterious tree. Scientists now know it is a genetic mutation. The relatively high rates of intermarriage  has concentrated the mutation. Until the 19th Century, this population in this mountainous remained rather isolated.

The malady is a type of early-onset Alzheimer’s Disease. Scientists call it the Paisa Mutation.

It Started with a Few Spanish Families

Broadly speaking, Paisa is the name for people from Colombia’s northwest corner of Colombia.  They descend primarily from a small group of 16th Century Spanish immigrants. Many Paisas have such a particular way of speaking Spanish that some writers refer to as español antioqueño.

A mutation occurs when DNA  is damaged or changed in such a way as to alter its genetic message; that message then passes down through the generations. (More about mutations here.) By studying this mutation, researchers hope to learn more about other forms of Alzheimer’s and its treatment. 

Pam Belluck shares the dramatic details on the disease and its discovery, along with hopes for treatment, in The New York Times. (There is an article, “Alzheimer’s Stalks a Colombian Family“, and a video, “The Vanishing Mind”)

This isn’t the first time that genetic discovery has taken place in the Paisa population. In fact, researchers studying this unique population have learned much about ADHD from them, too. For example, a genetic link between ADHD and conduct disorder/oppositional defiance disorder was discovered by studying selected Paisa families (multi-generational).

“Genetic Isolates” Reveal Heritable Traits

What’s so special about the Paisa?  They are a so-called genetic isolate population. For generations, they have mixed very little, genetically speaking, with outside populations.  As the population has increased, the gene pool has thus become “concentrated.”  Thus, they provide a rare opportunity to tease apart the link between genes and the human traits/diseases the population experiences at greater-than-average rates.

ADHD, Alzheimer's, and the "Paisa Mutation"

Ethnic Finns are considered a human genetic isolate (to read about the 40 rare hereditary diseases more prevalent in Finland than anywhere else in the world, click here).  So are the inhabitants of Tristan da Cunha, pictured above, a remote island in the south  Atlantic Ocean settled by British Marines in the early 1800s. Their population is beset by asthma in greater-than-average numbers.

The Paisa and ADHD: Genetic Research

The genetic isolate that has long interested ADHD researchers, however, is Colombia’s Paisa people.

Several years ago, I enjoyed a presentation by Max Muenke, MD, on the genetic links to ADHD.  At that time, Muenke was chief and senior investigator of the Medical Genetics Branch of the National Genome Research Institute.

His team published the research mentioned above (on ADHD and conduct disorder). Below is a figure from another study: “Attention-deficit/hyperactivity disorder (ADHD): Feasibility of linkage analysis in a genetic isolate using extended and multigenerational pedigrees“.

ADHD, Alzheimer's, and the "Paisa Mutation"
Figure 1: Pedigrees of five Paisa families segregating attention-deficit/hyperactivity disorder (ADHD). These families were identified through index cases who met the DSM-IV criteria for ADHD. Using structured interviews (detailed in the text and in Ref. 33) all children and adults in these pedigrees were evaluated for ADHD and biospecimens were obtained.

More recently, the research team discovered that certain variants in one gene (LPHN3) act as a trigger for ADHD. They did this by first analyzing data from their studies of the Paisa families. Then they validated their findings by replicating the study in samples from other populations. That included two in the U.S., indicating that the mutation is not likely to be a statistical curiosity restricted to the Paisas. (Perhaps your family participated in the research.)  You can read a report about the study: Researchers Identify Gene Associated with ADHD Susceptibility.

Is there a link between the “Paisa Mutation” and the higher-than-average prevalence of ADHD among the Paisa?  That has yet to be explored.  Stay tuned.

Meanwhile, here is a presentation from Dr. Muenke:

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Thank you, Gina Pera

10 thoughts on “ADHD, Alzheimer’s, and the “Paisa Mutation””

    1. Oh dear. How did I miss that? I know that it’s an “o” and not a “u” — and got it right in most of the story.

      I will blame auto-correct! 🙂

      Thanks so much for pointing it out. Fixed!


  1. I’m Paisa 10th of 11 children. ADD+depression. My IQ is higher than average(MD,MSMH) painter and self teaching Indian American flute.
    I’m sure this mutation may be in my family, none of them with addiction issues or severe mental illness; on the other hand most are pretty intelligent and driven to improve their lives. I think our genetics predispose 50%
    of our outcomes, but learning compensation mechanisms can lead to have a normal productive life.

    1. Hi David,

      Thanks for visiting. My understanding is that the Paisa are also known for being very good businesspeople. And of course, when we’re talking about millions of people, generalizations hardly hold true.

      I feel deeply for the minority of Paisa afflicted with this Alzheimer’s-like mutation, and I hope that scientists can soon learn enough to develop a gene therapy to help them.

      Perhaps they will discover some epigenetic factors, such as diet and water supply.


  2. Very interesting article. I have a son with ADHD, but as far as we know there is no Paisa in our background! What else can cause this diagnosis?

    In Australia there is a theory that with the onset of Greek migration, this syndrome has been introduced here. They too have secular populations due to the many islands that make up Greece. I have heard that there is also a connection with “the red hair gene”. Is there any truth in any of these theories?

    1. Hi Jean,

      Thanks for your comment.

      Just to be clear: It’s not that everyone who has ADHD is descended from the Paisas.

      Rather, it is that the original Spanish families (the ancestors of modern-day Paisa) obviously carried genetic traits strong for ADHD inter-married over many generations. In other words, inbreeding reinforced these traits.

      re: Australia. I had not heard that ADHD in the Australian population has been attributed to the Greeks. The theory I have heard is that ADHD might have been high among the convicts and indentured servants who were sent from Great Britain to populate the new country.

  3. I just googled this looking for a link between adhd and alzheimers. My great grand father and great grand mother had this. My son is showing signs of adhd and I’m slowly loosing my memory and have add. So i think it’s completely genetic. Please feel free to contact. Or update on further research.

    1. Excellent query, Joanna. I’d be interested in that, too.

      I’ve long been interested in the effects of local water and soil on the population, especially when they have migrated halfway across the world. Perhaps, by staying in a region for hundreds of years, there are adaptations. And certainly, there are in utero effects that can perpetuate generation after generation. And then to move to an area with very different soil and water (maybe even more toxic levels).

      I hope this is an area where strong cross-disciplinary knowledge is applied. I’m not holding my breath, though. 😉


  4. The Masked ADDer

    Great story, Gina. It’s fascinating to see how human understanding evolves from superstitious interpretations to genetic mutations as the causal factors.

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